Appl Microbiol Biotechnol . 2005 Jan 6; {Epub ahead of print} Hydrolysis of terpenyl glycosides in grape juice and other fruit juices: a review; Maicas S et al.; The importance of monoterpenes on varietal flavour of must and other fruit juices has been reviewed . These compounds were mainly found linked to sugar moieties in grape juice and wines, showing no olfactory characteristics . In this way, analytical techniques developed to study these compounds, in both free or glycosidically forms, are discussed . Mechanisms to liberate terpenes were studied, making a comparative study between acidic and enzymic hydrolysis of terpene glycosides; as enzymic hydrolysis seems to be the most natural way to liberate terpenes, the ability to use glycosidases from grapes, yeasts, bacterial or exogenous, i.e . fungal commercial preparations, were reviewed . Re-arrangements of terpenes after acidic hydrolysis of glycoconjugated are discussed as well as potential adverse effects of enzyme preparations. J Photochem Photobiol B, 2005 Jan 14, 78(1), 1 - 6 A comprehensive overview of photodynamic therapy in the treatment of superficial fungal infections of the skin; Calzavara-Pinton PG et al.; Photodynamic therapy (PDT) is a two-step procedure, involving the topical or systemic administration of a photosensitizer followed by selective illumination of the target lesion with visible light, which triggers the oxidative photodamage and subsequent cell death within the target area . In dermatology, PDT has proven to be a useful treatment for a variety of malignant tumors and selected inflammatory diseases . In addition, PDT of several infective viral or bacterial skin diseases has been investigated . These investigations grew out of the positive findings of studies of another important use of PDT: that of disinfection of blood products . Up to now, little has been published concerning the application of PDT to fungi, probably due to the fact that research funding has been mainly directed towards blood disinfection, and these pathogens show a low risk of transfusion transmission . However, preliminary findings have demonstrated that dermatophytes and yeasts can be effectively sensitized in vitro by administering photosensitizers belonging to four chemical groups: phenothiazine dyes, porphyrins and phthalocyanines, as well as aminolevulinic acid, which, while not a photosensitizer in itself, is effectively metabolized into protoporphyrin IX . Besides efficacy, PDT has shown other benefits . First, the sensitizers used are highly selective, i.e., fungi were killed at combinations of drug and light doses much lower than that needed for a similar effect on keratinocytes . Second, all investigated photosensitizers lack genotoxic and mutagenic activity . Finally, the hazard of selection of drug resistant fungal strains was never reported . This paper intends to provide a comprehensive overview of investigative studies about the effects of PDT on yeasts and dermatophytes, and bring attention to this application of PDT which we believe very important in that skin mycosis is so common and PDT is not only cost-effective, but also has the advantages of being highly selective and avoiding the occurrence of drug resistant strains. Ontogenez, 2004 Nov-Dec, 35(6), 415 - 23 {Similarity of domain organization of proteins in phylogenetically distant organisms as a basis of meiosis conservatism}; The search for new antifungal drugs and strategies continues; MWEC, Glasgow, UK . 100344.1432@compuserve.comMuch of the research presented at the 4th Congress of the European Confederation of Medical Mycology involved new ways of combating the problem of resistance to antifungal agents . Among the possible ways forward in medical mycology are improvements in the bioavailability of existing agents, more clinical testing of new agents and further development of the lipid formulations of amphotericin B . A current major concern of clinicians is that they are now seeing the appearance of cross-resistance between a number of previously very effective antifungals drugs . New in vitro results of terbinafine were presented at this congress, along with the latest information on voriconazole . There is little doubt that the only way to combat emerging drug resistance is at a subcellular level . This will require a much more detailed understanding than we have at present of how fungi and yeasts work . (c) 1998 Prous Science . All rights reserved. Biotechnol Lett, 2004 Sep, 26(18), 1413 - 20 Transgenic expression in tobacco of a poly-proctolin construct leading to production of the bioactive peptide; Rao R et al.; Short peptides can be expressed in plants using synthetic genes encoding multiple copies of the peptide spaced by dibasic endoproteolytic cleavage sites . A synthetic gene encoding an array of repeated copies of proctolin, a very well characterized insect myotropic peptide, spaced by Arg residues, was synthesized and expressed in tobacco plants . The successful production of bioactive proctolin from the precursor in transgenic plants was demonstrated by immunoblot, HPLC, mass spectrometry and a bioassay based on the contraction of isolated cockroach hindgut . These results suggest that in planta, as in animals and yeasts, endopeptidases of the serine proteases family may be involved in precursor processing. Int Rev Cytol, 2004, 242, 55 - 120 Morphodynamics of the Secretory Pathway; Kepes F et al.; A careful scrutiny of the dynamics of secretory compartments in the entire eukaryotic world reveals many common themes . The most fundamental theme is that the Golgi apparatus and related structures appear as compartments formed by the act of transporting cargo . The second common theme is the pivotal importance for endomembrane dynamics of shifting back and forth the equilibrium between full and perforated cisternae along the pathway . The third theme is the role of a continuous membrane flow in anterograde transfer of molecules from the endoplasmic reticulum through the Golgi apparatus . The last common theme is the self-regulatory balance between anatomical continuities and discontinuities of the endomembrane system . As this balance depends on secretory activity, it provides a source of morphological variability among cell types or, for a given cell type, according to environmental conditions . Beyond this first source of variability, it appears that divergent strategies pave the evolutionary routes in different eukaryotic kingdoms . These divergent strategies primarily affect the levels of stacking, of stabilization, and of clustering of the Golgi apparatus . They presumably underscore a trade-off between versatility and stability to adapt the secretory function to the degree of environmental variability . Nonequilibrium secretory structures would provide yeasts, and plants to a lesser extent, with the required versatility to cope with ever changing environments, by contrast to the stabler milieu interieur of homeothermic animals. Mol Biol Cell . 2004 Dec 9; {Epub ahead of print} EB1 Is Essential during Drosophila Development and Plays a Crucial Role in the Integrity of Chordotonal Mechanosensory Organs; Elliott SL et al.; Monitoring Editor: Lawrence Goldstein EB1 is a conserved microtubule plus end tracking protein considered to play crucial roles in microtubule organization and the interaction of microtubules with the cell cortex . Despite intense studies carried out in yeasts and cultured cells, the role of EB1 in multicellular systems remains to be elucidated . Here we describe the first genetic study of EB1 in developing animals . We show that one of the multiple Drosophila EB1 homologues, DmEB1, is ubiquitously expressed and has essential functions during development . Hypomorphic DmEB1 mutants show neuromuscular defects, including flightlessness and uncoordinated movement, without any general cell division defects . These defects can be partly explained by the malfunction of the chordotonal mechanosensory organs . In fact, electrophysiological measurements indicated that the auditory chordotonal organs show a reduced response to sound stimuli . The internal organization of the chordotonal organs is also affected in the mutant . Consistently, DmEB1 is enriched in those regions important for the structure and function of the organs . Therefore, DmEB1 plays a crucial role in the functional and structural integrity of the chordotonal mechanosensory organs in Drosophila. J Environ Monit, 2004 Nov, 6(11), 866 - 73 Epub 2004 Oct 07. Intervention study of airborne fungal spora in homes with portable HEPA filtration units; Cheong CD et al.; The concentrations and composition of airborne fungal spores in homes fitted with portable HEPA filtration units were examined to provide information to evaluate the importance of varying levels of fungal spores in residential environments in Perth, Australia . A novel method for simulating activity/impaction on carpeted environments was also investigated . Reductions in fungal (35%) and particulate (38%) levels were achieved in the air filter homes . Penicillium, Cladosporium and yeasts were the most common and widespread fungi recovered indoors and outdoors . Fungal range decreased over the study period but this could be due to an overall reduced dissemination of spores (less spores in the air). Proc Natl Acad Sci U S A, 2004 Nov 16, 101(46), 16379 - 84 Epub 2004 Nov 16. Activation of Arp2/3 complex-dependent actin polymerization by plant proteins distantly related to Scar/WAVE; Frank M et al.; The Arp2/3 complex, a highly conserved nucleator of F-actin polymerization, plays a key role in the regulation of actin dynamics eukaryotic cells . In animal cells and yeasts, Wiskott-Aldrich Syndrome protein (WASP)/suppressor of cAMP receptor (Scar)/WASP family verprolin homologous (WAVE) family proteins activate the Arp2/3 complex in response to localized cues . Like other eukaryotes, plants have an Arp2/3 complex, which has recently been shown to play an important role in F-actin organization and cell morphogenesis . However, no activators of the Arp2/3 complex have been identified in plants, which lack obvious homologs of WASP/Scar/WAVE family proteins . Here, we identify a family of Scar/WAVE-related plant Arp2/3 activators . Like Scar/WAVE proteins, four proteins identified in Arabidopsis thaliana (AtSCAR1 to AtSCAR4) and one in maize (ZmSCAR1) have a C-terminal WASP homology 2 (WH2)/acidic (WA)-verprolin homology/cofilin homology/acidic (VCA)-like domain, which we show can activate the bovine Arp2/3 complex . At their N termini, AtSCAR1 to ATSCAR4, along with a fifth protein lacking a VCA/WA-like domain at its C terminus (At4g18600), are related to the N-terminal Scar homology domains of Scar/WAVE family proteins . Analysis of gene expression patterns suggests functional redundancy among members of the AtSCAR family . Full-length AtSCAR1 and ATSCAR3 proteins and their Scar homology domains bind in vitro to AtBRICK 1 (AtBRK1), the Arabidopsis homolog of HSPC300, a WAVE-binding protein recently identified as a component of a complex implicated in the regulation of Scar/WAVE activity . Thus, AtSCAR proteins are likely to function in association with AtBRK1, and perhaps other Arabidopsis homologs of WAVE complex components, to regulate activation of the Arp2,3 complex in vivo. Blood Cells Mol Dis, 2004 Nov-Dec, 33(3), 248 - 55 Prospects for dendritic cell vaccination against fungal infections in hematopoietic transplantation; Perruccio K et al.; Dendritic cells (DCs) are uniquely able to initiate and control the immune response to fungi . DCs function at three levels in the manipulation of the immune response to these pathogens . First, they mount an immediate or innate response to them, for example, by producing inflammatory mediators upon capture and phagocytosis; second, through these preceding innate functions, they decode the fungus-associated information and translate it in qualitatively different Th responses, and third, they are key in containing and dampening inflammatory responses by tolerization through the induction of regulatory T cells (Treg) . DCs sense fungi in a morphotype-specific manner, through the engagement of distinct recognition receptors ultimately affecting cytokine production and costimulation . Both myeloid and plasmacytoid murine and human DCs phagocytose fungi and undergo functional maturation in response to them . However, their activation program for cytokine production was different, being IL-12 mainly produced by myeloid DCs and IL-12, IL-10 and IFN-alpha mainly produced by plasmacytoid DCs . This resulted in a distinct ability for T cell priming, being Th1, Th2, and Treg differently activated by the different DC subsets . The ability of fungus-pulsed DCs to prime for Th1 and Th2 cell activation upon adoptive transfer in vivo correlated with the occurrence of resistance and susceptibility to the infections, respectively . Antifungal protective immunity was also induced upon adoptive transfer of DCs transfected with fungal RNA . The efficacy was restricted to DCs transfected with RNA from yeasts or conidia but not with RNA from fungal hyphae . The effect was fungus-specific, as no cross-protection was observed upon adoptive transfer of DCs pulsed with either fungal species . The infusion of fungus-pulsed or RNA-transfected DCs accelerated the recovery of functional antifungal Th1 responses in mice with allogeneic hematopoietic stem cell transplantation (HSCT) and affected the outcome of the infections . As the ability of phagocytose fungi was defective in peripheral DCs from patients with HSCT, soon after the transplant, our findings suggest that the adoptive transfer of DCs may restore immunocompetence in HSCT by contributing to the educational program of T cells . Thus, the remarkable functional plasticity of DCs in response to fungi can be exploited for the deliberate targeting of cells and pathways of cell-mediated immunity in response to fungal vaccines. J Evol Biol, 2004 Nov, 17(6), 1204 - 14 A phylogenomic approach to reconstructing the diversification of serine proteases in fungi; Hu G et al.; Using a phylogenomic approach with 10 fungi of very different virulence and habitat, we determined that there was substantial diversification of subtilase-type proteases early in ascomycete history (with subsequent loss in many lineages) but with no comparable diversification of trypsins . Patterns of intron loss and the degree of divergence between paralogues demonstrated that the proliferation of proteinase K subtilases and subtilisin type subtilases seen in pathogenic ascomycetes (Metarhizium anisopliae, Magnaporthe grisea, Fusarium graminearum) occurred after the basidiomycete/ascomycete split but predated radiation of ascomycete lineages . This suggests that the early ascomycetes had a lifestyle that selected for multiple proteases, whereas the current disparity in gene numbers between ascomycete lineages results from retention of genes in at least some pathogens that have been lost in other lineages (yeasts, Aspergillus nidulans, Neurospora crassa) . A similar prevailing trend towards lineage specific gene loss of trypsins in saprophytes and some pathogens suggests that their phylogenetic breadth will have been much wider in early fungi than currently. Nat Rev Genet, 2004 Oct, 5(10), 773 - 82 How did alternative splicing evolve? Ast G. Alternative splicing creates transcriptome diversification, possibly leading to speciation . A large fraction of the protein-coding genes of multicellular organisms are alternatively spliced, although no regulated splicing has been detected in unicellular eukaryotes such as yeasts . A comparative analysis of unicellular and multicellular eukaryotic 5' splice sites has revealed important differences - the plasticity of the 5' splice sites of multicellular eukaryotes means that these sites can be used in both constitutive and alternative splicing, and for the regulation of the inclusion/skipping ratio in alternative splicing . So, alternative splicing might have originated as a result of relaxation of the 5' splice site recognition in organisms that originally could support only constitutive splicing. Mycoses, 2004 Oct, 47(9-10), 418 - 21 Itraconazole corneofungimetry bioassay on Malassezia species; Pierard GE et al.; Yeasts of the genus Malassezia are part of the normal skin biocenosis and are involved in a series of distinct skin disorders and specific dermatomycoses in man and animals . Several species are currently distinguished . Their relative in vitro susceptibility to antifungals appears different according to the species and to the nature and route of administration of the drug . Corneofungimetry is an ex vivo bioassay allowing to test the fungal response on human stratum corneum following oral intake of a given antifungal by volunteers . Two series of cyanoacrylate skin surface strippings (CSSS) were harvested from the volar forearm of 30 volunteers before and after a 2-week treatment with itraconazole 200 mg daily . They were coated by olive oil and inoculated with suspensions of seven different Malassezia spp . After a 1-week culture on CSSS, the amount of viable yeasts was assessed using neutral red staining assisted by computerized image analysis . Growth of the seven species was not similar on the CSSS from untreated stratum corneum . The ranking order from the most proliferative to the least was M . restricta, M . sympodialis, M . globosa, M . furfur, M . obtusa, M . slooffiae and M . pachydermatis . Their growth was abated to almost the same level after itraconazole treatment . It is concluded that in vivo treatment with itraconazole is highly active against all Malassezia spp . colonizing the human stratum corneum. Turk J Pediatr, 2004 Jul-Sep, 46(3), 245 - 50 The relationships between candidemia and candidal colonization and virulence factors of the colonizing strains in preterm infants; Cerikcioglu N et al.; Premature infants are at high risk of developing candidal infections originating from their own normal flora or from the hospital environment . This study involves the surveillance cultures and blood cultures of candidemic preterm infants with low birth weights who have been analyzed for colonization period and status, and for virulence factors such as acid proteinase and phospholipase . Arbitrarily primed-polymerase chain reaction (AP-PCR) was applied to the blood culture isolates of the babies with candidemia and their last colonizing strains in order to determine whether the source of fungemia was the rectum . Of 65 colonized infants, 6.2% developed candidemia with identical strains originating from their rectum according to their PCR patterns . Our findings indicate that the properties of the colonizing yeasts such as increase in number--although not statistically significant because of the small sample size--and/or exhibition of strong hydrolytic enzyme activities through a long duration of colonization might contribute to the development of candidemia in preterms. Mol Cell, 2004 Oct 22, 16(2), 235 - 44 Modulation of transcription affects mRNP quality; Jensen TH et al.; Cotranscriptional loading of proteins onto nascent transcripts contributes to the formation of messenger ribonucleoprotein particles (mRNPs) competent for nuclear export . The transcription machinery is believed to play a pivotal role in mRNP assembly, which is at least partially linked to the function of the THO/TREX complex and the mRNA termination/polyadenylation apparatus . Here we demonstrate a prominent role for the rate of transcription in the production of export-competent mRNPs . We show that a transcription-defective allele of the Rad3p helicase, a component of the TFIIH transcription initiation factor, suppresses several phenotypes associated with defective mRNA processing and export . Strikingly, the effects of compromised Rad3p activity can be phenocopied by a transcription elongation drug as well as by other mutations affecting transcription . Our results suggest that efficient mRNP assembly is under a kinetic control that is influenced by the rate of transcription. Annu Rev Genomics Hum Genet, 2004, 5, 15 - 56 Comparative genomics; Miller W et al.; The genomes from three mammals (human, mouse, and rat), two worms, and several yeasts have been sequenced, and more genomes will be completed in the near future for comparison with those of the major model organisms . Scientists have used various methods to align and compare the sequenced genomes to address critical issues in genome function and evolution . This review covers some of the major new insights about gene content, gene regulation, and the fraction of mammalian genomes that are under purifying selection and presumed functional . We review the evolutionary processes that shape genomes, with particular attention to variation in rates within genomes and along different lineages . Internet resources for accessing and analyzing the treasure trove of sequence alignments and annotations are reviewed, and we discuss critical problems to address in new bioinformatic developments in comparative genomics. Expert Rev Anti Infect Ther, 2004 Aug, 2(4), 485 - 97 Voriconazole: therapeutic review of a new azole antifungal; Herbrecht R; The new triazole antifungal, voriconazole (Vfend, Pfizer Ltd), was developed for the treatment of life-threatening fungal infections in immunocompromised patients . The drug, which is available for both oral and intravenous administration, has broad-spectrum activity against pathogenic yeasts, dimorphic fungi and opportunistic moulds . Unlike fluconazole (Diflucan, Pfizer Ltd), voriconazole has potent in vitro activity against Aspergillus spp., Fusarium spp . and Scedosporium apiospermum . In Phase II/III trials, voriconazole was well-tolerated and had excellent clinical efficacy in patients with fluconazole-sensitive and -resistant candida infection, aspergillosis, and various refractory fungal infections . The US Food and Drug Administration approved voriconazole in May 2002 for the treatment of invasive aspergillosis, and serious infections caused by Fusarium and S . apiospermum in patients who are intolerant of, or refractory to, other antifungal agents . In Europe, voriconazole is approved by the European Medicines Agency for the treatment of invasive aspergillosis, serious infections caused by Fusarium and S . apiospermum, and fluconazole-resistant serious invasive candida infections (including C . krusei). Rev Iberoam Micol, 2001 Mar, 18(1), 29 - 32 {Pityriasis versicolor in Santo Domingo, Dominican Republic . In vivo morphological data of Malasezzia spp . in 100 cases.}; Arenas R et al.; BACKGROUND: Pityriasis versicolor is caused by Malassezia spp . It is a common world wide mycosis . Seven species are known of the Malassezia genus, and are identified in vitro by their morphological characteristics, biochemical tests and by molecular biology . OBJECTIVES: to determine clinical and epidemiological data of pityriasis versicolor as well as morphological aspects of Malassezia in vivo . METHODOLOGY: we performed a direct examination of the scales and classified the microscopic mycological elements as oval and orbicular spores, short and long hyphae . RESULTS: pityriasis versicolor mainly affected the thorax . Orbiculare yeasts and short hyphae frequently present . We could corroborate the wide morphological range of Malassezia spp . CONCLUSIONS: The morphological study of Malassezia spp . in vivo is not sufficient to determine the distribution of the various species. J Clin Endocrinol Metab, 2004 Oct, 89(10), 5233 - 44 Wild-type p53 protein is up-regulated upon cyclic adenosine monophosphate-induced differentiation of human endometrial stromal cells; Pohnke Y et al.; Decidualization of the endometrial stromal compartment is critical for embryo implantation . Initiation of this differentiation process requires elevated intracellular cAMP levels . We now report a massive and sustained up-regulation of p53 tumor suppressor protein during cAMP-induced decidualization of cultured endometrial stromal cells . Nuclear accumulation of p53 was not accompanied by increased mRNA expression, suggesting stabilization of the protein as the underlying mechanism . Proteasomal degradation of p53 is known to be mediated by nuclear Mdm2 . Nuclear translocation of Mdm2, in turn, is dependent on phosphorylation by protein kinase B/Akt (PKB/Akt) . In cAMP-treated decidualized cells, p53 accumulation was associated with decreased nuclear Mdm2 and cytoplasmic PKB/Akt levels . Conversely, withdrawal of the decidualization stimulus resulted in morphological and biochemical dedifferentiation, disappearance of p53, but increased abundance of PKB/Akt . Furthermore, Western blot and immunohistochemical analyses of endometrial biopsies confirmed that p53 is expressed in vivo in the stromal compartment during the late secretory phase of the cycle . The observation that p53 protein expression is closely associated with decidual transformation indicates a novel role for this tumor suppressor in regulating human endometrial function. Nat Rev Mol Cell Biol, 2004 Oct, 5(10), 855 - 61 Imaging gene expression in single living cells; Shav-Tal Y et al.; Technical advances in the field of live-cell imaging have introduced the cell biologist to a new, dynamic, subcellular world . The static world of molecules in fixed cells has now been extended to the time dimension . This allows the visualization and quantification of gene expression and intracellular trafficking events of the studied molecules and the associated enzymatic processes in individual cells, in real time. BMC Genomics . 2004 Sep 20;5(1):69. Comparative genomics of cyclin-dependent kinases suggest co-evolution of the RNAP II C-terminal domain and CTD-directed CDKs; Guo Z et al.; BACKGROUND: Cyclin-dependent kinases (CDKs) are a large family of proteins that function in a variety of key regulatory pathways in eukaryotic cells, including control over the cell cycle and gene transcription . Among the most important and broadly studied of these roles is reversible phosphorylation of the C-terminal domain (CTD) of RNA polymerase II, part of a complex array of CTD/protein interactions that coordinate the RNAP II transcription cycle . The RNAP CTD is strongly conserved in some groups of eukaryotes, but highly degenerate or absent in others; the reasons for these differences in stabilizing selection on CTD structure are not clear . Given the importance of reversible phosphorylation for CTD-based transcription, the distribution and evolutionary history of CDKs may be a key to understanding differences in constraints on CTD structure; however, the origins and evolutionary relationships of CTD kinases have not been investigated thoroughly . Moreover, although the functions of most CDKs are reasonably well studied in mammals and yeasts, very little is known from most other eukaryotes . RESULTS: Here we identify 123 CDK family members from animals, plants, yeasts, and four protists from which genome sequences have been completed, and 10 additional CDKs from incomplete genome sequences of organisms with known CTD sequences . Comparative genomic and phylogenetic analyses suggest that cell-cycle CDKs are present in all organisms sampled in this study . In contrast, no clear orthologs of transcription-related CDKs are identified in the most putatively ancestral eukaryotes, Trypanosoma or Giardia . Kinases involved in CTD phosphorylation, CDK7, CDK8 and CDK9, all are recovered as well-supported and distinct orthologous families, but their relationships to each other and other CDKs are not well-resolved . Significantly, clear orthologs of CDK7 and CDK8 are restricted to only those organisms belonging to groups in which the RNAP II CTD is strongly conserved . CONCLUSIONS: The apparent origins of CDK7 and CDK8, or at least their conservation as clearly recognizable orthologous families, correlate with strong stabilizing selection on RNAP II CTD structure . This suggests co-evolution of the CTD and these CTD-directed CDKs . This observation is consistent with the hypothesis that CDK7 and CDK8 originated at about the same time that the CTD was canalized as the staging platform RNAP II transcription . Alternatively, extensive CTD phosphorylation may occur in only a subset of eukaryotes and, when present, this interaction results in greater stabilizing selection on both CTD and CDK sequences . Overall, our results suggest that transcription-related kinases originated after cell-cycle related CDKs, and became more evolutionarily and functionally diverse as transcriptional complexity increased. Nature, 2004 Sep 16, 431(7006), 364 - 70 The role of RNA interference in heterochromatic silencing; Lippman Z et al.; Soon after its discovery 75 years ago, heterochromatin, a dense chromosomal material, was found to silence genes . But its importance in regulating gene expression was controversial . Long thought to be inert, heterochromatin is now known to give rise to small RNAs, which, by means of RNA interference, direct the modification of proteins and DNA in heterochromatic repeats and transposable elements . Heterochromatin has thus emerged as a key factor in epigenetic regulation of gene expression, chromosome behaviour and evolution. J Clin Microbiol, 2004 Sep, 42(9), 4253 - 60 Identification and typing of Malassezia species by amplified fragment length polymorphism and sequence analyses of the internal transcribed spacer and large-subunit regions of ribosomal DNA; Gupta AK et al.; Malassezia yeasts are associated with several dermatological disorders . The conventional identification of Malassezia species by phenotypic methods is complicated and time-consuming, and the results based on culture methods are difficult to interpret . A comparative molecular approach based on the use of three molecular techniques, namely, amplified fragment length polymorphism (AFLP) analysis, sequencing of the internal transcribed spacer, and sequencing of the D1 and D2 domains of the large-subunit ribosomal DNA region, was applied for the identification of Malassezia species . All species could be correctly identified by means of these methods . The results of AFLP analysis and sequencing were in complete agreement with each other . However, some discrepancies were noted when the molecular methods were compared with the phenotypic method of identification . Specific genotypes were distinguished within a collection of Malassezia furfur isolates from Canadian sources . AFLP analysis revealed significant geographical differences between the North American and European M . furfur strains. Arch Pharm (Weinheim), 2004 Sep, 337(9), 493 - 501 Non-thiol farnesyltransferase inhibitors: utilization of the far aryl binding site by 5-cinnamoylaminobenzophenones; Mitsch A et al.; We recently described two novel aryl binding sites of farnesyltransferase . In this study, the cinnamoyl residue was designed as an appropriate substituent for our benzophenone-based AAX-peptidomimetic compound capable of occupying the far aryl binding site. Med Sci (Paris), 2004 Aug-Sep, 20(8-9), 761 - 6 {Dog as a mammalian genetic model}; Galibert F et al.; Up to recently, studies on dog genetics were rather scare notwithstanding the enormous potential that the canine model can offer in the study of the genotype/phenotype relationship and the analysis of the causes of many genetic diseases, with simple or complex inheritance, that affect dogs but also the human population . This potentiality is essentially due to the natural history of dogs whose domestication from wolves dated back 15,000 years, at least . All modern dogs originated from a limited number of female wolves from Eastern Asia . By applying a combination of selections and strong inbreeding practices, humans have created over 350 breeds, each of them corresponding to a genetic isolate and altogether offering a unique panel of polymorphism never encountered in any other mammals . In this review we summarized what makes dogs an unavoidable model . Contrary to the classical models like the two yeasts, nematode, fish, fly, mouse, or rat mainly used to understand the function of genes, dog with the creation across the centuries of numerous breeds offers a unique opportunity to study the role of their alleles . We report recent data on the construction of genomic maps and on the sequencing program of the dog genome launched by the National Institute of Health (NIH) . To take fully advantage of the canine model, we advocate for the systematic construction of a rich canine single nucleotide polymorphisms (SNP) ressource to perform linkage desiquilibrium studies of normal or pathological traits as well as to get insight into the genetic diversity of the canine species. Comp Med, 2004 Aug, 54(4), 434 - 7 Outbreak of sarcoptic mange and malasseziasis in rabbits (Oryctolagus cuniculus); Radi ZA; An outbreak of combined Sarcoptes and Malassezia spp . infection was diagnosed in a rabbitry . About 20 (4%) of 500 rabbits were affected . Two 6- to 8-month-old female Holland Lops rabbits were submitted to the Tifton Diagnostic & Investigational Laboratory at The University of Georgia for complete necropsy . Gross lesions consisted of marked multifocal areas of alopecia, crusting, and dermatitis around the eye and on ears, nose, lips, neck, abdomen, feet, and external genitalia . Histologic examination of the skin revealed epidermal acanthosis with marked parakeratotic hyperkeratosis and cross sections of embedded mites consistent with Sarcoptes sp . and budding yeasts consistent with Malassezia sp . To the best of the author's knowledge, this is the first case report of combined Sarcoptes and Malassezia spp . infection in rabbits. Clin Infect Dis, 2004 Sep 1, 39(5), 743 - 6 Epub 2004 Aug 13. Breakthrough fungal infections in stem cell transplant recipients receiving voriconazole; Imhof A et al.; Infection with voriconazole-resistant fungi may become problematic, because organisms with decreased susceptibility have been noted . Breakthrough fungal infections occurred in 13 of 139 patients who received voriconazole at our center during the period of September 1998 through September 2003 . Zygomycetes were found in 6 patients, and Candida glabrata bloodstream infection occurred in 4 patients . Minimal inhibitory concentrations were > or =1 microg/mL for all available isolates . Yeasts and molds with decreased susceptibility to voriconazole may cause invasive infection in patients treated successfully for aspergillosis. Plant Cell Physiol, 2004 Aug, 45(8), 1032 - 41 Identification of sorbitol transporters expressed in the phloem of apple source leaves; Watari J et al.; Sorbitol is a major photosynthetic product and a major phloem-translocated component in Rosaceae (e.g . apple, pear, peach, and cherry) . We isolated the three cDNAs, MdSOT3, MdSOT4, and MdSOT5 from apple (Malus domestica) source leaves, which are homologous to plant polyol transporters . Yeasts transformed with the MdSOTs took up sorbitol significantly . MdSOT3- and MdSOT5-dependent sorbitol uptake was strongly inhibited by xylitol and myo-inositol, but not or only weakly by mannitol and dulcitol . Apparent K(m) values of MdSOT3 and MdSOT5 for sorbitol were estimated to be 0.71 mM and 3.2 mM, respectively . The protonophore, carbonyl cyanide m-chlorophenylhydrazone (CCCP), strongly inhibited the sorbitol transport . MdSOT3 was expressed specifically in source leaves, whereas MdSOT4 and MdSOT5 were expressed in source leaves and also in some sink organs . MdSOT4 and MdSOT5 expressions were highest in flowers . Fruits showed no or only weak MdSOT expression . Although MdSOT4 and MdSOT5 were also expressed in immature leaves, MdSOT expressions increased with leaf maturation . In addition, in situ hybridization revealed that all MdSOTs were expressed to high levels in phloem of minor veins in source leaves . These results suggest that these MdSOTs are involved in sorbitol loading in Rosaceae. Langmuir, 2004 Sep 14, 20(19), 7926 - 32 Supramolecular assemblies of a naturally derived sophorolipid; Zhou S et al.; Acidic sophorolipid (SL) molecules derived from yeasts represent a novel type of asymmetrical bolaamphiphiles due to their unique structural features that include an asymmetrical polar head size (disaccharide vs COOH), a kinked hydrophobic core (cis-9-octadecenoic chain), and a non-amide polar-nonpolar linkage . Light microscopy, small- and wide-angle X-ray scattering, FT-IR spectroscopy, and dynamic laser light scattering were used to investigate the supramolecular structures of the self-assembled aggregates of SL molecules at different pH values . In acidic conditions (pH < 5.5), giant twisted and helical ribbons of 5-11 microm width and several hundreds of micrometers length were observed for the first time . Increase in solution pH values slowed ribbon formation, decreased ribbon yield, and increased the helicity and entanglements of the giant ribbons . An interdigitated lamellar packing model of acidic SL-COOH molecules with a long period of 2.78 nm, stabilized by both the strong hydrophobic association between the cis-9-octadecenoic chains and strong disaccharide-disaccharide hydrogen bonding, is proposed . The neutralization of SL-COOH in water to SL-COONa produced clear solutions with the formation of short-range ordered aggregates . At concentrations below 1.0 mg/mL, the size of self-assembled aggregates increased as the concentration increased . At concentrations above 1.0 mg/mL, narrowly distributed micellar aggregates with a constant hydrodynamic radius (R(h)) of about 100 nm are formed . The large micelles show strong angular dependence with the fast mode appearing at scattering angle theta >/= 60 degrees. Drugs, 2004, 64(18), 1997 - 2020 Newer systemic antifungal agents : pharmacokinetics, safety and efficacy; Boucher HW et al.; The past few years have seen the advent of several new antifungal agents, including those of a new class and a new generation of an existing class . Caspofungin, the first available echinocandin, has greatly expanded the antifungal armamentarium by providing a cell wall-active agent with candidacidal activity as well as demonstrated clinical efficacy in the therapy of aspergillosis refractory to available therapy . In addition, in clinical trials, caspofungin had comparable efficacy to amphotericin B for candidaemia and invasive Candida infections . Caspofungin and two more recently introduced echinocandins, micafungin and anidulafungin, are available as intravenous formulations only and characterised by potent anti-candidal activity, as well as few adverse events and drug interactions . Voriconazole, the first available second-generation triazole, available in both intravenous and oral formulations, has added a new and improved therapeutic option for primary therapy of invasive aspergillosis and salvage therapy for yeasts and other moulds . In a randomised trial, voriconazole demonstrated superior efficacy and a survival benefit compared with amphotericin B followed by other licensed antifungal therapy . This and data from a noncomparative study led to voriconazole becoming a new standard of therapy for invasive aspergillosis . Voriconazole has several important safety issues, including visual adverse events, hepatic enzyme elevation and skin reactions, as well as a number of drug interactions . Posaconazole, only available orally and requiring dose administration four times daily, shows encouraging efficacy in difficult to treat infections due to zygomycetes . Ravuconazole, available in both intravenous and oral formulations, has broad-spectrum in vitro potency and in vivo efficacy against a wide range of fungal pathogens . Clinical studies are underway . Despite the advances offered with each of these drugs, the morbidity and mortality associated with invasive fungal infections remains unacceptable, especially for the most at-risk patients . For individuals with severe immunosuppression as a result of chemotherapy, graft-versus-host disease and its therapy, or transplantation, new drugs and strategies are greatly needed. Biol Pharm Bull, 2004 Sep, 27(9), 1428 - 32 Difference in percutaneous absorption and intracutaneous distribution in guinea pigs among topical antifungal drugs (tioconazole solution, tioconazole cream, miconazole nitrate solution and bifonazole solution); Sobue S et al.; Tioconazole (TCZ) is an imidazole antifungal agent with broad spectrum activity . Percutaneous absorption and intracutaneous distribution of TCZ solution have been compared with TCZ cream, miconazole nitrate (MCZ) solution and bifonazole (BFZ) solution following a single topical application to abdominal skin of guinea pigs . Following application of TCZ solution, TCZ concentrations in the stratum corneum, epidermis-cutis and subcutaneous tissue were higher than those after TCZ cream application suggesting superior percutaneous penetration after TCZ solution application . The percutaneous penetration after applications of MCZ solution and BFZ solution was comparable to that of TCZ cream, but inferior to that of TCZ solution . TCZ concentrations in the stratum corneum were much higher than those in epidermis-cutis and subcutaneous tissue after applications of both TCZ formulations . The majority of applied TCZ remained in the stratum corneum at high levels for a long duration . TCZ concentrations in the stratum corneum within 24 h after applications of both TCZ formulations were more than several hundred times higher than the minimum inhibitory concentrations against most of the dermatophytes and yeasts . The effectiveness of both TCZ formulations against dermatophytoses may be due to this favorable pharmacokinetic property in the skin tissues, together with its potent antifungal activity . Percutaneous absorption of TCZ after applications of both formulations was negligible suggesting that these treatments are unlikely to produce systemic side effects. Skin Therapy Lett, 2004 Jun-Jul, 9(6), 4 - 5 Ciclopirox shampoo for treating seborrheic dermatitis; Gupta AK et al.; Seborrheic dermatitis is a common inflammatory skin disease, affecting between 1% and 3% of immunocompetent adults . While its cause is unknown, a number of predisposing factors have been reported, including the implications of Malassezia yeasts . Various treatment options are available, such as ciclopirox shampoo, which combines anti-Malassezia activity with an anti-inflammatory action . This agent has been shown to be an effective and safe treatment for seborrheic dermatitis of the scalp. Clin Lab Med, 2004 Sep, 24(3), 691 - 719, vi-vii Emerging fungal diseases: the importance of the host; Procop GW et al.; More yeasts and molds are now recognized to cause more human disease than ever before . This development is not due to a change in the virulence of these fungi, but rather to changes in the human host . These changes include immunosuppression secondary to the pandemic of HIV, the use of life-saving advances in chemotherapy and organ transplantation, and the use of corticosteroids and other immunosuppressive agents to treat a variety of diseases . Fungi that were once considered common saprophytes are now recognized as potential pathogens in these patients . This situation necessitates better communication than ever between the clinician, pathologist, and clinical mycologist to ensure the prompt and accurate determination of the cause of fungal diseases. Curr Biol, 2004 Aug 24, 14(16), 1487 - 91 Lsm proteins promote regeneration of pre-mRNA splicing activity; Verdone L et al.; Lsm proteins are ubiquitous, multifunctional proteins that affect the processing of most RNAs in eukaryotic cells, but their function is unknown . A complex of seven Lsm proteins, Lsm2-8, associates with the U6 small nuclear RNA (snRNA) that is a component of spliceosome complexes in which pre-mRNA splicing occurs . Spliceosomes contain five snRNAs, U1, U2, U4, U5, and U6, that are packaged as ribonucleoprotein particles (snRNPs) . U4 and U6 snRNAs contain extensive sequence complementarity and interact to form U4/U6 di-snRNPs . U4/U6 di-snRNPs associate with U5 snRNPs to form U4/U6.U5 tri-snRNPs prior to spliceosome assembly . Within spliceosomes, disruption of base-paired U4/U6 heterodimer allows U6 snRNA to form part of the catalytic center . Following completion of the splicing reaction, snRNPs must be recycled for subsequent rounds of splicing, although little is known about this process . Here we present evidence that regeneration of splicing activity in vitro is dependent on Lsm proteins . RNP reconstitution experiments with exogenous U6 RNA show that Lsm proteins promote the formation of U6-containing complexes and suggest that Lsm proteins have a chaperone-like function, supporting the assembly or remodeling of RNP complexes involved in splicing . Such a function could explain the involvement of Lsm proteins in a wide variety of RNA processing pathways. Int J Clin Pract, 2004 Jun, 58(6), 612 - 24 Posaconazole: a potent, extended-spectrum triazole anti-fungal for the treatment of serious fungal infections; Herbrecht R; Posaconazole is a potent, extended-spectrum, investigational triazole anti-fungal that is highly active in pre-clinical in vitro and in vivo models against a wide array of yeasts and moulds, including Aspergillus, Fusarium and Zygomycetes, which are often refractory to polyenes and older azoles . In humans, orally administered posaconazole is absorbed under fed or fasted conditions; however, absorption is significantly improved when it is coadministered with food or liquid nutritional supplements and when the daily dose is divided (into two or four daily doses) . Unlike newer azoles, posaconazole is not extensively metabolised by cytochrome P450 (CYP) enzymes and is primarily excreted as parent compound in the faeces . Posaconazole is a CYP3A4 inhibitor, but it does not inhibit the activity of other CYP enzymes . Therefore, in comparison with other azole anti-fungal drugs, posaconazole may have the potential for fewer drug interactions . The pharmacokinetics of posaconazole are not influenced by age, gender or race . Dose adjustments for renal or hepatic impairment do not appear to be indicated based on results from single-dose studies . Preliminary efficacy data from clinical trials are promising . As salvage therapy, posaconazole elicited complete or partial responses in 44 to 75% of patients (N = 97) with invasive fungal infections who were intolerant of, or who had disease refractory to, amphotericin B or itraconazole . In an analysis of patients with aspergillosis, a 42% success rate was observed in the posaconazole arm (n = 107) compared with a 26% success rate in the control arm (n = 86) . Importantly, Kaplan-Meier analysis demonstrated a survival benefit in posaconazole-treated patients . Moreover, posaconazole yielded complete or partial responses in 71% of patients with zygomycosis (N = 24) . Posaconazole appears to be well tolerated over long-term administration (>1 year) and may represent an important addition to the anti-fungal armamentarium. Am J Clin Dermatol, 2004, 5(4), 225 - 37 Optimal management of fungal infections of the skin, hair, and nails; Gupta AK et al.; Superficial fungal infections are chronic and recurring conditions . Tinea capitis is a scalp infection, primarily affecting prepubescent children . Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin . Tinea nigra is a rare mycotic infection that may be related to travel abroad . Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin . Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body . The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans . Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis . Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat . In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered . Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses. J Oral Sci, 2004 Jun, 46(2), 101 - 5 Oral colonization of Candida species in perinatally HIV-infected children in northern Thailand; Pongsiriwet S et al.; Human immunodeficiency virus (HIV) infection remains a serious problem in northern Thailand . A high prevalence of perinatally HIV-infected children with oral candidiasis has been observed in the region . The objective of this study was to determine oral colonization of Candida spp . in children with perinatal HIV infection . Samples were collected by oral rinse or oral swab from 40 HIV-infected children and from 15 HIV-negative children as a control group . Yeasts recovered in culture were identified and quantified . The mean ages of HIV-infected children and HIV-negative children were 5.5 years (SD = 3.5) and 2.9 years (SD = 2.0) respectively . Eighteen HIV-infected children (45%) had clinical symptoms of oral candidiasis while none of the HIV-negative children had any such symptoms . By culture technique, yeasts were isolated from 28/40 (70%) of the HIV-infected children and 6/15 (40%) of the HIV-negative children . C . albicans was the most common species recovered from HIV-infected and HIV-negative children . Statistically, HIV infection was significantly associated with Candida spp . detection (P-value = 0.04) . In contrast, the association between HIV infection and asymptomatic oral carriage of Candida spp . was not significant (P-value = 0.74) . These findings demonstrate that oral colonization of Candida spp . is prevalent in HIV-infected children and suggest that prevention and treatment of oral candidiasis is needed for these children. Mycopathologia, 2004 May, 157(4), 383 - 8 Occurrence of Malassezia species in healthy and dermatologically diseased dogs; Nardoni S et al.; The presence of Malassezia spp . yeasts was investigated in dermatological specimens of 224 dogs, 164 dermatologically diseased and 60 normal dogs . Subjects included in the study were of different breed, age, sex and habitat . Malassezia spp . positive cultures were obtained in 142 (63.4%) specimens: 67.6% from dermatologically diseased subjects and 51.6% from healthy dogs . Malassezia pachydermatis, either as a pure culture or in association with lipid-dependent species, was identified in 138 (97%) specimens . Malassezia furfur was identified in 69 (48.6%) specimens and was associated with other Malassezia species in 68 dogs, as a pure culture in one subject: at the best of our knowledge, this species was identified before as the sole species from canine dermatitis . Malassezia sympodialis was identified in 11 (7.7%) specimens, always in association with other species: it was never isolated from kennel dogs . Statistical analysis of data showed a very significant difference (P < 0.01) in the prevalence of isolation of Malassezia spp . between animals with and without dermatological signs, and in the distribution of cultural burden between diseased and healthy dogs . A statistically significant difference (P<0.05) was also detected in the group of animals between 1- and 5-years of age . No significant difference was found between male and female dogs. Proc Natl Acad Sci U S A, 2004 Aug 3, 101(31), 11263 - 8 Epub 2004 Jul 27. Alternate, virus-induced membrane rearrangements support positive-strand RNA virus genome replication; Schwartz M et al.; All positive-strand RNA {(+)RNA} viruses replicate their RNA on intracellular membranes, often in association with spherular invaginations of the target membrane . For brome mosaic virus, we previously showed that such spherules serve as compartments or mini-organelles for RNA replication and that their assembly, structure, and function have similarities to the replicative cores of retrovirus and double-stranded RNA virus virions . Some other (+)RNA viruses conduct RNA replication in association with individual or clustered double-membrane vesicles, appressed double membranes, or other structures whose possible relationships to the spherular invaginations are unclear . Here we show that modulating the relative levels and interactions of brome mosaic virus replication factors 1a and 2a polymerase (2apol) shifted the membrane rearrangements associated with RNA replication from small invaginated spherules to large, karmellae-like, multilayer stacks of appressed double membranes that supported RNA replication as efficiently as spherules . Spherules were induced by expressing 1a, which has functional similarities to retrovirus virion protein Gag, or 1a plus low levels of 2apol . Double-membrane layers were induced by 1a plus higher levels of 2apol and were suppressed by deleting the major 1a-interacting domain from 2apol . The stacked, double-membrane layers alternated with spaces that, like spherule interiors, were 50-60 nm wide, connected to the cytoplasm, and contained 1a and 2apol . These and other results suggest that seemingly diverse membrane rearrangements associated with RNA replication by varied (+)RNA viruses may represent topologically and functionally related structures formed by similar protein-protein and protein-membrane interactions and interconverted by altering the balances among those interactions. Int J Dermatol, 2004 Jul, 43 Suppl 1, 17 - 20 Safety and efficacy of ciclopirox 1% shampoo for the treatment of seborrheic dermatitis of the scalp in the US population: results of a double-blind, vehicle-controlled trial; Lebwohl M et al.; BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder . Yeasts of the genus Malassezia have been implicated in the etiology of seborrheic dermatitis, although this connection remains controversial . Ciclopirox is a synthetic, hydroxypyridone-derived, broad-spectrum antifungal agent with anti-inflammatory properties . METHODS: A total of 499 US patients with seborrheic dermatitis of the scalp were randomized to apply either ciclopirox shampoo 1% or vehicle twice weekly for 4 weeks . The main efficacy parameters were based on 6-point ordinal scales describing the disease's signs and symptoms (scaling, erythema and itching) and a 6-point scale providing a global evaluation of the status of seborrheic dermatitis . RESULTS: Ciclopirox was significantly better than vehicle in effectively treating seborrheic dermatitis . 'Effective treatment' (score of 0 or 1 for disease status, scaling and erythema) was achieved in 26.0% of ciclopirox-treated patients compared with 12.9% of vehicle-treated patients (P = 0.0001; OR: 2.383, 95% CI: 1.494-3.799) . The majority of subjects experienced adverse events that were mild in intensity, with skin and appendage reactions the most commonly reported, at similar frequency in both groups . CONCLUSIONS: Ciclopirox shampoo 1% is effective and safe in the treatment of seborrheic dermatitis of the scalp. Int J Dermatol, 2004 Jul, 43 Suppl 1, 13 - 6 Rationale of frequency of use of ciclopirox 1% shampoo in the treatment of seborrheic dermatitis: results of a double-blind, placebo-controlled study comparing the efficacy of once, twice, and three times weekly usage; Abeck D; Loprox Shampoo Dosing Study Group; BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder . Although the precise etiology of seborrheic dermatitis is uncertain, yeasts of the genus Malassezia have been implicated . Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent with anti-inflammatory properties . METHODS: A total of 183 patients were enrolled in this randomized, parallel-group, double-blind, vehicle-controlled trial designed to compare three different application frequencies of ciclopirox 1% shampoo: once, twice, and three times weekly . The main efficacy parameters were based on 6-point ordinal scales describing the disease's signs and symptoms (scaling, inflammation and itching), global status of seborrheic dermatitis, and global change of seborrheic dermatitis . RESULTS: Each application frequency of ciclopirox 1% shampoo was found to significantly improve the signs and symptoms of seborrheic dermatitis of the scalp after 4 weeks of treatment . Furthermore, the therapeutic index calculated from the global change in seborrheic dermatitis score increased with increasing application frequency; therapeutic index scores increased from vehicle (1.25) to ciclopirox 1% once (3.30), twice (3.50), and three times (3.56) weekly . No serious adverse events were recorded during the course of the study . CONCLUSIONS: Ciclopirox 1% shampoo, applied once, twice or three times weekly, is a safe and acceptable preparation that improves seborrheic dermatitis of the scalp, suggesting that this is an alternative treatment for this indication. Int J Dermatol, 2004 Jul, 43 Suppl 1, 9 - 12 Efficacy of different concentrations of ciclopirox shampoo for the treatment of seborrheic dermatitis of the scalp: results of a randomized, double-blind, vehicle-controlled trial; Altmeyer P et al.; BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder affecting 1-3% of the population . It is thought to be linked to dandruff via a common etiology, yeasts of the genus Malassezia . Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent with anti-inflammatory properties . METHODS: A total of 203 patients were enrolled in this vehicle-controlled, double-blind, randomized study designed to compare vehicle with three different concentrations of ciclopirox shampoo: 0.1%, 0.3% and 1%, with each applied twice a week . The main efficacy parameters were based on 6-point ordinal scales describing the disease's signs and symptoms (scaling, inflammation and itching), global status of disease, and global change in disease . RESULTS: A tendency towards improvement of the sum score from baseline was found in all ciclopirox treatment groups . The most pronounced improvement was found in the ciclopirox 1% group, which changed from a baseline sum score of 8.3 to 4.4 at the end of the 4-week study period (P-value vs . vehicle 0.0372) . In addition, the therapeutic index showed increasing efficacy with the use of increased concentrations of ciclopirox . CONCLUSIONS: The study supports the use of 1% ciclopirox shampoo in the treatment of seborrheic dermatitis of the scalp . Furthermore, ciclopirox shampoo at each concentration was found to be safe and well tolerated. Expert Opin Pharmacother, 2004 Aug, 5(8), 1755 - 65 Seborrhoeic dermatitis: current treatment practices; Gupta AK et al.; Seborrhoeic dermatitis (SD) is a recurrent, chronic inflammation of the skin that occurs on sebum rich areas such as the face, scalp and chest, characterised by red scaly lesions . The are many studies indicating that Malassezia yeasts play an important role in the aetiology of this condition, most of the evidence for which comes from demonstrated responsiveness to treatment with antifungal agents . Its aetiology, however, is far from being resolved . Some believe that it is the immune response of the skin to the Malassezia that is the cause of the disease . Traditional treatments of SD have been the use of keratolytic agents or corticosteroids . Since the discovery of ketoconazole, a considerable amount of research has been focused on determining the efficacy of various antifungal agents . This article reviews clinical trial data on treatment options available for SD. Microbiology, 2004 Jul, 150(Pt 7), 2029 - 35 Fungal cell wall chitinases and glucanases; Adams DJ; The fungal cell wall is a complex structure composed of chitin, glucans and other polymers, and there is evidence of extensive cross-linking between these components . The wall structure is highly dynamic, changing constantly during cell division, growth and morphogenesis . Hydrolytic enzymes, closely associated with the cell wall, have been implicated in the maintenance of wall plasticity and may have roles during branching and cross-linking of polymers . Most fungal cell wall hydrolases identified to date have chitinase or glucanase activity and this short article reviews the apparent functions of these enzymes in unicellular and filamentous fungi, and the mechanisms that regulate enzyme activity in yeasts. Bone Marrow Transplant, 2004 Sep, 34(5), 377 - 89 Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients; Hamza NS et al.; The incidence of invasive fungal infection (IFIs) in hematopoietic stem cell transplantation (HSCT) recipients ranges from 10 to 25% with an overall case fatality rate of up to 70-90% . Candida and Aspergillus genera remain the two most common pathogens . Although fluconazole prophylaxis in this population has been moderately effective in reducing mortality due to invasive candidiasis, this agent does not have activity against invasive aspergillosis (IA) and other mould . Several new agents such as voriconazole and caspofungin have enhanced potency and broad-spectrum antifungal activity and show promising results against yeasts and filamentous fungi when given as therapy and as chemoprophylaxis . Further, new diagnostic tools to detect circulating fungal antigens in biological fluids and PCR-based methods to detect species or genus-specific DNA or RNA have been developed . Incorporating these techniques along with clinical criteria appear to improve the accuracy of preclinical diagnosis of IFIs . Such approaches may alter the current treatment strategy from prophylaxis to pre-emptive therapy, thereby potentially decreasing cost and toxicity in high-risk patients. Ann Agric Environ Med, 2004, 11(1), 67 - 73 Airway toxicity of house dust and its fungal composition; Pieckova E et al.; House dust is an important source of different toxic metabolites as well as allergens, including those of fungal origin, in the indoor environment . A bio-assay employing 1-day-old chick tracheas was used to characterize airway effects of 2-butanone and dimethylsulphoxide (Me2SO) extracts of 23 dust samples collected from water damaged (13) and control (10) Danish schools . Direct microscopical analysis of samples, followed by cultivation on dichloran 18 % glycerol agar at 25 degrees C for 10 days to establish their mycoflora, was performed . The in vitro ciliostatic potential of the chloroform-extractable endo- and exometabolites of 41 representative fungal isolates was determined . Nine dust extracts in 2-butanone (2 from damp rooms) or 10 (6) in Me(2)SO showed some ciliostatic activity in the 3-days' experiment . Fungal composition of dust from buildings with leakage was almost identical with that from undamaged houses, as well as the fungal colony counts from the damp schools and the control samples . Aspergillus spp . were prevalent in the samples - 31 or 40 % of all fungi, followed by Penicillium spp . and Cladosporium cladosporioides . Alternaria spp., Chaetomium spp., Mucor spp., Mycelia sterilia, Paecilomyces variotii, Rhizopus sp., Ulocladium sp . and yeasts were each isolated in less than 8 % of the fungal content . No Aspergillus flavus isolate (8 in total) was aflatoxigenic,em>in vitro . Alternaria spp., Aspergillus spp., Botrytis cinerea, Penicillium spp., C . cladosporioides, Chaetomium spp . and Ulocladium sp.; in total, 88 % of all fungi tested, produced ciliostatically active metabolites . These toxigenic strains were also present in 4 dust samples from controls and 5 dust samples from water damaged buildings . Extracts of these dust samples were also toxic in bioassay . There were bio-detectable concentrations (10-20 microg of extracts/ml of the organ culture medium) of toxic compounds in house dust . Contribution of fungal metabolites to its toxic effect should be studied further. Prog Nucleic Acid Res Mol Biol, 2004, 78, 143 - 85 Transcriptional regulation of the metazoan stress protein response; Voellmy R; This review provides an updated account of the regulation of the metazoan stress protein response . Where indicated, observations made with yeasts are also included . However, a discussion of the plant stress protein response is intentionally omitted (for a review, see 1) . The stress protein response, as discussed hereafter, is understood to relate to the response by virtually all cells to heat and other stressors that results in the induced expression of so-called heat shock or stress genes . The protein products of these genes localize largely to the cytoplasm, nucleus, or organelles . An analogous response controls the expression of related genes, whose products reside in the endoplasmic reticulum . The response, termed ER stress response or unfolded protein response, is mediated by a separate regulation system that is not discussed in this review . Note, however, that recent work suggests the existence of commonalities between the regulatory systems controlling the stress protein and ER stress responses (2). Plant Physiol, 2004 Jun, 135(2), 1084 - 99 Genome-wide analysis of the cyclin family in Arabidopsis and comparative phylogenetic analysis of plant cyclin-like proteins; Wang G et al.; Cyclins are primary regulators of the activity of cyclin-dependent kinases, which are known to play critical roles in controlling eukaryotic cell cycle progression . While there has been extensive research on cell cycle mechanisms and cyclin function in animals and yeasts, only a small number of plant cyclins have been characterized functionally . In this paper, we describe an exhaustive search for cyclin genes in the Arabidopsis genome and among available sequences from other vascular plants . Based on phylogenetic analysis, we define 10 classes of plant cyclins, four of which are plant-specific, and a fifth is shared between plants and protists but not animals . Microarray and reverse transcriptase-polymerase chain reaction analyses further provide expression profiles of cyclin genes in different tissues of wild-type Arabidopsis plants . Comparative phylogenetic studies of 174 plant cyclins were also performed . The phylogenetic results imply that the cyclin gene family in plants has experienced more gene duplication events than in animals . Expression patterns and phylogenetic analyses of Arabidopsis cyclin genes suggest potential gene redundancy among members belonging to the same group . We discuss possible divergence and conservation of some plant cyclins . Our study provides an opportunity to rapidly assess the position of plant cyclin genes in terms of evolution and classification, serving as a guide for further functional study of plant cyclins. Curr Biol, 2004 Jun 22, 14(12), R452 - 3 Changing places . Interview by Graham Tebb; Nasmyth K; Kim Nasmyth is set to move from the Institute of Molecular Pathology in Vienna to take up a new post in Oxford . He talks to Graham Tebb about his reasons for returning to the UK and plans for the future. Curr Opin Genet Dev, 2004 Apr, 14(2), 210 - 7 At the crossroads of growth control; making ribosomal RNA; Moss T; Although the mechanisms of cell cycle control are well established, the factors controlling cell growth and target size are still poorly understood . Much evidence suggests that ribosome biogenesis, and in particular the synthesis of the rRNAs, plays a central role not only in permitting growth, but also in regulating it . In the past few years we have begun to penetrate the network linking rRNA gene transcription to growth. Curr Opin Genet Dev, 2004 Apr, 14(2), 196 - 202 Linking lipids to chromatin; Jones DR et al.; Dynamic regulation of chromatin structure is thought to be a prerequisite for nuclear functions that require accessibility to DNA such as replication, transcription and DNA repair . The phosphoinositide (PI) pathway is a second messenger signalling system regulated in response to a variety of extracellular (growth factors, differentiation signals) and intracellular (cell cycle progression, DNA damage) stimuli . The presence of a PI pathway in the nucleus together with the recent findings that specific nuclear proteins can interact with and are regulated by phosphoinositides suggest that changes in the nuclear phosphoinositide profile may have a direct role in modulating chromatin structure. Curr Opin Struct Biol, 2004 Jun, 14(3), 335 - 43 RNA structure and function in C/D and H/ACA s(no)RNPs; Henras AK et al.; From archaea to humans, C/D- and H/ACA-type small ribonucleoprotein particles play key roles in crucial RNA processing events . Various such particles are required for pre-rRNA cleavage steps and/or for chemical modification of rRNAs, spliceosomal small nuclear RNAs, tRNAs and perhaps even mRNAs . Each C/D-type particle contains a small RNA possessing conserved C and D, as well as related C' and D', sequence motifs, whereas each H/ACA-type particle contains a small RNA featuring conserved H and ACA sequence elements . Recently published studies highlight the importance of sequence and structural elements of these RNAs in the localization, activity and assembly of the ribonucleoprotein particles . A novel sequence element, the Cajal body box, found at the apex of stem structures within a subset of H/ACA small RNAs, mediates the specific retention of particles containing these elements inside nucleoplasmic Cajal bodies . Two highly conserved elements, the m1 and m2 boxes, have been identified in the 3' stem of the atypical H/ACA snR30/U17 RNAs . These conserved sequence elements are necessary for early pre-rRNA cleavage events and consequently for mature 18S rRNA production . Finally, convincing evidence has been provided that the conserved C and D sequence motifs of C/D-type small RNAs fold into a helix-bulge-helix structure, called a kink-turn, that provides a platform for assembly of C/D-type ribonucleoprotein particles. Lett Appl Microbiol, 2004, 39(1), 7 - 12 In vitro fungitoxic activity of Larrea divaricata cav . extracts; Quiroga EN et al.; AIMS: To evaluate the fungitoxic activity of Larrea divaricata Cav . extract and one of its components against yeasts and fungi . This activity was compared with the action of ketoconazole, a known synthetic antimycotic . METHODS AND RESULTS: Antifungal activity of Larrea divaricata extract and of a fraction (Fr . B) purified by thin layer chromatography, was investigated using different methodologies . Both exhibited strong activity against the majority of the assayed fungi . Only Fusarium oxysporum and Schizophyllum commune growth was not affected with the assayed conditions . The fungitoxic and cytotoxic activity of the ethanolic extract and ketoconazole were compared . CONCLUSIONS: Ethanolic extracts of L . divaricata Cav . produce growth inhibition of several fungi . One of its constituents with the same activity was purified and identified as a glycoside of a flavanone . A comparison with the action of ketoconazole, which is currently used as antimycotic and can cause adverse health effects was made . SIGNIFICANCE AND IMPACT OF THE STUDY: Our data suggest that L . divaricata extract contains, at least, one compound of phenolic nature, with fungitoxic potency against yeasts and fungi. Mycoses, 2004 Jun, 47(5-6), 249 - 51 Pityriasis versicolor on the groin mimicking erythrasma; Aste N et al.; Pityriasis versicolor (PV) is a widespread dermatomycosis caused by yeasts . Erythrasma is a superficial bacterial skin disease affecting the major folds of the body, particularly the groin . We report the case of a 45-year-old man, affected by PV, exclusively localized in the inguinal folds and in the inner surface of the thighs, characterized by lesions clinically reproducing erythrasma . The authors underline the possibility that PV mimics erythrasma and vice versa, especially in those countries in which both diseases are quite common, and stress the importance of performing a simple mycological examination to avoid gross diagnostic and therapeutic errors. Biol Cell, 2004 Apr, 96(3), 237 - 40 The mitotic spindle and actin tails; Karsenti E et al.; To segregate their chromosomes, eukaryotic cells rely on a dynamic structure made of microtubules: the mitotic spindle . This structure can form in cells lacking centrosomes, because their chromosomes also nucleate microtubules . This second assembly pathway is observed even in some cells that naturally have centrosomes, for example when the centrosomes are ablated by laser surgery . Recent results have started to address the complementary question of whether centrosome-nucleated microtubules alone could sustain the formation of a functional mitotic spindle . We wonder in this respect whether lower eukaryotes such as yeasts are different from higher eukaryotes such as vertebrates. Tsitologiia, 2004, 46(2), 136 - 50 {The role of phosphoinositide signaling in the lower eukaryotes}; Shemarova IV; The recent achievements on phosphoinositide signaling in the unicellular eukaryotes have been reviewed . Special attention is paid to mechanisms of phospholipase C (PLC) activation and its interaction with both cell surface receptors and effector cytoplasm targets . We discuss the role of protein kinase C (PKC) in intracellular signaling, and the relationship between the PI-signal pathway key enzymes with protein kinases of cAMP-PKA and MAP-kinase pathways. Curr Opin Genet Dev, 2004 Jun, 14(3), 292 - 300 Redundancy, insult-specific sensors and thresholds: unlocking the S-phase checkpoint response; Cobb JA et al.; DNA damage that is not properly repaired during genomic replication is a major source of gross chromosomal rearrangements and sequence loss during cell proliferation . In higher eukaryotes such mutations increase the risk of cancer . Eukaryotic cells have multiple checkpoint responses activated by DNA damage and stalled replication forks . We focus here on fork-associated events that activate and respond to S-phase checkpoint kinases. Novartis Found Symp, 2004, 259, 78 - 98; discussion 98-101, 163-9 Structural and chemical basis of histone acetylation; Marmorstein R; Histones are the predominant protein components of chromatin and are subject to a variety of specific post-translational modifications that are correlated with transcriptional competence . Among these modifications are reversible acetylation that is mediated by acetyltransferases that mediate transcriptional activation and deactylases that mediate transcriptional repression and gene silencing . Structural studies have provided important insights into the mechanism of substrate specific binding and catalysis by the enzymes that mediate reversible acetylation . In this paper I will review structural work from my laboratory on histone acetyltransferases (HATs) and the Sir2 family of histone deacetylases (HDACs), with a specific focus on catalysis and substrate-specific binding by these enzymes. Biochemistry, 2004 Jun 8, 43(22), 7127 - 42 In vitro activity differences between proteins of the ADF/cofilin family define two distinct subgroups; Chen H et al.; The actin depolymerizing factor (ADF)/cofilins are an essential group of proteins that are important regulators of actin filament turnover in vivo . Although protists and yeasts express only a single member of this family, metazoans express two or more members in many cell types . In cells expressing both ADF and cofilin, differences have been reported in the regulation of their expression, their pH sensitivity, and their intracellular distribution . Each member has qualitatively similar interactions with actin, but quantitative differences have been noted . Here we compared quantitative differences between chick ADF and chick cofilin using several assays that measure G-actin binding, actin filament length distribution, and assembly/disassembly dynamics . Quantitative differences were measured in the critical concentrations of the complexes required for assembly, in the effects of nucleotide and divalent metal on actin monomer binding, in pH-dependent severing, in enhancement of filament minus end off-rates, and in steady-state filament length distributions generated in similar mixtures . Some of these assays were used to compare the activities of several ADF/cofilins from across phylogeny, most of which fall into one of two groups based upon their behavior . The ADF-like group has higher affinities for Mg(2+)-ATP-G-actin than the cofilin-like group and a greater pH-dependent depolymerizing activity. Mol Biol Evol, 2004 Aug, 21(8), 1572 - 82 Epub 2004 May 21. Comparison of diverse protein sequences of the nuclear-encoded subunits of cytochrome C oxidase suggests conservation of structure underlies evolving functional sites; Das J et al.; Interspecific comparisons of protein sequences can reveal regions of evolutionary conservation that are under purifying selection because of functional constraints . Interpreting these constraints requires combining evolutionary information with structural, biochemical, and physiological data to understand the biological function of conserved regions . We take this integrative approach to investigate the evolution and function of the nuclear-encoded subunits of cytochrome c oxidase (COX) . We find that the nuclear-encoded subunits evolved subsequent to the origin of mitochondria and the subunit composition of the holoenzyme varies across diverse taxa that include animals, yeasts, and plants . By mapping conserved amino acids onto the crystal structure of bovine COX, we show that conserved residues are structurally organized into functional domains . These domains correspond to some known functional sites as well as to other uncharacterized regions . We find that amino acids that are important for structural stability are conserved at frequencies higher than expected within each taxon, and groups of conserved residues cluster together at distances of less than 5 A more frequently than do randomly selected residues . We, therefore, suggest that selection is acting to maintain the structural foundation of COX across taxa, whereas active sites vary or coevolve within lineages. FEBS Lett, 2004 May 21, 566(1-3), 110 - 4 Ubiquilin interacts with ubiquitylated proteins and proteasome through its ubiquitin-associated and ubiquitin-like domains; Seok Ko H et al.; Mammalian cells acquire tolerance against multiple stressors through the high-level expression of stress-responsible genes . We have previously demonstrated that protein-disulfide isomerase (PDI) together with ubiquilin are up-regulated in response to hypoxia/brain ischemia, and play critical roles in resistance to these damages . We show here that ubiquilin interacts preferentially with poly-ubiquitin chains and 19S proteasome subunits . Taken together, these results suggest that ubiquitin could serve as an adaptor protein that both interacts with PDI and mediates the delivery of poly-ubiquitylated proteins to the proteasome in the cytosol in the vicinity of the endoplasmic reticulum membrane. Hum Mutat, 2004 Jun, 23(6), 552 - 8 Identification of a new complementation group of the peroxisome biogenesis disorders and PEX14 as the mutated gene; Shimozawa N et al.; Peroxisome biogenesis disorders (PBD) are lethal hereditary diseases caused by abnormalities in the biogenesis of peroxisomes . At present, 12 different complementation groups have been identified and to date, all genes responsible for each of these complementation groups have been identified . The peroxisomal membrane protein PEX14 is a key component of the peroxisomal import machinery and may be the initial docking site for the two import receptors PEX5 and PEX7 . Although PEX14 mutants have been identified in yeasts and CHO-cells, human PEX14 deficiency has apparently not been documented . We now report the identification of a new complementation group of the peroxisome biogenesis disorders with PEX14 as the defective gene . Indeed, human PEX14 rescues the import of a PTS1-dependent as well as a PTS2-dependent protein into the peroxisomes in fibroblasts from a patient with Zellweger syndrome belonging to the new complementation group . This patient was homozygous for a nonsense mutation in a putative coiled-coil region of PEX14, c.553C>T (p.Q185X) . Furthermore, we showed that the patient's fibroblasts lacked PEX14 as determined by immunocytochemical analysis . These findings indicate that there are 13 genotypes in PBD and that the role of PEX14 is also essential in humans . Klin Mikrobiol Infekc Lek, 2004 Apr, 10(2), 88 - 95 {Monitoring the occurrence of fungi in the air and environment at the Hemato-Oncology Clinic of the Faculty Hospital in Brno-Bohunice}; Drevova J et al.; OBJECTIVE: The air can be one of the ways of transmission of fungal infections in hospital environment . This is why we examined the occurence of fungi in the air of units where patients with hemato-oncology disorders, naturally predisposed to fungal infections, are hospitalized . MATERIALS AND METHODS: We performed the search at four sampling sites with different grade of reverse isolation . (unit for allogeneis transplantation, unit for autologous transplantation, intensive care unit and standard three-bed room . Air samples were collected by a special instrument for aeroscopic sampling (Biotest RCS Plus) during two consecutive periods in 2002, in summer (June - July) and in fall (November - December) . and compared with each other . RESULTS: Forty-four samples of air were collected, which yielded 147 fungal isolates, representing 41 genera . The growth of fungi was recorded in 34 samples of air (77.3 %), 10 samples were free of fungi . Yeasts were not taken into consideration in this study . The isolates belonged mostly to the genera Cladosporium (33,9 %), Penicillium (23,9 %), Aspergillus (12,8 %), Acremonium (5,6 %) and Alternaria (5,6 %), the other genera represented 18,2 % altogether . CONCLUSION: Increasing occurence of fungi was found at the unit for autologous transplantation and in the standard room . The results led to reconsideration of the daily regime and of environmental factors in both units and relevant preventive measures were proposed. Proc Natl Acad Sci U S A, 2004 May 18, 101(20), 7805 - 8 Epub 2004 May 10. Frequent fusion and fission of plant mitochondria with unequal nucleoid distribution; Arimura S et al.; The balance between mitochondrial fusion and fission influences the reticular shape of mitochondria in yeasts . Little is known about whether mitochondria fusion occurs in plants . Plant mitochondria are usually more numerous and more grain-shaped than animal mitochondria . BLAST searches of the nuclear and mitochondrial genome sequences of Arabidopsis thaliana did not find any obvious homologue of mitochondrial fusion genes found in animals and yeasts . To determine whether mitochondrial fusion actually occurs in plants, we labeled mitochondria in onion epidermal cells with a mitochondria-targeted, photoconvertible fluorescent protein Kaede and then altered the fluorescence of some of the mitochondria within a cell from green to red . Frequent and transient fusion of red and green mitochondria was demonstrated by the appearance of yellow mitochondria that subsequently redivided . We also show that mitochondrial fission occasionally occurs without an equal distribution of the nucleoid (DNA-protein complex in mitochondria), resulting in the coexistence of mitochondria containing various amounts of DNA within a single cell . The heterogeneity of DNA contents in mitochondria may be overcome by the frequent and transient fusion of mitochondria. Genetika, 2004 Mar, 40(3), 293 - 310 {Key events in the cell cycle, their regulation and organization}; Omel'ianchuk LV et al.; The review surveys the studies of molecular genetic mechanisms of the cell cycle control on various eukaryotic models . The major cell cycle phenomena are considered: (1) checkpoints and their role in preserving DNA integrity and fidelity of mitosis, (2) the cell oscillator model, and (3) the role of cyclins in timing of cell division and coordination of mitotic events . The main classes of regulatory proteins involved in the cell cycle are discussed in detail. Exp Cell Res, 2004 May 15, 296(1), 91 - 7 The link between mRNA processing and transcription: communication works both ways; Zorio DA et al.; Many pre-mRNA processing events including 5' end capping, splicing out introns, and 3' end maturation by cleavage or polyadenylation occur while the nascent RNA chain is being synthesized by RNA polymerase II . As a consequence of this arrangement, the physiological substrate for most processing factors is not a solitary pre-RNA but instead a ternary complex comprising a growing RNA chain spewing from the exit channel of an RNA polymerase II molecule as it speeds along a chromatin template at 1000-2000 bases/min . mRNA processing factors make protein-protein contacts with elongating pol II in a complex we have dubbed the "mRNA factory," which carries out synthesis, processing, and packaging of the transcript . Recent studies have shown that the "mRNA factory" is a dynamic complex whose composition changes as it traverses the length of a gene . This complex is also the setting for a growing number of regulatory interactions, which influence the function of both the processing and transcription machineries. Exp Cell Res, 2004 May 15, 296(1), 80 - 5 The mechanism of sister chromatid cohesion; Uhlmann F; Each of our cells inherit their genetic information in the form of chromosomes from a mother cell . In order that we obtain the full genetic complement, cells need to ensure that replicated chromosomes are accurately split and distributed during cell division . Mistakes in this process lead to aneuploidies, cells with supernumerous or missing chromosomes . Most aneuploid human embryos are not viable, and if they are, they develop severe birth defects . Aneuploidies later in human life are frequently found associated with the development of malignant cancer . DNA replication during S-phase is linked to segregation of the sister copies in mitosis by sister chromatid cohesion . A chromosomal protein complex, cohesin, holds replicated sister DNA strands together after their synthesis . This allows pairs of replication products to be recognised by the spindle apparatus in mitosis for segregation into opposite direction . At anaphase onset, cohesin is destroyed by a site-specific protease, separase . Here I review what we have learned about the molecular mechanism of sister chromatid cohesion . Cohesin forms a large proteinaceous ring that may hold sister chromatids by encircling and topological trapping . To understand how cohesin links newly synthesised replication products, biochemical assays to study the enzymology of cohesin will be required. Exp Cell Res, 2004 May 15, 296(1), 43 - 50 Ribosome biogenesis: of knobs and RNA processing; Granneman S et al.; The synthesis of ribosomes in eukaryotes involves processing of pre-ribosomal RNA (pre-rRNA) and sequential assembly of a large number of ribosomal proteins on the rRNAs . Although we have gained tremendous insights into the processing of pre-rRNA intermediates in the last three decades, little was known about the dynamic nature of ribosome biogenesis . Only recently the development of efficient affinity-purification procedures and mass-spectrometry techniques has allowed the isolation of large pre-ribosomal complexes, which led to the identification of several ribosome assembly intermediates and a large number of novel ribosome assembly factors . In this mini-review, we summarize some of the discoveries that have been made in the field of ribosome biogenesis in the past 30 years and highlight some key aspects about what remains to be learned. Ann Trop Med Parasitol, 2004 Apr, 98(3), 279 - 82 Use of CHROMagar medium in the differentiation of Candida species: is it cost-effective in developing countries? Iyampillai T, Michael JS, Mathai E, Mathews MS. The opportunistic infection of humans with Candida is becoming more common . As several species of Candida are relatively insusceptible to the commonly used antifungal drugs, rapid identification of the species involved can facilitate effective treatment . CHROMagar Candida medium (CCM) is a commercial product designed to allow the rapid identification of Candida to species level . To explore the potential usefulness of CCM in a developing country, attempts were made to identify the Candida species in 107 Indian isolates (obtained, consecutively, from 90 clinical specimens, over a year-long period, in a tertiary-level teaching hospital), using CCM and more conventional methods in parallel . The most common species appeared to be C . tropicalis (representing 40% of the isolates), followed by C . albicans (28%) and C . glabrata (23%) . Although use of CCM allowed the isolates from 84 (93.3%) of the clinical specimens to identified to species level within 48 h, it took at least 7 days to identify the yeasts in 90% of the specimens using the more conventional procedures . With the results of the conventional methods set as the 'gold standard', the use of CCM appeared to allow all of the C . albicans, C . tropicalis and C . krusei isolates and most (92%) of the C . glabrata to be correctly identified . The costs/isolate identified with the CCM were no more than those of the conventional methods . As many (67%) of the isolates examined were of potentially drug-resistant yeasts (C . tropicalis, C . glabrata or C . krusei), there is clearly a need to identify local isolates quickly, to prevent treatment with ineffective drugs . In terms of both performance and cost, CCM appears to be a good method to use. J Proteome Res, 2004 Mar-Apr, 3(2), 179 - 96 Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine; Weston AD et al.; The emergence of systems biology is bringing forth a new set of challenges for advancing science and technology . Defining ways of studying biological systems on a global level, integrating large and disparate data types, and dealing with the infrastructural changes necessary to carry out systems biology, are just a few of the extraordinary tasks of this growing discipline . Despite these challenges, the impact of systems biology will be far-reaching, and significant progress has already been made . Moving forward, the issue of how to use systems biology to improve the health of individuals must be a priority . It is becoming increasingly apparent that the field of systems biology and one of its important disciplines, proteomics, will have a major role in creating a predictive, preventative, and personalized approach to medicine . In this review, we define systems biology, discuss the current capabilities of proteomics and highlight some of the necessary milestones for moving systems biology and proteomics into mainstream health care. Mar Pollut Bull, 2004 May, 48(9-10), 863 - 72 Synergistic effect of sophorolipid and loess combination in harmful algal blooms mitigation; Sun XX et al.; The inhibition effect of sophorolipid and removal efficiency of loess on Cochlodinium polykrikoides and Alexandrium tamarense was investigated separately in the laboratory . Based on this, the combination of sophorolipid and loess for harmful algal bloom mitigation was proposed . Algal sedimentation tests in the laboratory and in the field revealed that the combination of sophorolipid and loess showed synergistic effects both on the removal efficiencies and on the mitigation cost . The concentration of 1 g/l loess and 5 mg/l sophorolipid was determined as the optimum ratio for C . polykrikoides mitigation . In the field test, the effective concentration of loess and sophorolipid in the combination group was reduced to 10% and 25%, respectively, compared to the non-combination group, and the cost decreased more than 60% . The combination of loess and sophorolipid was considered as a promising novel method in harmful algal bloom mitigation. Biochem Pharmacol, 2004 Mar 1, 67(5), 1001 - 9 Inhibitors of gelatinase B/matrix metalloproteinase-9 activity comparison of a peptidomimetic and polyhistidine with single-chain derivatives of a neutralizing monoclonal antibody; Hu J et al.; Matrix metalloproteinases form a proteinase family with at least 20 members, which are involved in several pathological conditions and which fulfill a large number of physiological functions . Gelatinase A/MMP-2 is a constitutively produced homeostatic enzyme, whereas gelatinase B/MMP-9 is upregulated in acute and chronic inflammations and forms a target for the development of therapeutic inhibitors . We have used a recently developed assay with fluorescent gelatin to analyze gelatinase inhibitors . A peptidomimetic, based on the consensus sequence of the cleavage sites in type II collagen, and various derivatives of a neutralizing antibody were compared as gelatinase inhibitors . A single-chain variable fragment (scFv) derived from the gelatinase B-selective monoclonal antibody REGA-3G12 was tagged with oligohistidine and was also compared with the untagged scFv . Both scFv derivatives inhibited gelatinase B but the peptidomimetic was inefficient . As an extra control and serendipitously it was found that polyhistidine is an inhibitor of gelatinases, presumably by altering the active site by chelation of the catalytic Zn2+. J Drugs Dermatol, 2004 Mar-Apr, 3(2), 155 - 8 Seborrheic dermatitis of the scalp: etiology and treatment; Gupta AK et al.; Seborrheic dermatitis is a common chronic infection of the lipid-rich areas of skin . While seborrheic dermatitis has been a recognized clinical entity for decades, its etiology is far from clear . Early investigators of the development of seborrheic dermatitis focused on the role of the Malassezia (previously Pityrosporum) yeasts . These yeasts are also normal skin commensals, thus their importance as pathogens in this disorder came to be doubted . However, it was subsequently found that treatment of seborrheic dermatitis with an antifungal agent not only resulted in clinical improvement but also reduced the number of Malassezia yeasts on the skin . This has resulted in a resurgence of interest in the Malassezia yeasts . It has been hypothesized that there is an immunological component to seborrheic dermatitis, possibly representing an abnormal host response to the Malassezia yeasts . This paper will discuss the role of Malassezia in the etiology of seborrheic dermatitis, as well as the various treatment options. J Am Acad Dermatol, 2004 May, 50(5), 748 - 52 Epidemiologic surveillance of cutaneous fungal infection in the United States from 1999 to 2002; Foster KW et al.; BACKGROUND: Cutaneous fungal infections are common in the United States, and causative organisms include dermatophytes, yeasts, and nondermatophyte molds . These organisms are in constant competition for their particular environmental niche, often resulting in the emergence of one or more predominant pathogens and displacement of other less competitive species . Changes in the incidence of fungal pathogens can be followed from laboratory culture results of infected cutaneous tissues over time . These data can be used to ascertain past and present trends in incidence, predict increases in antifungal resistance and the adequacy of our current pharmacologic repertoire, and provide insight into future developments . OBJECTIVE: This study identifies epidemiologic trends and the predominant organisms causing superficial fungal infections in the United States . METHODS: A total of 15,381 specimens were collected from clinically suspected tinea corporis, tinea cruris, tinea capitis, tinea faciei, tinea pedis, tinea manuum, and finger and toe onychomycosis from 1999 through 2002 . Specimens were submitted to the Center for Medical Mycology in Cleveland, Ohio, for fungal culture and identification, and the incidence of each species was calculated . RESULTS: Dermatophytes remain the most commonly isolated fungal organisms except from clinically suspected finger onychomycosis, in which case Candida species comprise >70% of isolates . Trichophyton rubrum remains the most prevalent fungal pathogen, and increased incidence of this species was observed in finger and toe onychomycosis, tinea corporis and tinea cruris, tinea manuum, and tinea pedis . As the causal agent of tinea capitis, T tonsurans continues to increase in incidence, achieving near exclusionary proportions in the United States . CONCLUSION: Consideration of the current epidemiologic trends in the incidence of cutaneous fungal pathogens is of key importance to investigational efforts, diagnosis, and treatment. Nucleic Acids Res, 2004 Apr 19, 32(7), 2171 - 80 Print 2004. Human telomerase catalyzes nucleolytic primer cleavage; Huard S et al.; Telomerase is a reverse transcriptase that uses an integral RNA molecule to add de novo G-rich repeats onto telomeric DNA, or onto nontelomeric DNA generated during chromosome fragmentation and breakage events . A telomerase-mediated DNA substrate cleavage activity has been reported in ciliates and yeasts . Nucleolytic cleavage may serve a proofreading function, enhance processivity or ensure that nontemplate telomerase RNA sequences are not copied into DNA . We identified and characterized a human telomerase-mediated nucleolytic cleavage activity using enzyme reconstituted in a rabbit reticulocyte lysate in vitro transcription/translation system and native enzyme extracted from cells . We found that telomerase catalyzed the removal of nucleotides from DNA substrates including those that can form a mismatch with the RNA template or that contain nontelomeric sequences located 3' to a telomeric sequence . Unlike Tetrahymena telomerase, human telomerase catalyzed the removal of more than one nucleotide (up to 13) from telomeric primers . DNA substrates predicted to align at the 3'-end of the RNA template were not cleaved, consistent with cleavage being dictated by the template 5'-end . We also found some differences in the nuclease activity between RRL-reconstituted human telomerase and native enzyme. Environ Pollut, 1995, 90(2), 143 - 52 Foliage responses of spruce trees to long-term low-grade sulfur dioxide deposition; Meng FR et al.; Foliage on spruce trees (Picea rubens Sarg.) growing on dry SO(2) deposition zones (dry SO(2) deposition ranging from 0.5 and 8.5 S kg ha(-1) year(-1)) downwind from a SO(2) emission source was analyzed to assess chronic effects of long-term low-grade SO(2) deposition on net photosynthesis, stomatal conductance, dark respiration, stomatal antechamber wax structures, elemental concentrations in and on foliage (bulk and surficial concentrations), and types of epiphytic fungi that reside in the phylloplane . Elemental distributions on stomatal antechambers, on fungal colonies, and on smooth surfaces between stomates and fungus colonies were determined with a scanning electronic microscope (SEM) by way of X-ray scanning . It was found that net photosynthesis of newly developed spruce foliage (current-year, and 1-year-old) was not significantly affected by the local SO(2) deposition rates . Sulfur dioxide deposition, however, may have contributed to the gradual decrease in net photosynthesis with increasing needle age . Dark respiration rates were significantly higher on foliage taken from high SO(2) deposition zones . Stomatal rod-web structures deteriorated to flakes with increasing needle age and increasing SO(2) deposition . Further inspection of the needle surfaces revealed an increasing abundance of fungal colonies with increasing needle age . Many fungal taxa were isolated and identified . It was found that black yeasts responded positively, and Xylohypha pinicola responded negatively to high rates of SO(2) deposition . Surficial concentrations of elements such as P, S, K, Cl, Ca were about 10 times higher on fungal colonies than on smooth needle surfaces . Surficial Ca contents on 4 or 5-year-old needles decreased with increasing SO(2) deposition, but surficial S concentrations remained the same . In contrast, bulk foliar Ca and S concentrations increased with increasing SO(2) deposition. Neuroreport, 2004 Apr 9, 15(5), 873 - 6 Gigaxonin is associated with the Golgi and dimerises via its BTB domain; Cullen VC et al.; Mutations in the gigaxonin gene cause giant axonal neuropathy . The amino-terminus of gigaxonin contains a BTB domain but no binding partners for this domain have so far been identified . Here, we demonstrate that the gigaxonin BTB domain forms homodimers . Other BTB-bearing proteins have also been shown to dimerise via their BTB domains with the dimers then capable of interacting with other ligands . Thus, the gigaxonin BTB domain may function in a similar manner . We also demonstrate that gigaxonin is expressed in a wide variety of neuronal cell types where a significant proportion exists in cell bodies . Confocal microscope studies of gigaxonin-transfected COS-7 cells and cultured neurones revealed that a proportion of gigaxonin localises to the Golgi and endoplasmic reticulum. J Mol Biol, 2004 Apr 23, 338(2), 203 - 6 High pressure promotes circularly shaped insulin amyloid; Jansen R et al.; Amyloids, initially associated with certain degenerative diseases, and recently with the prions and prion-based inheritance in yeasts, are linearly-ordered beta-sheet-rich protein aggregates, presently thought to represent a rather common generic trait of proteins as polymers . Regardless of genetic origins and properties of precursor protein molecules, amyloids share many physicochemical properties, including the linear fibrillar morphology . Here, we show that under high hydrostatic pressure insulin forms amyloids of a unique circular morphology . Despite a degree of size-distribution, the smallest forms of the approximate radius of 340-420 nm are most abundant among the ring-shaped structures . The circular amyloid is accompanied by bent 20-100 nm long fibrils . The pressure-enhancement of a ring-like supramolecular fold suggests an anisotropic distribution of void volumes in regular amyloid fibres . While the ability of high pressure to evoke such drastic perturbations on an amyloidogenic pathway may help tune conformation of amyloid templates (e.g . inducing the PrP(Sc)-type infectivity in amyloids grown in vitro from recombinant PrP), the very finding raises new questions concerning possible consequences for high-pressure food processing. Cell, 2004 Apr 2, 117(1), 17 - 28 The protein kinase CK2 facilitates repair of chromosomal DNA single-strand breaks; Loizou JI et al.; CK2 was the first protein kinase identified and is required for the proliferation and survival of mammalian cells . Here, we have identified an unanticipated role for CK2 . We show that this essential protein kinase phosphorylates the scaffold protein XRCC1 and thereby enables the assembly and activity of DNA single-strand break repair protein complexes in vitro and at sites of chromosomal breakage . Moreover, we show that inhibiting XRCC1 phosphorylation by mutation of the CK2 phosphorylation sites or preventing CK2 activity using a highly specific inhibitor ablates the rapid repair of cellular DNA single-strand breaks by XRCC1 . These data identify a direct role for CK2 in the repair of chromosomal DNA strand breaks and in maintaining genetic integrity. Neuron, 2004 Apr 8, 42(1), 113 - 28 Transcriptional modification by a CASK-interacting nucleosome assembly protein; Wang GS et al.; CASK acts as a coactivator for Tbr-1, an essential transcription factor in cerebral cortex development . Presently, the molecular mechanism of the CASK coactivation effect is unclear . Here, we report that CASK binds to another nuclear protein, CINAP, which binds histones and facilitates nucleosome assembly . CINAP, via its interaction with CASK, forms a complex with Tbr-1, regulating expression of the genes controlled by Tbr-1 and CASK, such as NR2b and reelin . A knockdown of endogenous CINAP in hippocampal neurons reduces the promoter activity of NR2b . Moreover, NMDA stimulation results in a reduction in the level of CINAP protein, via a proteasomal degradation pathway, correlating with a decrease in NR2b expression in neurons . This study suggests that reduction of the CINAP protein level by synaptic stimulation contributes to regulation of the transcriptional activity of the Tbr-1/CASK/CINAP protein complex and thus modifies expression of the NR2b gene. Neuron, 2004 Apr 8, 42(1), 89 - 99 Calcium channel function regulated by the SH3-GK module in beta subunits; McGee AW et al.; beta subunits of voltage-gated calcium channels (VGCCs) regulate channel trafficking and function, thereby shaping the intensity and duration of intracellular changes in calcium . beta subunits share limited sequence homology with the Src homology 3-guanylate kinase (SH3-GK) module of membrane-associated guanylate kinases (MAGUKs) . Here, we show biochemical similarities between beta subunits and MAGUKs, revealing important aspects of beta subunit structure and function . Similar to MAGUKs, an SH3-GK interaction within beta subunits can occur both intramolecularly and intermolecularly . Mutations that disrupt the SH3-GK interaction in beta subunits alter channel inactivation and can inhibit binding between the alpha(1) and beta subunits . Coexpression of beta subunits with complementary mutations in their SH3 and GK domains rescues these deficits through intermolecular beta subunit assembly . In MAGUKs, the SH3-GK module controls protein scaffolding . In beta subunits, this module regulates the inactivation of VGCCs and provides an additional mechanism for tuning calcium responsiveness. Eur J Neurosci, 2004 Mar, 19(6), 1535 - 44 RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells; von Buchholtz L et al.; Abstract G-protein-mediated signalling processes are involved in sweet and bitter taste transduction . In particular, the G protein alpha-subunit gustducin has been implicated in these processes . One of the limiting factors for the time-course of cellular responses induced by tastants is therefore the intrinsic GTPase activity of alpha-gustducin, which determines the lifetime of the active G protein complex . In several signalling systems specific 'regulator of G protein signalling' (RGS) proteins accelerate the GTPase activity of G protein alpha-subunits . Using differential screening approaches, we have identified a novel RGS protein termed RGS21, which represents the smallest known member of this protein family . Reverse transcription polymerase chain reaction and in situ hybridization experiments demonstrated that RGS21 is expressed selectively in taste tissue where it is found in a subpopulation of sensory cells . Furthermore, it is coexpressed in individual taste cells with bitter and sweet transduction components including alpha-gustducin, phospholipase Cbeta2, T1R2/T1R3 sweet taste receptors and T2R bitter taste receptors . In vitro binding assays demonstrate that RGS21 binds alpha-gustducin in a conformation-dependent manner and has the potential to interact with the same Galpha subtypes as T1R receptors . These results suggest that RGS21 could play a regulatory role in bitter as well as sweet taste transduction processes. J Chromatogr A, 2004 Apr 2, 1032(1-2), 165 - 71 High-magnetic-field electromagnetophoresis of micro-particles in a capillary flow system; Iiguni Y et al.; The electromagnetophoretic migration of micro-particles in a capillary flow system was demonstrated using a homogeneous magnetic field applied at right angles to an electric current . We utilized a high-magnetic-field of 10 T for observing this phenomenon . When the direction of the electric current was alternatively changed, polystyrene latex particles in a flowing aqueous medium migrated zigzag affected by a Lorentz force exerted on the medium . Carbon particles also migrated in the same manner with polystyrene particles . Further, we tried the electromagnetophoretic migration of biological particles, such as yeasts and human red blood cells . The migration velocity component perpendicular to the flow was proportional to both the electric current and the magnetic flux density . These results proved that the dominant force of the zigzag migration was an electromagnetophoretic buoyancy generated in the flowing medium . Moreover, it was found that the force exerted on the particles in the magnetic field of 10 T was sufficient for the desorption of particles adsorbed on the capillary wall. Dermatology, 2004, 208(2), 89 - 93 Etiology and management of Seborrheic dermatitis; Gupta AK et al.; Seborrheic dermatitis (SD) is a common dermatological disorder that varies greatly in severity between individuals and with time . The etiology of this disease is poorly understood . Early investigators focused on the role of Malassezia (previously Pityrosporum) yeasts in the development of SD . Some researchers have hypothesized that there is an immunological component to SD and that this disease is caused by an altered immune response to Malassezia yeasts . However, other researchers view this condition as the result of hyperproliferation . Both antifungal and anti-inflammatory preparations have been used to treat SD effectively and safely . The wide range of antifungal formulations available (creams, shampoos, oral drugs) provides safe, effective and flexible treatment options for SD . Mycoses, 2003, 46 Suppl 2, 3 - 7 {Experience with voriconazole in invasive aspergillosis}; Thiel E et al.; Invasive aspergillosis causes a markable part of infection-associated morbidity and mortality in immunocompromised patients . For none of hitherto available antimycotic agents a significant superiority could be demonstrated which all are characterised by unsatisfactory response rates . The newly developed and approved voriconazole is characterized by broad antifungal activity against numerous yeasts and filamentous fungi, including Aspergillus species . Voriconazole is available for intravenous administration and shows excellent bioavailability with oral application . The profile of toxicity is typical for azoles with the particularity of causing obviously substance-specific transient, benign visual disturbances . In clinical studies could be shown that voriconazole is significantly superior to the previous antimycotic standard, amphotericin B, with regard to therapy response and survival . In patients with invasive aspergillosis the therapy response with voriconazole is about 45% even in otherwise therapy-resistant cases. Cytogenet Genome Res, 2003, 103(3-4), 256 - 66 Insights into regulation of the mammalian cell cycle from studies on spermatogenesis using genetic approaches in animal models; Wolgemuth DJ; The genetic hierarchy controlling mitosis and especially meiosis during gamete formation is not well understood, even in less complicated systems such as the yeasts . Meiotic divisions are obviously restricted to germ line cells and as such likely require mechanisms of cell cycle control that do not function and may not exist in somatic cells . While male and female germ cells have stages of cell cycle regulation in common, the timing of these events and the stage of development at which these events occur differ in the two sexes . Understanding the genetic program controlling the mitotic and meiotic divisions of the germ line represents a unique opportunity for providing insight into cell cycle control in vivo . Elucidating the key control points and proteins may also enhance our understanding of the etiology of infertility and provide new directions for contraception . Curr Opin Chem Biol, 2004 Feb, 8(1), 20 - 5 ORFeome projects: gateway between genomics and omics; Rual JF et al.; The availability of entire genome sequences is expected to revolutionize the way in which biology and medicine are conducted for years to come . However, achieving this promise still requires significant effort in the areas of gene annotation, cloning and expression of thousands of known and heretofore unknown protein-encoding genes . Traditional technologies of manipulating genes are too cumbersome and inefficient when one is dealing with more than a few genes at a time . Entire libraries composed of all protein-encoding open reading frames (ORFs) cloned in highly flexible vectors will be needed to take full advantage of the information found in any genome sequence . The creation of such ORFeome resources using novel technologies for cloning and expressing entire proteomes constitutes an effective gateway from whole genome sequencing efforts to downstream 'omics' applications. Plant Cell, 2004 Apr, 16(4), 945 - 55 Epub 2004 Mar 18. B1-type cyclin-dependent kinases are essential for the formation of stomatal complexes in Arabidopsis thaliana; Boudolf V et al.; Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle . In yeasts, only one CDK is sufficient to drive cells through the cell cycle, whereas higher eukaryotes developed a family of related CDKs . Curiously, plan