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A single zinc finger optimizes the DNA interactions of the nucleocapsid protein of the yeast retrotransposon Ty3.Reverse transcription in retroviruses and retrotransposons requires nucleic acid chaperones, which drive the rearrangement of nucleic acid conformation. The nucleic acid chaperone properties of the human immunodeficiency virus type-1 (HIV-1) nucleocapsid (NC) protein have been extensively studied, and nucleic acid aggregation, duplex destabilization and rapid binding kinetics have been identified as major components of its activity. However, the properties of other nucleic acid chaperone protein ...201121917850
cross-reactive hiv-1-neutralizing human monoclonal antibodies identified from a patient with 2f5-like antibodies.the genes encoding broadly hiv-1-neutralizing human monoclonal antibodies (mabs) are highly divergent from their germ line counterparts. we have hypothesized that such high levels of somatic hypermutation could pose a challenge for elicitation of the broadly neutralizing (bn) abs and that identification of less somatically mutated bn abs may help in the design of effective vaccine immunogens. in a quest for such bn abs, phage- and yeast-displayed antibody libraries, constructed using peripheral ...201121880764
The antifungal mechanism of action of zinc pyrithione.Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT.201121919897
Anti-Candida albicans biofilm activity by Cassia spectabilis standardized methanol extract: an ultrastructural study.Candida (C.) albicans infection in its biofilm mode of growth has taken centre point with the increasing recognition of its role in human infections due to the development of resistance to the commonly used antibiotic or phenotypic adaptation within the biofilm. Hence, in this study the inhibitory effect of methanol extract of Cassia (C.) spectabilis leaves was evaluated against biofilm forming C. albicans.201121845797
new insights into the ca2+-atpases that contribute to cadmium tolerance in yeast.cadmium (cd(2+)) is a toxic heavy metal which triggers several toxic effects in eukaryotes, including neurotoxicity and impaired calcium metabolism. in the model organism saccharomyces cerevisiae, the best characterized pathway for cd(2+) detoxification involves conjugation with glutathione (gsh) and subsequent transport to vacuoles by ycf1p, an atpase homologous to human mrp1 (multidrug resistance associated protein 1). however, cd(2+) tolerance also can be mediated by pmr1p, a ca(2+) pump loca ...201121911041
Some amino acids of the Pseudomonas aeruginosa MutL D(Q/M)HA(X)(2)E(X)(4)E conserved motif are essential for the in vivo function of the protein but not for the in vitro endonuclease activity.Human and Saccharomyces cerevisiae MutLa, and some bacterial MutL proteins, possess a metal ion-dependent endonuclease activity which is important for the in vivo function of these proteins. Conserved amino acids of the C-terminal region of human PMS2, S. cerevisiae PMS1 and of some bacterial MutL proteins have been implicated in the metal-binding/endonuclease activity. However, the contribution of individual amino acids to these activities has not yet been fully elucidated. In this work we show ...201121889424
neurobiology of huntington's disease: applications to drug discoveryduring the past decade, drosophila and caenorhabditis elegans genetics have emerged as powerful approaches for the study of cellular responses to neurodegenerative disease proteins. such studies have provided new strategies and rationales for the development of neuroprotective drugs, such as the pharmacological manipulation of longevity modulator networks. this chapter will describe how and why these model systems may be used as efficient translational research tools for huntington’s disease (hd ...201121882411
the global transcriptional response of fission yeast to hydrogen sulfide.hydrogen sulfide (h(2)s) is a newly identified member of the small family of gasotransmitters that are endogenous gaseous signaling molecules that have a fundamental role in human biology and disease. although it is a relatively recent discovery and the mechanism of h(2)s activity is not completely understood, it is known to be involved in a number of cellular processes; h(2)s can affect ion channels, transcription factors and protein kinases in mammals.201122164259
ubiquitin ligase nedd4 promotes alpha-synuclein degradation by the endosomal-lysosomal pathway.α-synuclein is an abundant brain protein that binds to lipid membranes and is involved in the recycling of presynaptic vesicles. in parkinson disease, α-synuclein accumulates in intraneuronal inclusions often containing ubiquitin chains. here we show that the ubiquitin ligase nedd4, which functions in the endosomal-lysosomal pathway, robustly ubiquitinates α-synuclein, unlike ligases previously implicated in its degradation. purified nedd4 recognizes the carboxyl terminus of α-synuclein (residue ...201121953697
a new high resolution screening method for study of phenotype stress responses of saccharomyces cerevisae mutants.a high resolution high throughput screening method has been developed for stress response phenotyping of the global saccharomyces cerevisiae knock out mutant collection. stress causing agent is added at three concentrations to individual mutant cultures growing in early exponentially phase in 384-well microplates, and the dynamic effect of stress agent exposure is measured by following subsequent growth profiles of individual mutants with a resolution of three optical density measurements per ho ...201122008504
oxidative protein folding: selective pressure for prolamin evolution in rice.during seed development, endosperm cells of highly productive cereals, including rice, synthesize disulfide-rich proteins in large amounts and deposit them into storage organelles. disulfide bond formation involves electron transfer and generates h 2o 2 as a by-product. to ensure proper development and maturation of seeds, the endosperm cells must supply large amounts of oxidizing equivalents to dithiols in nascent proteins in a controlled manner. this review compares multiple oxidative protein ...201122112460
the tpr-containing domain within est1 homologs exhibits species-specific roles in telomerase interaction and telomere length homeostasis.the first telomerase-associated protein (est1) was isolated in yeast due to its essential role in telomere maintenance. the human counterparts est1a, est1b, and est1c perform diverse functions in nonsense-mediated mrna decay (nmd), telomere length homeostasis, and telomere transcription. although est1 and est1a/b interact with the catalytic subunit of yeast and human telomerase (est2 and tert, respectively), the molecular determinants of these interactions have not been elaborated fully.201122011238
proteome-wide detection of abl1 sh3 binding peptides by integrating computational prediction and peptide microarray.protein-protein interactions are essential for regulating almost all aspects of cellular functions. many of these interactions are mediated by weak and transient protein domain-peptide binding, but they are often underrepresented in high throughput screening of protein-protein interactions using techniques such as yeast two hybrid and mass spectrometry. on the other hand, computational predictions and in vitro binding assays are valuable in providing clues of in vivo interactions. we present her ...201122023807
myst protein acetyltransferase activity requires active site lysine autoacetylation.the myst protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, dna repair, cell-cycle regulation, stem cell homeostasis and development. here, we demonstrate that myst protein acetyltransferase activity requires active site lysine autoacetylation. the x-ray crystal structures of yeast esa1 (yesa1/kat5) bound to a bisubstrate h4k16coa inhibitor and human mof (hmof/kat8/myst1) ...201122020126
interaction profiling identifies the human nuclear exosome targeting complex.the rna exosome is a conserved degradation machinery, which obtains full activity only when associated with cofactors. the most prominent activator of the yeast nuclear exosome is the rna helicase mtr4p, acting in the context of the trf4p/air2p/mtr4p polyadenylation (tramp) complex. the existence of a similar activator(s) in humans remains elusive. by establishing an interaction network of the human nuclear exosome, we identify the trimeric nuclear exosome targeting (next) complex, containing hm ...201121855801
hepatic sirt1 deficiency in mice impairs mtorc2/akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance.insulin resistance is a major risk factor for type 2 diabetes mellitus. the protein encoded by the sirtuin 1 (sirt1) gene, which is a mouse homolog of yeast sir2, is implicated in the regulation of glucose metabolism and insulin sensitivity; however, the underlying mechanism remains elusive. here, using mice with a liver-specific null mutation of sirt1, we have identified a signaling pathway involving sirt1, rictor (a component of mtor complex 2 [mtorc2]), akt, and foxo1 that regulates gluconeog ...201121965330
structural and binding studies of the c-terminal domains of yeast tfiif subunits tfg1 and tfg2.the general transcription factor tfiif plays essential roles at several steps during eukaryotic transcription. while several studies have offered insights into the structure/function relationship in human tfiif, much less is known about the yeast system. here, we describe the first nmr structural and binding studies of the c-terminal domains (ctds) of tfg1 and tfg2 subunits of saccharomyces cerevisiae tfiif. we used the program cs-rosetta to determine the three-dimensional folds of these domains ...201122095626
insights into noncanonical e1 enzyme activation from the structure of autophagic e1 atg7 with atg8.autophagy is the degradation of cellular organelles via the lysosomal pathway. the autophagic ubiquitin-like (ubl) molecule atg8 is activated by the e1-like enzyme atg7. as this noncanonical e1 enzyme's domain organization is unique among ubl-activating e1 enzymes, the structural basis for its interactions with atg8 and partner e2 enzymes remains obscure. here we present the structure of the n-terminal domain of atg7, revealing a unique protein fold and interactions with both autophagic e2 enzym ...201122056771
ms3 eliminates ratio distortion in isobaric multiplexed quantitative proteomics.quantitative mass spectrometry-based proteomics is highly versatile but not easily multiplexed. isobaric labeling strategies allow mass spectrometry-based multiplexed proteome quantification; however, ratio distortion owing to protein quantification interference is a common effect. we present a two-proteome model (mixture of human and yeast proteins) in a sixplex isobaric labeling system to fully document the interference effect, and we report that applying triple-stage mass spectrometry (ms3) a ...201121963607
cpth6, a thiazole derivative, induces histone hypoacetylation and apoptosis in human leukemia cells.purpose: we previously identified novel thiazole derivatives able to reduce histone acetylation and histone acetyltransferase (hat) activity in yeast. among these compounds, 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (cpth6) has been selected and used throughout this study. experimental design: the effect of cpth6 on histone acetylation, cell viability and differentiation, cell-cycle distribution, and apoptosis in a panel of acute myeloid leukemia and solid tumor cell ...201122068659
Feature Article: From the Cover: A yeast functional screen predicts new candidate ALS disease genes.Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates ...201122065782
uptake of various yeast genera by antigen-presenting cells and influence of subcellular antigen localization on the activation of ovalbumin-specific cd8 t lymphocytes.yeasts of the genus saccharomyces expressing recombinant antigens are currently evaluated as candidate t cell vaccines. here, we compared the interaction kinetics between four biotechnologically relevant yeast genera (saccharomyces cerevisiae, schizosaccharomyces pombe, kluyveromyces lactis and pichia pastoris) and human dendritic cells as well as the involvement of dectin-1 and mannose receptor in phagocytosis. further, we analyzed the activation capacity of recombinant yeasts expressing ovalbu ...201121856351
An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor gene in breast cancer.Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. TSGs containing nonsense mutations may not be expressed because of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process, which clears transcripts that contain nonsense mutations, with the application of high-density single-nucleotide polymorphism arrays analysis to discriminate allelic content in ...201121892209
mutations in the dimer interface of dihydrolipoamide dehydrogenase promote site-specific oxidative damages in yeast and human cells.dihydrolipoamide dehydrogenase (dld) is a multifunctional protein well characterized as the e3 component of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes. previously, conditions predicted to destabilize the dld dimer revealed that dld could also function as a diaphorase and serine protease. however, the relevance of these cryptic activities remained undefined. we analyzed human dld mutations linked to strikingly different clinical phenotypes, including e340k, d444v, r447 ...201121930696
recql5 cooperates with topoisomerase ii alpha in dna decatenation and cell cycle progression.dna decatenation mediated by topoisomerase ii is required to separate the interlinked sister chromatids post-replication. sgs1, a yeast homolog of the human recq family of helicases interacts with topoisomerase ii and plays a role in chromosome segregation, but this functional interaction has yet to be identified in higher organisms. here, we report a physical and functional interaction of topoisomerase iiα with recql5, one of five mammalian recq helicases, during dna replication. direct interac ...201122013166
Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy.Autophagy, the primary recycling pathway of cells, plays a critical role in mitochondrial quality control under normal growth conditions and in the response to cellular stress. The Hsp90-Cdc37 chaperone complex coordinately regulates the activity of select kinases to orchestrate many facets of the stress response. Although both maintain mitochondrial integrity, the relationship between Hsp90-Cdc37 and autophagy has not been well characterized. Ulk1, one of the mammalian homologs of yeast Atg1, i ...201121855797
Functional links between Aß toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast.Aß (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aß toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aß was previously unknown. The factors identified in yeast modified Aß toxicity in glutamatergic neurons of Caenorhabditis elega ...201122033521
comparison of humoral immune responses to epstein-barr virus and kaposi's sarcoma-associated herpesvirus using a viral proteome microarray.epstein-barr virus (ebv) is a ubiquitous herpesvirus, and kaposi's sarcoma-associated herpesvirus (kshv) has a restricted seroprevalence. both viruses are associated with malignancies that have an increased frequency in individuals who are coinfected with human immunodeficiency virus type 1 (hiv-1).201121990424
Toxoplasma gondii Sis1-like J-domain protein is a cytosolic chaperone associated to HSP90/HSP70 complex.Toxoplasma gondii is an obligate intracellular protozoan parasite in which 36 predicted Hsp40 family members were identified by searching the T. gondii genome. The predicted protein sequence from the gene ID TGME49_065310 showed an amino acid sequence and domain structure similar to Saccharomyces cerevisiae Sis1. TgSis1 did not show differences in its expression profile during alkaline stress by microarray analysis. Furthermore, TgSis1 showed to be a cytosolic Hsp40 which co-immunoprecipitated w ...201122209934
flavivirus ns3 and ns5 proteins interaction network: a high-throughput yeast two-hybrid screen.the genus flavivirus encompasses more than 50 distinct species of arthropod-borne viruses, including several major human pathogens, such as west nile virus, yellow fever virus, japanese encephalitis virus and the four serotypes of dengue viruses (denv type 1-4). each year, flaviviruses cause more than 100 million infections worldwide, some of which lead to life-threatening conditions such as encephalitis or haemorrhagic fever. among the viral proteins, ns3 and ns5 proteins constitute the major e ...201122014111
Copper Chaperone-Dependent and -Independent Activation of Three Copper-Zinc Superoxide Dismutase Homologs Localized in Different Cellular Compartments in Arabidopsis.Superoxide dismutases (SODs) are important antioxidant enzymes that catalyze the disproportionation of superoxide anion to O2 and H2O2 to guard cells against superoxide toxicity. The major pathway for activation of Cu-Zn SOD (CuZnSOD; CSD) involves a Cu chaperone for SOD (CCS) and an additional minor CCS-independent pathway reported in mammals. We characterized the CCS-dependent and -independent activation pathways for three CSDs localized in different cellular compartments in Arabidopsis thalia ...201122186608
wdr36 acts as a scaffold protein tethering a g-protein-coupled receptor, gαq and phospholipase cβ in a signalling complex.we identified the wd-repeat-containing protein, wdr36, as an interacting partner of the β isoform of thromboxane a(2) receptor (tpβ) by yeast two-hybrid screening. we demonstrated that wdr36 directly interacts with the c-terminus and the first intracellular loop of tpβ by in vitro gst-pulldown assays. the interaction in a cellular context was observed by co-immunoprecipitation, which was positively affected by tpβ stimulation. tpβ-wdr36 colocalization was detected by confocal microscopy at the p ...201121940795
cancer. aneuploidy drives a mutator phenotype in cancer. 201121852477
fukutin-related protein resides in the golgi cisternae of skeletal muscle fibres and forms disulfide-linked homodimers via an n-terminal interaction.limb-girdle muscular dystrophy type 2i (lgmd2i) is an inheritable autosomal, recessive disorder caused by mutations in the fukutin-related protein (fkrp) gene (fkrp) located on chromosome 19 (19q13.3). mutations in fkrp are also associated with congenital muscular dystrophy (mdc1c), walker-warburg syndrome (wws) and muscle eye brain disease (meb). these four disorders share in common an incomplete/aberrant o-glycosylation of the membrane/extracellular matrix (ecm) protein α-dystroglycan. however ...201121886772
glutamine analogs promote cytoophidium assembly in human and drosophila cells.ctp synthase is compartmentalized within a subcellular structure, termed the cytoophidium, in a range of organisms including bacteria, yeast, fruit fly and rat. here we show that ctp synthase is also compartmentalized into cytoophidia in human cells. surprisingly, the occurrence of cytoophidia in human cells increases upon treatment with a glutamine analog 6-diazo-5-oxo-l-norleucine (don), an inhibitor of glutamine-dependent enzymes including ctp synthase. experiments in flies confirmed that don ...201121930098
production of ibuprofen acyl glucosides by human ugt2b7.udp-glycosyltransferases (ugts) are an important group of enzymes that participate in phase ii metabolism of xenobiotics and use the cofactor udp-glucuronic acid for the production of glucuronides. when acting on molecules bearing a carboxylic acid they can form acyl glucuronides, a group of metabolites that has gained significant interest in recent years because of concerns about their potential role in drug toxicity. in contrast, reports about the production of drug acyl glucosides (which migh ...201121862693
granulomatous dermatitis due to malassezia sympodialis.a 67-year-old man, with multiple skin lesions that appeared over 2 years, had biopsies that disclosed granulomatous dermatitis with associated small yeasts. the urinary antigen test results were negative for histoplasma infection; cultures from the biopsies did not grow any fungi or other potential pathogens. the chest roentgenogram results were normal. morphologic examination revealed features of a malassezia species. broad-range fungal polymerase chain reaction and dna sequencing disclosed tha ...201121877990
backbone resonances assignment of 19 kda cd1 domain of human mitotic checkpoint serine/threonine-protein kinase, bub1.bub1 is an evolutionarily conserved mitotic checkpoint control protein that is present in diverse organisms including yeast and humans. bub1 is a serine/threonine protein kinase and is required for recruitment of mad1, mad2, bub3, and cenp-e to kinetochores (sharp-baker and chen in j cell biol 153:1239-1250, 2001). the evolutionarily conserved amino acid region in the n-terminus has been called as the cd1 domain. to clarify the action mechanism of bub1 in controlling check point signals, we init ...201121904986
human yeast-specific cd8 t lymphocytes show a nonclassical effector molecule profile.pathogenic yeast and fungi represent a major group of human pathogens. the consequences of infections are diverse and range from local, clinically uncomplicated mycosis of the skin to systemic, life-threatening sepsis. despite extensive mhc class i-restricted frequencies of yeast-specific cd8 t lymphocytes in healthy individuals and the essential role of the cell-mediated immunity in controlling infections, the characteristics and defense mechanisms of antifungal effector cells are still unclear ...201121947167
commitment to a cellular transition precedes genome-wide transcriptional change.in budding yeast, commitment to cell division corresponds to activating the positive feedback loop of g1 cyclins controlled by the transcription factors sbf and mbf. this pair of transcription factors has over 200 targets, implying that cell-cycle commitment coincides with genome-wide changes in transcription. here, we find that genes within this regulon have a well-defined distribution of transcriptional activation times. combinatorial use of sbf and mbf results in a logical or function for gen ...201121855792
bnrch gene inhibits cell growth of hela cells through increasing the g2 phase of cell cycle.the ubiquitin-proteasome pathway (upp) is an important protein degradation system universally existing in eukaryotic organisms from yeast to human. in this system, hundreds of e3 ubiquitin-protein ligases are most important because they provide the substrate specificity and control many cellular processes. upp has been found to be relevant to cancer development. bnrch, the protein product from a novel gene isolated from brassica napus, also has e3 ubiquitin-protein ligase activity. in order to e ...201122038067
elevated levels of renal and circulating nop-7-associated 2 (nsa2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy.aims/hypothesis: we previously found that nop-7-associated 2 (nsa2), which is involved in ribosomal biogenesis in yeast and is a putative cell cycle regulator in mammalian cells, is elevated in the kidney of goto-kakizaki (gk) rat, a spontaneous model of type 2 diabetes. here we tested the hypothesis that elevated nsa2 is involved in diabetic nephropathy (dn). methods: we examined nsa2/nsa2 expression and nsa2 pr ...201122095236
recombinant antibodies and their use in biosensors.inexpensive, noninvasive immunoassays can be used to quickly detect disease in humans. immunoassay sensitivity and specificity are decidedly dependent upon high-affinity, antigen-specific antibodies. antibodies are produced biologically. as such, antibody quality and suitability for use in immunoassays cannot be readily determined or controlled by human intervention. however, the process through which high-quality antibodies can be obtained has been shortened and streamlined by use of genetic en ...201122159424
non-coding telomeric and subtelomeric transcripts are differentially regulated by telomeric and heterochromatin assembly factors in fission yeast.while telomere repeat-containing non-coding rna has been identified in a variety of eukaryotes, its biological role is not yet clear. we have identified telomeric transcripts in fission yeast, a model system that combines precise genetic manipulability with telomeres remarkably similar to those of human. like human and budding yeast, fission yeast harbours a population of telomeric rna molecules containing g-rich telomeric repeats transcribed from the subtelomere to the telomere. in addition, we ...201122139922
the two-component histidine kinases drka and slna are required for in vivo growth in the human pathogen penicillium marneffei.in order to cause disease fungal pathogens must be capable of evading or tolerating the host immune defence system. one commonly utilized evasion mechanism is the ability to continually reside within macrophages of the innate immune system and survive subsequent phagocytic destruction. for intracellular growth to occur, fungal pathogens which typically grow in a filamentous hyphal form in the environment must be able to switch growth to a unicellular yeast growth form in a process known as dimor ...201122059885
control of mucin-type o-glycosylation - a classification of the polypeptide galnac-transferase gene family.glycosylation of proteins is an essential process in all eukaryotes and a great diversity in types of protein glycosylation exists in animals, plants and microorganisms. mucin-type o-glycosylation, consisting of glycans attached via o-linked galnac to ser and thr residues, is one of the most abundant forms of protein glycosylation in animals. while most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for initiation of glycosylation, i.e. the step where th ...201122183981
fhl2 protein is a novel co-repressor of nuclear receptor nur77.the three members of the nr4a orphan nuclear receptor subfamily nur77, nurr1, and nor-1, regulate a variety of biological functions including vascular disease and metabolism. in this study, we identified four and a half lim domains protein-2 (fhl2) as a novel interacting protein of nr4a nuclear receptors by yeast two-hybrid screen and co-immunoprecipitation studies. each of the four lim domains of fhl2 can bind nur77, and both the amino-terminal domain and the dna binding domain of nur77 are inv ...201122049082
inner nuclear membrane protein ima1 is dispensable for intranuclear positioning of centromeres.inner nuclear membrane (inm) proteins play a role in spatial organization of chromosomes within the nucleus. in the fission yeast schizosaccharomyces pombe, sad1, an inm protein of the conserved sun-domain family, plays an active role in moving chromosomes along the nuclear membranes during meiotic prophase. ima1 is another conserved inm protein recently identified. a previous study claimed that ima1 is essential for mitotic cell growth, linking centromeric heterochromatin to the spindle-pole bo ...201121880100
antifungal action of human cathelicidin fragment (ll13-37) on candida albicans.human cathelicidin ll37 and its fragments ll13-37 and ll17-32 exhibited similar potencies in inhibiting growth of the yeast candida albicans. after treatment with 0.5 μm and 5 μm ll13-37, the hyphae changed from a uniformly thick to an increasingly slender appearance, with budding becoming less normal in appearance and cell death could be detected. only the yeast form and no hyphal form could be observed following exposure to 50 μm ll13-37. ll13-37 at a concentration of 5 μm was able to permeabi ...201121889964
the effects of the influence of pretreating serum samples on the performance of a latex agglutination test for serodiagnosis of paracoccidioidomycosis.paracoccidioidomycosis (pcm) is a fungal disease caused by paracoccidioides brasiliensis, and brazil is one of its principal endemic countries. diagnosis is based on the observation of budding yeast in clinical specimens from patients; however, the sensitivity of the visualization of fungi is low, indicating that serologic tests are used for early diagnosis. the double-immunodiffusion test (id) is the gold standard test for serology in pcm; although, the execution of this test requires the avail ...201122205661
studies on differential nuclear translocation mechanism and assembly of the three subunits of the arabidopsis thaliana transcription factor nf-y.the eukaryotic transcription factor nf-y consists of three subunits (a, b, and c), which are encoded in arabidopsis thaliana in multigene families consisting of 10, 13, and 13 genes, respectively. in principle, all potential combinations of the subunits are possible for the assembly of the heterotrimeric complex. we aimed at assessing the probability of each subunit to participate in the assembly of nf-y. the evaluation of physical interactions among all members of the nf-y subunit families indi ...201122199235
reduced protein stability of human dj-1/park7 l166p, linked to autosomal recessive parkinson disease, is due to direct endoproteolytic cleavage by the proteasome.parkinson's disease (pd) is characterized by dopaminergic dysfunction and degeneration. dj-1/park7 mutations have been linked with a familial form of early onset pd. in this study, we found that human dj-1 wild type and the missense mutants m26i, r98q, a104t and d149a were stable proteins in cells, only the l166p mutant was unstable. in parallel, the former were not degraded and the l166p mutant was directly degraded in vitro by proteasome-mediated endoproteolytic cleavage. furthermore, genetic ...201122173095
alfa-class prefoldin protein uxt is a novel interacting partner of amyotrophic lateral sclerosis 2 (als2) protein.mutations in als2 gene cause several autosomal recessive forms of motor neuron diseases including juvenile amyotrophic lateral sclerosis (jals), juvenile primary lateral sclerosis (plsj) and infantile-onset ascending hereditary spastic paralysis (iahsp). to find novel protein-protein interactions of als2 protein we performed a yeast two hybrid screen and fished out the ubiquitously expressed transcript (uxt) protein. uxt is a novel gene encoding for an α-class prefoldin type chaperone which acts ...201121907703
human cytomegalovirus primase ul70 specifically interacts with cellular factor snapin.genomic dna synthesis is a universally conserved process for all herpesviruses, including human cytomegalovirus (hcmv). hcmv ul70 is believed to encode the primase of the dna replication machinery, a function which requires localization in the nucleus, the site of viral dna synthesis. no host factors that interact with ul70 have been reported. in this study, we provide the first direct evidence that ul70 specifically interacts with snapin, a human protein that is predominantly localized in the c ...201121917956
options for the production of selenized chicken meat.a 42-day experiment was conducted to compare the effects of various levels of sodium selenite (ss) and se-enriched yeast (sy) on chicken productivity, carcass traits, and breast se concentration. six hundred 1-day-old cobb 500 broiler chicks were placed on 1 of 6 experimental treatments. the treatments consisted of feeding a diet without se supplementation (basal diet) or basal diet with 0.6 mg/kg supplemented se supplied by ss, sy, or a mix of the two (0.45 ss + 0.15 sy; 0.3 ss + 0.3 sy; 0.15 s ...201121986861
aggresome formation and segregation of inclusions influence toxicity of α-synuclein and synphilin-1 in yeast.pd (parkinson's disease) is a neurodegenerative disorder, caused by a selective loss of dopaminergic neurons in the substantia nigra, which affects an increasing number of the elderly population worldwide. one of the major hallmarks of pd is the occurrence of intracellular protein deposits in the dying neurons, termed lewy bodies, which contain different proteins, including aggregated α-synuclein and its interacting protein synphilin-1. during the last decade, a number of groups developed yeast ...201121936837
endoplasmic reticulum-associated degradation (erad) and free oligosaccharide generation in saccharomyces cerevisiae.in saccharomyces cerevisiae, proteins with misfolded lumenal, membrane, and cytoplasmic domains are cleared from the endoplasmic reticulum (er) by er-associated degradation (erad)-l, -m, and -c, respectively. erad-l is n-glycan-dependent and is characterized by er mannosidase (mns1p) and er mannosidase-like protein (mnl1p), which generate man(7)glcnac(2) (d1) n-glycans with non-reducing α1,6-mannosyl residues. glycoproteins bearing this motif bind yos9p and are dislocated into the cytoplasm and ...201121979948
peptides from aminoacyl-trna synthetases can cure the defects due to mutations in mt trna genes.recent results from several laboratories have confirmed that human and yeast leucyl- and valyl-trna synthetases can rescue the respiratory defects due to mutations in mitochondrial trna genes. in this report we show that this effect cannot be ascribed to the catalytic activity per se and that isolated domains of aminoacyl-trna synthetases and even short peptides thereof have suppressing effects.201121903180
The Human Nucleolar Protein FTSJ3 Associates with NIP7 and Functions in Pre-rRNA Processing.NIP7 is one of the many trans-acting factors required for eukaryotic ribosome biogenesis, which interacts with nascent pre-ribosomal particles and dissociates as they complete maturation and are exported to the cytoplasm. By using conditional knockdown, we have shown previously that yeast Nip7p is required primarily for 60S subunit synthesis while human NIP7 is involved in the biogenesis of 40S subunit. This raised the possibility that human NIP7 interacts with a different set of proteins as com ...201122195017
caffeine abolishes the ultraviolet-induced rev3 translesion replication pathway in mouse cells.when a replicative dna polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s), which insert nucleotide(s) opposite the lesion. using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed uv-induced translesion replication (uv-tls) into two types. in human cancer cells or xeroderma pigmentosum variant (xp-v) cells, uv-tls was inhibited by caffeine or proteasome inhibitor ...201122272088
help3 directly modulates the expression of hsp70 gene in hela cells via hat activity.human elongator complex, which plays a key role in transcript elongation in vitro assay, is incredibly similar in either components or function to its yeast counterpart. however, there are only a few studies focusing on its target gene characterization in vivo. we studied the effect of down-regulation of the human elongation protein 3 (help3) on the expression of hsp70 through antisense strategy. transfecting antisense plasmid p1107 into hela cells highly suppressed help3 expression, and substan ...201122216241
Chronological lifespan in stationary culture: from yeast to human cells.Comment on: Leontieva OV and Blagosklonny MV. Yeast-like chronological senescence in mammalian cells: phenomenon, mechanism and pharmacological suppression. Aging 2011; 3: this issue. This first paper defines the field, providing description of the phenomenon, its mechanism and the ways of pharmacological manipulation. It illuminates the place of yeast CS in aging research and its indirect (via common signaling pathways) relevance to cancer and organismal aging. It also rules out altruistic (pro ...201122156408
Ex Vivo and In Vivo Inhibition of Human Rhinovirus Replication by a New Pseudosubstrate of Viral 2A Protease.Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A(pro)) and inhibited its activity. This peptide was chemically modified with a reactiv ...201222072773
isoleucyl-trna synthetase levels modulate the penetrance of a homoplasmic m.4277t>c mitochondrial trna(ile) mutation causing hypertrophic cardiomyopathy.the genetic and epigenetic factors underlying the variable penetrance of homoplasmic mitochondrial dna mutations are poorly understood. we investigated a 16-year-old patient with hypertrophic cardiomyopathy harboring a homoplasmic m.4277t>c mutation in the mt-trna(ile) (mtti) gene. skeletal muscle showed multiple respiratory chain enzyme abnormalities and a decreased steady-state level of the mutated mt-trna(ile). transmitochondrial cybrids grown on galactose medium demonstrated a functional eff ...201221945886
structure of hdac3 bound to co-repressor and inositol tetraphosphate.histone deacetylase enzymes (hdacs) are emerging cancer drug targets. they regulate gene expression by removing acetyl groups from lysine residues in histone tails, resulting in chromatin condensation. the enzymatic activity of most class i hdacs requires recruitment into multi-subunit co-repressor complexes, which are in turn recruited to chromatin by repressive transcription factors. here we report the structure of a complex between an hdac and a co-repressor, namely, human hdac3 with the deac ...201222230954
chemical reactivity and microbicidal action of bethoxazin.bethoxazin is a new broad spectrum industrial microbicide with applications in material and coating preservation. however, little is known of its reactivity profile and mechanism of action. in this study, we examined the reactivity of bethoxazin toward biologically important nucleophilic groups using uv-vis spectroscopy and lc-ms/ms techniques and found the molecule to be highly electrophilic. bethoxazin reacted with molecules containing free sulfhydryl groups such as gsh and human serum albumin ...201222264763
roles of candida albicans gat2, a gata-type zinc finger transcription factor, in biofilm formation, filamentous growth and virulence.candida albicans is the most common human fungal pathogen, causing not only superficial infections, but also life-threatening systemic disease. c. albicans can grow in several morphological forms including unicellular yeast-form, elongated hyphae and pseudohyphae. in certain natural environments, c. albicans also exists as biofilms, which are structured and surface-attached microbial communities. transcription factors play a critical role in morphogenesis and biofilm development. in this study, ...201222276126
target-binding proteins based on the 10th human fibronectin type iii domain ((10)fn3).we describe concepts and methods for generating a family of engineered target-binding proteins designed on the scaffold of the 10th human fibronectin type iii domain ((10)fn3), an extremely stable, single-domain protein with an immunoglobulin-like fold but lacking disulfide bonds. large libraries of possible target-binding proteins can be constructed on the (10)fn3 scaffold by diversifying the sequence and length of its surface loops, which are structurally analogous to antibody complementarity- ...201222230568
structure-based alteration of substrate specificity and catalytic activity of sulfite oxidase from sulfite oxidation to nitrate reduction †eukaryotic sulfite oxidase is a dimeric protein that contains the molybdenum cofactor and catalyzes the metabolically essential conversion of sulfite to sulfate as the terminal step in the metabolism of cysteine and methionine. nitrate reductase is an evolutionally related molybdoprotein in lower organisms that is essential for growth on nitrate. in this study we describe human and chicken sulfite oxidase variants in which the active site has been modified to alter substrate specificity and act ...201222263579
safety evaluation of a proprietary food-grade, dried fermentate preparation of saccharomyces cerevisiae.a safety evaluation was performed for epicor, a product produced by a proprietary fermentation process using saccharomyces cerevisiae. studies included the following assays: bacterial reverse mutation, mouse lymphoma cell mutagenicity, mitogenicity assay in human peripheral lymphocytes, and a cytochrome p450 ([cyp] cyp1a2 and cyp3a4) induction assessment as well as 14-day acute, 90-day subchronic, and 1-year chronic oral toxicity studies in rats. no evidence of genotoxicity or mitogenicity was s ...201222222580
a novel antirecombinase gains parity.in this issue, moldovan et al. (2012) report the identification of pari, a putative human ortholog of the yeast srs2 protein, which potentially regulates homologous recombination repair via its ability to disrupt the function of rad51.201222244326
A Monod-Wyman-Changeux Mechanism Can Explain G Protein-coupled Receptor (GPCR) Allosteric Modulation.The Monod-Wyman-Changeux (MWC) model was initially proposed to describe the allosteric properties of regulatory enzymes and subsequently extended to receptors. Yet despite GPCRs representing the largest family of receptors and drug targets, no study has systematically evaluated the MWC mechanism as it applies to GPCR allosteric ligands. We reveal how the recently described allosteric modulator, benzyl quinolone carboxylic acid (BQCA), behaves according to a strict, two-state MWC mechanism at the ...201222086918
cuedc2 (cue domain-containing 2) and socs3 (suppressors of cytokine signaling 3) cooperate to negatively regulate janus kinase 1/signal transducers and activators of transcription 3 signaling.janus kinase 1/signal transducers and activators of transcription 3 (jak1/stat3) pathway is one of the recognized oncogenic signaling pathways that frequently overactivated in a variety of human tumors. despite rapid progress in elucidating the molecular mechanisms of activation of jak/stat pathway, the processes that regulate jak/stat deactivation need to be further clarified. here we demonstrate that cue domain-containing 2 (cuedc2) inhibits cytokine-induced phosphorylation of jak1 and stat3 a ...201222084247
Expression of Multisubunit Proteins in Leishmania tarentolae.Heterologous gene expression in mammalian cells is the first choice for the production of recombinant proteins when posttranslational modifications affect the biological activity of target proteins. However, the expression efficiency of mammalian cells is relatively low compared to other expression systems, such as Escherichia coli or yeast. Recently, a novel protein expression system based on Leishmania tarentolae, a protozoan parasite of gecko, was developed. This system allows not only easy h ...201222160906
Cell-penetrating peptides as antifungals towards Malassezia sympodialis.Aim: To determine whether different antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) are able to inhibit the growth of the commensal yeast Malassezia sympodialis, which can act as a trigger factor in different skin disorders, such as atopic eczema (AE), seborrhoeic eczema (SE) and dandruff. Methods and results: The antifungal activity of 21 different AMPs and CPPs was investigated by microdilution assay and plate counting to determine the number of colony forming units. Five ...201222023266
actinomyces naturae sp. nov., the first actinomyces sp. isolated from a non-human or animal source.three facultatively anaerobic, gram-positive staining, rod-shaped, non-spore forming, flagellated bacterial strains, bl-75, bl-79(t) and bl-104, were isolated from chlorinated solvent-contaminated groundwater. phylogenetic analysis based on 16s rrna gene sequence comparisons showed them to represent a distinct lineage within the genus actinomyces with sequence identities in the range of <88-95.4% with previously described actinomyces species. the strains were oxidase and catalase negative. nitra ...201221965039
The genome maintenance factor Mgs1 is targeted to sites of replication stress by ubiquitylated PCNA.Mgs1, the budding yeast homolog of mammalian Werner helicase-interacting protein 1 (WRNIP1/WHIP), contributes to genome stability during undisturbed replication and in response to DNA damage. A ubiquitin-binding zinc finger (UBZ) domain directs human WRNIP1 to nuclear foci, but the functional significance of its presence and the relevant ubiquitylation targets that this domain recognizes have remained unknown. Here, we provide a mechanistic basis for the ubiquitin-binding properties of the prote ...201221911365
mechanism of start site selection by rna polymerase ii: interplay between tfiib and ssl2/xpb helicase subunit of tfiih.tfiib is essential for transcription initiation by rna polymerase ii. tfiib also cross-links to terminator regions and is required for gene loops that juxtapose promoter-terminator elements in a transcription-dependent manner. the saccharomyces cerevisiae sua7-1 mutation encodes an altered form of tfiib (e62k) that is defective for both start site selection and gene looping. here we report the isolation of an ssl2 mutant, encoding an altered form of tfiih, as a suppressor of the cold-sensitive g ...201222081613
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