bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fungal Type II Myosin in Penicillium marneffei, MyoB, Is Essential for Chitin Deposition at Nascent Septation Sites but Not Actin Localization
Authors: Cánovas David , Boyce Kylie J. , Andrianopoulos Alex 
Published: December 2010

ABSTRACT

Cytokinesis is essential for proliferative growth but also plays equally important roles during morphogenesis and development. The human pathogen
Penicillium marneffei
is capable of dimorphic switching in response to temperature, growing in a multicellular filamentous hyphal form at 25°C and in a unicellular yeast form at 37°C.
P. marneffei
also undergoes asexual development at 25°C to produce multicellular differentiated conidiophores. Thus,
P. marneffe
i exhibits cell division with and without cytokinesis and division by budding and fission, depending on the cell type. The type II myosin gene,
myoB
, from
P. marneffei
plays important roles in the morphogenesis of these cell types. Deletion of
myoB
leads to chitin deposition defects at sites of cell division without perturbing actin localization. In addition to aberrant hyphal cells, distinct conidiophore cell types are lacking due to malformed septa and nuclear division defects. At 37°C, deletion of
myoB
prevents uninucleate yeast cell formation, instead producing long filaments resembling hyphae at 25°C. The Δ
myoB
cells also often lyse due to defects in cell wall biogenesis. Thus, MyoB is essential for correct morphogenesis of all cell types regardless of division mode (budding or fission) and defines differences between the different types of growth.
A Single Mating-Type Locus Composed of Homeodomain Genes Promotes Nuclear Migration and Heterokaryosis in the White-Rot Fungus Phanerochaete chrysosporium
Authors: James Timothy Y. , Lee Maria , van Diepen Linda T. A. 
Published: December 2010

ABSTRACTThe white-rot basidiomycete fungusPhanerochaete chrysosporium(Agaricomycetes) is a model species that produces potent wood-degrading enzymes. The mating system of the species has been difficult to characterize due to its cryptic fruiting habit and lack of clamp connections in the heterokaryotic phase. By exploiting the draft genome sequence, we reevaluated the mating system ofP. chrysosporiumby studying the inheritance and segregation of putative mating-type gene homologues, the homeodomain transcription factor genes (MAT-A) and the pheromone receptors (MAT-B). A pattern of mating incompatibility and fructification consistent with a bipolar system with a singleMATlocus was observed, but the rejection response was much weaker than that seen in other agaricomycete species, leading to stable heterokaryons with identicalMATalleles. The homeodomain genes appear to comprise the singleMATlocus because they are heterozygous in wild strains and hyperpolymorphic at the DNA sequence level and promote aspects of sexual reproduction, such as nuclear migration, heterokaryon stability, and basidiospore formation. The pheromone receptor loci that might constitute aMAT-Blocus, as in many other Agaricomycetes, are not linked to theMAT-Alocus and display low levels of polymorphism. This observation is inconsistent with a bipolar mating system that includes pheromones and pheromone receptors as mating-type determinants. The partial uncoupling of nuclear migration and mating incompatibility in this species may be predicted to lead to parasexual recombination and may have contributed to the homothallic behavior observed in previous studies.
Fungal Skn7 Stress Responses and Their Relationship to Virulence
Authors: Fassler Jan S. , West Ann H. 
Published: December 2010

ABSTRACT

The histidine kinase-based phosphorelay has emerged as a common strategy among bacteria, fungi, protozoa, and plants for triggering important stress responses and interpreting developmental cues in response to environmental as well as chemical, nutritional, and hormone signals. The absence of this type of signaling mechanism in animals makes the so-called “two-component” pathway an attractive target for development of antimicrobial agents. The best-studied eukaryotic example of a two-component pathway is the SLN1 pathway in
Saccharomyces cerevisiae
, which responds to turgor and other physical properties associated with the fungal cell wall. One of the two phosphoreceiver proteins known as response regulators in this pathway is Skn7, a highly conserved stress-responsive transcription factor with a subset of activities that are dependent on SLN1 pathway phosphorylation and another subset that are independent. Interest in Skn7as a determinant in fungal virulence stems primarily from its well-established role in the oxidative stress response; however, the involvement of Skn7 in maintenance of cell wall integrity may also be relevant. Since the cell wall is crucial for fungal survival, structural and biosynthetic proteins affecting wall composition and signaling pathways that respond to wall stress are likely to play key roles in virulence. Here we review the molecular and phenotypic characteristics of different fungal Skn7 proteins and consider how each of these properties may contribute to fungal virulence.
Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata
Authors: Paul Sanjoy , Schmidt Jennifer A. , Moye-Rowley W. Scott 
Published: December 2010

ABSTRACT

Candida glabrata
is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing transcriptional regulator
C. glabrata
Pdr1 (CgPdr1). CgPdr1 induces the expression of an ATP-binding cassette (ABC) transporter-encoding gene, Cg
CDR1
.
Saccharomyces cerevisiae
has two CgPdr1 homologues called ScPdr1 and ScPdr3. These factors control the expression of an ABC transporter-encoding gene called Sc
PDR5
, which encodes a homologue of Cg
CDR1
. Loss of the mitochondrial genome (ρ
0
cell) or overexpression of the mitochondrial enzyme ScPsd1 induces Sc
PDR5
expression in a strictly ScPdr3-dependent fashion. ScPdr3 requires the presence of a transcriptional Mediator subunit called Gal11 (Med15) to fully induce Sc
PDR5
transcription in response to ρ
0
signaling. ScPdr1 does not respond to either ρ
0
signals or ScPsd1 overproduction. In this study, we employed transcriptional fusions between CgPdr1 target promoters, like Cg
CDR1
, to demonstrate that CgPdr1 stimulates gene expression via binding to elements called pleiotropic drug response elements (PDREs). Deletion mapping and electrophoretic mobility shift assays demonstrated that a single PDRE in the Cg
CDR1
promoter was capable of supporting ρ
0
-induced gene expression. Removal of one of the two ScGal11 homologues from
C. glabrata
caused a major defect in drug-induced expression of Cg
CDR1
but had a quantitatively minor effect on ρ
0
-stimulated transcription. These data demonstrate that CgPdr1 appears to combine features of ScPdr1 and ScPdr3 to produce a transcription factor with chimeric regulatory properties.
Regulation of
nleA
in Shiga Toxin-Producing
Escherichia coli
O84:H4 Strain 4795/97
Authors: Schwidder Maike , Hensel Michael , Schmidt Herbert 
Published: December 2010

ABSTRACT

Many Shiga toxin-producing
Escherichia coli
(STEC) strains express a type III secretion system (TTSS) encoded by the locus of enterocyte effacement (LEE). Using the TTSS, STEC is able to inject effector proteins directly into eukaryotic host cells, where they cause characteristic attaching and effacing (A/E) lesions. In addition to the LEE-encoded effectors, a number of non-LEE-encoded effectors, located on phage-associated elements, have been described. One of them, the
n
on-
L
EE-encoded
e
ffector
A
(NleA), is widely distributed among pathogenic
E. coli
. In this study, we investigated the influence of environmental conditions on the expression of the phage-encoded effector
nleA
gene (designated
nleA
4795
) present in STEC O84:H4 strain 4795/97. We demonstrated that a particular NaCl concentration and starvation stress increase the activity of the
nleA
4795
promoter. Moreover, several regulators that control
nleA
4795
expression were identified. The involvement of the LEE regulators Ler, GrlA, and GrlR show that
nleA
4795
is integrated in the LEE regulation circuit. Furthermore, the binding of Ler to sequences upstream of
nleA
4795
underlined these findings.
DifA, a Methyl-Accepting Chemoreceptor Protein-Like Sensory Protein, Uses a Novel Signaling Mechanism to Regulate Exopolysaccharide Production inMyxococcus xanthus
Authors: Xu Qian , Black Wesley P. , Nascimi Heidi M. , Yang Zhaomin 
Published: December 2010

ABSTRACTDifA is a methyl-accepting chemotaxis protein (MCP)-like sensory transducer that regulates exopolysaccharide (EPS) production inMyxococcus xanthus. Here mutational analysis and molecular biology were used to probe the signaling mechanisms of DifA in EPS regulation. We first identified the start codon of DifA experimentally; this identification extended the N terminus of DifA for 45 amino acids (aa) from the previous bioinformatics prediction. This extension helped to address the outstanding question of how DifA receives input signals from type 4 pili without a prominent periplasmic domain. The results suggest that DifA uses its N-terminus extension to sense an upstream signal in EPS regulation. We suggest that the perception of the input signal by DifA is mediated by protein-protein interactions with upstream components. Subsequent signal transmission likely involves transmembrane signaling instead of direct intramolecular interactions between the input and the output modules in the cytoplasm. The basic functional unit of DifA for signal transduction is likely dimeric as mutational alteration of the predicted dimeric interface of DifA significantly affected EPS production. Deletions of 14-aa segments in the C terminus suggest that the newly defined flexible bundle subdomain in MCPs is likely critical for DifA function because shortening of this bundle can lead to constitutively active mutations.
A Caffeyl-Coenzyme A Synthetase Initiates Caffeate Activation prior to Caffeate Reduction in the Acetogenic Bacterium
Acetobacterium woodii
Authors: Hess Verena , Vitt Stella , Müller Volker 
Published: December 2010

ABSTRACT

The anaerobic acetogenic bacterium
Acetobacterium woodii
couples the reduction of caffeate with electrons derived from hydrogen to the synthesis of ATP by a chemiosmotic mechanism using sodium ions as coupling ions, but the enzymes involved remain to be established. Previously, the electron transfer flavoproteins EtfA and EtfB were found to be involved in caffeate respiration. By inverse PCR, we identified three genes upstream of
etfA
and
etfB
:
carA
,
carB
, and
carC. carA
encodes a potential coenzyme A (CoA) transferase,
carB
an acyl-CoA synthetase, and
carC
an acyl-CoA dehydrogenase.
carA
, -
B
, and -
C
are located together with
etfA/carE
and
etfB/carD
on one polycistronic message, indicating that CarA, CarB, and CarC are also part of the caffeate respiration pathway. The genetic data suggest an initial ATP-dependent activation of caffeate by CarB. To prove the proposed function of CarB, the protein was overproduced in
Escherichia coli
, and the recombinant protein was purified. Purified CarB activates caffeate to caffeyl-CoA in an ATP- and CoA-dependent reaction. The enzyme has broad pH and temperature optima and requires K
+
for activity. In addition to caffeate, it can use ρ-coumarate, ferulate, and cinnamate as substrates, with 50, 15, and 9%, respectively, of the activity obtained with caffeate. Expression of the
car
operon is induced not only by caffeate, ρ-coumarate, ferulate, and cinnamate but also by sinapate. There is no induction by ρ-hydroxybenzoate or syringate.
Canonical Protein Splicing of a Class 1 Intein That Has a Class 3 Noncanonical Sequence Motif
Authors: Reitter Julie N. , Mills Kenneth V. 
Published: December 2010

ABSTRACT

A
Thermobifida fusca
intein has two characteristics of class 3 inteins: a noncontiguous covariant Trp-Cys-Thr triplet and a Ser flanking its C terminus. However, it has Cys at position one, characteristic of class 1 inteins. Splicing does not require the internal Cys, which may instead coordinate the active site. Therefore, the intein is class 1.
Complete Genome Sequence of
Burkholderia rhizoxinica
, an Endosymbiont of
Rhizopus microsporus
Authors: Lackner Gerald , Moebius Nadine , Partida-Martinez Laila , Hertweck Christian 
Published: December 2010

ABSTRACT

Burkholderia rhizoxinica
is an intracellular symbiont of the phytopathogenic fungus
Rhizopus microsporus
. The vertically transmitted endosymbiont not only delivers the antimitotic macrolide rhizoxin to its host but is also essential for vegetative spore formation of the fungus. To shed light on the genetic equipment of this model organism, we sequenced the whole genome of
B. rhizoxinica
HKI 0454, thus providing the first genomic insight into an intracellular mutualist of a fungal species. The 3.75-Mb genome consists of a chromosome and two strain-specific plasmids. The primary metabolism appears to be specialized for the uptake of fungal metabolites. Besides the rhizoxin biosynthesis gene cluster, there are 14 loci coding for nonribosomal peptide synthetase (NRPS) assembly lines, which represent novel targets for genomic mining of cryptic natural products. Furthermore, the endosymbionts are equipped with a repertoire of virulence-related factors, which can now be studied to elucidate molecular mechanisms underlying bacterial-fungal interaction.
Genome Sequence of
Lactobacillus amylovorus
GRL1112
Authors: Kant Ravi , Paulin Lars , Alatalo Edward , de Vos Willem M. , Palva Airi 
Published: December 2010

ABSTRACT

Lactobacillus amylovorus
is a common member of the normal gastrointestinal tract (GIT) microbiota in pigs. Here, we report the genome sequence of
L. amylovorus
GRL1112, a porcine feces isolate displaying strong adherence to the pig intestinal epithelial cells. The strain is of interest, as it is a potential probiotic bacterium.
Complete Genome Sequence of
Streptococcus thermophilus
Strain ND03
Authors: Sun Zhihong , Chen Xia , Wang Jicheng , Zhao Wenjing , Shao Yuyu , Wu Lan , Zhou Zhemin , Sun Tiansong , Wang Lei , Meng He , Zhang Heping , Chen Wei 
Published: December 2010

ABSTRACT

Streptococcus thermophilus
strain ND03 is a Chinese commercial dairy starter used for the manufacture of yogurt. It was isolated from naturally fermented yak milk in Qinghai, China. We present here the complete genome sequence of ND03 and compare it to three other published genomes of
Streptococcus thermophilus
strains.
Zeb1 and twist are more commonly expressed in metastatic than primary lung tumours and show inverse associations with claudins
Authors: Merikallio Heta , Kaarteenaho Riitta , Pääkkö Paavo , Lehtonen Siri , Hirvikoski Pasi , Mäkitaro Riitta , Harju Terttu , Soini Ylermi 
Published: December 2010

BackgroundZeb1 and twist regulate expression of genes which take part in epitheliomesenchymal transition (EMT). Claudins are tight junctional proteins regulating polarity and paracellular permeability of epithelial cells.Aims and methodsTo study Zeb1 and twist in 289 primary and 54 metastatic lung tumours and their relation to expression of claudins 1–5 and 7 by immunohistochemistry.ResultsMetastatic tumours showed a significantly lower expression of zeb1 and twist (33.0% and 38.0% vs 5.0% and 14.5%, p<0.001 for both) and they also had a significantly lower expression of claudin 1 (p<0.001), claudin 4 (p<0.001), claudin 5 (p=0.001) and claudin 7 (p<0.001) than did primary tumours. Primary lung tumours showed a strong inverse association between zeb1 and claudin 1 (p=0.024) and claudin 2 (p=0.003). For twist an inverse association was found with claudin 5 (p=0.007). In metastatic tumours zeb1 was inversely associated with claudin 7 (p=0.050) and twist with claudin 5 (p=0.025). Overexpression of claudin 5 was associated with decreased survival (p=0.017). For zeb1 or twist, no association with survival was observed in primary or metastatic tumours.ConclusionsAccording to protein expression, involvement of zeb1 and twist in EMT in primary lung tumours is relatively infrequent. Carcinomas metastatic to the lung showed a significantly higher expression of these transcriptional factors than primary lung tumours, indicating their probable importance in the metastatic process. Zeb1 and twist were inversely associated with several claudins, indicating a role in their down-regulation.
Lung cancer and occupational exposures other than cotton dust and endotoxin among women textile workers in Shanghai, China
Authors: Checkoway H , Ray R M , Lundin J I , Astrakianakis G , Seixas N S , Camp J E , Wernli K J , Fitzgibbons E D , Li W , Feng Z , Gao D L , Thomas D B 
Published: December 2010

ObjectivesNumerous epidemiological studies of lung cancer among textile workers worldwide consistently indicate reduced risks related to cotton dust exposure, presumably due to endotoxin contamination. Our objective was to investigate associations with other exposures potentially related to lung cancer, including wool and synthetic fibre dusts, formaldehyde, silica, dyes and metals, that have only been studied to a limited extent in the textile industry.MethodsWe conducted a case–cohort study nested within a cohort of 267 400 women textile workers in Shanghai, China. We compared work assignments and exposure histories of 628 incident lung cancer cases, diagnosed during 1989–1998, with those of a reference subcohort of 3188 workers. We reconstructed exposures with a job–exposure matrix developed specifically for textile factories. Cox proportional hazards modelling was applied to estimate age/smoking-adjusted relative risks (hazard ratios) and risk gradients associated with job assignments and specific agents other than cotton dust and endotoxin.ResultsNo associations were observed for lung cancer with wool, silk or synthetic fibre dusts, or with most other agents. However, increased risks, although statistically imprecise, were noted for ≥10 years’ exposures to silica (adjusted HR 3.5, 95% CI 1.0 to 13) and ≥10 years’ exposures to formaldehyde (adjusted HR 2.1, 95% CI 0.4 to 11).ConclusionsExposures to silica and formaldehyde, although not widespread among the cohort, may have increased lung cancer risk. Silica is an established human lung carcinogen, whereas there is only weak prior evidence supporting an association with formaldehyde. Both exposures warrant consideration as potential lung carcinogens in textile manufacturing.
Spectrum of tardive syndromes: clinical recognition and management
Authors: Bhidayasiri Roongroj , Boonyawairoj Suthida 
Published: December 2010

ABSTRACT
Tardive syndrome (TS) refers to a group of delayed onset disorders characterised by abnormal movements and caused by dopamine receptor blocking agents (DRBAs). Classical tardive dyskinesia is a specific type of oro-buccal-lingual dyskinesia. However, TS may exist in other forms—for example, stereotypy, dystonia, and akathisia—and frequently occur in combination. The onset typically is insidious and after reaching its maximum severity it often stabilises. Frequently reported risk factors are age, dose and duration of neuroleptic exposure, the use of conventional DRBAs, and co-existing mood disorders. This review highlights the broad spectrum of TS, not limited to classical tardive dyskinesia, as well as the clues for its recognition. Despite challenges in the treatment of TS, dictated by the different phenomenology, severity of TS and the need for ongoing neuroleptic treatment, the authors provide evidence based recommendations for patient management, which is not restricted to only withdrawal of the offending neuroleptics or the selection of an alternative medication, such as clozapine. In a minority of cases with significant functional disability, symptomatic or suppressive treatments should be considered. Recently, there has been a resurgence of stereotactic pallidal surgery for the treatment of TS. Although the efficacy of both pallidotomy and pallidal deep brain stimulation in dystonia has been encouraging, the evidence is still limited.
Antitumor Activity of BIBF 1120, a Triple Angiokinase Inhibitor, and Use of VEGFR2+pTyr+ Peripheral Blood Leukocytes as a Pharmacodynamic Biomarker In Vivo
Authors: Kudo Kanae , Arao Tokuzo , Tanaka Kaoru , Nagai Tomoyuki , Furuta Kazuyuki , Sakai Kazuko , Kaneda Hiroyasu , Matsumoto Kazuko , Tamura Daisuke , Aomatsu Keiichi , De Velasco Marco A. , Fujita Yoshihiko , Saijo Nagahiro , Kudo Masatoshi , Nishio Kazuto 
Published: December 2010

Abstract
Purpose: BIBF 1120 is a potent, orally available triple angiokinase inhibitor that inhibits VEGF receptors (VEGFR) 1, 2, and 3, fibroblast growth factor receptors, and platelet-derived growth factor receptors. This study examined the antitumor effects of BIBF 1120 on hepatocellular carcinoma (HCC) and attempted to identify a pharmacodynamic biomarker for use in early clinical trials.
Experimental Design: We evaluated the antitumor and antiangiogenic effects of BIBF 1120 against HCC cell line both in vitro and in vivo. For the pharmacodynamic study, the phosphorylation levels of VEGFR2 in VEGF-stimulated peripheral blood leukocytes (PBL) were evaluated in mice inoculated with HCC cells and treated with BIBF 1120.
Results: BIBF 1120 (0.01 μmol/L) clearly inhibited the VEGFR2 signaling in vitro. The direct growth inhibitory effects of BIBF 1120 on four HCC cell lines were relatively mild in vitro (IC50 values: 2–5 μmol/L); however, the oral administration of BIBF 1120 (50 or 100 mg/kg/d) significantly inhibited the tumor growth and angiogenesis in a HepG2 xenograft model. A flow cytometric analysis revealed that BIBF 1120 significantly decreased the phosphotyrosine (pTyr) levels of VEGFR2+CD45dim PBLs and the percentage of VEGFR2+pTyr+ PBLs in vivo; the latter parameter seemed to be a more feasible pharmacodynamic biomarker.
Conclusions: We found that BIBF 1120 exhibited potent antitumor and antiangiogenic activity against HCC and identified VEGFR2+pTyr+ PBLs as a feasible and noninvasive pharmacodynamic biomarker in vivo. Clin Cancer Res; 17(6); 1373–81. ©2010 AACR.