bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mating Type Protein Mat1-2 from Asexual
Aspergillus fumigatus
Drives Sexual Reproduction in Fertile
Aspergillus nidulans
Authors: Pyrzak Wioletta , Miller Karen Y. , Miller Bruce L. 
Published: February 2008

ABSTRACT

The lack of an experimentally amenable sexual genetic system in
Aspergillus fumigatus
is a major limitation in the study of the organism's pathogenesis. A recent comparative genome analysis revealed evidence for potential sexuality in
A. fumigatus
. Homologs of mating type genes as well as other genes of the “sexual machinery” have been identified in anamorphic
A. fumigatus
. The
mat1
-
2
gene encodes a homolog of MatA, an HMG box mating transcriptional factor (Mat
HMG
) that regulates sexual development in fertile
Aspergillus nidulans
. In this study, the functionalities of
A. fumigatus mat1
-
2
and the Mat1-2 protein were determined by interspecies gene exchange between sterile
A. fumigatus
and fertile
A. nidulans
. Ectopically integrated
A. fumigatus mat1
-
2
(driven by its own promoter) was not functional in a sterile
A. nidulans
Δ
matA
strain, and no sexual development was observed. In contrast, the
A. fumigatus mat1
-
2
open reading frame driven by the
A. nidulans matA
promoter and integrated by homologous gene replacement at the
matA
locus was functional and conferred full fertility. This is the first report showing that cross species mating type gene exchange between closely related
Ascomycetes
did not function in sexual development. This is also the first report demonstrating that a Mat
HMG
protein from an asexual species is fully functional, with viable ascospore differentiation, in a fertile homothallic species. The expression of
mat1
-
2
was assessed in
A. fumigatus
and
A. nidulans
. Our data suggest that
mat1
-
2
may not be properly regulated to allow sexuality in
A. fumigatus
. This study provides new insights about
A. fumigatus
asexuality and also suggests the possibility for the development of an experimentally amenable sexual cycle.
Coordinated Regulation of Expression ofSalmonellaPathogenicity Island 1 and Flagellar Type III Secretion Systems by ATP-Dependent ClpXP Protease
Authors: Kage Hirokazu , Takaya Akiko , Ohya Mai , Yamamoto Tomoko 
Published: February 2008

ABSTRACTSalmonella entericaserovar Typhimurium delivers a variety of proteins via theSalmonellapathogenicity island 1 (SPI1)-encoded type III secretion system into host cells, where they elicit several physiological changes, including bacterial invasion, macrophage apoptosis, and enteropathogenesis. OnceSalmonellahas established a systemic infection, excess macrophage apoptosis would be detrimental to the pathogen, as it utilizes macrophages as vectors for systemic dissemination throughout the host. Therefore, SPI1 expression must be restricted to one or a few specific locations in the host. In the present study, we have demonstrated that the expression of this complex of genes is repressed by the ATP-dependent ClpXP protease, which therefore suppresses macrophage apoptosis. Depletion of ClpXP caused significant increases in the amounts of two SPI1-encoded transcriptional regulators, HilC and HilD, leading to the stimulation ofhilAinduction and therefore activation of SPI1 expression. Our evidence shows that ClpXP regulates cellular levels of HilC and HilD via the control of flagellar gene expression. Subsequent experiments demonstrated that the flagellum-related gene product FliZ controls HilD posttranscriptionally, and this in turn activates HilC. These findings suggest that the ClpXP protease coregulates SPI1-related virulence phenotypes and motility. ClpXP is a member of the stress protein family induced in bacteria exposed to hostile environments such as macrophages.
Reduction of Turgor Is Not the Stimulus for the Sensor Kinase KdpD ofEscherichia coli
Authors: Hamann Knut , Zimmann Petra , Altendorf Karlheinz 
Published: February 2008

ABSTRACTStimulus perception by the KdpD/KdpE two-component system ofEscherichia coliis still controversial with respect to the nature of the stimulus that is perceived by the sensor kinase KdpD. Limiting potassium concentrations in the medium or high osmolality leads to KdpD/KdpE signal transduction, resulting inkdpFABCexpression. It has been hypothesized that changes in turgor are sensed by KdpD through alterations in the physical state of the cytoplasmic membrane. However, in this study the quantitative determination of expression levels of thekdpFABCoperon revealed that the system responds very effectively to K+-limiting conditions in the medium but barely and to various degrees to salt and sugar stress. Since the current view of stimulus perception calls for mainly intracellular parameters, which might be sensed by KdpD, we set out to test the cytoplasmic concentrations of ATP, K+, Na+, glutamate, proline, glycine, trehalose, putrescine, and spermidine under K+-limiting conditions. As a first result, the determination of the cytoplasmic volume, which is a prerequisite for such measurements, revealed that a transient shrinkage of the cytoplasmic volume, which is indicative of a reduction in turgor, occurred only under osmotic upshift but not under K+-limiting conditions. Furthermore, the intracellular ATP concentration significantly increased under osmotic upshift, whereas only a slight increase occurred after a potassium downshift. Finally, the cytoplasmic K+concentration rose severalfold only after an osmotic upshock. For the first time, these data indicate that stimulus perception by KdpD correlates neither with changes in the cytoplasmic volume nor with changes in the intracellular ATP or K+concentration or those of the other solutes tested. In conclusion, we propose that a reduction in turgor cannot be the stimulus for KdpD.
The Complete Genome Sequence ofEscherichia coliDH10B: Insights into the Biology of a Laboratory Workhorse
Authors: Durfee Tim , Nelson Richard , Baldwin Schuyler , Plunkett Guy , Burland Valerie , Mau Bob , Petrosino Joseph F. , Qin Xiang , Muzny Donna M. , Ayele Mulu , Gibbs Richard A. , Csörgő Bálint , Pósfai György , Weinstock George M. , Blattner Frederick R. 
Published: February 2008

ABSTRACTEscherichia coliDH10B was designed for the propagation of large insert DNA library clones. It is used extensively, taking advantage of properties such as high DNA transformation efficiency and maintenance of large plasmids. The strain was constructed by serial genetic recombination steps, but the underlying sequence changes remained unverified. We report the complete genomic sequence of DH10B by using reads accumulated from the bovine sequencing project at Baylor College of Medicine and assembled with DNAStar's SeqMan genome assembler. The DH10B genome is largely colinear with that of the wild-type K-12 strain MG1655, although it is substantially more complex than previously appreciated, allowing DH10B biology to be further explored. The 226 mutated genes in DH10B relative to MG1655 are mostly attributable to the extensive genetic manipulations the strain has undergone. However, we demonstrate that DH10B has a 13.5-fold higher mutation rate than MG1655, resulting from a dramatic increase in insertion sequence (IS) transposition, especially IS150. IS elements appear to have remodeled genome architecture, providing homologous recombination sites for a 113,260-bp tandem duplication and an inversion. DH10B requires leucine for growth on minimal medium due to the deletion ofleuLABCDand harbors both therelA1andspoT1alleles causing both sensitivity to nutritional downshifts and slightly lower growth rates relative to the wild type. Finally, while the sequence confirms most of the reported alleles, the sequence ofdeoRis wild type, necessitating reexamination of the assumed basis for the high transformability of DH10B.
Differential Substrate Specificity and Kinetic Behavior of
Escherichia coli
YfdW and
Oxalobacter formigenes
Formyl Coenzyme A Transferase
Authors: Toyota Cory G. , Berthold Catrine L. , Gruez Arnaud , Jónsson Stefán , Lindqvist Ylva , Cambillau Christian , Richards Nigel G. J. 
Published: February 2008

ABSTRACT

The
yfdXWUVE
operon appears to encode proteins that enhance the ability of
Escherichia coli
MG1655 to survive under acidic conditions. Although the molecular mechanisms underlying this phenotypic behavior remain to be elucidated, findings from structural genomic studies have shown that the structure of YfdW, the protein encoded by the
yfdW
gene, is homologous to that of the enzyme that mediates oxalate catabolism in the obligate anaerobe
Oxalobacter formigenes
,
O. formigenes
formyl coenzyme A transferase (FRC). We now report the first detailed examination of the steady-state kinetic behavior and substrate specificity of recombinant, wild-type YfdW. Our studies confirm that YfdW is a formyl coenzyme A (formyl-CoA) transferase, and YfdW appears to be more stringent than the corresponding enzyme (FRC) in
Oxalobacter
in employing formyl-CoA and oxalate as substrates. We also report the effects of replacing Trp-48 in the FRC active site with the glutamine residue that occupies an equivalent position in the
E. coli
protein. The results of these experiments show that Trp-48 precludes oxalate binding to a site that mediates substrate inhibition for YfdW. In addition, the replacement of Trp-48 by Gln-48 yields an FRC variant for which oxalate-dependent substrate inhibition is modified to resemble that seen for YfdW. Our findings illustrate the utility of structural homology in assigning enzyme function and raise the question of whether oxalate catabolism takes place in
E. coli
upon the up-regulation of the
yfdXWUVE
operon under acidic conditions.
Flagellin and Outer Surface Proteins from
Borrelia burgdorferi
Are Not Glycosylated
Authors: Štěrba Ján , Vancová Marie , Rudenko Nataliia , Golovchenko Maryna , Tremblay Tammy-Lynn , Kelly John F. , MacKenzie C. Roger , Logan Susan M. , Grubhoffer Libor 
Published: February 2008

ABSTRACT

We investigated the presence of glycoproteins in
Borrelia burgdorferi
. We did not find any evidence for glycosylation of the major outer membrane proteins OspA and OspB or the structural flagellar proteins FlaB and FlaA. We suggest that glycoproteins present on the surface of
B. burgdorferi
may be tightly bound culture medium glycoproteins.
Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages
Authors: Oliver B G G , Lim S , Wark P , Laza-Stanca V , King N , Black J L , Burgess J K , Roth M , Johnston S L 
Published: February 2008

Background:Rhinovirus infection is responsible for considerable morbidity and mortality as the major cause of exacerbations of asthma, and is also known to induce exacerbations of cystic fibrosis and chronic obstructive pulmonary disease. Exacerbations of these diseases are also frequently associated with bacterial and atypical bacterial infection. Alveolar macrophages are the major immune cells in the airways and are important in defence against bacterial infections.Methods:The authors investigated whether rhinovirus modifies cytokine release, the pattern recognition receptor expression and phagocytosis by human alveolar macrophages in response to bacterial products.Results:Viable rhinovirus was detected in macrophages up to 3 days after exposure and viral RNA expression persisted for 10 days. Infectious but not UV inactivated rhinovirus increased tumour necrosis factor α (TNFα) and interleukin (IL)8 release by macrophages. In contrast, infectious rhinovirus impaired lipopolysaccharide and lipoteichoic acid induced TNFα and IL8 secretion by macrophages. Rhinovirus induced impairment of macrophage antibacterial immune responses did not involve IL10, prostaglandin E2 or downregulation of Toll-like receptor 2. Furthermore, the macrophage phagocytic response to labelled bacterial particles, but not to latex beads, was impaired.Conclusion:The authors have identified impairment of cytokine responses to bacterial lipopolysaccharide and lipoteichoic acid by alveolar macrophages in response to infectious rhinovirus. Virus induced impairment of antibacterial host defence has important implications in the pathogenesis of exacerbations of respiratory diseases.
Short term improvement in exercise capacity and symptoms following exercise training in interstitial lung disease
Authors: Holland A E , Hill C J , Conron M , Munro P , McDonald C F 
Published: February 2008

Background:Interstitial lung disease (ILD) is characterised by exertional dyspnoea, exercise limitation and reduced quality of life. The role of exercise training in this diverse patient group is unclear. The aims of this study were to establish the safety of exercise training in ILD; its effects on exercise capacity, dyspnoea and quality of life; and whether patients with idiopathic pulmonary fibrosis (IPF) had similar responses to those with other types of ILD.Methods:57 subjects with ILD (34 IPF) were randomised to receive 8 weeks of supervised exercise training or weekly telephone support. The 6 min walk distance (6MWD), incremental exercise test, modified Medical Research Council (MRC) dyspnoea score and Chronic Respiratory Disease Questionnaire (CRDQ) were performed at baseline, following intervention and at 6 months.Results:80% of subjects completed the exercise programme and no adverse events were recorded. The 6MWD increased following training (mean difference to control 35 m, 95% CI 6 to 64 m). A significant reduction in MRC score was observed (0.7 points, 95% CI 0.1 to 1.3) along with improvements in dyspnoea (p = 0.04) and fatigue (p<0.01) on the CRDQ. There was no change in peak oxygen uptake; however, exercise training reduced heart rate at maximum isoworkload (p = 0.01). There were no significant differences in response between those with and without IPF. After 6 months there were no differences between the training and control group for any outcome variable.Conclusions:Exercise training improves exercise capacity and symptoms in patients with ILD, but these benefits are not sustained 6 months following intervention.Trial registration number:NCT00168285
Mesothelin Promotes Anchorage-Independent Growth and Prevents Anoikis via Extracellular Signal-Regulated Kinase Signaling Pathway in Human Breast Cancer Cells
Authors: Uehara Norihisa , Matsuoka Yoichiro , Tsubura Airo 
Published: February 2008

Abstract
Mesothelin (MSLN) is a glycoprotein that is overexpressed in various tumors. MSLN is present on the cell surface and is also released into body fluids or culture supernatants from MSLN-positive tumor cells. Despite intensive study of MSLN as a diagnostic marker or target for immunotherapy, its biological function is largely unknown. In the present study, we examined the effects of ectopic expression of MSLN in human breast cancer cell lines (MCF-7, T47D, and MDA-MB-231). We found that overexpression of MSLN promoted anchorage-independent growth in soft agar. In addition, MDA-MB-231 cells expressing high levels of MSLN exhibited resistance to anoikis (a type of apoptosis induced by detachment from substratum), as indicated by decreased DNA fragmentation and down-regulation of the proapoptotic protein Bim. Incubating MSLN-expressing MDA-MB-231 cells in the presence of U0126, an inhibitor of mitogen-activated protein/extracellular-signal-regulated kinase kinase, induced accumulation of Bim and restored susceptibility to anoikis. Western blot analysis also revealed that overexpression of MSLN resulted in sustained activation of extracellular signal-regulated kinase 1/2 and suppression of Bim. The present results constitute novel evidence that MSLN enables cells to survive under anchorage-independent conditions by suppressing Bim induction via the extracellular signal-regulated kinase signaling pathway. (Mol Cancer Res 2008;6(2):186–93)
Sterol Regulatory Element–Binding Protein-1c Represses the Transactivation of Androgen Receptor and Androgen-Dependent Growth of Prostatic Cells
Authors: Suh Ji Ho , Gong Eun-Yeung , Kim Jae Bum , Lee In-Kyu , Choi Hueng-Sik , Lee Keesook 
Published: February 2008

Abstract
Sterol regulatory element-binding protein-1c (SREBP-1c) is a basic helix-loop-helix transcription factor that plays an important role in lipid homeostasis. Here, we show that SREBP-1c regulates androgen receptor (AR) transactivation through direct interaction with AR and represses androgen-dependent growth of prostatic cells. Transient transfection studies show that SREBP-1c specifically inhibits the transactivation of AR. Chromatin immunoprecipitation assays reveal that SREBP-1c is recruited with AR onto the endogenous AR target promoter. Moreover, adenovirus-mediated overexpression of SREBP-1c decreases the mRNA level of the prostate-specific antigen gene, an endogenous target gene of AR, supporting SREBP-1c modulation of AR transactivation. In vivo and in vitro protein interaction assays show that SREBP-1c directly interacts with AR through the activation function-1 domain of AR. In addition, transfection studies and glutathione S-transferase pull-down competition experiments reveal that the SREBP-1c–mediated repression of AR transactivation is accomplished through competition with certain AR coactivators for AR interaction. The SREBP-1c–mediated inhibition of AR transactivation also involves the recruitment of histone deacetylase 1. Finally, adenovirus-mediated overexpression of SREBP-1c inhibits androgen-induced proliferation of prostatic cells in vitro and in vivo, and small interfering RNA–mediated down-regulation of SREBP-1 enhances androgen-induced proliferation of prostatic cells as well as the transactivation of AR. Taken together, these results suggest that SREBP-1c acts as an AR corepressor and may play an important role in the regulation of AR-dependent prostatic cell growth. (Mol Cancer Res 2008;6(2):314–24)
PLUNC is a secreted product of neutrophil granules
Authors: Bartlett Jennifer A , Hicks Benjamin J , Schlomann Jamie M , Ramachandran Shyam , Nauseef William M , McCray Paul B 
Published: February 2008

AbstractAirway epithelia and neutrophils are frequently recruited to release host defense factors in response to a variety of pulmonary pathogens. One abundant product of airway epithelia is palate, lung, nasal epithelium clone (PLUNC), a proposed innate immune protein expressed in submucosal glands and surface airway epithelia. In this study, we report the expression of PLUNC in human neutrophils, a previously unrecognized source of this protein. Immunoblots performed on polymorphonuclear cell (PMN) lysates and PMN subcellular fractions indicated that PLUNC was present in the specific granules of the neutrophil. Furthermore, secretion assays demonstrated that PLUNC protein was released by neutrophils upon stimulation with secretogogues, including formyl methionyl leucyl phenylalanine and the calcium ionophore A23187. Although recombinant PLUNC protein failed to exhibit antibacterial activity in our studies, its storage and secretion by a professional phagocytic cell support the hypothesis that PLUNC participates in an aspect of the inflammatory response that contributes to host defense. These studies suggest that PLUNC expression is less restricted than previously believed, and highlight new avenues of research for the study of PLUNC function.
Do Children Differentiate Worry From Fear?
Authors: Szabó Marianna 
Published: February 2008

AbstractWorry has been defined as a primarily cognitive process closely related to fear or anxiety. This definition is widely accepted by clinicians and researchers investigating worry and is often provided to research participants, especially to children. The present study aimed to empirically test the proposition that both adults and children conceptualise worry as a cognitive process, and that they differentiate it from fear on the basis of worry's relatively stronger association with thinking. Groups of 45 adults and 70 children completed three versions of a worry list questionnaire, reporting on the extent to which they worry about, are afraid of, and think about a list of negative outcomes. Regression analyses showed that in adults, thinking about a negative outcome had a significant unique association with worrying. In children, however, worrying was more strongly associated with fear ratings, especially in the case of physical outcomes. The data suggest that adults and children report on different concepts when they rate their worries via questionnaires. This difference may reflect developmental changes in the worry process itself, or developmental changes in the way individuals interpret and respond to worry list questionnaires. Follow-up studies using alternative methodologies are now needed to further clarify the results.
The Efficacy and Acceptability of the Triple P-Positive Parenting Program With Japanese Parents
Authors: Matsumoto Yuki , Sofronoff Kate , Sanders Matthew R. 
Published: February 2008

AbstractThis study examined the efficacy of the Group Triple P-Positive Parenting Program with a Japanese population to evaluate the feasibility and acceptability of the program and the parenting skills taught in a crosscultural context. The study involved 50 Japanese parents living in Australia and used a randomised group comparison design with two conditions, Triple P group and a waitlist control group. The results revealed significant reductions in parent reported child behaviour problems, parental overreactivity and laxness, and parental conflict as well as increasing parental competence. The acceptability of the program was found to be high. Intervention effects and program acceptability in a Japanese context as well as limitations and future research are discussed.
Long-Term Accommodation and Support for People With Higher Levels of Challenging Behaviour
Authors: Kelly Glenn , Winkler Dianne 
Published: February 2008

AbstractThe purpose of the present article is to describe the issues associated with providing lifelong accommodation and support to people with severe brain injury, neurobehavioural disability, and overt challenging behaviours. In particular, the article focuses on two groups of people within an Australian context: (a) those who live in community settings but whose behaviour is not adequately managed even by specialist outreach behaviour management services, and (b) those who are confined to aged care residential facilities and who show challenging behaviour. These groups bring to the fore different lifelong behaviour management issues. At present, if community-based clients seriously offend or have an adequate psychiatric diagnosis, they may be placed in heavily secured psychiatric units or prison. Otherwise, by default, they will reside in less restrictive options such as family homes and shared supported accommodation. We will argue that the current service system lacks the ability to apply appropriate structure and control to many clients with serious challenging behaviours, and propose that specialised facilities would make an important addition to the service system. Conversely, young clients confined to residential aged care facilities live in impoverished environments that often contribute to challenging behaviour that can be enormously disruptive, distressing, and unsafe. We will review the recent Australian State and Federal Government initiative aimed at transitioning some young people out of nursing homes, and we raise considerations for future service development. There are many individuals with the potential to make significant gains in a tightly structured setting before returning to the community, while others will manage well with long-term placement in a setting designed for residents with neurobehavioural disability. Case studies and service data are used to support these arguments, and key elements of accommodation and rehabilitation models for those in need of long-term neurobehavioural support are described.