bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Basis for the Differential Binding Affinities of the HsfBD1 and HsfBD2 Domains in the
Haemophilus influenzae
Hsf Adhesin
Authors: Radin Jana N. , Grass Susan A. , Meng Guoyu , Cotter Shane E. , Waksman Gabriel , St. Geme Joseph W. 
Published: June 2009

ABSTRACT

Haemophilus influenzae
is a human-specific gram-negative coccobacillus that causes a variety of human infections ranging from localized respiratory infections to invasive diseases. Hsf is the major nonpilus adhesin in encapsulated strains of
H. influenzae
and belongs to the trimeric autotransporter family of proteins. The Hsf protein contains two highly homologous binding domains, designated HsfBD1 and HsfBD2. In this study we characterized the differential binding properties of HsfBD1 and HsfBD2. In assays using HeLa cells, we found that bacteria expressing either full-length Hsf or HsfBD1 by itself adhered at high levels, while bacteria expressing HsfBD2 by itself adhered at low levels. Immunofluorescence microscopy and a cellular enzyme-linked immunosorbent assay using purified proteins revealed that the binding affinity was significantly higher for HsfBD1 than for HsfBD2. Purified HsfBD1 was able to completely block adherence by bacteria expressing either HsfBD1 or HsfBD2, while purified HsfBD2 was able to block adherence by bacteria expressing HsfBD2 but had minimal activity against bacteria expressing HsfBD1. Conversion of the residue at position 1935 in the HsfBD1 binding pocket from Asp to Glu resulted in HsfBD2-like binding properties, and conversion of the residue at position 569 in the HsfBD2 binding pocket from Glu to Asp resulted in HsfBD1-like binding properties, as assessed by adherence assays with recombinant bacteria and by immunofluorescence microscopy with purified proteins. This work demonstrates the critical role of a single amino acid in the core of the binding pocket in determining the relative affinities of the HsfBD1 and HsfBD2 binding domains.
Overexpression of VpsS, a Hybrid Sensor Kinase, Enhances Biofilm Formation in
Vibrio cholerae
Authors: Shikuma Nicholas J. , Fong Jiunn C. N. , Odell Lindsay S. , Perchuk Barrett S. , Laub Michael T. , Yildiz Fitnat H. 
Published: June 2009

ABSTRACT

Vibrio cholerae
causes the disease cholera and inhabits aquatic environments. One key factor in the environmental survival of
V. cholerae
is its ability to form matrix-enclosed, surface-associated microbial communities known as biofilms. Mature biofilms rely on
Vibrio
polysaccharide to connect cells to each other and to a surface. We previously described a core regulatory network, which consists of two positive transcriptional regulators, VpsR and VpsT, and a negative transcriptional regulator HapR, that controls biofilm formation by regulating the expression of
vps
genes. In this study, we report the identification of a sensor histidine kinase, VpsS, which can control biofilm formation and activates the expression of
vps
genes. VpsS required the response regulator VpsR to activate
vps
expression. VpsS is a hybrid sensor histidine kinase that is predicted to contain both histidine kinase and response regulator domains, but it lacks a histidine phosphotransferase (HPT) domain. We determined that VpsS acts through the HPT protein LuxU, which is involved in a quorum-sensing signal transduction network in
V. cholerae
. In vitro analysis of phosphotransfer relationships revealed that LuxU can specifically reverse phosphotransfer to CqsS, LuxQ, and VpsS. Furthermore, mutational and phenotypic analyses revealed that VpsS requires the response regulator LuxO to activate
vps
expression, and LuxO positively regulates the transcription of
vpsR
and
vpsT
. The induction of
vps
expression via VpsS was also shown to occur independent of HapR. Thus, VpsS utilizes components of the quorum-sensing pathway to modulate biofilm formation in
V. cholerae
.
Transcriptional Profiling of Methyltransferase Genes during Growth of
Methanosarcina mazei
on Trimethylamine
Authors: Krätzer Christian , Carini Paul , Hovey Raymond , Deppenmeier Uwe 
Published: June 2009

ABSTRACT

The genomic expression patterns of
Methanosarcina mazei
growing with trimethylamine were measured in comparison to those of cells grown with methanol. We identified a total of 72 genes with either an increased level (49 genes) or a decreased level (23 genes) of mRNA during growth on trimethylamine with methanol-grown cells as the control. Major differences in transcript levels were observed for the
mta
,
mtb
,
mtt
, and
mtm
genes, which encode enzymes involved in methane formation from methanol and trimethylamine, respectively. Other differences in mRNA abundance were found for genes encoding enzymes involved in isopentenyl pyrophosphate synthesis and in the formation of aromatic amino acids, as well as a number of proteins with unknown functions. The results were verified by in-depth analysis of methyltransferase genes using specific primers for real-time quantitative reverse transcription-PCR (RT-PCR). The monitored transcript levels of genes encoding corrinoid proteins involved in methyl group transfer from methylated C
1
compounds (
mta
C,
mtb
C,
mtt
C, and
mtm
C) indicated increased amounts of mRNA from the
mtaBC1
,
mtaBC2
, and
mtaBC3
operons in methanol-grown cells, whereas mRNA of the
mtb1-mtt1
operon was found in high concentrations during trimethylamine consumption. The genes of the
mtb1-mtt1
operon encode methyltransferases that are responsible for sequential demethylation of trimethylamine. The analysis of product formation of trimethylamine-grown cells at different optical densities revealed that large amounts of dimethylamine and monomethylamine were excreted into the medium. The intermediate compounds were consumed only in the very late exponential growth phase. RT-PCR analysis of key genes involved in methanogenesis led to the conclusion that
M. mazei
is able to adapt to changing trimethylamine concentrations and the consumption of intermediate compounds. Hence, we assume that the organism possesses a regulatory network for optimal substrate utilization.
LytM-Domain Factors Are Required for Daughter Cell Separation and Rapid Ampicillin-Induced Lysis inEscherichia coli
Authors: Uehara Tsuyoshi , Dinh Thuy , Bernhardt Thomas G. 
Published: June 2009

ABSTRACTBacterial cytokinesis is coupled to the localized synthesis of new peptidoglycan (PG) at the division site. This newly generated septal PG is initially shared by the daughter cells. InEscherichia coliand other gram-negative bacteria, it is split shortly after it is made to promote daughter cell separation and allow outer membrane constriction to closely follow that of the inner membrane. We have discovered that the LytM (lysostaphin)-domain containing factors ofE. coli(EnvC, NlpD, YgeR, and YebA) are absolutely required for septal PG splitting and daughter cell separation. Mutants lacking all LytM factors form long cell chains with septa containing a layer of unsplit PG. Consistent with these factors playing a direct role in septal PG splitting, both EnvC-mCherry and NlpD-mCherry fusions were found to be specifically recruited to the division site. We also uncovered a role for the LytM-domain factors in the process of β-lactam-induced cell lysis. Compared to wild-type cells, mutants lacking LytM-domain factors were delayed in the onset of cell lysis after treatment with ampicillin. Moreover, rather than lysing from midcell lesions like wild-type cells, LytM−cells appeared to lyse through a gradual loss of cell shape and integrity. Overall, the phenotypes of mutants lacking LytM-domain factors bear a striking resemblance to those of mutants defective for theN-acetylmuramyl-l-alanine amidases: AmiA, AmiB, and AmiC.E. colithus appears to rely on two distinct sets of putative PG hydrolases to promote proper cell division.
Triacylglycerol Utilization Is Required for Regrowth of In Vitro Hypoxic Nonreplicating
Mycobacterium bovis
Bacillus Calmette-Guerin
Authors: Low Kai Leng , Rao P. S. Srinivasa , Shui Guanghou , Bendt Anne K. , Pethe Kevin , Dick Thomas , Wenk Markus R. 
Published: June 2009

ABSTRACT

Mycobacteria store triacylglycerols (TGs) under various stress conditions, such as hypoxia, exposure to nitric oxide, and acidic environments. These stress conditions are known to induce nonreplicating persistence in mycobacteria. The importance of TG accumulation and utilization during regrowth is not clearly understood. Here we specifically determined the levels of accumulated TG and TG lipase activity in
Mycobacterium bovis
bacillus Calmette-Guerin (BCG) in various different physiological states (logarithmic growth, aerated stationary phase, hypoxia-induced dormancy, and regrowth from dormancy). We found extensive accumulation and degradation of TGs in the bacilli during entry into and exit from hypoxia-induced dormancy, respectively. These processes are accompanied by dynamic appearance and disappearance of intracellular TG lipid particles. The reduction in TG levels coincides with an increase in cellular TG lipase activity in the regrowing bacilli. Tetrahydrolipstatin, an inhibitor of TG lipases, reduces total lipase activity, prevents breakdown of TGs, and blocks the growth of mycobacteria upon resuscitation with air. Our results demonstrate that utilization of TGs is essential for the regrowth of mycobacteria during their exit from the hypoxic nonreplicating state.
Hydroxyl Radicals Are Involved in Cell Killing by the Bacterial Topoisomerase I Cleavage Complex
Authors: Liu I-Fen , Annamalai Thirunavukkarasu , Sutherland Jeanette H. , Tse-Dinh Yuk-Ching 
Published: June 2009

ABSTRACT

Escherichia coli
expressing SOS-inducing mutant topoisomerase I was utilized to demonstrate that covalent protein-DNA complex accumulation results in oxidative damage. Hydroxyl radicals were detected following mutant topoisomerase induction. The presence of the Fe
2+
chelator 2,2′-dipyridyl and an
iscS
mutation affecting Fe-S cluster formation protect against topoisomerase I cleavage complex-mediated cell killing.
Working Time on Mars
Authors: Mirmalek Zara 
Published: June 2009

AbstractThe constancy of clock time as an effective work support technology has made it almost impossible to imagine a modern organization where time, specifically standard clock time, is not a component of the organizational infrastructure. Demonstrating the degree to which clock time has become embedded within the organizational sphere are the ways in which clock time operates as though it were a natural phenomenon, rather than a human-built technology (Adam, 1990; Anderson, 1964; Bluedorn, 2002; de Grazia, 1964; Zerubavel, 1981). The naturalization of clock time within organizations is evidenced by the reified assumption technology of clock time is fixed and cannot be modified to support contextually based temporal rhythms of work. The opportunity to challenge particular notions about the relationship between time and work is found in the organization of NASA's Mars Exploration Rovers mission (MER). In addition to standard clock time, the MER mission employed an extra-terrestrial version of standard clock time, known as “Mars time,” to track the presence and absence of sunlight on Mars. Drawing on empirical data, I foreground the inadequacies of the time support technologies that led me to question the use of standard clock time as a way of ordering the experience of time on Mars. I argue that the naturalization of clock time within post-industrial organizations contributed to this occasion in which the scientific exploration of Mars was conducted according to an agrarian era temporal rhythm but for which work support was organized around an industrial era time/work relationship.
Diurnally Asymmetric Trends of Temperature, Humidity, and Precipitation in Taiwan
Authors: Shiu Chein-Jung , Liu Shaw Chen , Chen Jen-Ping 
Published: June 2009

AbstractIn this work, 45 years (1961–2005) of hourly meteorological data in Taiwan, including temperature, humidity, and precipitation, have been analyzed with emphasis on their diurnal asymmetries. A long-term decreasing trend for relative humidity (RH) is found, and the trend is significantly greater in the nighttime than in the daytime, apparently resulting from a greater warming at night. The warming at night in three large urban centers is large enough to impact the average temperature trend in Taiwan significantly between 1910 and 2005. There is a decrease in the diurnal temperature range (DTR) that is largest in major urban areas, and it becomes smaller but does not disappear in smaller cities and offshore islands. The nighttime reduction in RH is likely the main cause of a significant reduction of fog events over Taiwan. The smaller but consistent reductions in DTR and RH in the three off-coast islands suggests that, in addition to local land use changes, a regional-scale process such as the indirect effect of anthropogenic aerosols may also contribute to these trends. A reduction in light precipitation (&lt;4 mm h−1) and an increase in heavy precipitation (&gt;10 mm h−1) are found over Taiwan and the offshore islands. The changes in precipitation are similar to the changes of other areas in Asia, but they are different from those of the United States, Europe, and the tropical oceans. The latter do not show any reduction in light precipitation.
The Current Financial Crisis
Authors: Boorman Jack 
Published: June 2009

It is now clear that the global economy is facing the worst economic and financial crisis since the Second World War. The crisis manifested itself initially in the subprime mortgage market in the US, but quickly spread to Europe; in the breakdown in the market for credit default swaps—a huge, unregulated and thoroughly opaque market; and in the general collapse of the markets for securitised instruments across the global financial system. It was aggravated, most analysts agree, by the initial policy missteps in handling the crisis, including in dealing with the problems at Lehman Brothers, which effectively froze the interbank market. This article discusses the origins, its impact as well as its policy implications of these developments. The article postulates that there were three basic root causes of the crisis: (a) the ‘search for yield’ and a weakening of—and lack of understanding of—risk management during the expansion phase of the credit cycle from 2002 to 2006; (b) the international fragmentation and lack of harmonisation of financial supervision and regulation in the face of rapid innovation in the financial markets—a phenomenon that gave rise to regulatory arbitrage by the global financial institutions; and (c) weaknesses in certain aspects of surveillance conducted by the IMF. It goes on to describe the unprecedented monetary and fiscal measures taken by the major countries since September 2008 to contain the crisis. It further lists the remaining policy agenda, including the reform of the global financial architecture and the author's views on how to move forward.
Efficacy of aprepitant in patients receiving high-dose chemotherapy with hematopoietic stem cell support
Authors: Paul Betsy , Trovato James A , Thompson Jennifer , Badros Ashraf Z , Goloubeva Olga 
Published: June 2009

Purpose. This study describes the efficacy of aprepitant in preventing nausea and vomiting associated with high-dose chemotherapy in hematopoietic stem cell transplant (HSCT) patients. Our hypothesis is the addition of aprepitant to 5-HT3 antagonists and dexamethasone would result in a 20% increase in complete response (CR) rates compared to CR rates from published studies evaluating antiemetic regimens without aprepitant. Methods. Adult HSCT patients receiving high-dose chemotherapy and aprepitant as part of their antiemetic regimen were included following written informed consent. CR was defined as no emesis, none to mild nausea, and no breakthrough antiemetic use. Daily patient diaries were used on days 1 through 7 following high-dose chemotherapy to collect severity of nausea, emetic episodes, breakthrough antiemetic use, and any antiemetic related side effects. Results. We accrued a total of 42 patients. CR rates ranged from 42.9% to 73.8% for the 7 days. The average CR rate for days 1 through 7 was 54%. Fourteen patients (33%) maintained a complete emetic response on each of the 7 days. The average CR rate for published studies in HSCT patients receiving an antiemetic regimen without aprepitant is 57%. Most common adverse effects reported by patients receiving aprepitant were hiccups (33%) and drowsiness (33%). Conclusions. The addition of aprepitant failed to meet our primary endpoint of increasing CR rates by 20%. The lower than expected CR rate was attributed to use of breakthrough antiemetics. Aprepitant did result in preventing emesis in the majority of patients and was associated with minimal side effects.
Review Article: Second-generation thrombopoietin agents for treatment of chronic idiopathic thrombocytopenic purpura in adults
Authors: Lam Masha SH 
Published: June 2009

Objective. To review the pharmacology, pharmacokinetics, efficacy, and safety of two new thrombopoietic (TPO) receptor agonists, romiplostim and eltrombopag, in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) in adults. Data sources. A MEDLINE search was conducted (1966 to March 2009) using the search terms romiplostim, AMG 531, eltrombopag, SB-497115, idiopathic thrombocytopenic purpura. Articles on phases 1—3 clinical trials in patients with ITP were identified and reviewed. References from manufacturer information, and abstracts from recent hematology meetings, were also evaluated. Study selection and data extraction. Controlled clinical trials evaluating romiplostim and eltrombopag for treatment of chronic ITP in adults were selected from the data sources. All published relevant abstracts were also included. Data synthesis. Limited randomized controlled trials and open-label ongoing long-term extension studies for romiplostim and eltrombopag, have shown that both TPO agonists are effective in improving the platelet count and reducing the bleeding episodes in adult patients with ITP unresponsive to at least one standard treatment. The most common adverse events associated with the drugs are mild to moderate headaches. The use of these agents has also been associated with rare but serious side-effects including bone marrow reticulin fibrosis, thrombotic events, and myeloid malignancies. Conclusions. Until more long-term follow-up data regarding the safety, as well as comparative studies that further define the role of TPO agonists versus other agents in the treatment of chronic ITP are available, these agents should be reserved for patients with ITP refractory or intolerant to standard therapy. J Oncol Pharm Practice (2010) 16: 89—103.
Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model
Authors: Desmarets Maxime , Cadwell Chantel M. , Peterson Kenneth R. , Neades Renee , Zimring James C. 
Published: June 2009

AbstractWhen successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization to antigens on transfused blood may prime BMT rejection. Using a novel mouse model of red blood cell (RBC) transfusion and major histocompatibility complex–matched bone marrow transplantation, we report that transfusion of RBC products induced BMT rejection across minor histocompatibility antigen (mHA) barriers. It has been proposed that contaminating leukocytes are responsible for transfusion-induced BMT rejection; however, filter leukoreduction did not prevent rejection in the current studies. Moreover, we generated a novel transgenic mouse with RBC-specific expression of a model mHA and demonstrated that transfusion of RBCs induced a CD8+ T-cell response. Together, these data suggest that mHAs on RBCs themselves are capable of inducing BMT rejection. Cellular immunization to mHAs is neither monitored nor managed by current transfusion medicine practice; however, the current data suggest that mHAs on RBCs may represent an unappreciated and significant consequence of RBC transfusion.
Speech target modulates speaking induced suppression in auditory cortex
Authors: Ventura Maria I , Nagarajan Srikantan S , Houde John F 
Published: June 2009

Abstract

Background
Previous magnetoencephalography (MEG) studies have demonstrated speaking-induced suppression (SIS) in the auditory cortex during vocalization tasks wherein the M100 response to a subject's own speaking is reduced compared to the response when they hear playback of their speech.

Results
The present MEG study investigated the effects of utterance rapidity and complexity on SIS: The greatest difference between speak and listen M100 amplitudes (i.e., most SIS) was found in the simple speech task. As the utterances became more rapid and complex, SIS was significantly reduced (p = 0.0003).

Conclusion
These findings are highly consistent with our model of how auditory feedback is processed during speaking, where incoming feedback is compared with an efference-copy derived prediction of expected feedback. Thus, the results provide further insights about how speech motor output is controlled, as well as the computational role of auditory cortex in transforming auditory feedback.
Bioinformatic analysis of xenobiotic reactive metabolite target proteins and their interacting partners
Authors: Fang Jianwen , Koen Yakov M , Hanzlik Robert P 
Published: June 2009

Abstract

Background
Protein covalent binding by reactive metabolites of drugs, chemicals and natural products can lead to acute cytotoxicity. Recent rapid progress in reactive metabolite target protein identification has shown that adduction is surprisingly selective and inspired the hope that analysis of target proteins might reveal protein factors that differentiate target- vs. non-target proteins and illuminate mechanisms connecting covalent binding to cytotoxicity.

Results
Sorting 171 known reactive metabolite target proteins revealed a number of GO categories and KEGG pathways to be significantly enriched in targets, but in most cases the classes were too large, and the "percent coverage" too small, to allow meaningful conclusions about mechanisms of toxicity. However, a similar analysis of the directlyinteracting partners of 28 common targets of multiple reactive metabolites revealed highly significant enrichments in terms likely to be highly relevant to cytotoxicity (e.g., MAP kinase pathways, apoptosis, response to unfolded protein). Machine learning was used to rank the contribution of 211 computed protein features to determining protein susceptibility to adduction. Protein lysine (but not cysteine) content and protein instability index (i.e., rate of turnover in vivo) were among the features most important to determining susceptibility.

Conclusion
As yet there is no good explanation for why some low-abundance proteins become heavily adducted while some abundant proteins become only lightly adducted in vivo. Analyzing the directly interacting partners of target proteins appears to yield greater insight into mechanisms of toxicity than analyzing target proteins per se. The insights provided can readily be formulated as hypotheses to test in future experimental studies.