bluuebunny/crossref_metadata_2025_split huggingface dataset:
Staphylococcus aureus
AI-2 Quorum Sensing Associates with the KdpDE Two-Component System To Regulate Capsular Polysaccharide Synthesis and Virulence
Authors: Zhao Liping , Xue Ting , Shang Fei , Sun Haipeng , Sun Baolin 
Published: May 2010

ABSTRACT

Autoinducer 2 (AI-2) is widely recognized as a signal molecule for intra- and interspecies communication in Gram-negative bacteria, but its signaling function in Gram-positive bacteria, especially in
Staphylococcus aureus
, remains obscure. Here we reveal the role of LuxS in the regulation of capsular polysaccharide synthesis in
S. aureus
NCTC8325 and show that AI-2 can regulate gene expression and is involved in some physiological activities in
S. aureus
as a signaling molecule. Inactivation of
luxS
in
S. aureus
NCTC8325 resulted in higher levels of transcription of capsular polysaccharide synthesis genes. The survival rate of the
luxS
mutant was higher than that of the wild type in both human blood and U937 macrophages. In comparison to the
luxS
mutant, a culture supplemented with chemically synthesized 4,5-dihydroxy-2,3-pentanedione (DPD), the AI-2 precursor molecule, restored all the parental phenotypes, suggesting that AI-2 has a signaling function in
S. aureus
. Furthermore, we demonstrated that the LuxS/AI-2 signaling system regulates capsular polysaccharide production via a two-component system, KdpDE, whose function has not yet been clarified in
S. aureus.
This regulation occurred via the phosphorylation of KdpE binding to the
cap
promoter.
Comparison of Flocked and Rayon Swabs for Detection of Nasal Carriage of
Staphylococcus aureus
among Pathology Staff Members
Authors: De Silva Sabine , Wood Gillian , Quek Tricia , Parrott Christine , Bennett Catherine M. 
Published: May 2010

ABSTRACT

Comparison of flocked swabs (E-swabs; Copan) to the standard rayon swabs (Copan) was undertaken for detection of
Staphylococcus aureus
nasal carriage among staff at Dorevitch Pathology in Heidelberg, Melbourne, Australia. Among 100 volunteers, 36 were found to be colonized with
S. aureus
by one or both swab results. The prevalence detected by E-swabs was 35%, and the prevalence through rayon swabs was 34% (95% confidence interval [CI] for the difference in proportions, −12 to 14). Thirty-three volunteers tested positive with both types of swabs, while 2 were detected on E-swabs alone and another on rayon swab testing alone. There was no evidence of a significant difference in carriage detected by E-swabs or rayon swabs.
Rothia aeria
as a Cause of Sepsis in a Native Joint
Authors: Verrall Ayesha J. , Robinson Philip C. , Tan Chor Ee , Mackie W. Grant , Blackmore Timothy K. 
Published: May 2010

ABSTRACT

Rothia aeria
is a recently described Gram-positive rod from the family
Micrococcaceae
. An elderly woman with rheumatoid arthritis and dental abscesses who was undergoing immunosuppression had
R
.
aeria
isolated from synovial fluid. This report characterizes this rare organism and contributes to the literature on its pathogenicity and likely oral source.
Enhanced Exposure of Human Immunodeficiency Virus Type 1 Primary Isolate Neutralization Epitopes through Binding of CD4 Mimetic Compounds
Authors: Yoshimura Kazuhisa , Harada Shigeyoshi , Shibata Junji , Hatada Makiko , Yamada Yuko , Ochiai Chihiro , Tamamura Hirokazu , Matsushita Shuzo 
Published: May 2010

ABSTRACT

N
-(4-Chlorophenyl)-
N′
-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide (NBD-556) is a low-molecular-weight compound that reportedly blocks the interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and its receptor CD4. We investigated whether the enhancement of binding of anti-gp120 monoclonal antibodies (MAbs) toward envelope (Env) protein with NBD-556 are similar to those of soluble CD4 (sCD4) by comparing the binding profiles of the individual MAbs to Env-expressing cell surfaces. In flow cytometric analyses, the binding profiles of anti-CD4-induced epitope (CD4i) MAbs toward NBD-556-pretreated Env-expressing cell surfaces were similar to the binding profiles toward sCD4-pretreated cell surfaces. To investigate the binding position of NBD-556 on gp120, we induced HIV-1 variants that were resistant to NBD-556 and sCD4
in vitro
. At passage 21 in the presence of 50 μM NBD-556, two amino acid substitutions (S375N in C3 and A433T in C4) were identified. On the other hand, in the selection with sCD4, seven mutations (E211G, P212L, V255E, N280K, S375N, G380R, and G431E) appeared during the passages. The profiles of the mutations after the selections with NBD-556 and sCD4 were very similar in their three-dimensional positions. Moreover, combinations of NBD-556 with anti-gp120 MAbs showed highly synergistic interactions against HIV-1. We further found that after enhancing the neutralizing activity by adding NBD-556, the contemporaneous virus became highly sensitive to antibodies in the patient's plasma. These findings suggest that small compounds such as NBDs may enhance the neutralizing activities of CD4i and anti-V3 antibodies
in vivo
.
In Vitro
and
In Vivo
Characterization of MicroRNA-Targeted Alphavirus Replicon and Helper RNAs
Authors: Kamrud Kurt I. , Coffield V. McNeil , Owens Gary , Goodman Christin , Alterson Kim , Custer Max , Murphy Michael A. , Lewis Whitney , Timberlake Sarah , Wansley Elizabeth K. , Berglund Peter , Smith Jonathan 
Published: May 2010

ABSTRACT

Alphavirus-based replicon vector systems (family
Togaviridae
) have been developed as expression vectors with demonstrated potential in vaccine development against both infectious diseases and cancer. The single-cycle nature of virus-like replicon particles (VRP), generated by supplying the structural proteins from separate replicable helper RNAs, is an attractive safety component of these systems. MicroRNAs (miRNAs) have emerged as important cellular RNA regulation elements. Recently, miRNAs have been employed as a mechanism to attenuate or restrict cellular tropism of replication-competent viruses, such as oncolytic adenoviruses, vesicular stomatitis virus, and picornaviruses as well as nonreplicating lentiviral and adenoviral vectors. Here, we describe the incorporation of miRNA-specific target sequences into replicable alphavirus helper RNAs that are used in
trans
to provide the structural proteins required for VRP production. VRP were found to be efficiently produced using miRNA-targeted helper RNAs if miRNA-specific inhibitors were introduced into cells during VRP production. In the absence of such inhibitors, cellular miRNAs were capable of downregulating helper RNA replication
in vitro
. When miRNA targets were incorporated into a replicon RNA, cellular miRNAs were capable of downregulating replicon RNA replication upon delivery of VRP into animals, demonstrating activity
in vivo
. These data provide the first example of miRNA-specific repression of alphavirus replicon and helper RNA replication and demonstrate the feasibility of miRNA targeting of expression vector helper functions that are provided in
trans
.
Phorbol Ester-Induced Human Cytomegalovirus Major Immediate-Early (MIE) Enhancer Activation through PKC-Delta, CREB, and NF-κB Desilences MIE Gene Expression in Quiescently Infected Human Pluripotent NTera2 Cells
Authors: Liu Xiaoqiu , Yuan Jinxiang , Wu Allen W. , McGonagill Patrick W. , Galle Courtney S. , Meier Jeffery L. 
Published: May 2010

ABSTRACT

The ways in which human cytomegalovirus (HCMV) major immediate-early (MIE) gene expression breaks silence from latency to initiate the viral replicative cycle are poorly understood. A delineation of the signaling cascades that desilence the HCMV MIE genes during viral quiescence in the human pluripotent N-Tera2 (NT2) cell model provides insight into the molecular mechanisms underlying HCMV reactivation. In this model, we show that phorbol 12-myristate 13-acetate (PMA) immediately activates the expression of HCMV MIE RNA and protein and greatly increases the MIE-positive (MIE
+
) NT2 cell population density; levels of Oct4 (pluripotent cell marker) and HCMV genome penetration are unchanged. Decreasing PKC-delta activity (pharmacological, dominant-negative, or RNA interference [RNAi] method) attenuates PMA-activated MIE gene expression. MIE gene activation coincides with PKC-delta Thr505 phosphorylation. Mutations in MIE enhancer binding sites for either CREB (cyclic AMP [cAMP] response element [CRE]) or NF-κB (κB) partially block PMA-activated MIE gene expression; the ETS binding site is negligibly involved, and κB does not confer MIE gene activation by vasoactive intestinal peptide (VIP). The PMA response is also partially attenuated by the RNAi-mediated depletion of the CREB or NF-κB subunit RelA or p50; it is not diminished by TORC2 knockdown or accompanied by TORC2 dephosphorylation. Mutations in both CRE and κB fully abolish PMA-activated MIE gene expression. Thus, PMA stimulates a PKC-delta-dependent, TORC2-independent signaling cascade that acts through cellular CREB and NF-κB, as well as their cognate binding sites in the MIE enhancer, to immediately desilence HCMV MIE genes. This signaling cascade is distinctly different from that elicited by VIP.
Tsg101 Is Recruited by a Late Domain of the Nucleocapsid Protein To Support Budding of Marburg Virus-Like Particles
Authors: Dolnik Olga , Kolesnikova Larissa , Stevermann Lea , Becker Stephan 
Published: May 2010

ABSTRACT
The nucleoprotein NP of Marburg virus (MARV) is the major component of the viral nucleocapsid, which also consists of the viral proteins VP35, L, and VP30, as well as the viral genome. During virus assembly at the plasma membrane, the nucleocapsids are enwrapped by the major matrix protein VP40 and the viral envelope, which contains the transmembrane glycoprotein GP. Upon recombinant expression, VP40 alone is able to induce the formation and release of virus-like particles (VLPs) that closely resemble the filamentous morphology of MARV particles. Release of these VP40-induced VLPs is partially dependent on the cellular ESCRT machinery, which interacts with a late-domain motif in VP40. Coexpression with NP significantly enhances the budding of VP40-induced VLPs by an unknown mechanism. In the present study we analyzed the impact of late domains present in NP on the release of VLPs. We observed that the ESCRT I protein Tsg101 was recruited by NP into NP-induced inclusions in the perinuclear region. In the presence of VP40, NP was then recruited to VP40-positive membrane clusters and, in turn, recruited Tsg101 via a C-terminal PSAP late-domain motif in NP. This PSAP motif also mediated a dramatically enhanced incorporation of Tsg101 into VLPs, and its deletion significantly diminished the positive effect of NP on the release of VLPs. Taken together, these data indicate that NP enhances budding of VLPs by recruiting Tsg101 to the VP40-positive budding site through a PSAP late-domain motif.
A Novel Motif in HIV-1 Nef That Regulates MIP-1β Chemokine Release in Macrophages
Authors: Dai Lue , Stevenson Mario 
Published: May 2010

ABSTRACT

All primate lentiviruses encode Nef, an accessory protein that is important for viral pathogenicity
in vivo
. Lentiviral Nef proteins regulate the release of chemokines (MIP-1 α/β) from infected macrophages, thereby enhancing virus dissemination (S. Swingler, A. Mann, J. Jacque, B. Brichacek, V. G. Sasseville, K. Williams, A. A. Lackner, E. N. Janoff, R. Wang, D. Fisher, and M. Stevenson, Nat. Med. 5:997-1003, 1999). In the current study, we have identified a novel domain within Nef (K
92
EK) that is required for Nef-dependent MIP-1β production by infected macrophages. Mutations in this domain abrogated MIP-1β induction but did not affect other Nef-ascribed activities, such as CD4 or major histocompatibility complex (MHC) class Ι downregulation. This further underscores Nef as a modular protein with genetically separable activities that may contribute to its role in viral replication and pathogenicity.
Lipoic Acid Metabolism in Microbial Pathogens
Authors: Spalding Maroya D. , Prigge Sean T. 
Published: May 2010

SUMMARYLipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging orde novosynthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.
Population structures ofAstragalus filipescollections from western North America
Authors: Bushman B. Shaun , Bhattarai Kishor , Johnson Douglas A. 
Published: May 2010

The majority of species used for revegetation in semi-arid western rangelands of North America are grasses, with few forbs and nearly no legumes. Astragalus filipes (Torr. Ex A. Gray) is a western North American legume and a promising candidate for use in rangeland revegetation, but assessments of plant species diversity and structure are necessary to determine which collections should be used to constitute a conservation unit or regional seed source. To address this issue, we characterized within-collection genetic diversity, identified genetically differentiated groups, and tested genetic correlations with environmental variables on 67 collections of A. filipes. Within-population genetic diversity was greatest for collections in Oregon and lowest for collections in British Columbia and central Nevada. Five genetically differentiated groups were detected: one with strong support from central Nevada, one with strong support from British Columbia, and three with weak support comprising all other collections throughout Oregon, Washington, California, Idaho, and Nevada. Although there was significant correlation between genetic and linear geographic distance matrices, there was no correlation between genetic and phenotypic, elevation, temperature, or precipitation distance matrices. These results show that geographic distance contributes to genetic differentiation, and that structured populations have occurred in northernmost and southernmost groups of collections of A. filipes.
DEFINING INTEGRALS OVER CONNECTIONS IN THE DISCRETIZED GRAVITATIONAL FUNCTIONAL INTEGRALS
Authors: KHATSYMOVSKY V. M. 
Published: May 2010

Integration over connection type variables in the path integral for the discrete form of the first-order formulation of general relativity theory is studied. The result (a generalized function of the rest of variables of the type of tetrad or elementary areas) can be defined through its moments, i.e. integrals of it with the area tensor monomials. In our previous paper these moments have been defined by deforming integration contours in the complex plane as if we had passed to a Euclidean-like region. In this paper we define and evaluate the moments in the genuine Minkowski region. The distribution of interest resulting from these moments in this non-positively defined region contains the divergences. We prove that the latter contribute only to the singular (δ-function like) part of this distribution with support in the non-physical region of the complex plane of area tensors while in the physical region this distribution (usual function) confirms that defined in our previous paper which decays exponentially at large areas. Besides that, we evaluate the basic integrals over which the integral over connections in the general path integral can be expanded.
CXCR2 Promotes Ovarian Cancer Growth through Dysregulated Cell Cycle, Diminished Apoptosis, and Enhanced Angiogenesis
Authors: Yang Gong , Rosen Daniel G. , Liu Guangzhi , Yang Fan , Guo Xiaoqing , Xiao Xue , Xue Fengxia , Mercado-Uribe Imelda , Huang Jiaoti , Lin Sue-Hwa , Mills Gordon B. , Liu Jinsong 
Published: May 2010

AbstractPurpose: Chemokine receptor CXCR2 is associated with malignancy in several cancer models; however, the mechanisms involved in CXCR2-mediated tumor growth remain elusive. Here, we investigated the role of CXCR2 in human ovarian cancer.Experimental Design: CXCR2 expression was silenced by stable small hairpin RNA in ovarian cancer cell lines T29Gro-1, T29H, and SKOV3. Western blotting, immunofluorescence, enzyme-linked immunosorbent assay, flow cytometry, electrophoretic mobility shift assay, and mouse assay were used to detect CXCR2, interleukin-8, Gro-1, cell cycle, apoptosis, DNA binding of NF-κB, and tumor growth. Immunohistochemical staining of CXCR2 was done in 240 high-grade serous ovarian carcinoma samples.Results: Knockdown of CXCR2 expression by small hairpin RNA reduced tumorigenesis of ovarian cancer cells in nude mice. CXCR2 promoted cell cycle progression by modulating cell cycle regulatory proteins, including p21 (waf1/cip1), cyclin D1, CDK6, CDK4, cyclin A, and cyclin B1. CXCR2 inhibited cellular apoptosis by suppressing phosphorylated p53, Puma, and Bcl-xS; suppressing poly(ADP-ribose) polymerase cleavage; and activating Bcl-xL and Bcl-2. CXCR2 stimulated angiogenesis by increasing levels of vascular endothelial growth factor and decreasing levels of thrombospondin-1, a process likely involving mitogen-activated protein kinase, and NF-κB. Overexpression of CXCR2 in high-grade serous ovarian carcinomas was an independent prognostic factor of poor overall survival (P &lt; 0.001) and of early relapse (P = 0.003) in the univariate analysis.Conclusions: Our data provide strong evidence that CXCR2 regulates the cell cycle, apoptosis, and angiogenesis through multiple signaling pathways, including mitogen-activated protein kinase and NF-κB, in ovarian cancer. CXCR2 thus has potential as a therapeutic target and for use in ovarian cancer diagnosis and prognosis. Clin Cancer Res; 16(15); 3875–86. ©2010 AACR.
Left Atrial Epicardial Adiposity and Atrial Fibrillation
Authors: Batal Omar , Schoenhagen Paul , Shao Mingyuan , Ayyad Ala Eddin , Van Wagoner David R. , Halliburton Sandra S. , Tchou Patrick J. , Chung Mina K. 
Published: May 2010

Background—
Atrial fibrillation (AF) has been linked to inflammatory factors and obesity. Epicardial fat is a source of several inflammatory mediators related to the development of coronary artery disease. We hypothesized that periatrial fat may have a similar role in the development of AF.

Methods and Results—

Left atrium (LA) epicardial fat pad thickness was measured in consecutive cardiac CT angiograms performed for coronary artery disease or AF. Patients were grouped by AF burden: no (n=73), paroxysmal (n=60), or persistent (n=36) AF. In a short-axis view at the mid LA, periatrial epicardial fat thickness was measured at the esophagus (LA-ESO), main pulmonary artery, and thoracic aorta; retrosternal fat was measured in axial view (right coronary ostium level). LA area was determined in the 4-chamber view. LA-ESO fat was thicker in patients with persistent AF versus paroxysmal AF (
P
=0.011) or no AF (
P
=0.003). LA area was larger in patients with persistent AF than paroxysmal AF (
P
=0.004) or without AF (
P
<0.001). LA-ESO was a significant predictor of AF burden even after adjusting for age, body mass index, and LA area (odds ratio, 5.30; 95% confidence interval, 1.39 to 20.24;
P
=0.015). A propensity score–adjusted multivariable logistic regression that included age, body mass index, LA area, and comorbidities was also performed and the relationship remained statistically significant (
P
=0.008).

Conclusions—
Increased posterior LA fat thickness appears to be associated with AF burden independent of age, body mass index, or LA area. Further studies are necessary to examine cause and effect, and if inflammatory, paracrine mediators explain this association.
Improvement of Cardiac Function by a Cardiac Myosin Activator in Conscious Dogs With Systolic Heart Failure
Authors: Shen You-Tang , Malik Fady I. , Zhao Xin , Depre Christophe , Dhar Sunil K. , Abarzúa Patricio , Morgans David J. , Vatner Stephen F. 
Published: May 2010

Background—
Therapy for chronic systolic heart failure (sHF) has improved over the past 2 decades, but the armamentarium of drugs is limited and consequently sHF remains a leading cause of death and disability. In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure.

Methods and Results—

Two different models of sHF were used: (1) pacing-induced sHF after myocardial infarction (MI-sHF) and (2) pacing-induced sHF after 1 year of chronic pressure overload left ventricular hypertrophy (LVH-sHF). Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. Omecamtiv mecarbil, infused for 24 hours, induced a sustained increase without desensitization (
P
<0.05) in wall thickening (25±6.2%), stroke volume (44±6.5%) and cardiac output (22±2.8%), and decreased heart rate (15±3.0%). The major differences between the effect of omecamtiv mecarbil on cardiac function and the effect induced by a catecholamine, for example, dobutamine, is that omecamtiv mecarbil did not increase LV dP/dt but rather increased LV systolic ejection time by 26±2.9% in sHF. Another key difference is that myocardial O
2
consumption (MVO
2
), which increases with catecholamines, was not significantly affected by omecamtiv mecarbil.

Conclusions—

These results demonstrate that chronic infusion of the cardiac myosin activator, omecamtiv mecarbil, improves LV function in sHF without the limitations of progressive desensitization and increased MVO
2.
This unique profile may provide a new therapeutic approach for patients with sHF.
The Added Value of Surface Data to Radar-Derived Rainfall-Rate Estimation Using an Artificial Neural Network
Authors: Root B. , Yu T-Y. , Yeary M. , Richman M. B. 
Published: May 2010

Abstract
Radar measurements are useful for determining rainfall rates because of their ability to cover large areas. Unfortunately, estimating rainfall rates from radar reflectivity data alone is prone to errors resulting from variations in drop size distributions, precipitation types, and other physics that cannot be represented in a simple, one-dimensional Z–R relationship. However, improving estimates is possible by utilizing additional inputs, thereby increasing the dimensionality of the model.
The main purpose of this study is to determine the value of surface observations for improving rainfall-rate estimation. This work carefully designed an artificial neural network to fit a model that would relate radar reflectivity, surface temperature, humidity, pressure, and wind to observed rainfall rates. Observations taken over 13 years from the Oklahoma Mesonet and the KTLX WSR-88D radar near Oklahoma City, Oklahoma, were used for the training dataset. While the artificial neural network underestimated rainfall rates for higher reflectivities, it did have an overall better performance than the best-fit Z–R relation. Most importantly, it is shown that the surface data contributed significant value to an unaugmented radar-based rainfall-rate estimation model.