bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of FtsE ATPase and FtsX Extracellular Loops 1 and 2 in FtsEX-PcsB Complex Function in Cell Division of Streptococcus pneumoniae D39
Authors: Sham Lok-To , Jensen Katelyn R. , Bruce Kevin E. , Winkler Malcolm E. 
Published: July 2013

ABSTRACT

The FtsEX protein complex has recently been proposed to play a major role in coordinating peptidoglycan (PG) remodeling by hydrolases with the division of bacterial cells. According to this model, cytoplasmic FtsE ATPase interacts with the FtsZ divisome and FtsX integral membrane protein and powers allosteric activation of an extracellular hydrolase interacting with FtsX. In the major human respiratory pathogen
Streptococcus pneumoniae
(pneumococcus), a large extracellular-loop domain of FtsX (ECL1
FtsX
) is thought to interact with the coiled-coil domain of the PcsB protein, which likely functions as a PG amidase or endopeptidase required for normal cell division. This paper provides evidence for two key tenets of this model. First, we show that FtsE protein is essential, that depletion of FtsE phenocopies cell defects caused by depletion of FtsX or PcsB, and that changes of conserved amino acids in the FtsE ATPase active site are not tolerated. Second, we show that temperature-sensitive (Ts)
pcsB
mutations resulting in amino acid changes in the PcsB coiled-coil domain (CC
PcsB
) are suppressed by
ftsX
mutations resulting in amino acid changes in the distal part of ECL1
FtsX
or in a second, small extracellular-loop domain (ECL2
FtsX
). Some FtsX suppressors are allele specific for changes in CC
PcsB
, and no FtsX suppressors were found for amino acid changes in the catalytic PcsB CHAP domain (CHAP
PcsB
). These results strongly support roles for both ECL1
FtsX
and ECL2
FtsX
in signal transduction to the coiled-coil domain of PcsB. Finally, we found that
pcsB
CC
(Ts) mutants (Ts mutants carrying mutations in the region of
pcsB
corresponding to the coiled-coil domain) unexpectedly exhibit delayed stationary-phase autolysis at a permissive growth temperature.

IMPORTANCE
Little is known about how FtsX interacts with cognate PG hydrolases in any bacterium, besides that ECL1
FtsX
domains somehow interact with coiled-coil domains. This work used powerful genetic approaches to implicate a specific region of pneumococcal ECL1
FtsX
and the small ECL2
FtsX
in the interaction with CC
PcsB
. These findings identify amino acids important for
in vivo
signal transduction between FtsX and PcsB for the first time. This paper also supports the central hypothesis that signal transduction between pneumococcal FtsX and PcsB is linked to ATP hydrolysis by essential FtsE, which couples PG hydrolysis to cell division. The classical genetic approaches used here can be applied to dissect interactions of other integral membrane proteins involved in PG biosynthesis. Finally, delayed autolysis of the
pcsB
CC
(Ts) mutants suggests that the FtsEX-PcsB PG hydrolase may generate a signal in the PG necessary for activation of the major LytA autolysin as pneumococcal cells enter stationary phase.
Alkali/Surfactant/Polymer Flooding in the Daqing Oilfield Class II Reservoirs Using Associating Polymer
Authors: Feng Ru-Sen , Guo Yong-Jun , Zhang Xin-Min , Hu Jun , Li Hua-Bing 
Published: July 2013

Hydrophobically modified associating polyacrylamide (HAPAM) has good compatibility with the Daqing heavy alkylbenzene sulfonate surfactant. The HAPAM alkali/surfactant/polymer (ASP) system can generate ultralow interfacial tension in a wide range of alkali/surfactant concentrations and maintain stable viscosity and interfacial tension for 120 days. The HAPAM ASP system has good injectivity for the Daqing class II reservoirs (100–300 × 10−3 μm2) and can improve oil recovery by more than 25% on top of water flooding. In the presence of both the alkali and the surfactant, the surfactant interacts with the associating groups of the polymer to form more micelles, which can significantly enhance the viscosity of the ASP system. Compared with using HPAM (Mw = 2.5 MDa), using HAPAM can reduce the polymer use by more than 40%.
Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature
Authors: Sharma Anu , Bode Beata , Studer Gabriela , Moch Holger , Okoniewski Michal , Knuth Alexander , von Boehmer Lotta , van den Broek Maries 
Published: July 2013

Abstract
Purpose: The tumor immune microenvironment plays a crucial role in the development and progression of cancer. Sarcomas are a group of heterogeneous soft tissue malignancies that are often treated with radiotherapy as a part of the treatment concept. There is increasing evidence that radiotherapy leads to alterations in the tumor microenvironment, particularly with respect to the immune infiltrate. This study has been carried out to develop a better understanding of such changes following radiotherapy.
Experimental Design: We retrospectively analyzed the expression of 35 immune response-related genes by quantitative reverse transcription PCR analysis and immunohistochemistry on paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients before and after radiotherapy.
Results: We observed that radiotherapy results in a significant upregulation of several immune effectors and cancer-testis antigens and a concomitant downregulation of immune suppressors, indicating that radiotherapy may support the immune defense in sarcomas.
Conclusions: These novel findings may have implications for the design of therapeutic regimens which exploite the immune system in sarcoma patients by combining standard radiotherapy with immunotherapeutic strategies. Clin Cancer Res; 19(17); 4843–53. ©2013 AACR.
Inhibition of ABCB1 Expression Overcomes Acquired Docetaxel Resistance in Prostate Cancer
Authors: Zhu Yezi , Liu Chengfei , Nadiminty Nagalakshmi , Lou Wei , Tummala Ramakumar , Evans Christopher P. , Gao Allen C. 
Published: July 2013

Abstract
Docetaxel is the first-line standard treatment for castration-resistant prostate cancer. However, relapse eventually occurs due to the development of resistance to docetaxel. To unravel the mechanism of acquired docetaxel resistance, we established docetaxel-resistant prostate cancer cells, TaxR, from castration-resistant C4-2B prostate cancer cells. The IC50 for docetaxel in TaxR cells was about 70-fold higher than parental C4-2B cells. Global gene expression analysis revealed alteration of expression of a total of 1,604 genes, with 52% being upregulated and 48% downregulated. ABCB1, which belongs to the ATP-binding cassette (ABC) transporter family, was identified among the top upregulated genes in TaxR cells. The role of ABCB1 in the development of docetaxel resistance was examined. Knockdown of ABCB1 expression by its specific shRNA or inhibitor resensitized docetaxel-resistant TaxR cells to docetaxel treatment by enhancing apoptotic cell death. Furthermore, we identified that apigenin, a natural product of the flavone family, inhibits ABCB1 expression and resensitizes docetaxel-resistant prostate cancer cells to docetaxel treatment. Collectively, these results suggest that overexpression of ABCB1 mediates acquired docetaxel resistance and targeting ABCB1 expression could be a potential approach to resensitize docetaxel-resistant prostate cancer cells to docetaxel treatment. Mol Cancer Ther; 12(9); 1829–36. ©2013 AACR.
The Pathobiology of Collagens in Glioma
Authors: Payne Leo S. , Huang Paul H. 
Published: July 2013

Abstract
Malignant gliomas are characterized by a diffuse infiltration into the surrounding brain parenchyma. Infiltrating glioma cells exist in close proximity with components of the tumor microenvironment, including the extracellular matrix (ECM). Whereas levels of collagens in the normal adult brain are low, in glioma, collagen levels are elevated and play a vital role in driving tumor progression. This article provides a comprehensive overview of the nature of collagens found in gliomas and offers unique insight into the mechanisms by which cancer cells interact with this ECM via cellular factors such as integrins, discoidin domain receptors, and mannose receptors. Also discussed are the major remodeling pathways of brain tumor collagen, mediated primarily by matrix metalloproteinases, and the reciprocal relationship between these enzymes and the collagen receptors. Finally, a concluding perspective is offered on how the biophysical properties of the collagen ECM, in particular, mechanical stiffness and compliance, influence malignant outcome. A better understanding of the complex molecular interactions between glioma cells and the collagen ECM will provide new avenues to combat the rampant tumor progression and chemoresistance in brain cancer patients. Mol Cancer Res; 11(10); 1129–40. ©2013 AACR.
Whole Exome Sequencing Identifies a Causal
RBM20
Mutation in a Large Pedigree With Familial Dilated Cardiomyopathy
Authors: Wells Quinn S. , Becker Jason R. , Su Yan R. , Mosley Jonathan D. , Weeke Peter , D’Aoust Laura , Ausborn Natalie L. , Ramirez Andrea H. , Pfotenhauer Jean P. , Naftilan Allen J. , Markham Larry , Exil Vernat , Roden Dan M. , Hong Charles C. 
Published: July 2013

Background—
Whole exome sequencing is a powerful technique for Mendelian disease gene discovery. However, variant prioritization remains a challenge. We applied whole exome sequencing to identify the causal variant in a large family with familial dilated cardiomyopathy of unknown pathogenesis.

Methods and Results—

A large family with autosomal dominant, familial dilated cardiomyopathy was identified. Exome capture and sequencing were performed in 3 remotely related, affected subjects predicted to share <0.1% of their genomes by descent. Shared variants were filtered for rarity, evolutionary conservation, and predicted functional significance, and remaining variants were filtered against 71 locally generated exomes. Variants were also prioritized using the Variant Annotation Analysis and Search Tool. Final candidates were validated by Sanger sequencing and tested for segregation. There were 664 shared heterozygous nonsense, missense, or splice site variants, of which 26 were rare (minor allele frequency ≤0.001 or not reported) in 2 public databases. Filtering against internal exomes reduced the number of candidates to 2, and of these, a single variant (c.1907 G>A) in
RBM20
, segregated with disease status and was absent in unaffected internal reference exomes. Bioinformatic prioritization with Variant Annotation Analysis and Search Tool supported this result.

Conclusions—

Whole exome sequencing of remotely related dilated cardiomyopathy subjects from a large, multiplex family, followed by systematic filtering, identified a causal
RBM20
mutation without the need for linkage analysis.
Does Gender Influence Participation?
Authors: Hawkins Jaclynn , Kieffer Edith C. , Sinco Brandy , Spencer Michael , Anderson Michael , Rosland Ann-Marie 
Published: July 2013

Purpose The purpose of the study was to determine the effects of gender on participation in a community-based, culturally tailored diabetes lifestyle intervention, led by trained community health workers (CHW) and conducted with African Americans and Latinos with type 2 diabetes. Methods This study utilized data collected from 180 participants. Multivariable binary and cumulative logistic regression models were used to analyze associations between gender and race/ethnicity with study completion and participation in 3 aspects of the intervention: group classes, CHW home visits, and CHW-accompanied doctor visits. Results Among Latinos, men were less likely than women to complete the study, attend group classes, and complete CHW home visits. There were no gender differences in participation seen among African Americans. Conclusions Diabetes management interventions may need to adapt their designs to optimize retention and participation of Latino men. Among African American men, the CHW model may be promising. Reasons for low participation among Latino men should receive more study. Future studies should assess whether similar findings apply in other communities and populations.
Relationship between stress and coronary heart disease
Authors: Kurd Bushra Jawaid , Dar Mudassir Iqbal , Shoaib Maria , Malik Laraib , Aijaz Zobia , Asif Iqra 
Published: July 2013

Background Coronary heart disease is the leading cause of death worldwide and accounts for 13.7% of deaths in countries like Pakistan. Its association with stress has not been well considered in our setup. Patients with coronary artery disease admitted for coronary artery bypass grafting may have a high prevalence of stress that might increase the risk of adverse outcomes. Methods 60 patients with coronary artery disease admitted to the Civil Hospital Karachi for coronary artery bypass graft surgery from January 1 to March 31, 2012, were evaluated using a stress evaluation scale. Results Stress of varying degrees was found to be a significant independent risk factor in patients with coronary heart disease. Analysis of our collected sample of patients with stress showed 60% with high stress ( p = 0.025) and 36.7% moderate stress ( p = 0.0025). An appreciable relationship was found between stress and patient age, sex, body mass index, blood group, and the incidence of myocardial infarction. Conclusion Our study found evidence of an independent causative association between psychological stress and coronary heart disease, of a similar order to the more conventional coronary heart disease risk factors.
Patients' and carers' views on communication and information provision when undergoing assessments in memory services
Authors: Abley Clare , Manthorpe Jill , Bond John , Keady John , Samsi Kritika , Campbell Sarah , Watts Sue , Robinson Louise 
Published: July 2013

Objectives To explore patients' and carers' views on what constitutes high-quality communication and information provision during diagnostic assessment in memory clinic services in three areas of England. Methods Interviews with 27 people with cognitive impairment (13 with confirmed dementia) and 26 carers (20 matched pairs). Interviews continued until theoretical saturation was reached. Interview transcripts were subject to constant comparative analysis; data interpretation occurred in ‘data clinics’. Results People with memory problems undergoing assessment often have unmet information needs, especially patients with a diagnosis other than Alzheimer's disease and those who do not receive a diagnosis. Patients wish to be kept informed about both the assessment and its outcomes. Some have unrealistic expectations of the process (expecting assessment and diagnosis to be complete in two weeks) and some experience what appear to be long delays (over 12 months) in receiving results. Most appreciated clear and honest communication about any diagnosis. Post-diagnostic groups, organized by local memory services, afford opportunities to learn practical strategies and gain informal peer support. Voluntary organizations may be an essential source of information. Conclusions Communication and information need improvement for patients undergoing assessment for possible dementia, especially for those considered unlikely to benefit from medication and those with mild cognitive impairment.
Effective policy mechanisms for an equitable geographical distribution of general practitioners: a qualitative comparative analysis of the accessibility of primary care in Europe
Authors: Ozegowski Susanne 
Published: July 2013

Objectives To explore the effectiveness of four different policy mechanisms in achieving a more equitable geographical distribution of general practitioners (GPs) in European countries. The following mechanisms were analysed: (1) interventions during medical training; (2) financial incentives; (3) quotas to allocate GPs to regions and (4) capitation-based remuneration. Methods A macro-comparative method, namely, fuzzy set qualitative comparative analysis, was employed to explore the distributional effectiveness of the four mechanisms. A literature review yielded information on the use of these mechanisms in the 21 European countries included, while country-specific equity in the geographic GP distribution served as the outcome variable. Results Quotas determining the number of GPs per region proved to be highly effective in producing an equitable GP distribution if calculated based on health care needs. Remunerating GPs largely through capitation payments also proved to be an effective policy mechanism. Financial bonuses to GPs practising in under-served areas and interventions during medical training had little or no impact. Conclusion Several high income countries have a maldistribution of primary care physicians to the detriment of rural or socially deprived areas. Policy makers have instituted a variety of policies to counter this. This study helps to identify mechanisms which are likely to be more and less effective.
Development and implementation of a nurse-led walk-in centre: evidence lost in translation?
Authors: Desborough Jane , Parker Rhian , Forrest Laura 
Published: July 2013

Objectives The design of the first Australian public nurse-led primary care walk-in centre was modelled on those established in the English National Health Service (NHS). An independent evaluation of the first 12 months of operation of the Australian Capital Territory (ACT) Health walk-in centre, in 2011, analysed the translation of evidence from the national evaluation of the NHS walk-in centres to the policy development and implementation of the ACT walk-in centre. Whilst in a number of ways the evidence was used well, our interest for this paper was to examine three areas identified as problematic and to identify the points at which the evidence was lost or diluted. Methods In addition to data obtained through nurse and key stakeholder interviews for the evaluation, an analysis was undertaken of documents on the planning and establishment of the ACT walk-in centre, either provided to the evaluation team or made publicly available. Results Three areas were identified as problematic in the way that evidence from the NHS evaluation was translated: the use of clinical decision support software (CDSS); the marketing of the walk-in centre; and its location. Conclusions Our examination indicates that despite seeking evidence to inform the development of the ACT walk-in centre, the evidence was not fully used and some clear lessons ignored, resulting in much of the evidence being lost in translation.
Neurohospitalists: Perceived Need and Training Requirements in Academic Neurology
Authors: Probasco John C. , George Benjamin P. , Dorsey E. Ray , Venkatesan Arun 
Published: July 2013

Background and Purpose: We sought to determine the current practices and plans for departmental hiring of neurohospitalists at academic medical centers and to identify the core features of a neurohospitalist training program. Methods: We surveyed department chairs or residency program directors at 123 Accreditation Council for Graduate Medical Education (ACGME)-accredited US adult neurology training programs. Results: Sixty-three(51% response rate) responded, 76% of whom were program directors. In all, 24 (38%) academic neurology departments reported employing neurohospitalists, and an additional 10 departments have plans to hire neurohospitalists in the next year. In all, 4 academic neurology departments have created a neurohospitalist training program, and 10 have plans to create a training program within the next 2 years. Hospitals were the most frequent source of funding for established and planned programs (93% of those reporting). Most (n = 39; 65%) respondents felt that neurohospitalist neurology should be an ACGME-accredited fellowship. The highest priority neurohospitalist training elements among respondents included stroke, epilepsy, and consult neurology as well as patient safety and cost-effective inpatient care. The most important procedural skills for a neurohospitalist, as identified by respondents, include performance of brain death evaluations, lumbar punctures, and electroencephalogram interpretation. Conclusions: Neurohospitalists have emerged as subspecialists within neurology, growing both in number and in scope of responsibilities in practice. Neurohospitalists are in demand among academic departments, with many departments developing their existing presence or establishing a new presence in the field. A neurohospitalist training program may encompass training in stroke, epilepsy, and consult neurology with additional focus on patient safety and cost-effective care.
An evolutionarily conserved program of B-cell development and activation in zebrafish
Authors: Page Dawne M. , Wittamer Valerie , Bertrand Julien Y. , Lewis Kanako L. , Pratt David N. , Delgado Noemi , Schale Sarah E. , McGue Caitlyn , Jacobsen Bradley H. , Doty Alyssa , Pao Yvonne , Yang Hongbo , Chi Neil C. , Magor Brad G. , Traver David 
Published: July 2013

Key Points
B cells appear in zebrafish by 3 weeks of development, supporting previous data that this is the transition point to adult hematopoiesis. Shifting sites of B-cell development likely occur in all jawed vertebrates.
Mer receptor tyrosine kinase is a therapeutic target in pre–B-cell acute lymphoblastic leukemia
Authors: Linger Rachel M. A. , Lee-Sherick Alisa B. , DeRyckere Deborah , Cohen Rebecca A. , Jacobsen Kristen M. , McGranahan Amy , Brandão Luis N. , Winges Amanda , Sawczyn Kelly K. , Liang Xiayuan , Keating Amy K. , Tan Aik Choon , Earp H. Shelton , Graham Douglas K. 
Published: July 2013

Key Points
Mer tyrosine kinase is aberrantly expressed in ∼30% of pediatric pre–B-ALL patients, including most patients with an E2A-PBX1 translocation. Mer inhibition decreased B-ALL cell survival signal transduction, caused chemosensitization, and prolonged survival in a xenograft model.
Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial
Authors: Cutler Corey , Kim Haesook T. , Bindra Bhavjot , Sarantopoulos Stefanie , Ho Vincent T. , Chen Yi-Bin , Rosenblatt Jacalyn , McDonough Sean , Watanaboonyongcharoen Phandee , Armand Philippe , Koreth John , Glotzbecker Brett , Alyea Edwin , Blazar Bruce R. , Soiffer Robert J. , Ritz Jerome , Antin Joseph H. 
Published: July 2013

Key PointsRituximab prevents steroid-requiring chronic graft-vs-host disease when given after peripheral blood stem cell transplantation. Overall survival is improved with rituximab after allogeneic peripheral blood stem cell transplantation when compared with a control cohort.