bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Genome Sequencing of Rickettsia rickettsii Strains That Differ in Virulence
Authors: Clark Tina R. , Noriea Nicholas F. , Bublitz DeAnna C. , Ellison Damon W. , Martens Craig , Lutter Erika I. , Hackstadt Ted 
Published: February 2015

ABSTRACT

Rickettsia rickettsii
is an obligate intracellular pathogen that is the causative agent of Rocky Mountain spotted fever. Strains of
R. rickettsii
differ dramatically in virulence. In a guinea pig model of infection, the severity of disease as assessed by fever response varies from the most virulent, Sheila Smith, to Iowa, which causes no fever. To identify potential determinants of virulence in
R. rickettsii
, the genomes of two additional strains were sequenced for comparison to known sequences (comparative genome sequencing [CGS]).
R. rickettsii
Morgan and R strains were compared to the avirulent
R. rickettsii
Iowa and virulent
R. rickettsii
Sheila Smith strains. The Montana strains Sheila Smith and R were found to be highly similar while the eastern strains Iowa and Morgan were most similar to each other. A major surface antigen, rickettsial outer membrane protein A (rOmpA), is severely truncated in the Iowa strain. The region of
ompA
containing 13 tandem repeats was sequenced, revealing only seven shared SNPs (four nonsynonymous) for R and Morgan strains compared to Sheila Smith, with an additional 17 SNPs identified in Morgan. Another major surface antigen and autotransporter, rOmpB, exhibits a defect in processing in the Iowa strain such that the beta fragment is not cleaved. Sequence analysis of
ompB
reveals identical sequences between Iowa and Morgan strains and between the R and Sheila Smith strains. The number of SNPs and insertions/deletions between sequences of the two Montana strains and the two eastern strains is low, thus narrowing the field of possible virulence factors.
Genome-Based Analysis and Gene Dosage Studies Provide New Insight into 3-Hydroxy-4-Methylvalerate Biosynthesis in Ralstonia eutropha
Authors: Saika Azusa , Ushimaru Kazunori , Mizuno Shoji , Tsuge Takeharu 
Published: February 2015

ABSTRACT

Recombinant
Ralstonia eutropha
strain PHB
−
4 expressing the broad-substrate-specificity polyhydroxyalkanoate (PHA) synthase 1 from
Pseudomonas
sp. strain 61-3 (PhaC1
Ps
) synthesizes a PHA copolymer containing the branched side-chain unit 3-hydroxy-4-methylvalerate (3H4MV), which has a carbon backbone identical to that of leucine. Mutant strain 1F2 was derived from
R. eutropha
strain PHB
−
4 by chemical mutagenesis and shows higher levels of 3H4MV production than does the parent strain. In this study, to understand the mechanisms underlying the enhanced production of 3H4MV, whole-genome sequencing of strain 1F2 was performed, and the draft genome sequence was compared to that of parent strain PHB
−
4. This analysis uncovered four point mutations in the 1F2 genome. One point mutation was found in the
ilvH
gene at amino acid position 36 (A36T) of IlvH.
ilvH
encodes a subunit protein that regulates acetohydroxy acid synthase III (AHAS III). AHAS catalyzes the conversion of pyruvate to 2-acetolactate, which is the first reaction in the biosynthesis of branched amino acids such as leucine and valine. Thus, the A36T IlvH mutation may show AHAS tolerance to feedback inhibition by branched amino acids, thereby increasing carbon flux toward branched amino acid and 3H4MV biosynthesis. Furthermore, a gene dosage study and an isotope tracer study were conducted to investigate the 3H4MV biosynthesis pathway. Based on the observations in these studies, we propose a 3H4MV biosynthesis pathway in
R. eutropha
that involves a condensation reaction between isobutyryl coenzyme A (isobutyryl-CoA) and acetyl-CoA to form the 3H4MV carbon backbone.
devIIs an Evolutionarily Young Negative Regulator of Myxococcus xanthus Development
Authors: Rajagopalan Ramya , Wielgoss Sébastien , Lippert Gerardo , Velicer Gregory J. , Kroos Lee 
Published: February 2015

ABSTRACTDuring starvation-induced development ofMyxococcus xanthus, thousands of rod-shaped cells form mounds in which they differentiate into spores. Thedevlocus includes eight genes followed by clustered regularly interspaced short palindromic repeats (CRISPRs), comprising a CRISPR-Cas system (Cas stands for CRISPR associated) typically involved in RNA interference. Mutations indevSordevRof a lab reference strain permit mound formation but impair sporulation. We report that natural isolates ofM. xanthuscapable of normal development are highly polymorphic in the promoter region of thedevoperon. We show that thedevpromoter is predicted to be nonfunctional in most natural isolates and is dispensable for development of a laboratory reference strain. Moreover, deletion of thedevpromoter or the small gene immediately downstream of it, here designateddevI(developmentinhibitor), suppressed the sporulation defect ofdevSordevRmutants in the lab strain. Complementation experiments and the result of introducing a premature stop codon indevIsupport a model in which DevRS proteins negatively autoregulate expression ofdevI, whose 40-residue protein product DevI inhibits sporulation if overexpressed. DevI appears to act in a cell-autonomous manner since experiments with conditioned medium and with cell mixtures gave no indication of extracellular effects. Strikingly, we report thatdevIis entirely absent from mostM. xanthusnatural isolates and was only recently integrated into the developmental programs of some lineages. These results provide important new insights into both the evolutionary history of thedevoperon and its mechanistic role inM. xanthussporulation.IMPORTANCECertain mutations in thedevCRISPR-Cas (clustered regularly interspaced short palindromic repeat-associated) system ofMyxococcus xanthusimpair sporulation. The link between development and a CRISPR-Cas system has been a mystery. Surprisingly, DNA sequencing of natural isolates revealed that many appear to lack a functionaldevpromoter, yet these strains sporulate normally. Deletion of thedevpromoter or the small gene downstream of it suppressed the sporulation defect of a lab strain with mutations indevgenes encoding Cas proteins. The results support a model in which the Cas proteins DevRS prevent overexpression of the small genedevI, which codes for an inhibitor of sporulation. Phylogenetic analysis of natural isolates suggests thatdevIand thedevpromoter were only recently acquired in some lineages.
The prevalence, incidence and severity of low back pain among international-level rowers
Authors: Newlands Craig , Reid Duncan , Parmar Priya 
Published: February 2015

Background/aimsThere is a paucity of prospective cohort studies investigating the incidence of low back pain (LBP) in rowing. We investigated (1) the prevalence and incidence of LBP among international-level rowers in New Zealand, (2) the relationship between training volume and LBP and (3) the effect of LBP on rowers’ ability to train and compete.MethodsThis was a prospective cohort study of 76 New Zealand representative rowers, including 46 men (mean age 22, SD=4) and 30 women (mean age 21, SD=4). Data were collected using an online questionnaire repeated monthly for 12 months.ResultsThe prevalence of LBP ranged from 6% to 25% throughout the year. The incidence of episodes of LBP was 1.67 per 1000 exposure-hours. A total of 72 episodes of LBP were reported by 40 rowers (53%) during 12 months. Of these, 45% had an incidental effect on training. 29% minor, 18% moderate and 9% had a major effect as determined by the length of time the training was interrupted. There was a high correlation between new LBP and total training hours per month (r=0.83, p<0.01). A previous history of LBP was a risk factor in developing new LBP (OR 2.06, 95% CI 1.22 to 3.48, p=0.01). Age was also a risk factor, with the likelihood of developing LBP increasing for every year (OR 1.08, 95% CI 1.01 to 1.15, p=0.02).ConclusionsLBP is common among New Zealand representative rowers. There is a high correlation between training load and the development of LBP.
Characterizing patterns of endothelialization following coil embolization: a whole-mount, dual immunostaining approach
Authors: Dai Daying , Ding Yong-Hong , Rezek Issa , Kallmes David F , Kadirvel Ramanathan 
Published: February 2015

BackgroundThe extent, rate, and source of endothelialization following coil embolization of saccular aneurysms remains poorly understood. We performed a whole tissue mount, dual immunohistochemical analysis of experimental aneurysms to characterize the state of endothelialization over time after platinum coil embolization.Method and materialElastase-induced rabbit aneurysms were created and treated with bare platinum coils. Samples were harvested at 4 and 8 weeks (n=6 for each). En face whole tissue mount staining with antibodies to CD31 and α-smooth muscle actin was used to identify endothelial cells and smooth muscle cells, respectively. Sytox green stain was used to demonstrate nuclear morphology for identification of inflammatory cells. The extent of endothelialization was measured in relation to the aneurysm neck–parent artery interface.ResultsAt 4 weeks after coil embolization, very localized membranous tissue and neoendothelial cells were detected on the coil loops immediately adjacent to the parent artery–neck interface, but the remainder of the coil loops remained devoid of endothelial cells. At 8 weeks neoendothelial cells were more confluent over the coils than at 4 weeks, and extended up to 900 µm from the parent artery–neck interface. However, the surfaces of the coils farther away than this region harbored no endothelial cells. Scattered inflammatory cells, including neutrophils and monocytes, were seen on the coil surface at the neck central area, where the coil surface was bare at the 4 and 8 weeks’ follow-up.ConclusionsPlatinum coil embolization supports gradual but limited endothelialization, where endothelial cells migrate directly from the adjacent parent artery.
FDA Approval: Idelalisib Monotherapy for the Treatment of Patients with Follicular Lymphoma and Small Lymphocytic Lymphoma
Authors: Miller Barry W. , Przepiorka Donna , de Claro R. Angelo , Lee Kyung , Nie Lei , Simpson Natalie , Gudi Ramadevi , Saber Haleh , Shord Stacy , Bullock Julie , Marathe Dhananjay , Mehrotra Nitin , Hsieh Li Shan , Ghosh Debasis , Brown Janice , Kane Robert C. , Justice Robert , Kaminskas Edvardas , Farrell Ann T. , Pazdur Richard 
Published: February 2015

Abstract
On July 23, 2014, the FDA granted accelerated approval to idelalisib (Zydelig tablets; Gilead Sciences, Inc.) for the treatment of patients with relapsed follicular B-cell non–Hodgkin lymphoma or relapsed small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies. In a multicenter, single-arm trial, 123 patients with relapsed indolent non–Hodgkin lymphomas received idelalisib, 150 mg orally twice daily. In patients with follicular lymphoma, the overall response rate (ORR) was 54%, and the median duration of response (DOR) was not evaluable; median follow-up was 8.1 months. In patients with SLL, the ORR was 58% and the median DOR was 11.9 months. One-half of patients experienced a serious adverse reaction of pneumonia, pyrexia, sepsis, febrile neutropenia, diarrhea, or pneumonitis. Other common adverse reactions were abdominal pain, nausea, fatigue, cough, dyspnea, and rash. Common treatment-emergent laboratory abnormalities were elevations in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, absolute lymphocytes, and triglycerides. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials. Clin Cancer Res; 21(7); 1525–9. ©2015 AACR.
See related article by Gandhi et al., p. 1537
Pancreatic Cancer–Associated Diabetes Is an “Exosomopathy”
Authors: Korc Murray 
Published: February 2015

Abstract
Diabetes may be a consequence of pancreatic cancer, preceding cancer diagnosis. The underlying mechanism is the release of exosomes delivering adrenomedullin to β cells, inducing endoplasmic reticulum stress and perturbations in the unfolded protein response, leading to β-cell dysfunction and death. This knowledge could lead to improved diagnostic strategies for pancreatic cancer. Clin Cancer Res; 21(7); 1508–10. ©2015 AACR.
See related article by Javeed et al. p. 1722
New Blocking Antibodies against Novel AGR2–C4.4A Pathway Reduce Growth and Metastasis of Pancreatic Tumors and Increase Survival in Mice
Authors: Arumugam Thiruvengadam , Deng Defeng , Bover Laura , Wang Huamin , Logsdon Craig D. , Ramachandran Vijaya 
Published: February 2015

Abstract
Anterior gradient 2 (AGR2) promotes cancer growth, metastasis, and resistance to therapy via unknown mechanisms. We investigated the effects of extracellular AGR2 signaling through the orphan glycosylphosphatidylinositol-linked receptor C4.4A in pancreatic ductal adenocarcinoma (PDAC). Proliferation, migration, invasion, and apoptosis were measured using colorimetric, Boyden chamber, and FACS analyses. We developed blocking mAbs against AGR2 and C4.4A and tested their effects, along with siRNAs, on cancer cell functions and on orthotopic tumors in nude mice. Extracellular AGR2 stimulated proliferation, migration, invasion, and chemoresistance of PDAC cell lines. AGR2 interacted with C4.4A in cell lysates and mixtures of recombinant proteins. Knockdown of C4.4A reduced migration and resistance to gemcitabine. PDAC tissues, but not adjacent healthy pancreatic tissues, expressed high levels of AGR2 and C4.4A. AGR2 signaling through C4.4A required laminins 1 or 5 and integrin β1. Administration of antibodies against AGR2 and C4.4A reduced growth and metastasis and caused regression of aggressive xenograft tumors, leading to increased survival of mice. These data support a model in which AGR2 binds and signals via C4.4A in an autocrine loop and promotes the growth of pancreas tumors in mice. Blocking mAbs against AGR2 and C4.4A may have therapeutic potential against PDAC. Mol Cancer Ther; 14(4); 941–51. ©2015 AACR.
Reflexões sobre a imagem como gesto: apontamentos a partir do manuscrito Paris, BNF, Latin 9449
Authors: Aubert Eduardo Henrik 
Published: February 2015

<p>Este artigo propõe que compreender a imagem como gesto pode ser um modo frutífero de incrementar sua inteligibilidade, libertando a imagem do paradigma da representação, entendendo-a antes como veículo de ação social. Para tanto, estrutura-se em duas partes: uma primeira destinada à discussão historiográfica e conceitual direta, e uma segunda dedicada a um estudo de caso centrado no manuscrito Paris, BnF, latin 9449, originário de Nevers nos meados do século XI. Analisando as imagens desse manuscrito, em sua relação com o contexto do livro em que se inserem e com uma série de outros testemunhos nivernenses coevos, pretendemos avançar a factibilidade e o interesse de tal abordagem. </p>
Resenha do livro "A revolução americana"
Authors: Pandolfi Fernanda Cláudia 
Published: February 2015

<p>(primeiro parágrafo do texto)</p><p>O livro <em>A Revolução Americana</em> de Gordon Wood é um exemplo da importância dos livros de divulgação científica para difusão do conhecimento histórico. Publicado originalmente em inglês em 2002, o livro refina e aplica interpretações desenvolvidas pelo autor em trabalhos anteriores, por exemplo, Wood (1991), que lhe deu o prêmio Pulitzer de 1991, e Wood (1969). Com linguagem acessível ao público não especializado e capítulos dispostos cronologicamente, o autor analisa os efeitos que a Revolução Americana produziu na vida cotidiana daquela sociedade. Sua principal contribuição neste e em outros trabalhos tem sido a de criticar ou, em alguns casos, qualificar tanto análises que tendem a criar uma aura de divindade sobre a geração dos líderes revolucionários como os estudos produzidos principalmente na primeira metade do século XX, que tendem a privilegiar os aspectos de conflitos de classes na revolução. Autor de reconhecida produção acadêmica, Gordon Wood concluiu o doutorado em Harvard e leciona atualmente na Universidade Brown. </p><div> </div>
Tablet-based education to reduce depression-related stigma
Authors: Lu Catherine , Winkelman Megan , Wong Shane Shucheng 
Published: February 2015

Objectives: This study investigated the efficacy of a tablet-based multimedia education application, the Project Not Alone Depression Module, in improving depression literacy and reducing depression stigma among a community-based mental health clinic population. Methods: A total of 93 participants completed either a tablet-based multimedia education or a print education module containing the same content on depression. Primary outcomes were changes in depression literacy as measured by a knowledge quiz and stigma as measured by the Depression Stigma Scale administered before and after the education intervention. Secondary outcomes included participant preference, ease of use, and likeliness to discuss topic with a physician. Results: In comparison to print education, tablet-based multimedia education significantly increased depression-related knowledge and reduced depression stigma ( p < .05). Among all participants, a reduction in the personal stigma score was correlated with an increase in knowledge score ( p < .05). Participants preferred the tablet-based module to a human health educator ( p < .05). Conclusion: With advantages of scalability, user preference, and efficacy in improving depression literacy and stigma, tablet-based multimedia education has the potential to improve the health outcomes of mental health clinic populations. Although the study findings are limited by small sample size and lack of randomisation, the results are encouraging for future research and development in tablet-based multimedia patient education.
Potentially deceptive health nutrition–related advertising claims: The role of inoculation in conferring resistance
Authors: Mason Alicia M , Miller Claude H 
Published: February 2015

Objective: This study sought to examine the efficacy of inoculation message treatments to facilitate resistance to health nutrition–related (HNR) commercial food advertising claims. Design: Data were collected across three phases extending across a 5-week period conducted over two semesters at a Midwest US university. A 2 × 3 between-subjects factorial design was adopted, with multivariate and univariate analyses being used to interpret the results. Setting: Pittsburg, USA. Method: Participants were emerging adult undergraduate students (aged 18–25 years) recruited from introductory communication courses. A total of 167 students participated in Phase 1 of the work, of whom 152 completed Phase 2 and 145 completed Phase 3 (resulting in an 86.8% retention rate). Among these, 45% were men. Results: The results indicated ( F(3, 129) = 9.83, p < .001, partial η2 = .18) that compared to control ( M = 5.20, standard deviation [ SD] = .84), participants who received an inoculation treatment experienced greater Phase 3 attitude strength ( M = 5.73, SD = .77) to the position that eating healthy food is necessary to maintaining a healthy life. Inoculated participants reported greater Phase 3 attitude certainty ( M = 77.15, SD = 19.21) for the above position than the control group ( M = 65.43, SD = 25.48). Inoculated participants held less favourable views towards the source of the HNR claims ( M = 4.80, SD = 1.18) relative to controls ( M = 5.73, SD = 1.36) and generated greater numbers of counter-arguments ( M = 3.90, SD = 1.74) compared to control groups ( M = 2.75, SD = 1.69), thus demonstrating resistance to persuasion. Conclusion: Inoculation was demonstrated to be an effective preemptive strategy against potentially deceptive HNR advertising claims. Hence, it may offer an effective strategy for helping to protect the health-conscious attitudes of emerging adults by providing resistance to the ‘pufferised’ appeals used by many commercial food advertisers.
What should the ventilation objectives be for retrofit energy efficiency interventions of dwellings?
Authors: Milner James , Hamilton Ian , Shrubsole Clive , Das Payel , Chalabi Zaid , Davies Michael , Wilkinson Paul 
Published: February 2015

Major energy efficiency refurbishment of the UK housing stock is needed to help attain emission reduction targets of greenhouse gases. Such measures typically entail some planned or incidental reduction of uncontrolled ventilation in dwellings. This paper examines the trade-offs for health and sustainability objectives of typical retrofit refurbishments in UK homes. While reducing ventilation can help protect against the ingress of harmful pollutants from the outdoor air, our results demonstrate that reducing permeability to low levels, without additional purpose-provided ventilation, is likely to lead to substantial increases in pollutants derived from indoor sources, including indoor-generated particles, radon and environmental tobacco smoke. The monetised equivalent cost of the health dis-benefits associated with these exposures may exceed the potential benefits of reducing energy costs and greenhouse gas emissions. Practical application: Reducing uncontrolled ventilation of dwellings helps to improve energy efficiency and can protect against the ingress of pollutants from the outdoor environment. However, simulation studies suggest that at high degrees of airtightness (very low permeability) there is a potentially steep rise in pollutants of indoor origin, whose adverse effects on health may outweigh the benefits of reduced energy use, lower CO2 emissions and protection against outdoor pollution. Though the optimal permeability level for a given dwelling will vary with local circumstances, considerations of health protection suggest the need to avoid reducing permeability to low levels.