bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasopressin and metabolic disorders: translation from experimental models to clinical use
Authors: Nakamura K. , Velho G. , Bouby N. 
Published: July 2017

AbstractVasopressin has many physiological actions in addition to its well‐defined role in the control of fluid homeostasis and urine concentration. An increasing body of evidence suggests that the vasopressin–hydration axis plays a role in glucose homeostasis. This review summarizes the knowledge accumulated over the last decades about the influence of vasopressin in the short‐term regulation of glycaemia. It describes the possible role of this hormone through activation of V1a and V1b receptors on liver and pancreas functions and on the hypothalamic–pituitary–adrenal axis. Moreover, we report recent in vivo studies demonstrating the role of vasopressin in the long‐term regulation of glycaemia. Indeed, V1a‐ or double‐V1aV1b‐receptor knockout mice display significant changes in the glucose and lipid metabolism. In rats, sustained high V1aR activation increases basal glycaemia and aggravates glucose intolerance in obese rats. Finally, the translation from animal findings to human was evidenced by epidemiological and genetic studies that showed that high vasopressin level is a risk factor for hyperglycaemia, metabolic disorders and diabetes.
Inhibitory effects of sodium silicate on the fungal growth and secretion of cell wall‐degrading enzymes by Trichothecium roseum
Authors: Ge Yonghong , Chen Yanru , Li Canying , Wei Meilin , Lv Jingyi , Meng Kun 
Published: July 2017

AbstractTrichothecium roseum causes decay in muskmelons, apples, tomatoes and mangoes, which leads to economic losses. In this study, we investigated the effect of sodium silicate on the growth of T. roseum and the cell wall‐degrading enzymes (CWDEs) secreted by the hyphae. The results indicated that sodium silicate significantly inhibited mycelial growth and spore germination of T. roseum. The sodium silicate treatment also retarded the secretion of several CWDEs, including pectate lyase (PL), polygalacturonic acid transeliminase (PGTE), pectin methyltranseliminase (PMTE), pectin methylgalacturonase (PMG), polygalacturonase (PG), cellulase (Cx) and β‐glucosidase. These results suggest that sodium silicate exerts its effects on T. roseum through direct inhibition of its growth and secretion of CWDEs.
Comparative selective retention of particle size classes in the gastrointestinal tract of ponies and goats
Authors: Hummel J. , Scheurich F. , Ortmann S. , Crompton L. A. , Gerken M. , Clauss M. 
Published: July 2017

SummaryThere is a discrepancy in the literature on potential digesta separation mechanisms in horses, with both a selective retention of fine and of large particles postulated in different publications. To assess the net effect of such mechanisms, we fed ponies on a hay‐only diet a pulse dose of whole (unchopped) marked hay together with a solute marker, collected faeces on a regular basis, measured marker concentrations in whole faeces and in their large (2.0–16 mm), medium (0.5–1.0 mm) and small (0.063–0.25 mm) particle fraction, and calculated the corresponding mean retention times (MRTs). For comparison, the same experiment was performed in goats. In goats, as expected,MRTsolute(35 hr) was significantly shorter thanMRTparticle(51 hr); only a very small fraction of particle marker was excreted as large particles (2%); and theMRTof these large particles was significantly shorter than that of small particles (with a relevant difference of 8.6 hr), indicating that those few large particles that escape the rumen do so mostly soon after ingestion. In ponies,MRTsolute(24 hr) did not differ fromMRTparticle(24 hr); a higher fraction of particle marker was excreted as large particles (5%); and theMRTof these large particles was longer than that of small particles (but with a non‐relevant difference of less than 1 hr). These results indicate that no relevant net separation of digesta phases occurs in horses and that selective particle retention mechanisms in the large intestine are unlikely to represent important characteristics of the horse's digestive physiology.
Short Food Supply Chains, Long Working Days: Active Work and the Construction of Professional Satisfaction in French Diversified Organic Market Gardening
Authors: Dupré Lucie , Lamine Claire , Navarrete Mireille 
Published: July 2017

AbstractThis article analyses professional satisfaction of farm managers of organic diversified market garden farms selling through short food supply chains, in the south of France. Faced with strong economic and agronomic constraints, the cropping arrangements on these farms result in very tense experiences, both spatially and temporally. However, our analysis shows that while diversified organic market gardening is a demanding farm work environment, it paradoxically can create high professional satisfaction as a result of the complex integration of different elements, including social support and decision latitude. Indeed, the diversity of tasks, farmers’ autonomy, their role in decision‐making, and the challenging dimensions of organic farming contribute to what Karasek and Theorell call ‘active work’. Nevertheless, our research concludes that social support appears to be necessary to reach a good level of work satisfaction. Our findings also identify future research opportunities to examine, for example, how diversification impacts the work and the professional satisfaction of hired workers in organic market gardening contexts.
Biofilms Formed by Isolates from Recurrent Vulvovaginal Candidiasis Patients Are Heterogeneous and Insensitive to Fluconazole
Authors: Sherry Leighann , Kean Ryan , McKloud Emily , O'Donnell Lindsay E. , Metcalfe Rebecca , Jones Brian L. , Ramage Gordon 
Published: July 2017

ABSTRACT

Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We report a shifting prevalence of
Candida
species with heterogeneous biofilm-forming capacity, which is associated with altered antifungal drug sensitivity.
Identification of the ATPase Subunit of the Primary Maltose Transporter in the Hyperthermophilic Anaerobe Thermotoga maritima
Authors: Singh Raghuveer , White Derrick , Blum Paul 
Published: July 2017

ABSTRACT

Thermotoga maritima
is a hyperthermophilic anaerobic bacterium that produces molecular hydrogen (H
2
) by fermentation. It catabolizes a broad range of carbohydrates through the action of diverse ABC transporters. However, in
T. maritima
and related species, highly similar genes with ambiguous annotation obscure a precise understanding of genome function. In
T. maritima
, three putative
malK
genes, all annotated as ATPase subunits, exhibited high identity to each other. To distinguish between these genes,
malK
disruption mutants were constructed by gene replacement, and the resulting mutant cell lines were characterized. Only a disruption of
malK3
produced a defect in maltose catabolism. To verify that the mutant phenotype arose specifically from
malK3
inactivation, the
malK3
mutation was repaired by recombination, and maltose catabolism was restored. This study demonstrates the importance of a maltose ABC-type transporter and its relationship to sugar metabolism in
T. maritima
.

IMPORTANCE
The application and further development of a genetic system was used here to investigate gene paralogs in the hyperthermophile
Thermotoga maritima
. The occurrence of three ABC transporter ATPase subunits all annotated as
malK
was evaluated using a combination of genetic and bioinformatic approaches. The results clarify the role of only one
malK
gene in maltose catabolism in a nonmodel organism noted for fermentative hydrogen production.
Shiga Toxin-Producing Serogroup O91 Escherichia coli Strains Isolated from Food and Environmental Samples
Authors: Feng Peter C. H. , Delannoy Sabine , Lacher David W. , Bosilevac Joseph M. , Fach Patrick , Beutin Lothar 
Published: July 2017

ABSTRACT

Shiga toxin-producing
Escherichia coli
(STEC) strains of the O91:H21 serotype have caused severe infections, including hemolytic-uremic syndrome. Strains of the O91 serogroup have been isolated from food, animals, and the environment worldwide but are not well characterized. We used a microarray and other molecular assays to examine 49 serogroup O91 strains (environmental, food, and clinical strains) for their virulence potential and phylogenetic relationships. Most of the isolates were identified to be strains of the O91:H21 and O91:H14 serotypes, with a few O91:H10 strains and one O91:H9 strain being identified. None of the strains had the
eae
gene, which codes for the intimin adherence protein, and many did not have some of the genetic markers that are common in other STEC strains. The genetic profiles of the strains within each serotype were similar but differed greatly between strains of different serotypes. The genetic profiles of the O91:H21 strains that we tested were identical or nearly identical to those of the clinical O91:H21 strains that have caused severe diseases. Multilocus sequence typing and clustered regularly interspaced short palindromic repeat analyses showed that the O91:H21 strains clustered within the STEC 1 clonal group but the other O91 serotype strains were phylogenetically diverse.

IMPORTANCE
This study showed that food and environmental O91:H21 strains have similar genotypic profiles and Shiga toxin subtypes and are phylogenetically related to the O91:H21 strains that have caused hemolytic-uremic syndrome, suggesting that these strains may also have the potential to cause severe illness.
Progress in Our Understanding of Wzx Flippase for Translocation of Bacterial Membrane Lipid-Linked Oligosaccharide
Authors: Hong Yaoqin , Liu Michael A. , Reeves Peter R. 
Published: July 2017

ABSTRACT
Translocation of lipid-linked oligosaccharides is a common theme across prokaryotes and eukaryotes. For bacteria, such activity is used in cell wall construction, polysaccharide synthesis, and the relatively recently discovered protein glycosylation. To the best of our knowledge, the Gram-negative inner membrane flippase Wzx was the first protein identified as being involved in oligosaccharide translocation, and yet we still have only a limited understanding of this protein after 3 decades of research. At present, Wzx is known to be a multitransmembrane protein with enormous sequence diversity that flips oligosaccharide substrates with varied degrees of preference. In this review, we provide an overview of the major findings for this protein, with a particular focus on substrate preference.
Defining the Functionally Important Domain and Amino Acid Residues in Mycobacterium tuberculosis Integration Host Factor for Genome Stability, DNA Binding, and Integrative Recombination
Authors: Sharadamma Narayanaswamy , Harshavardhana Yadumurthy , Muniyappa K. 
Published: July 2017

ABSTRACT

The integration host factor of
Mycobacterium tuberculosis
(mIHF) consists of a single polypeptide chain, the product of the
ihf
gene. We previously revealed that mIHF is a novel member of a new class of nucleoid-associated proteins that have important roles in DNA damage response, nucleoid compaction, and integrative recombination. The mIHF contains a region of 86 amino acids at its N terminus, absent from both α- and β-subunits of
Escherichia coli
IHF. However, the functional significance of an extra 86-amino-acid region in the full-length protein remains unknown. Here, we report the structure/function relationship of the DNA-binding and integrative recombination-stimulating activity of mIHF. Deletion mutagenesis showed that an extra 86-amino-acid region at the N terminus is dispensable; the C-terminal region possesses the sequences essential for its known biological functions, including the ability to suppress the sensitivity of
E. coli
Δ
ihfA
and Δ
ihfB
cells to DNA-damaging agents, DNA binding, DNA multimerization-circularization, and stimulation of phage L5 integrase-catalyzed integrative recombination. Single and double alanine substitutions at positions Arg170 and Arg171, located at the mIHF DNA-binding site, abrogated its capacity to suppress the sensitivity of
E. coli ΔihfA
and Δ
ihfB
cells to DNA-damaging agents. The variants encoded by these mutant alleles failed to bind DNA and stimulate integrative recombination. Interestingly, the DNA-binding activity of the mIHF-R173A variant remained largely unaffected; however, it was unable to stimulate integrative recombination, thus revealing a separation-of-function allele of mIHF. The functional and structural characterization of this separation-of-function allele of mIHF could reveal previously unknown functions of IHF.

IMPORTANCE
The integration host factor of
Mycobacterium tuberculosis
is a novel nucleoid-associated protein. mIHF plays a vital role in DNA damage response, nucleoid compaction, and integrative recombination. Intriguingly, mIHF contains an extra 86-amino-acid region at its N terminus, absent from both α- and β-subunits of
Escherichia coli
IHF, whose functional significance is unknown. Furthermore, a triad of arginine residues located at the mIHF-DNA interface have been implicated in a range of its functions. Here, we reveal the roles of N- and C-terminal regions of mIHF and the individual residues in the Arg triad for their ability to provide protection
in vivo
against DNA damage, bind DNA, and stimulate integrase-catalyzed site-specific recombination.
Kindlin-2 Regulates the Growth of Breast Cancer Tumors by Activating CSF-1–Mediated Macrophage Infiltration
Authors: Sossey-Alaoui Khalid , Pluskota Elzbieta , Bialkowska Katarzyna , Szpak Dorota , Parker Yvonne , Morrison Chevaun D. , Lindner Daniel J. , Schiemann William P. , Plow Edward F. 
Published: July 2017

Abstract
Interplay between tumor cells and host cells in the tumor microenvironment dictates the development of all cancers. In breast cancer, malignant cells educate host macrophages to adopt a protumorigenic phenotype. In this study, we show how the integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic progression of breast cancer through the recruitment and subversion of host macrophages. Kindlin-2 expression was elevated in breast cancer biopsy tissues where its levels correlated with reduced patient survival. On the basis of these observations, we used CRISPR/Cas9 technology to ablate Kindlin-2 expression in human MDA-MB-231 and murine 4T1 breast cancer cells. Kindlin-2 deficiency inhibited invasive and migratory properties in vitro without affecting proliferation rates. However, in vivo tumor outgrowth was inhibited by &gt;80% in a manner associated with reduced macrophage infiltration and secretion of the macrophage attractant and growth factor colony-stimulating factor-1 (CSF-1). The observed loss of CSF-1 appeared to be caused by a more proximal deficiency in TGFβ-dependent signaling in Kindlin-2–deficient cells. Collectively, our results illuminate a Kindlin-2/TGFβ/CSF-1 signaling axis employed by breast cancer cells to capture host macrophage functions that drive tumor progression. Cancer Res; 77(18); 5129–41. ©2017 AACR.
Posttranscriptional Regulation of PARG mRNA by HuR Facilitates DNA Repair and Resistance to PARP Inhibitors
Authors: Chand Saswati N. , Zarei Mahsa , Schiewer Matthew J. , Kamath Akshay R. , Romeo Carmella , Lal Shruti , Cozzitorto Joseph A. , Nevler Avinoam , Scolaro Laura , Londin Eric , Jiang Wei , Meisner-Kober Nicole , Pishvaian Michael J. , Knudsen Karen E. , Yeo Charles J. , Pascal John M. , Winter Jordan M. , Brody Jonathan R. 
Published: July 2017

Abstract
The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 3′ untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to inhibit HuR directly promoted DNA damage accumulation, inefficient PAR removal, and persistent PARP-1 residency on chromatin (PARP-1 trapping). Immunoprecipitation assays demonstrated that the PARP-1 protein binds and posttranslationally modifies HuR in PARPi-treated PDAC cells. In a mouse xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing of HuR significantly reduced tumor growth compared with PARPi therapy alone. Our results highlight the HuR–PARG axis as an opportunity to enhance PARPi-based therapies. Cancer Res; 77(18); 5011–25. ©2017 AACR.
Temporal Trends of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Coronary Artery Disease
Authors: Jouni Hayan , Askew J. Wells , Crusan Daniel J. , Miller Todd D. , Gibbons Raymond J. 
Published: July 2017

Background—
There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously.

Methods and Results—

We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 (
P
<0.001).

Conclusions—
In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.
Validity of Cardiovascular Data From Electronic Sources
Authors: Ahmad Faraz S. , Chan Cheeling , Rosenman Marc B. , Post Wendy S. , Fort Daniel G. , Greenland Philip , Liu Kiang J. , Kho Abel N. , Allen Norrina B. 
Published: July 2017

Background:
Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal was to evaluate the degree of agreement of electronic data research networks in comparison with data collected by standardized research approaches in a cohort study.

Methods:

We linked individual-level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from 6 Chicago health systems. To evaluate the correlation and agreement of blood pressure in HealthLNK in comparison with in-person MESA examinations, and body mass index in HealthLNK in comparison with MESA, we used Pearson correlation coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion standard, we calculated the performance of HealthLNK for hypertension, obesity, and diabetes mellitus diagnosis by using
International Classification of Diseases, Ninth Revision
codes and clinical data. We also identified potential myocardial infarctions, strokes, and heart failure events in HealthLNK and compared them with adjudicated events in MESA.

Results:

Of the 1164 MESA participants enrolled at the Chicago Field Center, 802 (68.9%) participants had data in HealthLNK. The correlation was low for systolic blood pressure (0.39;
P
<0.0001). In comparison with MESA, HealthLNK overestimated systolic blood pressure by 6.5 mm Hg (95% confidence interval, 4.2–7.8). There was a high correlation between body mass index in MESA and HealthLNK (0.94;
P
<0.0001). HealthLNK underestimated body mass index by 0.3 kg/m
2
(95% confidence interval, –0.4 to –0.1). With the use of
International Classification of Diseases, Ninth Revision
codes and clinical data, the sensitivity and specificity of HealthLNK queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%, and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated cardiovascular events in MESA, the concordance rates for myocardial infarction, stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and 62.5% (10/16).

Conclusions:
These findings illustrate the limitations and strengths of electronic data repositories in comparison with information collected by traditional standardized epidemiological approaches for the ascertainment of cardiovascular risk factors and events.
Immediate Vascular Imaging Needed for Efficient Triage of Patients With Acute Ischemic Stroke Initially Admitted to Nonthrombectomy Centers
Authors: Boulouis Gregoire , Siddiqui Khawja-Ahmeruddin , Lauer Arne , Charidimou Andreas , Regenhardt Robert W. , Viswanathan Anand , Leslie-Mazwi Thabele M. , Rost Natalia , Schwamm Lee H. 
Published: July 2017

Background and Purpose—
Current guidelines for endovascular thrombectomy (EVT) used to select patients for transfer to thrombectomy-capable stroke centers (TSC) may result in unnecessary transfers. We sought to determine the impact of simulated baseline vascular imaging on reducing unnecessary transfers and clinical-imaging factors associated with receiving EVT after transfer.

Methods—
We identified patients with stroke transferred for EVT from 30 referring hospitals between 2010 and 2016 who had a referring hospitals brain computed tomography and repeat imaging on TSC arrival available for review. Initial Alberta Stroke Program Early CT scores and TSC vascular occlusion level were assessed. The main outcome variable was receiving EVT at TSC. Models were simulated to derive optimal triaging parameters for EVT.

Results—
A total of 508 patients were included in the analysis (mean age, 69±14 years; 42% women). Application at referring hospitals of current guidelines for EVT yielded sensitivity of 92% (95% confidence interval, 0.84–0.96) and specificity of 53% (95% confidence interval, 0.48–0.57) for receiving EVT at TSC. Repeated simulations identified optimal selection criteria for transfer as National Institute of Health Stroke Scale >8 plus baseline vascular imaging (sensitivity=91%; 95% confidence interval, 0.83–0.95; and specificity=80%; 95% confidence interval, 0.75–0.83).

Conclusions—
Our findings provide quantitative estimates of the claim that implementing vascular imaging at the referring hospitals would result in significantly fewer futile transfers for EVT and a data-driven framework to inform transfer policies.