bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Risk of Nitrofurantoin Lung Injury and Its Efficacy in Diminished Kidney Function in Older Adults in a Large Integrated Healthcare System: A Matched Cohort Study
Authors: Santos Jody M. , Batech Michael , Pelter Mitchell A. , Deamer Robert L. 
Published: April 2016

ObjectivesTo determine the risk to older adults of lung injury associated with treatment of cystitis using nitrofurantoin and the risk of treatment failure in the presence of diminished creatinine clearance (CrCl).DesignRetrospective, matched cohort.SettingIntegrated healthcare system.ParticipantsIndividuals aged 65 and older with a diagnosis of cystitis between 2007 and 2012 who were given nitrofurantoin (N = 13,421) were matched 1:3 on age, sex, race and ethnicity, and prescription date with individuals who were given other antibiotics for cystitis.MeasurementsConditional logistic regression determined the association between nitrofurantoin and lung injury in the matched cohort. In participants exposed to nitrofurantoin, chronic treatment was compared with acute treatment using multivariable logistic regression. Treatment failure was compared in three CrCl groups.ResultsNitrofurantoin exposure was not statistically significantly associated with lung injury (adjusted risk ratio (aRR) = 0.90, 95% confidence interval (CI) = 0.80–1.00), but chronic nitrofurantoin therapy was associated with greater risk of lung injury than acute exposure (aRR = 1.53, 95% CI = 1.04, 2.24). Treatment failure rates did not differ according to CrCl.ConclusionThis large, retrospective, matched‐cohort study conducted in older adults supports the 2012 American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommendations against the use nitrofurantoin for long‐term suppressive treatment of cystitis but not the recommendation against its use in poor renal function because of the risk of treatment failure.
Angiotensin II regulation of angiotensin‐converting enzymes in spontaneously hypertensive rat primary astrocyte cultures
Authors: Gowrisankar Yugandhar V. , Clark Michelle A. 
Published: April 2016

AbstractAngiotensin (Ang) II plays a critical role in cardiovascular and blood pressure regulation. Ang II is produced by angiotensin‐converting enzyme (ACE) and it interacts with the Ang AT1 receptor to cause much of its well‐known cardiovascular effects. Ang‐(1–7) is another active peptide produced by the rennin‐angiotensin system. This peptide is produced from Ang I or Ang II by the catalytic activity of ACE2. Ang‐(1–7) interacts with the Mas receptor to counteract many of the effects of Ang II. Thus, the ACE2/Ang‐(1–7)/Mas axis acts opposite of the ACE/Ang II/AT1 axis. In this study we investigated how Ang II regulates the key enzymes of these axes, ACE and its homolog ACE2, and determined whether they are dysregulated in the hypertensive condition. Brainstem and cerebellum astrocytes isolated from the spontaneously hypertensive rat (SHR) were used in these studies. Ang II effect on the enzymes’ mRNA and protein levels was measured using quantitative PCR and western blotting techniques, respectively. Results from this study showed that Ang II up‐regulated ACE protein levels, but down‐regulated ACE mRNA levels in brainstem and cerebellum astrocytes in both models. Ang II also reduced ACE2 mRNA expression in SHR and Wistar astrocytes isolated from both brain regions. Ang II effects on ACE2 protein were biphasic. In SHR astrocytes, Ang II‐mediated ACE2 protein initially increased then decreased at later time points. In contrast, in Wistar astrocytes, Ang II initially decreased ACE2 protein expression, but up‐regulated the protein at later time points. The findings of these studies suggest that Ang II has a differential effect on ACE and ACE2 expression. Furthermore, in the SHR model there may be alteration in the ACE/ACE2 balance in a manner that favors increased Ang II generation and decreased Ang‐(1–7) production contributing to the hypertensive phenotype observed in this model.
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The levels of angiotensin (Ang) II depend on the actions of angiotensin‐converting enzyme (ACE) and ACE2. We showed in astrocytes isolated from the SHRs that Ang II differentially affects ACE and ACE2 expression. There may be an alteration in the ACE/ACE2 balance favoring Ang II generation. This imbalance may contribute to the hypertensive phenotype observed in this SHR model.
Regenerative approaches for the cornea
Authors: Griffith M. , Alarcon E. I. , Brunette I. 
Published: April 2016

AbstractThe cornea is the transparent front part of the eye that transmits light to the back of the eye to generate vision. Loss of corneal transparency, if irreversible, leads to severe vision loss or blindness. For decades, corneal transplantation using human donor corneas has been the only option for treating corneal blindness. Despite recent improvement in surgical techniques, donor cornea transplantation remains plagued by risks of suboptimal optical results and visual acuity, immune rejection and eventually graft failure. Furthermore, the demand for suitable donor corneas is increasing faster than the number of donors, leaving thousands of curable patients untreated worldwide. Here, we critically review the state of the art of biomaterials for corneal regeneration. However, the lessons learned from the use of the cornea as a disease model will allow for extension of the biomaterials and techniques for regeneration of more complex organs such as the heart.
Investigating population differentiation in a major African agricultural pest: evidence from geometric morphometrics and connectivity suggests high invasion potential
Authors: Karsten M. , Addison P. , Jansen van Vuuren B. , Terblanche J. S. 
Published: April 2016

AbstractThe distribution, spatial pattern and population dynamics of a species can be influenced by differences in the environment across its range. Spatial variation in climatic conditions can cause local populations to undergo disruptive selection and ultimately result in local adaptation. However, local adaptation can be constrained by gene flow and may favour resident individuals over migrants—both are factors critical to the assessment of invasion potential. The Natal fruit fly (Ceratitis rosa) is a major agricultural pest in Africa with a history of island invasions, although its range is largely restricted to south east Africa. Across Africa,C. rosais genetically structured into two clusters (R1 and R2), with these clusters occurring sympatrically in the north of South Africa. The spatial distribution of these genotypic clusters remains unexamined despite their importance for understanding the pest's invasion potential. Here,C. rosa, sampled from 22 South African locations, were genotyped at 11 polymorphic microsatellite loci and assessed morphologically using geometric morphometric wing shape analyses to investigate patterns of population structure and determine connectedness of pest‐occupied sites. Our results show little to no intraspecific (population) differentiation, high population connectivity, high effective population sizes and only one morphological type (R2) within South Africa. The absence of the R1 morphotype at sites where it was previously found may be a consequence of differences in thermal niches of the two morphotypes. Overall, our results suggest high invasion potential of this species, that area‐wide pest management should be undertaken on a country‐wide scale, and that border control is critical to preventing further invasions.
Conservation genomics of natural and managed populations: building a conceptual and practical framework
Authors: Benestan Laura Marilyn , Ferchaud Anne‐Laure , Hohenlohe Paul A. , Garner Brittany A. , Naylor Gavin J. P. , Baums Iliana Brigitta , Schwartz Michael K. , Kelley Joanna L. , Luikart Gordon 
Published: April 2016

AbstractThe boom of massive parallel sequencing (MPS) technology and its applications in conservation of natural and managed populations brings new opportunities and challenges to meet the scientific questions that can be addressed. Genomic conservation offers a wide range of approaches and analytical techniques, with their respective strengths and weaknesses that rely on several implicit assumptions. However, finding the most suitable approaches and analysis regarding our scientific question are often difficult and time‐consuming. To address this gap, a recent workshop entitled ‘ConGen 2015’ was held at Montana University in order to bring together the knowledge accumulated in this field and to provide training in conceptual and practical aspects of data analysis applied to the field of conservation and evolutionary genomics. Here, we summarize the expertise yield by each instructor that has led us to consider the importance of keeping in mind the scientific question from sampling to management practices along with the selection of appropriate genomics tools and bioinformatics challenges.
Congruent patterns of connectivity can inform management for broadcast spawning corals on the Great Barrier Reef
Authors: Lukoschek Vimoksalehi , Riginos Cynthia , van Oppen Madeleine J. H. 
Published: April 2016

AbstractConnectivity underpins the persistence and recovery of marine ecosystems. The Great Barrier Reef (GBR) is the world's largest coral reef ecosystem and managed by an extensive network of no‐take zones; however, information about connectivity was not available to optimize the network's configuration. We use multivariate analyses, Bayesian clustering algorithms and assignment tests of the largest population genetic data set for any organism on the GBR to date (Acropora tenuis, >2500 colonies; >50 reefs, genotyped for ten microsatellite loci) to demonstrate highly congruent patterns of connectivity between this common broadcast spawning reef‐building coral and its congener Acropora millepora (~950 colonies; 20 reefs, genotyped for 12 microsatellite loci). For both species, there is a genetic divide at around 19°S latitude, most probably reflecting allopatric differentiation during the Pleistocene. GBR reefs north of 19°S are essentially panmictic whereas southern reefs are genetically distinct with higher levels of genetic diversity and population structure, most notably genetic subdivision between inshore and offshore reefs south of 19°S. These broadly congruent patterns of higher genetic diversities found on southern GBR reefs most likely represent the accumulation of alleles via the southward flowing East Australia Current. In addition, signatures of genetic admixture between the Coral Sea and outer‐shelf reefs in the northern, central and southern GBR provide evidence of recent gene flow. Our connectivity results are consistent with predictions from recently published larval dispersal models for broadcast spawning corals on the GBR, thereby providing robust connectivity information about the dominant reef‐building genus Acropora for coral reef managers.
Using dense locality sampling resolves the subtle genetic population structure of the dispersive fish species Plecoglossus altivelis
Authors: Takeshima Hirohiko , Iguchi Kei'ichiro , Hashiguchi Yasuyuki , Nishida Mutsumi 
Published: April 2016

AbstractIn dispersive species with continuous distributions, genetic differentiation between local populations is often absent or subtle and thus difficult to detect. To incorporate such subtle differentiation into management plans, it may be essential to analyse many samples from many localities using adequate numbers of high‐resolution genetic markers. Here, we evaluated the usefulness of dense locality sampling in resolving genetic population structure in the ayu (Plecoglossus altivelis), a dispersive fish important in Japanese inland fisheries. Genetic variability in, and differentiation between, ayu populations around the Japan–Ryukyu Archipelago were investigated in 4746 individuals collected from 120 localities by genotyping 12 microsatellite markers. These individuals represented the two subspecies of ayu, namely the Ryukyuan subspecies (Plecoglossus altivelis ryukyuensis) and both amphidromous and landlocked forms of the nominotypical subspecies (P. a. altivelis) along the archipelago. We successfully detected an absence of genetic differentiation within the landlocked form and subtle but significant differentiation and clear geographic patterns of genetic variation among populations of the amphidromous form, which had been considered genetically homogeneous. This suggests that dense locality sampling effectively resolves subtle differences in genetic population structure, reducing stochastic deviation in the detection of genetic differentiation and geographic patterns in local populations of this dispersive species. Resampling analyses based on empirical data sets clearly demonstrate the effectiveness of increasing the number of locality samples for stable and reliable estimations of genetic fixation indices. The genetic population structure observed within the amphidromous form provides useful information for identifying management or conservation units in ayu.
Biogeographic patterns of soil diazotrophic communities across six forests in the North America
Authors: Tu Qichao , Deng Ye , Yan Qingyun , Shen Lina , Lin Lu , He Zhili , Wu Liyou , Van Nostrand Joy D. , Buzzard Vanessa , Michaletz Sean T. , Enquist Brian J. , Weiser Michael D. , Kaspari Michael , Waide Robert B. , Brown James H. , Zhou Jizhong 
Published: April 2016

AbstractSoil diazotrophs play important roles in ecosystem functioning by converting atmospheric N2 into biologically available ammonium. However, the diversity and distribution of soil diazotrophic communities in different forests and whether they follow biogeographic patterns similar to macroorganisms still remain unclear. By sequencing nifH gene amplicons, we surveyed the diversity, structure and biogeographic patterns of soil diazotrophic communities across six North American forests (126 nested samples). Our results showed that each forest harboured markedly different soil diazotrophic communities and that these communities followed traditional biogeographic patterns similar to plant and animal communities, including the taxa–area relationship (TAR) and latitudinal diversity gradient. Significantly higher community diversity and lower microbial spatial turnover rates (i.e. z‐values) were found for rainforests (~0.06) than temperate forests (~0.1). The gradient pattern of TARs and community diversity was strongly correlated (r2 > 0.5) with latitude, annual mean temperature, plant species richness and precipitation, and weakly correlated (r2 < 0.25) with pH and soil moisture. This study suggests that even microbial subcommunities (e.g. soil diazotrophs) follow general biogeographic patterns (e.g. TAR, latitudinal diversity gradient), and indicates that the metabolic theory of ecology and habitat heterogeneity may be the major underlying ecological mechanisms shaping the biogeographic patterns of soil diazotrophic communities.
Tolerance to ischemia reperfusion injury in a congenital heart disease model
Authors: Asada Dai , Itoi Toshiyuki , Nakamura Akihiro , Hamaoka Kenji 
Published: April 2016

AbstractBackgroundOpen heart surgery‐associated ischemia/reperfusion (I/R) injury affects postoperative outcome, and a leading cause of this is lipid peroxidation. Congenital heart disease (CHD) patients, however, are less sensitive to I/R injury. Although little is known about the underlying molecular mechanisms, CHD‐associated hypoxia alters the polyunsaturated fatty acid (PUFA) composition of membranes, which are the preferential targets for reactive oxygen species (ROS) generated during I/R. Here, using an animal model, we investigated the molecular mechanisms underlying I/R tolerance in CHD.MethodsIn order to reproduce I/R injury in vitro, we used a working heart perfusion model, isolated from juvenile control and CHD model rats (CHD rats), and examined the recovery of cardiac function during a period of I/R. PUFA composition of the plasma membrane was determined on gas chromatography/mass spectrometry. Oxidative stress‐related cellular responses were investigated on immunoblotting, using antibodies against nuclear factor erythroid 2‐related factor (Nrf‐2), hemeoxygenase‐1 (HO‐1), and 4‐hydroxy‐2‐hexanal (4‐HHE)‐modified protein.ResultsIschemia/reperfusion‐induced cardiac dysfunction was markedly suppressed in CHD rats, compared with the control rats. n‐3/n‐6 PUFA ratio was significantly increased in both the pre‐ and post‐I/R phase in CHD rats, but not in the controls. Four‐HHE‐modified protein, Nrf‐2, and HO‐1 were significantly increased in CHD rats as well, compared with the controls.ConclusionsFollowing open heart surgery in CHD patients, the increased n‐3/n‐6 PUFA ratio may lead to the upregulation of cellular antioxidative system components through the oxidation product, 4‐HHE, resulting in an increased tolerance to I/R injury.
Trends in prevalence of soil‐transmitted helminth and major intestinal protozoan infections among school‐aged children in Nepal
Authors: Kunwar Ritu , Acharya Lokendra , Karki Surendra 
Published: April 2016

AbstractObjectivesTo assess the trends in prevalence of soil‐transmitted helminths (STHs), Entamoeba histolytica and Giardia lamblia among school‐aged children in Nepal between 1990 and 2015.MethodsSystematic literature search in PubMed, MEDLINE, EMBASE, Google Scholar and local peer‐reviewed journals for papers published between 1990 and December 2015. We conducted metaregression and meta‐analyses to pool studies where applicable.ResultsThirty‐nine studies that examined a total of 14 729 stool specimens were included in the meta‐analyses. The metaregression of prevalence of hookworms, roundworm, and whipworm showed a significantly decreasing trend over time. In or after 2004, the pooled prevalence of hookworm infections was 1.53% (95% CI, 0.73–2.59), of roundworm 4.31% (95% CI, 2.52–6.53) and of whipworm 2.89% (95% CI, 1.33–4.97) vs. 16.54% (95% CI, 7.64–27.97) for hookworm, 25.20% (95% CI, 13.59–38.97) for roundworm and 11.54% (95% CI 4.25–21.76) for whipworm in 1993–2003. E. histolytica and G. lamblia had stable prevalence since early 1990s, with a pooled prevalences of 4.12% (95% CI, 2.73–5.77) and 9.40% (95% CI, 7.15–11.92), respectively. The prevalence of G. lamblia was significantly higher in urban areas.ConclusionsWe observed a sharp decrease in prevalence of STHs among school‐aged children in Nepal in the past decade with prevalences dropping below 5% for STHs with no variation in prevalence in rural and urban areas. However, the prevalence of E. histolytica and G. lamblia remained stable over time. These results suggest that school‐based deworming programmes rolled out during the study period had an observable impact on prevalence of STHs.
Evaluation of immunomodulatory effect of recombinant human granulocyte‐macrophage colony‐stimulating factor on polymorphonuclear cell from dogs with cancer in vitro
Authors: Zhang Y. , Axiak‐Bechtel S. , Friedman Cowan C. , Amorim J. , Tsuruta K. , DeClue A. E. 
Published: April 2016

AbstractThe objective of this in vitro study was to evaluate the immunomodulatory effects of recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) on polymorphonuclear cell (PMN) function in dogs with cancer. PMNs were harvested from dogs with naturally developing cancer as a pre‐clinical model to evaluate the immunomodulatory effects of rhGM‐CSF on PMN phagocytic and cytotoxic functions, cytokine production and receptor expression. Some aspects of cancer‐related PMN dysfunction in dogs with cancer were restored following incubation with rhGM‐CSF including PMN phagocytosis, respiratory burst and LPS‐induced TNF‐α production. In addition, rhGM‐CSF increased surface HLA‐DR expression on the PMNs of dogs with cancer. These data suggests that dysfunction of innate immune response in dogs with cancer may be improved by rhGM‐CSF. The results of this study provided a pathophysiologic rationale for the initiation of clinical trials to continue evaluating rhGM‐CSF as an immunomodulatory therapy in dogs with cancer.
The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation
Authors: Dauber Bianca , Poon David , dos Santos Theodore , Duguay Brett A. , Mehta Ninad , Saffran Holly A. , Smiley James R. 
Published: April 2016

ABSTRACT
The herpes simplex virus (HSV) virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs, suppresses host protein synthesis, dampens antiviral responses, and stimulates translation of viral mRNAs. vhs mutants display a host range phenotype: translation of viral true late mRNAs is severely impaired and stress granules accumulate in HeLa cells, while translation proceeds normally in Vero cells. We found that vhs-deficient virus activates the double-stranded RNA-activated protein kinase R (PKR) much more strongly than the wild-type virus does in HeLa cells, while PKR is not activated in Vero cells, raising the possibility that PKR might play roles in stress granule induction and/or inhibiting translation in restrictive cells. We tested this possibility by evaluating the effects of inactivating PKR. Eliminating PKR in HeLa cells abolished stress granule formation but had only minor effects on viral true late protein levels. These results document an essential role for PKR in stress granule formation by a nuclear DNA virus, indicate that induction of stress granules is the consequence rather than the cause of the translational defect, and are consistent with our previous suggestion that vhs promotes translation of viral true late mRNAs by preventing mRNA overload rather than by suppressing eIF2α phosphorylation.

IMPORTANCE
The herpes simplex virus vhs RNase plays multiple roles during infection, including suppressing PKR activation, inhibiting the formation of stress granules, and promoting translation of viral late mRNAs. A key question is the extent to which these activities are mechanistically connected. Our results demonstrate that PKR is essential for stress granule formation in the absence of vhs, but at best, it plays a secondary role in suppressing translation of viral mRNAs. Thus, the ability of vhs to promote translation of viral mRNAs can be largely uncoupled from PKR suppression, demonstrating that this viral RNase modulates at least two distinct aspects of RNA metabolism.