bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coalescing molecular evolution andDNAbarcoding
Authors: Zinger Lucie , Philippe Hervé 
Published: May 2016

TheDNAbarcoding concept (Woeseet al.; Hebertet al.) has considerably boosted taxonomy research by facilitating the identification of specimens and discovery of new species. Used alone or in combination withDNAmetabarcoding on environmental samples (Taberletet al.), the approach is becoming a standard for basic and applied research in ecology, evolution and conservation across taxa, communities and ecosystems (Schefferset al.; Kresset al.). However,DNAbarcoding suffers from several shortcomings that still remain overlooked, especially when it comes to species delineation (Collins & Cruickshank). In this issue ofMolecular Ecology, Barley & Thomson () demonstrate that the choice of models of sequence evolution has substantial impacts on inferred genetic distances, with a propensity of the widely used Kimura 2‐parameter model to lead to underestimated species richness. WhileDNAbarcoding has been and will continue to be a powerful tool for specimen identification and preliminary taxonomic sorting, this work calls for a systematic assessment of substitution models fit on barcoding data used for species delineation and reopens the debate on the limitation of this approach.
Structural insights into the inhibition mechanism of bacterial toxin LsoA by bacteriophage antitoxin Dmd
Authors: Wan Hua , Otsuka Yuichi , Gao Zeng‐Qiang , Wei Yong , Chen Zhen , Masuda Michiaki , Yonesaki Tetsuro , Zhang Heng , Dong Yu‐Hui 
Published: May 2016

SummaryBacteria have obtained a variety of resistance mechanisms including toxin‐antitoxin (TA) systems against bacteriophages (phages), whereas phages have also evolved to overcome bacterial anti‐phage mechanisms. Dmd from T4 phage can suppress the toxicities of homologous toxins LsoA and RnlA from Escherichia coli, representing the first example of a phage antitoxin against multiple bacterial toxins in known TA systems. Here, the crystal structure of LsoA‐Dmd complex showed Dmd is inserted into the deep groove between the N‐terminal repeated domain (NRD) and the Dmd‐binding domain (DBD) of LsoA. The NRD shifts significantly from a ‘closed’ to an ‘open’ conformation upon Dmd binding. Site‐directed mutagenesis of Dmd revealed the conserved residues (W31 and N40) are necessary for LsoA binding and the toxicity suppression as determined by pull‐down and cell toxicity assays. Further mutagenesis identified the conserved Dmd‐binding residues (R243, E246 and R305) of LsoA are vital for its toxicity, and suggested Dmd and LsoB may possess different inhibitory mechanisms against LsoA toxicity. Our structure‐function studies demonstrate Dmd can recognize LsoA and inhibit its toxicity by occupying the active site possibly via substrate mimicry. These findings have provided unique insights into the defense and counter‐defense mechanisms between bacteria and phages in their co‐evolution.
Biophysico‐functional compatibility of Seoul National University (SNU) miniature pig cornea as xenocorneal graft for the use of human clinical trial
Authors: Kim Dong Hyun , Kim Jaeyoung , Jeong Hyun Jeong , Lee Hyun Ju , Kim Mee Kum , Wee Won Ryang 
Published: May 2016

AbstractBackgroundXenocorneal transplantation is one of the solutions for shortage of donor cornea, and remarkable advances have been made in pig‐to‐rhesus studies from the immunological perspective. Most successful preclinical trials have been carried out with corneas of the Seoul National University (SNU) miniature pig (SNU pig, genetically unmodified) as donor tissues; however, there has been no biophysico‐functional evaluation of the SNU pig cornea as a substitute for human cornea. The purpose of this study was to investigate the biophysical and functional compatibility of SNU pig cornea for use in human clinical trials.MethodsNinety‐three eyeballs obtained from 51 SNU pigs were used to evaluate the physical properties and changes in porcine corneal endothelial cells (PCECs) depending on preservation time and storage condition before surgery, proliferative and functional characteristics of PCECs, and the microbiologic safety of porcine cornea. Corneal diameters and curvatures, axial length, anterior chamber depth, and central corneal thickness were measured and compared with previously reported human data. Corneal endothelial cell density (ECD) was serially measured with a confocal microscope during 7 days of preservation in the same storage solution used for human corneas. Corneal endothelial cell proliferation and immunofluorescence staining of Na‐ and K‐dependent ATPase in PCECs were evaluated after 7 days of preservation. The corneoscleral rims of SNU pigs were cultured for gram‐positive bacteria, gram‐negative bacteria, and fungi to evaluate their microbiological safety.ResultsCorneal diameter and thickness in SNU pigs was larger than human and corneal curvature was flatter; however, they were within surgically operable ranges. Mean ECD (day 0) and ECD loss after 7 days of preservation were 2625 ± 81 cells/mm2 and 7.60 ± 1.53%, respectively, which is comparable to human ECD and ECD loss in the same conditions. The ECD of SNU pigs was inversely decreased with aging (R2 = 0.4034, P = 0.001), and the estimated ages of pigs whose mean ECD would be more than 2500 and 2200 cells/mm2 or more were 48 and 72 months or less, respectively. Mean doubling time of the endothelial cells was 52 to 96 h depending on the method used. The Na‐ and K‐dependent ATPase pump in SNU pig cornea was well maintained for 7 days. No cultured microorganisms were found upon using the modified European Eye Bank Association protocol, which included additional antiseptic management during the enucleation procedure.ConclusionsIn conclusion, SNU pig cornea is feasible for xenocorneal transplantation using the same preservation protocol as human with respect to biophysical and functional properties and can be stored for up to 7 days for transplantation in human clinical trials. An age limitation of donor pigs may be required for qualified corneal products to be used in human trials.
HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life
Authors: Nduati Eunice W. , Nkumama Irene N. , Gambo Faith K. , Muema Daniel M. , Knight Miguel G. , Hassan Amin S. , Jahangir Margaret N. , Etyang Timothy J. , Berkley James A. , Urban Britta C. 
Published: May 2016

ABSTRACT
Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected.
Arteriviruses, Pegiviruses, and Lentiviruses Are Common among Wild African Monkeys
Authors: Bailey Adam L. , Lauck Michael , Ghai Ria R. , Nelson Chase W. , Heimbruch Katelyn , Hughes Austin L. , Goldberg Tony L. , Kuhn Jens H. , Jasinska Anna J. , Freimer Nelson B. , Apetrei Cristian , O'Connor David H. 
Published: May 2016

ABSTRACT

Nonhuman primates (NHPs) are a historically important source of zoonotic viruses and are a gold-standard model for research on many human pathogens. However, with the exception of simian immunodeficiency virus (SIV) (family
Retroviridae
), the blood-borne viruses harbored by these animals in the wild remain incompletely characterized. Here, we report the discovery and characterization of two novel simian pegiviruses (family
Flaviviridae
) and two novel simian arteriviruses (family
Arteriviridae
) in wild African green monkeys from Zambia (malbroucks [
Chlorocebus cynosuros
]) and South Africa (vervet monkeys [
Chlorocebus pygerythrus
]). We examine several aspects of infection, including viral load, genetic diversity, evolution, and geographic distribution, as well as host factors such as age, sex, and plasma cytokines. In combination with previous efforts to characterize blood-borne RNA viruses in wild primates across sub-Saharan Africa, these discoveries demonstrate that in addition to SIV, simian pegiviruses and simian arteriviruses are widespread and prevalent among many African cercopithecoid (i.e., Old World) monkeys.

IMPORTANCE
Primates are an important source of viruses that infect humans and serve as an important laboratory model of human virus infection. Here, we discover two new viruses in African green monkeys from Zambia and South Africa. In combination with previous virus discovery efforts, this finding suggests that these virus types are widespread among African monkeys. Our analysis suggests that one of these virus types, the simian arteriviruses, may have the potential to jump between different primate species and cause disease. In contrast, the other virus type, the pegiviruses, are thought to reduce the disease caused by human immunodeficiency virus (HIV) in humans. However, we did not observe a similar protective effect in SIV-infected African monkeys coinfected with pegiviruses, possibly because SIV causes little to no disease in these hosts.
The effect of the Shorter Stays in Emergency Departments health target on the quality of ED discharge summaries
Authors: Harper Alana , Jones Peter , Wimsett Jordon , Stewart Joanna , Le Fevre James , Wells Susan , Curtis Elana , Reid Papaarangi , Ameratunga Shanthi 
Published: May 2016

ObjectiveTime targets for ED stays are used as a policy instrument to reduce ED crowding. There is debate whether such policies are helpful or harmful, as focus on a process target may divert attention from clinical care. The objective of this study is to investigate whether the Shorter Stays in Emergency Departments target in New Zealand was associated with a change in the quality of ED discharge information provided to primary care providers.MethodsThe quality of discharge summaries was assessed retrospectively over time using chart review. Logistic regression was used to account for secular trends with adequate or not as the dependent variable. Explanatory variables were: age, ethnicity, deprivation, triage category, year, the step at target introduction (2009) and the change in slope before and after the target.ResultsOf 500 randomly selected discharge summaries, 491 (98.2%) were included in the analysis. There was evidence of a decrease over time in the proportion of adequate discharge summaries before the introduction of the target (slope estimate (SE) −0.43 (0.20), p=0.02). A step at the target introduction could not be shown (p=0.47). There was evidence of an improvement over time from pre-target to post-target: slope afterwards 0.33, estimate of change in slope (SE) 0.76 (0.27), p=0.006.ConclusionsThere was no reduction in the quality of discharge summaries following the introduction of the shorter stays in ED target and trends in quality improved. These findings deserve replication in other hospitals which may experience different challenges.
Improving Allocative Efficiency of Scarce Water in Southern Alberta
Authors: Ali Md Kamar 
Published: May 2016

Using a positive mathematical programming (PMP) model with improved ‘wide-scope’ calibration, this study demonstrates how allocative efficiency of scarce water could be improved in the Bow- and Oldman River Sub Basins (BRSB and ORSB) of Southern Alberta, where 12 irrigation districts, two cities and three major industrial/commercial users withdraw bulk of the surface water for irrigation, municipal, industrial and commercial needs. Earlier studies ironically neglected the larger ORSB even though it is subject to the same water licensing and regulation policies as the BRSB. The inclusion of nine irrigation districts and non-irrigation users of ORSB enables this model to estimate allocative efficiency gains in a more comprehensive manner than before. Results indicate that ORSB has a relatively less elastic water demand curve primarily due to its more reliance on irrigation and less water saving/supply options. It is also less responsive to allocations with alternative policies as reflected in net returns, land use and cropping pattern changes due to its less elastic water demand.
Immunomodulatory Activity of Nivolumab in Metastatic Renal Cell Carcinoma
Authors: Choueiri Toni K. , Fishman Mayer N. , Escudier Bernard , McDermott David F. , Drake Charles G. , Kluger Harriet , Stadler Walter M. , Perez-Gracia Jose Luis , McNeel Douglas G. , Curti Brendan , Harrison Michael R. , Plimack Elizabeth R. , Appleman Leonard , Fong Lawrence , Albiges Laurence , Cohen Lewis , Young Tina C. , Chasalow Scott D. , Ross-Macdonald Petra , Srivastava Shivani , Jure-Kunkel Maria , Kurland John F. , Simon Jason S. , Sznol Mario 
Published: May 2016

AbstractPurpose: Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity of nivolumab in a hypothesis-generating prospective mRCC trial.Experimental Design: Nivolumab was administered intravenously every 3 weeks at 0.3, 2, or 10 mg/kg to previously treated patients and 10 mg/kg to treatment-naïve patients with mRCC. Baseline and on-treatment biopsies and blood were obtained. Clinical activity, tumor-associated lymphocytes, PD-L1 expression (Dako immunohistochemistry; ≥5% vs. &lt;5% tumor membrane staining), tumor gene expression (Affymetrix U219), serum chemokines, and safety were assessed.Results: In 91 treated patients, median overall survival [95% confidence interval (CI)] was 16.4 months [10.1 to not reached (NR)] for nivolumab 0.3 mg/kg, NR for 2 mg/kg, 25.2 months (12.0 to NR) for 10 mg/kg, and NR for treatment-naïve patients. Median percent change from baseline in tumor-associated lymphocytes was 69% (CD3+), 180% (CD4+), and 117% (CD8+). Of 56 baseline biopsies, 32% had ≥5% PD-L1 expression, and there was no consistent change from baseline to on-treatment biopsies. Transcriptional changes in tumors on treatment included upregulation of IFNγ-stimulated genes (e.g., CXCL9). Median increases in chemokine levels from baseline to C2D8 were 101% (CXCL9) and 37% (CXCL10) in peripheral blood. No new safety signals were identified.Conclusions: Immunomodulatory effects of PD-1 inhibition were demonstrated through multiple lines of evidence across nivolumab doses. Biomarker changes from baseline reflect nivolumab pharmacodynamics in the tumor microenvironment. These data may inform potential combinations. Clin Cancer Res; 22(22); 5461–71. ©2016 AACR.
PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer
Authors: Jhuraney Ankita , Woods Nicholas T. , Wright Gabriela , Rix Lily , Kinose Fumi , Kroeger Jodi L. , Remily-Wood Elizabeth , Cress W. Douglas , Koomen John M. , Brantley Stephen G. , Gray Jhanelle E. , Haura Eric B. , Rix Uwe , Monteiro Alvaro N. 
Published: May 2016

Abstract
The DNA damage response (DDR) involves a complex network of signaling events mediated by modular protein domains such as the BRCA1 C-terminal (BRCT) domain. Thus, proteins that interact with BRCT domains and are a part of the DDR constitute potential targets for sensitization to DNA-damaging chemotherapy agents. We performed a pharmacologic screen to evaluate 17 kinases, identified in a BRCT-mediated interaction network as targets to enhance platinum-based chemotherapy in lung cancer. Inhibition of mitotic kinase WEE1 was found to have the most effective response in combination with platinum compounds in lung cancer cell lines. In the BRCT-mediated interaction network, WEE1 was found in complex with PAXIP1, a protein containing six BRCT domains involved in transcription and in the cellular response to DNA damage. We show that PAXIP1 BRCT domains regulate WEE1-mediated phosphorylation of CDK1. Furthermore, ectopic expression of PAXIP1 promotes enhanced caspase-3–mediated apoptosis in cells treated with WEE1 inhibitor AZD1775 (formerly, MK-1775) and cisplatin compared with cells treated with AZD1775 alone. Cell lines and patient-derived xenograft models expressing both PAXIP1 and WEE1 exhibited synergistic effects of AZD1775 and cisplatin. In summary, PAXIP1 is involved in sensitizing lung cancer cells to the WEE1 inhibitor AZD1775 in combination with platinum-based treatment. We propose that WEE1 and PAXIP1 levels may be used as mechanism-based biomarkers of response when WEE1 inhibitor AZD1775 is combined with DNA-damaging agents. Mol Cancer Ther; 15(7); 1669–81. ©2016 AACR.
АНАЛІЗ ЯКОСТІ НАВЧАННЯ МЕДИЧНИХ СЕСТЕР ЗАКАРПАТСЬКОГО БАЗОВОГО МЕДИЧНОГО КОЛЕДЖУ ЗА РЕЗУЛЬТАТАМИ СТАНДАРТИЗОВАНОГО ТЕСТОВОГО ДЕРЖАВНОГО ІСПИТУ «КРОК М»
Authors: Hintsyak V. T. , Rega N. I. 
Published: May 2016

<p>У статті проаналізовано результати стандартизованого тестового державного іспиту «Крок М» у випускників Закарпатського базового медичного коледжу за 2011‒2014 рр. та запропоновано сучасні методи покращення якості навчання у вищих навчальних медичних закладах. </p>
Quasi-Spherical Ice in Convective Clouds
Authors: Järvinen Emma , Schnaiter Martin , Mioche Guillaume , Jourdan Olivier , Shcherbakov Valery N. , Costa Anja , Afchine Armin , Krämer Martina , Heidelberg Fabian , Jurkat Tina , Voigt Christiane , Schlager Hans , Nichman Leonid , Gallagher Martin , Hirst Edwin , Schmitt Carl , Bansemer Aaron , Heymsfield Andy , Lawson Paul , Tricoli Ugo , Pfeilsticker Klaus , Vochezer Paul , Möhler Ottmar , Leisner Thomas 
Published: May 2016

Abstract
Homogeneous freezing of supercooled droplets occurs in convective systems in low and midlatitudes. This droplet-freezing process leads to the formation of a large amount of small ice particles, so-called frozen droplets, that are transported to the upper parts of anvil outflows, where they can influence the cloud radiative properties. However, the detailed microphysics and, thus, the scattering properties of these small ice particles are highly uncertain. Here, the link between the microphysical and optical properties of frozen droplets is investigated in cloud chamber experiments, where the frozen droplets were formed, grown, and sublimated under controlled conditions. It was found that frozen droplets developed a high degree of small-scale complexity after their initial formation and subsequent growth. During sublimation, the small-scale complexity disappeared, releasing a smooth and near-spherical ice particle. Angular light scattering and depolarization measurements confirmed that these sublimating frozen droplets scattered light similar to spherical particles: that is, they had angular light-scattering properties similar to water droplets. The knowledge gained from this laboratory study was applied to two case studies of aircraft measurements in midlatitude and tropical convective systems. The in situ aircraft measurements confirmed that the microphysics of frozen droplets is dependent on the humidity conditions they are exposed to (growth or sublimation). The existence of optically spherical frozen droplets can be important for the radiative properties of detraining convective outflows.
Time-Varying Response of ENSO-Induced Tropical Pacific Rainfall to Global Warming in CMIP5 Models. Part I: Multimodel Ensemble Results
Authors: Huang Ping 
Published: May 2016

Abstract
El Niño–Southern Oscillation (ENSO) is one of the most important drivers of climatic variability on the global scale. Much of this variability arises in response to ENSO-driven changes in tropical Pacific rainfall. Previous research has shown that the ENSO-driven tropical Pacific rainfall variability can shift east and intensify in response to global warming, even if ENSO-related SST variability remains unchanged. Here, the twenty-first century changes in ENSO-driven tropical Pacific rainfall variability in 32 CMIP5 models forced under the representative concentration pathway 8.5 (RCP8.5) scenario are examined, revealing that the pattern of changes in ENSO-driven rainfall is not only gradually enhanced but also shifts steadily eastward along with the global-mean temperature increase. Using a recently developed moisture budget decomposition method, it is shown that the projected changes in ENSO-driven rainfall variability in the tropical Pacific can be primarily attributed to a projected increase in both mean-state surface moisture and spatially relative changes in mean-state SST, defined as the departure of local SST changes from the tropical mean. The enhanced moisture increase enlarges the thermodynamic component of ENSO rainfall changes. The enhanced El Niño–like changes in mean-state SST steadily move the dynamic component of changes in ENSO-driven rainfall variability to the central-eastern Pacific, along with increasing global-mean temperature.
High-Impact Social Work Scholars
Authors: Hodge David R. , Kremer Kristen P. , Vaughn Michael G. 
Published: May 2016

Objective: The purpose of this study was to identify and describe the bibliometric contributions of high-impact social work faculty. Methods: Toward this end, we used a sample comprising fellows ( N = 143) affiliated with the Society for Social Work and Research (SSWR) and the American Academy of Social Work and Social Welfare (AASWSW). To quantify impact, we relied primarily upon the h-index (a measure of lifetime scholarly impact) and the m-index (which adjusts for career length). Results: Analyses revealed the mean h-index value for SSWR fellows ( M = 26.44, SD = 14.72) was substantially lower than the mean for AASWSW fellows ( M = 32.52, SD = 15.96), but minimal differences existed in m-index values. H- and m-index values for the 40 highest impact scholars ranged, respectively, from 33 to 93 and 1.13 to 3.33. Conclusions: The results indicate the social work profession includes many researchers who are making an exceptional scientific impact.