bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Randomized Switch From Nevirapine-Based Antiretroviral Therapy to Single Tablet Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in Virologically Suppressed Human Immunodeficiency Virus-1-Infected Rwandans
Authors: Collins Sean E. , Grant Philip M. , Uwinkindi Francois , Talbot Annie , Seruyange Eric , Slamowitz Deborah , Mugeni Adeline , Remera Eric , Niyonsenga Simon Pierre , Nyirimigabo Josbert , Uwizihiwe Jean Paul , Dongier Pierre , Muhayimpundu Ribakare , Mazarati Jean-Baptiste , Zolopa Andrew , Nsanzimana Sabin 
Published: July 2016

AbstractBackground.  Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy.Methods.  We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] &lt; 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA &lt; 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%.Results.  Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level &lt;200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm.Conclusions.  A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.
Cross-species genome-wide identification of evolutionary conserved microProteins
Authors: Straub Daniel , Wenkel Stephan 
Published: July 2016

ABSTRACTMicroProteins are small single domain proteins that act by engaging their targets into non-productive protein complexes. In order to identify novel microProteins in any sequenced genome of interest, we have developed miPFinder, a program that identifies and classifies potential microProteins. In the past years, several microProteins have been discovered in plants where they are mainly involved in the regulation of development. The miPFinder algorithm identifies all up to date known plant microProteins and extends the microProtein concept to other protein families. Here, we reveal potential microProtein candidates in several plant and animal reference genomes. A large number of these microProteins are species-specific while others evolved early and are evolutionary highly conserved. Most known microProtein genes originated from large ancestral genes by gene duplication, mutation and subsequent degradation. Gene ontology analysis shows that putative microProtein ancestors are often located in the nucleus, and involved in DNA binding and formation of protein complexes. Additionally, microProtein candidates act in plant transcriptional regulation, signal transduction and anatomical structure development. MiPFinder is freely available to find microProteins in any genome and will aid in the identification of novel microProteins in plants and animals
Shifts in outcrossing rates and changes to floral traits are associated with the evolution of herbicide resistance in the common morning glory
Authors: Kuester Adam , Fall Eva , Chang Shu-Mei , Baucom Regina S. 
Published: July 2016

AbstractHuman-mediated selection can strongly influence the evolutionary response of natural organisms within ecological timescales. But what traits allow for, or even facilitate, adaptation to the strong selection humans impose on natural systems? Using a combination of lab and greenhouse studies of 32 natural populations of the common agricultural weed,Ipomoea purpurea, we show that herbicide resistant populations self-fertilize more than susceptible populations. We likewise show that anther-stigma distance, a floral trait associated with self-fertilization in this species, exhibits a non-linear relationship with resistance such that the most and least resistant populations exhibit lower anther-stigma separation compared to populations with moderate levels of resistance. Overall, our results extend the general finding that plant mating can be impacted by human-mediated agents of selection to that of the extreme selection of the agricultural system. This work highlights the influence of human-mediated selection on rapid responses of natural populations that can lead to unexpected long-term evolutionary consequences.Statement of authorshipAK collected seeds, performed experiments, analyzed data and wrote the paper; EF collected data; SMC collected data and contributed to the manuscript; RSB designed the study, performed the analyses, and wrote the paper. All authors discussed the results and commented on the manuscript.Data accessibilityPrimary data used in these analyses will be made available in the public github repositoryhttps://github.com/rsbaucom/MatingSystem2015, which can be anonymously accessed. Upon acceptance, data will be made available through the Dryad public repository.
Tempus et Locus: a tool for extracting precisely dated viral sequences from GenBank, and its application to the phylogenetics of primate erythroparvovirus 1 (B19V)
Authors: Carter Alice R. , Gatherer Derek 
Published: July 2016

AbstractThe presence of data in the “collection_date” field of a GenBank sequence record is of great assistance in the use of that sequence for Bayesian phylogenetics using “tip-dating”. We presentTempus et Locus(TeL), a tool for extracting such sequences from a GenBank-formatted sequence database. TeL shows that 60% of viral sequences in GenBank have collection date fields, but that this varies considerably between species. Primate erythroparvovirus 1 (human parvovirus B19 or B19V) has only 40% of its sequences dated, of which only 112 are of more than 4 kb. 100 of these are from B19V sub-genotype 1a and were collected from a mere 6 studies conducted in 5 countries between 2002 and 2013. Nevertheless, Bayesian phylogenetic analysis of this limited set gives a date for the common ancestor of sub-genotype 1a in 1990 (95% HPD 1981-1996) which is in reasonable agreement with estimates of previous studies where collection dates have been assembled by more laborious methods of literature search and direct enquiries to sequence submitters. We conclude that although collection dates should become standard for all future GenBank submissions of virus sequences, accurate dating of ancestors is possible with even a small number of sequences if sampling information is high quality.
Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells
Authors: Pott Sebastian 
Published: July 2016

AbstractGaining insights into the regulatory mechanisms that underlie the transcriptional variation observed between individual cells necessitates the development of methods that measure chromatin organization in single cells. Here I adapted Nucleosome Occupancy and Methylome-sequencing (NOMe-seq) to measure chromatin accessibility and endogenous DNA methylation in single cells (scNOMe-seq). scNOMe-seq recovered characteristic accessibility and DNA methylation patterns at DNase hypersensitive sites (DHSs). An advantage of scNOMe-seq is that sequencing reads are sampled independently of the accessibility measurement. scNOMe-seq therefore controlled for fragment loss, which enabled direct estimation of the fraction of accessible DHSs within individual cells. In addition, scNOMe-seq provided high resolution of chromatin accessibility within individual loci which was exploited to detect footprints of CTCF binding events and to estimate the average nucleosome phasing distances in single cells. scNOMe-seq is therefore well-suited to characterize the chromatin organization of single cells in heterogeneous cellular mixtures.
Adaptation of the Arizona Cognitive Task Battery for use with the Ts65Dn Mouse Model (Mus musculus) of Down syndrome
Authors: Hunsaker Michael R. , Smith Genevieve K. , Kesner Raymond P. 
Published: July 2016

AbstractWe propose and validate a clear strategy to efficiently and comprehensively characterize neurobehavioral deficits in the Ts65Dn mouse model of Down syndrome. This novel approach uses neurocognitive theory to design and select behavioral tasks that test specific hypotheses concerning the results of Down syndrome. In this manuscript we model in Ts65Dn mice the Arizona Cognitive Task Battery used to study human populations with Down syndrome. We observed specific deficits for spatial memory, impaired long-term memory for visual objects, acquisition and reversal of motor responses, reduced motor dexterity, and impaired adaptive function as measured by nesting and anxiety tasks. The Ts65Dn mice showed intact temporal ordering, novelty detection, and visual object recognition with short delays. These results phenocopy the performance of participants with Down syndrome on the Arizona Cognitive Task Battery. This approach extends the utility of mouse models of Down syndrome by integrating the expertise of clinical neurology and cognitive neuroscience into the mouse behavioral laboratory. Further, by directly emphasizing the reciprocal translation of research between human disease states and the associated mouse models, we demonstrate that it is possible for both groups to mutually inform each others’ research to more efficiently generate hypotheses and elucidate treatment strategies.
Dysregulation of Long Non-coding RNA (lncRNA) Genes and Predicted lncRNA-Protein Interactions during Zika Virus Infection
Authors: Ramaiah Arunachalam , Contreras Deisy , Gangalapudi Vineela , Sameer Padhye Masumi , Tang Jie , Arumugaswami Vaithilingaraja 
Published: July 2016

ABSTRACTZika Virus (ZIKV) is a causative agent for poor pregnancy outcome and fetal developmental abnormalities, including microcephaly and eye defects. As a result, ZIKV is now a confirmed teratogen. Understanding host-pathogen interactions, specifically cellular perturbations caused by ZIKV, can provide novel therapeutic targets. In order to complete viral replication, viral pathogens control the host cellular machineries and regulate various factors, including long noncoding RNA (lncRNA) genes, at transcriptional levels. The role of lncRNA genes in the pathogenesis of ZIKV-mediated microcephaly and eye defects is currently unknown. To gain additional insights, we focused on profiling the differentially expressed lncRNA genes during ZIKV infection in mammalian cells. For this study, we employed a contemporary clinical Zika viral isolate, PRVABC59, of Asian genotype. We utilized an unbiased RNA sequencing approach to profile the lncRNA transcriptome in ZIKV infected Vero cells. We identified a total of 121 lncRNA genes that are differentially regulated at 48 hours post-infection. The majority of these genes are independently validated by reverse-transcription qPCR. A notable observation was that the lncRNAs, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and NEAT1 (Nuclear Paraspeckle Assembly Transcript 1), are down-regulated upon Zika viral infection. MALAT1 and NEAT1 are known as nuclear localized RNAs that regulate gene expression and cell proliferation. Protein-lncRNA interaction maps revealed that MALAT1 and NEAT1 share common interacting partners and form a larger network comprising of 71 cellular factors. ZIKV-mediated dysregulation of these two regulatory lncRNAs can alter the expression of respective target genes and associated biological functions, an important one being cell division. In conclusion, this investigation is the first to provide insight into the biological connection of lncRNAs and ZIKV which can be further explored for developing antiviral therapy and understanding fetal developmental processes.
An examination of the potential efficacy of high‐intensity fires for reversing woody encroachment in savannas
Authors: Smit Izak P. J. , Asner Gregory P. , Govender Navashni , Vaughn Nicholas R. , van Wilgen Brian W. 
Published: July 2016

Summary

Frequent fires are often proposed as a way of preventing woody encroachment in savannas, yet few studies have examined whether high‐intensity fires can effectively reverse woody encroachment.

We applied successive fire treatments to examine the effect of fire intensity on woody vegetation structure. The treatments included early dry season, low‐intensity fires; late dry season, higher‐intensity fires; and an unburnt control. We used pre‐ and post‐fire airborne LiDAR to compare vegetation structural changes brought about by fires of different intensity.

Early dry season fires were of lower intensity (1400–2100 kW m−1) than late dry season fires (2500–4300 kW m−1). The two treatments also differed in terms of fuel consumed, scorch heights and char heights, indicating that clear differences in fire intensity and severity were achieved.

After 4 years and two fire applications, relative woody cover increased by between 20 and 110% in different height categories following low‐intensity and control treatments and declined by between 3 and 70% following high‐intensity fire treatments. Declines were markedly higher following two repeated high‐intensity fires than following a high and then a moderate‐intensity fire. Because woody shrubs in lower height classes can recover rapidly, repeated high‐intensity fires would be needed to maintain lower cover.

Tall trees are often assumed to be unaffected by fires. However, we found that the rate of tree loss was directly related to fire intensity, where 36% of trees were lost following repeated high‐intensity fires, compared to 22% after a high‐ and then a moderate‐intensity fire and 6% after two low‐intensity fires (3% without fire).

Synthesis and applications. Using LiDAR data we show that high‐intensity fires can, at least in the short term, significantly reduce woody cover in South African savannas. The use of repeated high‐intensity fires simultaneously causes both a positive (reduction in cover of short shrubs) and a negative (loss of tall trees) outcome, and managers need to make trade‐offs when contemplating the use of fire intensity to achieve specific goals. One potential solution may be to repeatedly apply high‐intensity treatments to some areas, and not to others. This could generate a heterogeneous landscape where grasses become dominant and tall trees become scarce in some places, but in others, tall trees persist (or at least decline at slower rates), and shorter woody shrubs increase in dominance. Whether this would be acceptable, or practical, remains to be tested.
Avian pest control in vineyards is driven by interactions between bird functional diversity and landscape heterogeneity
Authors: Barbaro Luc , Rusch Adrien , Muiruri Evalyne W. , Gravellier Bastien , Thiery Denis , Castagneyrol Bastien 
Published: July 2016

Summary

Insectivorous birds are increasingly recognized for the crucial pest control services they provide to agroecosystems. While both the foraging activity and functional diversity of birds are enhanced by multiscale habitat heterogeneity, little is known about how these relationships may influence avian top‐down control of insects. Specifically, interactive effects of bird community structure and habitat heterogeneity on pest control across spatial scales have rarely been explored.

We sampled bird communities and measured avian predation on plasticine model prey, as a proxy for lepidopteran pest control, in 20 vineyards of south‐western France. Vineyards differed both in sward heterogeneity at the local scale and amount of surrounding semi‐natural habitats at the landscape scale. Functional diversity metrics and community‐weighted mean traits were computed for bird communities based on a species–trait table including diet, foraging method, nesting site, migration strategy, laying date, home range size, clutch size and body mass. We used mixed models to test for the interacting effects of habitat heterogeneity and bird functional diversity on avian predation rates of plasticine prey.

Contrary to expectations, bird functional diversity decreased with landscape‐scale heterogeneity, but was higher in vineyards managed with heterogeneous sward structures. In contrast, foliage‐gleaning insectivores were more abundant in landscapes supporting more semi‐natural habitats, suggesting an increase in their contribution to pest control along the landscape heterogeneity gradient. Accordingly, we found that avian predation on plasticine prey increased with bird functional evenness both in more heterogeneous vineyards at the local scale and in landscape mosaics supporting more semi‐natural habitats.

Synthesis and applications. Our study demonstrates that habitat heterogeneity at both local and landscape scales influenced avian insectivory in vineyard agroecosystems by interacting with bird community structure. It provides important insights for ecological intensification in vineyards, pointing out that management options need to be adapted to both the functional composition of local bird communities and landscape context. We suggest that both on‐field and off‐field management can be used to enhance natural pest control services provided by birds in vineyards, especially by favouring sward heterogeneity and patches of semi‐natural habitats within large vineyard stands at the landscape scale.
Landscape structure influences urban vegetation vertical structure
Authors: Mitchell Matthew G. E. , Wu Dan , Johansen Kasper , Maron Martine , McAlpine Clive , Rhodes Jonathan R. 
Published: July 2016

Summary

Vegetation vertical structure is important for biodiversity and ecosystem service provision. In cities, however, while variation in the spatial extent and distribution of vegetation has been widely investigated, vertical vegetation structure and its potential drivers have not. Understanding how vegetation vertical structure varies across cities and identifying the potential drivers of this variation will improve the management of urban vegetation for biodiversity and ecosystem services.

We used light detection and ranging (LiDAR) data to quantify the vertical structure of vegetation across Brisbane, Australia, at 1‐km2 and 1‐ha spatial scales and investigated how this structure varied in response to biophysical, socioeconomic, urban form and landscape structure variables.

Using model selection techniques, we found that landscape structure variables related to tree cover (tree cover extent and spatial configuration) best explained the vegetation vertical structure at both spatial scales. Biophysical and urban form variables were also important, but only in combination with landscape structure.

Mean vegetation vertical complexity, foliage projective cover and canopy height at a site all decreased as the treed proportion of the surrounding urban landscape decreased. In general, these vertical structure variables also increased where patches of vegetation were clustered together spatially.

Synthesis and applications. Using light detection and ranging (LiDAR) data and model selection techniques, we show that the extent and vertical structure of urban vegetation are not independent and that reduced extent and increased fragmentation of urban vegetation are associated with simplification of its vertical structure. If common, this relationship means that managing urban vegetation for biodiversity and ecosystem services should not focus solely on the amount of tree cover or green space present across cities, but also on identifying where interventions to improve vegetation vertical complexity are required. Our study provides important insights into where these locations may be in cities.
Comparison of insulin lispro mix 25 with insulin lispro mix 50 as insulin starter in Chinese patients with type 2 diabetes mellitus (CLASSIFY study): Subgroup analysis of a Phase 4 open‐label randomized trial
Authors: Su Qing , Liu Chao , Zheng Hongting , Zhu Jun , Li Peng Fei , Qian Lei , Yang Wen Ying 
Published: July 2016

AbstractBackgroundPremixed insulins are recommended starter insulins in Chinese patients after oral antihyperglycemic medication (OAM) failure. In the present study, we compared the efficacy and safety of insulin lispro mix 25 (LM25) twice daily (b.i.d.) and insulin lispro mix 50 (LM50) b.i.d. as a starter insulin regimen in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with OAMs.MethodsThe primary efficacy outcome in the present open‐label parallel randomized clinical trial was change in HbA1c from baseline to 26 weeks. Patients were randomized in a ratio of 1:  1 to LM25 (n = 80) or LM50 (n = 76). A mixed‐effects model with repeated measures was used to analyze continuous variables. The Cochran–Mantel–Haenszel test with stratification factor was used to analyze categorical variables.ResultsAt the end of the study, LM50 was more efficacious than LM25 in reducing mean HbA1c levels (least‐squares [LS] mean difference 0.48; 95 % confidence interval [CI] 0.22, 0.74; P < 0.001). More subjects in the LM50 than LM25 group achieved HbA1c targets of <7.0 % (72.4 % vs 45.0 %; P = 0.001) or ≤6.5 % (52.6 % vs 20.0 %; P < 0.001). Furthermore, LM50 was more effective than LM25 at reducing HbA1c in patients with baseline HbA1c, blood glucose excursion, and postprandial glucose greater than or equal to median levels (P ≤ 0.001). The rate and incidence of hypoglycemic episodes and increase in weight at the end of the study were similar between treatment groups.ConclusionsIn Chinese patients with T2DM, LM50 was more efficacious than LM25 as a starter insulin.
Investment Financing of Organizational Capital
Authors: Jiang Daniel X. , Luo Miao , Cai Jun 
Published: July 2016

AbstractWe identify that the cost of external capital and the frontier technology (FT) shock level are two important factors affecting external capital supply. We explore how they interact to affect the investment financing of organizational capital (OC). We show that the FT shock level has experienced a dramatic change from being counter‐cyclical before 1991 to pro‐cyclical after 1991. This structural break alters the OC investment sensitivities during the two sub‐periods. We find that the OC investment‐cash flow sensitivity is low and the OC investment‐q sensitivity is high only when the cost of external capital is low and the FT shock level is simultaneously high. These patterns are mainly driven by financially constrained firms. In addition, our empirical findings suggest that OC investments made during recessions when the FT shock level is also low generate higher productivity than in other conditions.