bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achieving Greater HIV Prevention Impact Through CDC's National HIV Behavioral Surveillance System
Authors: Wejnert Cyprian , Raymond Henry Fisher , Robbins Taylor , Prejean Joseph , Hall H. Irene , McCray Eugene , Paz-Bailey Gabriela ,   for the NHBS study group
Published: June 2017

Abstract:
The National HIV Behavioral Surveillance system was designed to monitor risk factors for HIV infection and HIV prevalence among individuals at higher risk for HIV infection, that is, sexually active men who have sex with men who attend venues, persons who recently injected drugs, and heterosexuals of low socioeconomic status living in urban areas. These groups were selected as priorities for behavioral surveillance because they represent the major HIV transmission routes and the populations with the highest HIV burden. Accurate data on the behaviors in these populations are critical for understanding trends in HIV infections and planning and evaluating effective HIV prevention activities. The articles in this supplement illustrate how National HIV Behavioral Surveillance data can be used to assess HIV risk behaviors, prevalence, and service utilization of the populations most affected by HIV in the United States and guide local and national high-impact prevention strategies to meet national HIV prevention goals.
Multicountry Validation of SAMBA - A Novel Molecular Point-of-Care Test for HIV-1 Detection in Resource-Limited Setting
Authors: Ondiek Johnson , Namukaya Zikulah , Mtapuri-Zinyowera Sekesai , Balkan Suna , Elbireer Ali , Ushiro Lumb Ines , Kiyaga Charles , Goel Neha , Ritchie Allyson , Ncube Patience , Omuomu Kenneth , Ndiege Kenneth , Kekitiinwa Adeodata , Mangwanya Douglas , Fowler Mary G. , Nadala Lou , Lee Helen 
Published: June 2017

Introduction:
Early diagnosis of HIV-1 infection and the prompt initiation of antiretroviral therapy are critical to achieving a reduction in the morbidity and mortality of infected infants. The Simple AMplification-Based Assay (SAMBA) HIV-1 Qual Whole Blood Test was developed specifically for early infant diagnosis and prevention of mother-to-child transmission programs implemented at the point-of-care in resource-limited settings.

Methods:
We have evaluated the performance of this test run on the SAMBA I semiautomated platform with fresh whole blood specimens collected from 202 adults and 745 infants in Kenya, Uganda, and Zimbabwe. Results were compared with those obtained with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 assay as performed with fresh whole blood or dried blood spots of the same subjects, and discrepancies were resolved with alternative assays.

Results:
The performance of the SAMBA and CAP/CTM assays evaluated at 5 laboratories in the 3 countries was similar for both adult and infant samples. The clinical sensitivity, specificity, positive predictive value, and negative predictive value for the SAMBA test were 100%, 99.2%, 98.7%, and 100%, respectively, with adult samples, and 98.5%, 99.8%, 99.7%, and 98.8%, respectively, with infant samples.

Discussion:
Our data suggest that the SAMBA HIV-1 Qual Whole Blood Test would be effective for early diagnosis of HIV-1 infection in infants at point-of-care settings in sub-Saharan Africa.
Meta-analysis of Cytometry Data Reveals Racial Differences in Immune Cells
Authors: Hu Zicheng , Jujjavarapu Chethan , Hughey Jacob J. , Andorf Sandra , Lee Hao-Chih , Gherardini Pier Federico , Spitzer Matthew H. , Dunn Patrick , Thomas Cristel G. , Campbell John , Wiser Jeff , Kidd Brian A. , Dudley Joel T. , Nolan Garry P. , Bhattacharya Sanchita , Butte Atul J. 
Published: June 2017

AbstractWhile meta-analysis has demonstrated increased statistical power and more robust estimations in studies, the application of this commonly accepted methodology to cytometry data has been challenging. Different cytometry studies often involve diverse sets of markers. Moreover, the detected values of the same marker are inconsistent between studies due to different experimental designs and cytometer configurations. As a result, the cell subsets identified by existing auto-gating methods cannot be directly compared across studies. We developed MetaCyto for automated meta-analysis of both flow and mass cytometry (CyTOF) data. By combining clustering methods with a silhouette scanning method, MetaCyto is able to identify commonly labeled cell subsets across studies, thus enabling meta-analysis. Applying MetaCyto across a set of 10 heterogeneous cytometry studies totaling 2926 samples enabled us to identify multiple cell populations exhibiting differences in abundance between White and Asian adults. Software is released to the public through GitHub (github.com/hzc363/MetaCyto).
Measuring Protein Binding to Lipid Vesicles by Fluorescence Cross-Correlation Spectroscopy
Authors: Krüger Daniela , Ebenhan Jan , Bacia Kirsten 
Published: June 2017

AbstractFluorescence Correlation Spectroscopy (FCS) has been previously used to investigate peptide and protein binding to lipid membranes, as it allows for very low amounts of sample, short measurement times and equilibrium binding conditions. Labeling only one of the binding partners however comes with certain drawbacks, as it relies on identifying binding events by a change in diffusion coefficient. Since peptide and protein aggregation can obscure specific binding and since non-stoichiometric binding necessitates the explicit choice of a statistical distribution for the number of bound ligands, we additionally label the liposomes and perform dual-color Fluorescence Cross-Correlation Spectroscopy (dcFCCS). We develop a theoretical framework showing that dcFCCS amplitudes allow calculation of the degree of ligand binding and the concentration of unbound ligand, leading to a binding model-independent binding curve. As the degree of labeling of the ligands does not factor into the measured quantities, it is permissible to mix labeled and unlabeled ligand, thereby extending the range of usable protein concentrations and accessible dissociation constantsKD. The total protein concentration, but not the fraction of labeled protein needs to be known. In this work, we apply our dcFCCS analysis scheme to Sar1p, a protein of the COPII complex, which binds ‘major-minor-mix’ liposomes. A Langmuir isotherm model yieldsKD= (2.1±1.1)μMas the single site dissociation constant. The dual-color FCCS framework presented here is highly versatile for biophysical analysis of binding interactions. It may be applied to many types of fluorescently labeled ligands and small diffusing particles, including nanodiscs and liposomes containing membrane protein receptors.
Segway 2.0: Gaussian mixture models and minibatch training
Authors: Chan Rachel C.W. , Libbrecht Maxwell W. , Roberts Eric G. , Noble William Stafford , Hoffman Michael M. 
Published: June 2017

AbstractSummarySegway performs semi-automated genome annotation, discovering joint patterns across multiple genomic signal datasets. We discuss a major new version of Segway and highlight its ability to model data with substantially greater accuracy. Major enhancements in Segway 2.0 include the ability to model data with a mixture of Gaussians, enabling capture of arbitrarily complex signal distributions, and minibatch training, leading to better learned parameters.Availability and ImplementationSegway and its source code are freely available for download athttps://segway.hoffmanlab.org. We have made available scripts (https://doi.org/10.5281/zenodo.802940) and datasets (https://doi.org/10.5281/zenodo.802907) for this paper’s analysis.Contactmichael.hoffman@utoronto.ca
Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map
Authors: Smith Ian , Greenside Peyton G , Wadden David , Tirosh Itay , Natoli Ted , Narayan Rajiv , Root David E , Golub Todd R , Subramanian Aravind , Doench John G 
Published: June 2017

AbstractThe application of RNA interference (RNAi) to mammalian cells has provided the means to perform phenotypic screens to determine the functions of genes. Although RNAi has revolutionized loss of function genetic experiments, it has been difficult to systematically assess the prevalence and consequences of off-target effects. The Connectivity Map (CMAP) represents an unprecedented resource to study the gene expression consequences of expressing short hairpin RNAs (shRNAs). Analysis of signatures for over 13,000 shRNAs applied in 9 cell lines revealed that miRNA-like off-target effects of RNAi are far stronger and more pervasive than generally appreciated. We show that mitigating off-target effects is feasible in these datasets via computational methodologies to produce a Consensus Gene Signature (CGS). In addition, we compared RNAi technology to clustered regularly interspaced short palindromic repeat (CRISPR)-based knockout by analysis of 373 sgRNAs in 6 cells lines, and show that the on-target efficacies are comparable, but CRISPR technology is far less susceptible to systematic off-target effects. These results will help guide the proper use and analysis of loss-of-function reagents for the determination of gene function.
ESCRT-III acts in scissioning new peroxisomes from the ER
Authors: Mast Fred D. , Herricks Thurston , Strehler Kathleen M. , Miller Leslie R. , Saleem Ramsey A. , Rachubinski Richard A. , Aitchison John D. 
Published: June 2017

AbstractDynamic control of peroxisome proliferation is integral to the peroxisome’s many functions. A breakdown in the ability of cells to form peroxisomes is linked to many human health issues, including defense against infectious agents, cancer, aging, heart disease, obesity and diabetes, and forms the basis of a spectrum of peroxisomal genetic disorders that cause severe neuropathologies. The ER serves as a source for preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and to support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. Here we show that the evolutionarily ancient endosomal sorting complexes required for transport (ESCRT)-III are peroxisome biogenesis factors that function to cleave PPVs budding from the ER into the cytosol. Using comprehensive morphological and genetic assays of peroxisome formation and function we find that absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay we show that ESCRT-III proteins Vps20 and Snf7 are required to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and towards the cytosol, a finding that has important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.
Combining global tree cover loss data with historical national forest-cover maps to look at six decades of deforestation and forest fragmentation in Madagascar
Authors: Vieilledent Ghislain , Grinand Clovis , Rakotomalala Fety A. , Ranaivosoa Rija , Rakotoarijaona Jean-Roger , Allnutt Thomas F. , Achard Frédéric 
Published: June 2017

AbstractThe island of Madagascar has a unique biodiversity, mainly located in the tropical forests of the island. This biodiversity is highly threatened by anthropogenic deforestation. Existing historical forest maps at national level are scattered and have substantial gaps which prevent an exhaustive assessment of long-term deforestation trends in Madagascar. In this study, we combined historical national forest cover maps (covering the period 1953-2000) with a recent global annual tree cover loss dataset (2001-2014) to look at six decades of deforestation and forest fragmentation in Madagascar (from 1953 to 2014). We produced new forest cover maps at 30 m resolution for the year 1990 and annually from 2000 to 2014 over the full territory of Madagascar. We estimated that Madagascar has lost 44% of its natural forest cover over the period 1953-2014 (including 37% over the period 1973-2014). Natural forests cover 8.9 Mha in 2014 (15% of the national territory) and include 4.4 Mha (50%) of moist forests, 2.6 Mha (29%) of dry forests, 1.7 Mha of spiny forests (19%) and 177,000 ha (2%) of mangroves. Since 2005, the annual deforestation rate has progressively increased in Madagascar to reach 99,000 ha/yr during 2010-2014 (corresponding to a rate of 1.1%/yr). Around half of the forest (46%) is now located at less than 100 m from the forest edge. Our approach could be replicated to other developing countries with tropical forest. Accurate forest cover change maps can be used to assess the effectiveness of past and current conservation programs and implement new strategies for the future. In particular, forest maps and estimates can be used in the REDD+ framework which aims at “Reducing Emissions from Deforestation and forest Degradation” and for optimizing the current protected area network.
Decoding the orientation of contrast edges from MEG evoked and induced responses
Authors: Pantazis Dimitrios , Fang Mingtong , Qin Sheng , Mohsenzadeh Yalda , Li Quanzheng , Cichy Radoslaw Martin 
Published: June 2017

1AbstractVisual gamma oscillations have been proposed to subserve perceptual binding, but their strong modulation by diverse stimulus features confounds interpretations of their precise functional role. Overcoming this challenge necessitates a comprehensive account of the relationship between gamma responses and stimulus features. Here we used multivariate pattern analyses on human MEG data to characterize the relationships between gamma responses and one basic stimulus feature, the orientation of contrast edges. Our findings confirmed we could decode orientation information from induced responses in two dominant frequency bands at 24-32 Hz and 50-58 Hz. Decoding was higher for cardinal than oblique orientations, with similar results also obtained for evoked MEG responses. In contrast to multivariate analyses, orientation information was mostly absent in univariate signals: evoked and induced responses in early visual cortex were similar in all orientations, with only exception an inverse oblique effect observed in induced responses, such that cardinal orientations produced weaker oscillatory signals than oblique orientations. Taken together, our results showed multivariate methods are well suited for the analysis of gamma oscillations, with multivariate patterns robustly encoding orientation information and predominantly discriminating cardinal from oblique stimuli.
Principles that govern competition or co-existence in Rho-GTPase driven polarization
Authors: Chiou Jian-geng , Elston Timothy C. , Witelski Thomas P. , Schaeffer David G. , Lew Daniel J. 
Published: June 2017

AbstractRho-GTPases are master regulators of polarity establishment and cell morphology. Positive feedback enables concentration of Rho-GTPases into clusters at the cell cortex, from where they regulate the cytoskeleton. Different cell types reproducibly generate either one (e.g. the front of a migrating cell) or several clusters (e.g. the multiple dendrites of a neuron), but the mechanistic basis for uni-polar or multi-polar outcomes is unclear. The design principles of Rho-GTPase circuits are captured by reaction-diffusion models based on conserved aspects of Rho-GTPase biochemistry. Some such models display rapid winner-takes-all competition between clusters, yielding a unipolar outcome. Other models allow prolonged co-existence of clusters. We derive a “saturation rule” general to all relevant models that governs the timescale of competition, and thereby predicts whether the system will generate uni-polar or multi-polar outcomes. We suggest that the saturation rule is a fundamental property of the Rho-GTPase polarity machinery, regardless of the specific feedback mechanism.
Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions
Authors: Dalin Martin G. , Katabi Nora , Persson Marta , Lee Ken-Wing , Makarov Vladimir , Desrichard Alexis , Walsh Logan A. , West Lyndsay , Nadeem Zaineb , Ramaswami Deepa , Havel Jonathan J. , Kuo Fengshen , Chadalavada Kalyani , Nanjangud Gouri J. , Riaz Nadeem , Ho Alan L , Antonescu Cristina R. , Ghossein Ronald , Stenman Göran , Chan Timothy A. , Morris Luc G.T. 
Published: June 2017

AbstractMyoepithelial carcinoma (MECA) is an aggressive type of salivary gland cancer with largely unknown molecular features. MECA may arise de novo or result from oncogenic transformation of a pre-existing pleomorphic adenoma (MECA ex-PA). We comprehensively analyzed the molecular alterations in MECA with integrated genomic analyses. We identified a low mutational load (0.5/MB), but a high prevalence of fusion oncogenes (28/40 tumors; 70%). We foundFGFR1-PLAG1in 7 (18%) cases, and the novelTGFBR3-PLAG1fusion in 6 (15%) cases.TGFBR3-PLAG1was specific for MECA de novo tumors or the malignant component of MECA ex-PA, was absent in 723 other salivary gland tumors, and promoted a tumorigenic phenotype in vitro. We discovered other novelPLAG1fusions, includingND4-PLAG1,which is an oncogenic fusion between mitochondrial and nuclear DNA. One tumor harbored anMSN-ALKfusion, which was tumorigenic in vitro, and targetable with ALK inhibitors. Certain gene fusions were predicted to result in neoantigens with high MHC binding affinity. A high number of copy number alterations was associated with poorer prognosis. Our findings indicate that MECA is a fusion-driven disease, nominateTGFBR3-PLAG1as a hallmark of MECA, and provide a framework for future steps of diagnostic and therapeutic research in this lethal cancer.
Multiple conserved cell adhesion protein interactions mediate neural wiring of a sensory circuit inC. elegans
Authors: Kim Byunghyuk , Emmons Scott W. 
Published: June 2017

ABSTRACTNervous system function relies on precise synaptic connections. A number of widely-conserved cell adhesion proteins are implicated in cell recognition between synaptic partners, but how these proteins act as a group to specify a complex neural network is poorly understood. Taking advantage of known connectivity inC. elegans, we identified and studied cell adhesion genes expressed in three interacting neurons in the mating circuits of the adult male. Two interacting pairs of cell surface proteins independently promote fasciculation between sensory neuron HOA and its postsynaptic target interneuron AVG: BAM-2/neurexin-related in HOA binds to CASY-1/calsyntenin in AVG; SAX-7/L1CAM in sensory neuron PHC binds to RIG-6/contactin in AVG. A third, basal pathway results in considerable HOA-AVG fasciculation and synapse formation in the absence of the other two. The features of this multiplexed mechanism help to explain how complex connectivity is encoded and robustly established during nervous system development.
Renewed diversification following Miocene landscape turnover in a Neotropical butterfly radiation
Authors: Chazot Nicolas , Willmott Keith R. , Lamas Gerardo , Freitas André V. L. , Piron-Prunier Florence , Arias Carlos F. , Mallet Jim , De-Silva Donna Lisa , Elias Marianne 
Published: June 2017

Abstract“This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100032)”The Neotropical region has experienced a dynamic landscape evolution throughout the Miocene, with the large wetland Pebas occupying western Amazonia until 11-8 my ago and continuous uplift of the Andes mountains along the western edge of South America. Although the complex dynamics between the Andes and Amazonia may have strongly affected the trajectory of Neotropical biodiversity, there is little evidence for such an influence from time-calibrated phylogenies of groups that diversified during this period. Here, we generate one of the most comprehensive time-calibrated molecular phylogenies of a group of Neotropical insects: the butterfly tribe Ithomiini. Our tree includes 340 species (87% of extant species), spanning 26 million years of diversification in the Neotropics. We investigate temporal and spatial patterns of diversification, focusing on the influence of Miocene landscape tranformations on the dynamics of speciation, extinction and biotic interchanges at the Amazonia/Andes interface. We find that Ithomiini likely began diversifying at the interface between the Andes and the Amazonia around 26.4 my ago. Five subtribes with a very low extant diversity started diversifying early in western Amazonia, but a rapid decrease in diversification rate due to increased extinction rate between 20 and 10 my ago suggests a negative impact of the Pebas wetland system on these early lineages. By contrast, the clade containing the five most species-rich subtribes (85% of extant species) was characterized by a high, positive net diversification rate. This clade diversified exclusively in the Central Andes from 20 to 10 my ago. After the demise of the Pebas system (11-8 my ago), we found a sudden increase of interchanges with the Northern Andes and Amazonia, followed by local diversification, which led to a substantial renewal of diversification. In general, ecological turnovers throughout the Miocene strongly determined the dynamics of speciation, and extinction and interchanges, and appear as a key driving force shaping the region’s current extraordinary biodiversity.
aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda inDrosophilaneuroblasts
Authors: Hannaford Matthew , Ramat Anne , Loyer Nicolas , Januschke Jens 
Published: June 2017

SUMMARYCell fate generation can rely on the unequal distribution of molecules during progenitor cell division in the nervous system of vertebrates and invertebrates. Here we address asymmetric fate determinant localization in the developingDrosophilanervous system, focussing on the control of asymmetric Miranda distribution in larval neuroblasts. We used live imaging of neuroblast polarity reporters at endogenous levels of expression to address Miranda localization during the cell cycle. We reveal that the regulation and dynamics of cortical association of Miranda in interphase and mitosis are different. In interphase Miranda binds directly to the plasma membrane. At the onset of mitosis, Miranda is phosphorylated by aPKC and displaced from the PM. After nuclear envelope breakdown asymmetric localization of Miranda requires actomyosin activity. Therefore, Miranda phosphorylation by aPKC and differential binding to the actomyosin network are required at distinct phases of the cell cycle to polarize fate determinant localization.