bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in Number and Composition of Sex Partners Among Men Who Have Sex With Men in the United States, National HIV Behavioral Surveillance, 2008–2014
Authors: Chapin-Bardales Johanna , Rosenberg Eli S. , Sullivan Patrick S. , Jenness Samuel M. , Paz-Bailey Gabriela ,   for the NHBS Study Group
Published: March 2019

Background:
Social and legal acceptance of long-term same-sex partnerships in the United States has increased over the past decade which may impact sexual partnering among men who have sex with men (MSM). Identifying whether and how partnering trends have evolved at a national level could improve understanding of HIV transmission and prevention among MSM partnerships.

Methods:
We used Centers for Disease Control and Prevention's National HIV Behavioral Surveillance data (2008, 2011, and 2014) to study trends in the number and partner type composition (main/casual) of male sex partners among US MSM. Changes over time were assessed in Poisson regression models with the link function tailored to the count and binary outcomes.

Results:
The mean total number of partners in the past year increased, while the mean number of main partners remained stable. The percentage of MSM with both main and casual partners increased, and we observed a shift from having ≥1 main and 0 casual partners to having ≥1 main and ≥2 casual partners. Condomless anal sex in the past year increased regardless of partner composition.

Discussion:
Findings suggest casual partnering among MSM has increased in recent years, including among those with ≥1 main partners. Both partner-based and individual prevention programs remain critical to reaching MSM.
Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation
Authors: Vo Ashley A. , Aubert Olivier , Haas Mark , Huang Edmund , Zhang Xiaohai , Choi Jua , Peng Alice , Najjar Reiad , Sethi Supreet , Ammerman Nori , Lim Kathlyn , Jordan Stanley C. 
Published: March 2019

Background.
Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA− at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA− patients.

Methods.
From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA− = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant.

Results.
Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/− (n=19), DSA−/+ (n=10), and DSA−/− (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/− (11%), and DSA−/− (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar.

Conclusions.
Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.
Two fiber pathways connecting amygdala and prefrontal cortex in humans and monkeys
Authors: Folloni Davide , Sallet Jérôme , Khrapitchev Alexandre A. , Sibson Nicola R. , Verhagen Lennart , Mars Rogier B. 
Published: March 2019

AbstractThe interactions between amygdala and prefrontal cortex are pivotal to many neural processes involved in learning, decision-making, emotion, and social regulation. The broad functional role of amygdala-prefrontal interplay may reflect the diversity of its anatomical connections. Little, however, is known of the structural wiring linking amygdala and prefrontal cortex in humans. Using diffusion imaging techniques, we reconstructed connections between amygdala, anterior temporal and prefrontal cortex in human and macaque brains. First, by studying macaques we were able to assess which aspects of connectivity known from tracer studies could be identified with diffusion imaging. Second, by comparing diffusion imaging results in humans and macaques we were able to estimate amygdala-prefrontal connection patterns in humans and compare them with those in the monkey. We observed a prominent and well-preserved bifurcation of connections between amygdala and frontal lobe into two fiber networks – an amygdalofugal path and an uncinate fascicle path – in both species.
Epstein-Barr virus inactivates the transcriptome and disrupts the chromatin architecture of its host cell in the first phase of lytic reactivation
Authors: Buschle Alexander , Mrozek-Gorska Paulina , Krebs Stefan , Blum Helmut , Cernilogar Filippo M. , Schotta Gunnar , Pich Dagmar , Straub Tobias , Hammerschmidt Wolfgang 
Published: March 2019

ABSTRACTEpstein-Barr virus (EBV), a herpes virus also termed HHV 4 and the first identified human tumor virus, establishes a stable long-term latent infection in human B cells, its preferred host. Upon induction of EBV’s lytic phase the latently infected cells turn into a virus factory, a process, that is governed by EBV. In the lytic, productive phase all herpesviruses ensure the efficient induction of all lytic viral genes to produce progeny, but certain of these genes also repress the ensuing antiviral responses of the virally infected host cells, regulate their apoptotic death or control the cellular transcriptome. We now find that EBV causes previously unknown massive and global alterations in the chromatin of its host cell upon induction of the viral lytic phase and prior to the onset of viral DNA replication. The viral initiator protein of the lytic cycle, BZLF1, binds to >105binding sites with different sequence motifs in cellular chromatin and in a concentration dependent manner. Concomitant with DNA binding, silent chromatin opens locally as shown by ATAC-seq experiments, while previously wide-open cellular chromatin becomes inaccessible on a global scale within hours. While viral transcripts increase drastically, the induction of the lytic phase results in a massive reduction of cellular transcripts and a loss of chromatin-chromatin interactions of cellular promoters with their distal regulatory elements as shown in Capture-C experiments. Our data document that EBV’s lytic cycle induces discrete early processes that disrupt the architecture of host cellular chromatin and repress the cellular epigenome and transcriptome likely supporting the efficientde novosynthesis of this herpesvirus.
A stable pollination environment limits current but not potential evolution of floral traits
Authors: Castellanos Maria Clara , Montero-Pau Javier , Ziarsolo Peio , Blanca Jose Miguel , Cañizares Joaquin , Pausas Juli G. 
Published: March 2019

AbstractThe vast variation in floral traits at a macroevolutionary level is often interpreted as the result of adaptation to pollinators. However, studies in wild populations often find no evidence of pollinator-mediated selection on flowers. Evolutionary theory predicts this could be the outcome of long periods of stasis under stable conditions, followed by shorter periods of pollinator change that provide selection for innovative phenotypes. We asked if periods of stasis are caused by stabilizing selection, absence of other forms of selection on floral traits, or by low trait ability to respond even if selection is present. We studiedUlex parviflorus, a plant predominantly pollinated by one bee species across its range. We measured heritability and evolvability of floral traits, using genome-wide molecular relatedness in a large wild population, and combined this with estimates of selection on the same individuals. We found evidence for both stabilizing selection and low trait heritability as explanations for stasis in flowers. The area of the standard petal is under stabilizing selection, but the variability observed in the wild is not heritable. A separate trait, floral weight, in turn presents high heritability, but is not currently under selection. We show how a stable environment can lead to a lack of evolutionary change, yet maintain heritable variation to respond to future selection pressures.
Identification and classification of hubs in miRNA target gene networks in human neural stem/progenitor cells following Japanese encephalitis virus infection
Authors: Mukherjee Sriparna , Akbar Irshad , Bhagat Reshma , Hazra Bibhabasu , Bhattacharyya Arindam , Seth Pankaj , Roy Dipanjan , Basu Anirban 
Published: March 2019

AbstractMicro RNA dysregulation is observed in many viral diseases. RNA viruses modulate host miRNA machinery for their own benefit. JEV, a neurotropic RNA virus has been reported to manipulate several miRNAs in neuron or microglia. However, no report indicates a complete sketch of the miRNA profile of NSPCs contributing to viral persistence; hence being focused in our current study. We performed a miRNA array of 84 miRNAs in human neuronal progenitor cell line and primary neural precursor cells isolated from aborted foetus. Several fold down-regulation of hsa-miR-9-5p, hsa-miR-22-3p, hsa-miR-124-3p and hsa-miR-132-3p were found in both of the cells. Subsequently, we screened for the target genes of these miRNAs and looked for the important biological pathways the genes significantly regulate. Then we sorted out the target genes which are involved in two or more than two pathways. We constructed a protein-protein interaction (PPI) network of the miRNA target genes based on their interaction patterns. A binary adjacency matrix for each gene network was prepared. Different modules or communities were identified in those networks using community detection algorithms. Mathematically, we identified the hub genes by analyzing their degree centrality and participation co-efficient in the network. The hub genes were classified either as provincial (P<0.4) or connector hubs (P>0.4). We validated the expression of hub genes in both cell line and primary cells through qRT-PCR post JEV infection and respective miR-mimic transfection. Taken together, our findings highlight the importance of specific target gene networks of miRNAs affected by JEV infection in NSPCs.ImportanceJEV damages the neural stem/progenitor cell population of mammalian brain. However, JEV induced alteration in miRNA expression pattern of the cell population remains an open question, hence warrants our present study. In this study, we specifically address the down-regulation of four miRNAs and we prepared a protein-protein interaction network of miRNA target genes. We identified two types of hub genes in the PPI network namely connector hubs and provincial hubs. These two types of miRNA target hub genes critically influence the participation strength in the networks and thereby significantly influence up and down regulation in several key biological pathways. Computational analysis of the PPI networks identifies key protein interactions and hubs in those modules which opens up the possibility of precise identification and classification of host factors for viral infection in NSPCs and how RNA viruses modulate host miRNA machinery for their own benefit post JEV infection to the cells.
Effect of Antimicrobial Stewardship with Rapid MALDI-TOF Identification and Vitek 2 Antimicrobial Susceptibility Testing on Hospitalization Outcome
Authors: Cavalieri Stephen J , Kwon Seunghyug , Vivekanandan Renuga , Ased Sumaya , Carroll Cassara , Anthone Jennifer , Schmidt David , Baysden Maddy , Destache Christopher J 
Published: March 2019

AbstractIntroductionRapid organism identification (ID) and antimicrobial susceptibility testing (AST) along with antibiotic stewardship (ASP) are critical to appropriate treatment. We sought to capture time for bacterial culture and initiation of appropriate therapy for patients, from 2017 (without MALDI-TOF/Vitek 2 and ASP) and 2018 (with MALDI-TOF/Vitek 2 and ASP).MethodsEligible patients admitted to our hospital with a positive sputum, blood, or urine culture. Sequential patients were retrospectively obtained from March 1 to May 31, 2017. Seventy-seven patients from 2017 were compared to 77 patients from 2018. A time-in-motion study was performed to compare time to identification (ID), AST results, and ASP team intervention for the two periods. Data were entered into SPSS (ver 25) for analysis. Results are reported as mean (± SD) or percentage.ResultsTime to organism ID was significantly faster in 2018 (2018 24.9 ± 14.4, 2017 33.8 ± 17 h, p=0.001). Time to AST results was also significantly faster for patients in 2018 compared to 2017 (18.2 ± 14 compared to 28.5 ± 14.9 h, p<0.001). ASP team recommended significantly more adjustments to empiric antimicrobial therapy in 2018 (28% of 2018 vs. 2% in 2017, p< 0.001). Length of hospital stay was significantly shorter in 2018 compared to 2017 (2018 10.7 ± 11.1 days and 2017 15.5 ± 18.1 days, p=0.05).ConclusionsUse of MALDI-TOF/Vitek 2 leads to an average 21.5 h faster ID and AST results that can be acted upon by ASP for appropriate antimicrobial recommendations.
Protein Structural Information and Evolutionary Landscape by In Vitro Evolution
Authors: Fantini Marco , Lisi Simonetta , De Los Rios Paolo , Cattaneo Antonino , Pastore Annalisa 
Published: March 2019

AbstractProtein structure is tightly inter-twined with function according to the laws of evolution. Understanding how structure determines function has been the aim of structural biology for decades. Here, we have wondered instead whether it is possible to exploit the function for which a protein was evolutionary selected to gain information on protein structure and on the landscape explored during the early stages of molecular and natural evolution. To answer to this question, we developed a new methodology, which we named CAMELS (Coupling Analysis by Molecular Evolution Library Sequencing), that is able to obtain the in vitro evolution of a protein from an artificial selection based on function. We were able to observe with CAMELS many features of the TEM-1 beta lactamase local fold exclusively by generating and sequencing large libraries of mutational variants. We demonstrated that we can, whenever a functional phenotypic selection of a protein is available, sketch the structural and evolutionary landscape of a protein without utilizing purified proteins, collecting physical measurements or relying on the pool of natural protein variants.
The Zymoseptoria tritici ORFeome: a functional genomics community resource
Authors: Chaudhari Yogesh , Cairns Timothy C. , Sidhu Yaadwinder , Attah Victoria , Thomas Graham , Csukai Michael , Talbot Nicholas J. , Studholme David J. , Haynes Ken 
Published: March 2019

AbstractLibraries of protein-encoding sequences can be generated by identification of open reading frames (ORFs) from a genome of choice that are then assembled into collections of plasmids termed ORFeome libraries. These represent powerful resources to facilitate functional genomic characterization of genes and their encoded products. Here, we report the generation of an ORFeome for Zymoseptoria tritici, which causes the most serious disease of wheat in temperate regions of the world. We screened the genome of strain IP0323 for high confidence gene models, identifying 4075 candidates from 10,933 predicted genes. These were amplified from genomic DNA, cloned into the Gateway® Entry Vector pDONR207, and sequenced, providing a total of 3022 quality-controlled plasmids. The ORFeome includes genes predicted to encode effectors (n = 410) and secondary metabolite biosynthetic proteins (n = 171), in addition to genes residing at dispensable chromosomes (n= 122), or those that are preferentially expressed during plant infection (n = 527). The ORFeome plasmid library is compatible with our previously developed suite of Gateway® Destination vectors, which have various combinations of promoters, selection markers, and epitope tags. The Z. tritici ORFeome constitutes a powerful resource for functional genomics, and offers unparalleled opportunities to understand the biology of Z. tritici.
Synonymous SNP: Rare versus frequent codon can cause Phenotypic changes in the human genome
Authors: Srivastav Ashu 
Published: March 2019

ABSTRACTSince the initial sequencing of the human genome, many projects are underway to understand the effects of genetic variation and phenotypic changes between individuals. Single nucleotide polymorphisms (SNPs) are an increasingly important tool for genetic and biomedical research. Synonymous Single Nucleotide Polymorphisms (sSNP) is an important source of human genome variability. It does not produce altered coding sequences therefore expected not to change the function of protein in which they occur. Examination of synonymous SNPs that change a rarely used codon into a frequently used one or vice versa may help in predicting their phenotypic effect on the individual carrying the change. Detail information of Human Synonymous Single-nucleotide-polymorphism may accelerate the research of personalized medicine since it has the crucial impact in the field of non-synonymous SNP.
Deletion of the creatine transporter gene in neonatal, but not adult, mice lead to cognitive deficits
Authors: Udobi Kenea C. , Delcimmuto Nicholas , Kokenge Amanda N. , Abdulla Zuhair I. , Perna Marla K. , Skelton Matthew R. 
Published: March 2019

AbstractCreatine (Cr) is a guanidino compound that provides readily-available phosphate pools for the regeneration of spent ATP. The lack of brain Cr causes moderate to severe intellectual disability, language impairment, and epilepsy. The most prevalent cause of Cr deficiency are mutations in the X-linkedSLC6A8(Creatine transporter; CrT) gene, known as CrT deficiency (CTD). There are no current treatments for CTD and the mechanisms that underlie the cognitive deficits are poorly understood. One of the most critical areas that need to be addressed is if Cr is necessary for brain development. To address this concern, theSlc6a8gene was knocked out in either neonatal (postnatal day (P)5) or adult (P60) mice. The P5 knockout mice showed deficits in the Morris water maze and novel object recognition, while there were no deficits in P60 knockout mice. Interestingly, the P5 knockout mice showed hyperactivity during the dark phase; however, when examining control mice, the effect was due to the administration of tamoxifen from P5-10. Taken together, the results of this study show that Cr is necessary during periods of brain development involved in spatial and object learning. This study also highlights the continued importance of using proper control groups for behavioral testing.Take-home messageThe learning and memory deficits seen in Slc6a8-deficient mice are likely due to the developmental loss of Cr.
Intrinsic Disorder and Degeneracy in Molecular Scale Organization of Biological Membrane
Authors: Iyer Sahithya S. , Srivastava Anand 
Published: March 2019

AbstractThe scale-rich spatiotemporal organization in biological membrane dictates the “molecular encounter” and in turn the larger scale biological processes such as molecular transport, trafficking and cellular signalling. In this work, we explore the degeneracy in lateral organization in lipid bilayer systems from the perspective of energy landscape theory. Our analysis on molecular trajectories show that bilayers with lipids havingin-vivocharacteristics have a highly frustrated energy landscape as opposed to a funnel-like energy landscape inin-vitrosystems. Lattice evolution simulations, with Hamiltonian trained from atomistic trajectories using lipids topology and non-affine displacement measures to characterize the extent of order-disorder in the bilayer, show that the inherent frustration inin-vivolike systems renders them with the ability to access a wide range of nanoscale patterns with equivalent energy penalty. We posit that this structural degeneracy could provide for a larger repository to functionally important molecular organization inin-vivosettings.
Characterizing neuronal synaptic transmission using stochastic hybrid systems
Authors: vahdat Zahra , Xu Zikai , Singh Abhyudai 
Published: March 2019

AbstractAction potential-triggered release of neurotransmitters at chemical synapses forms the key basis of communication between two neurons. To quantify the stochastic dynamics of the number of neurotransmitters released, we investigate a model where neurotransmitter-filled vesicles attach to a finite number of docking sites in the axon terminal, and are subsequently released when the action potential arrives. We formulate the model as a Stochastic Hybrid System (SHS) that combines three key noise mechanisms: random arrival of action potentials, stochastic refilling of docking sites, and probabilistic release of docked vesicles. This SHS representation is used to derive exact analytical formulas for the mean and noise (as quantified by Fano factor) in the number of vesicles released per action potential. Interestingly, results show that in relevant parameter regimes, noise in the number of vesicles released is sub-Poissonian at low frequencies, super-Poissonian at intermediate frequencies, and approaches a Poisson limit at high frequencies. In contrast, noise in the number of neurotransmitters in the synaptic cleft is always super-Poissonian, but is lowest at intermediate frequencies. We further investigate changes in these noise properties for non-Poissonian arrival of action potentials, and when the probability of release is frequency dependent. In summary, these results provide the first glimpse into synaptic parameters not only determining the mean synaptic strength, but also shaping its stochastic dynamics that is critical for information transfer between neurons.
Dissecting the cognitive phenotype of post-stroke fatigue using drift diffusion modeling of sustained attention
Authors: Ulrichsen Kristine M. , Alnæs Dag , Kolskår Knut K. , Richard Geneviève , Sanders Anne-Marthe , Dørum Erlend S. , Ihle-Hansen Hege , Pedersen Mads L. , Tornås Sveinung , Nordvik Jan E. , Westlye Lars T. 
Published: March 2019

AbstractPost-stroke fatigue (PSF) is a prevalent symptom among stroke patients. Its symptom burden is pervasive, persistent and associated with poor rehabilitation outcomes, though its mechanisms are poorly understood. Many patients with PSF experience cognitive difficulties, but studies aiming to identify cognitive correlates of PSF have been largely inconclusive. In contrast to conventional neuropsychological assessment, computational modeling of behavioral data allows for a dissection of specific cognitive processes associated with group or individual differences in fatigue. With the aim to zero in on the cognitive phenotype of PSF, we fitted a hierarchical drift diffusion model (hDDM) to response time data from Attention Network Test (ANT) obtained from 53 chronic stroke patients. The computational model accurately reconstructed the individual level response time distributions in the different ANT conditions, and hDDM regressions identified an interaction between trial number and fatigue symptoms on non-decision time, intuitively indicating that the cognitive phenotype of fatigue entails an increased vulnerability to sustained attentional effort. These novel results demonstrate the significance of considering the sustained nature of cognitive effort when defining the cognitive phenotype of post-stroke fatigue, and suggest that the use of computational approaches offers a further characterization of the specific processes underlying observed behavioral differences.