bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive CD8β depletion does not prevent control of viral replication or protection from challenge in macaques chronically infected with a live attenuated simian immunodeficiency virus
Authors: Sutton Matthew S. , Ellis-Connell Amy , Balgeman Alexis J. , Barry Gabrielle , Weiler Andrea M. , Hetzel Scott J. , Zhou Yan , Kilby Annie , Mason Rosemarie D. , Biris Kristin K. , Mascola John R. , Sullivan Nancy J. , Roederer Mario , Friedrich Thomas C. , O’Connor Shelby L. 
Published: April 2019

AbstractWe evaluated the contribution of CD8αβ+ T cells on control of live-attenuated simian immunodeficiency virus (LASIV) replication during chronic infection and subsequent protection from pathogenic SIV challenge. Unlike previous reports with a CD8α-specific depleting monoclonal antibody (mAb), the CD8β-specific mAb CD8β255R1 selectively depleted CD8αβ+ T cells without also depleting non-CD8+ T cell populations that express CD8α, such as natural killer (NK) cells and γδ T cells. Following infusion with CD8β255R1, plasma viremia transiently increased coincident with declining peripheral CD8αβ+ T cells. Interestingly, plasma viremia returned to pre-depletion levels even when peripheral CD8αβ+ T cells did not. Although depletion of CD8αβ+ T cells in the lymph node (LN) was incomplete, frequencies of these cells were three-fold lower (p=0.006) in animals that received CD8β255R1 compared to control IgG. It is possible that these residual SIV-specific CD8αβ+ T cells may have contributed to suppression of viremia during chronic infection. We also determined whether infusion of CD8β255R1 in the LASIV-vaccinated animals increased their susceptibility to infection following intravenous challenge with pathogenic SIVmac239. We found that 7/8 animals infused with CD8β255R1, and 3/4 animals infused with the control IgG, were resistant to SIVmac239 infection. These results suggest that infusion with CD8β255R1 did not eliminate the protection afforded to LASIV vaccination. This provides a comprehensive description of the impact of CD8β255R1 infusion on the immunological composition of the host, when compared to an isotype matched control IgG, while showing that the control of LASIV viremia and protection from challenge can occur even after CD8β255R1 administration.ImportanceStudies of SIV-infected macaques that deplete CD8+ T cellsin vivowith monoclonal antibodies have provided compelling evidence for their direct antiviral role. These studies utilized CD8α-specific mAbs that target both the major (CD8αβ+) and minor (CD8αα+) populations of CD8+ T cells, but additionally deplete non-CD8+ T cell populations that express CD8α, such as NK cells and γδ T cells. In the current study, we administered the CD8β-specific depleting mAb CD8β255R1 to cynomolgus macaques chronically infected with a LASIV to selectively deplete CD8αβ+ T cells without removing CD8αα+ lymphocytes. We evaluated the impact on control of virus replication and protection from pathogenic SIVmac239 challenge. These results underscore the utility of CD8β255R1 for studying the direct contribution of CD8αβ+ T cells in various disease states.
miR-9 mediated noise optimization of the her6 oscillator is needed for cell state progression in the Zebrafish hindbrain
Authors: Soto Ximena , Biga Veronica , Kursawe Jochen , Lea Robert , Doostdar Parnian , Papalopulu Nancy 
Published: April 2019

AbstractUltradian oscillations of key transcription factors, such as members of the Hes family, are thought to be important in Neural Progenitor Cell (NPC) maintenance and miR-9 acts as a tuner of these oscillations in vitro. However, the existence and the role of such dynamic oscillatory expression in vivo is poorly understood. Here, we have generated a Zebrafish CRISPR knock-in Her6::venus fusion (Hes1 orthologue) to study endogenous dynamic gene expression in the embryonic hindbrain. We show that Her6 undergoes a transition from irregular, noisy, fluctuations to periodic oscillations as neurogenesis proceeds. In the absence of miR-9 input, noise in the Her6 oscillator increases and NPCs are unable to transit away from an intermediary state where they co-express progenitor and early differentiation markers. Thus, Her6 oscillations are facilitated by noise optimization mediated by miR-9 and this noise-tuning step is functionally important for cells to transition to differentiation.
Functional Territories of Human Dentate Nucleus
Authors: Guell Xavier , D’Mello Anila M , Hubbard Nicholas A , Romeo Rachel R , Gabrieli John DE , Whitfield-Gabrieli Susan , Schmahmann Jeremy D , Anteraper Sheeba Arnold 
Published: April 2019

ABSTRACTAnatomical connections link the cerebellar cortex with multiple distinct sensory, motor, association, and paralimbic areas of the cerebrum. These projections allow a topographically precise cerebellar modulation of multiple domains of neurological function, and underscore the relevance of the cerebellum for the pathophysiology of numerous disorders in neurology and psychiatry. The majority of fibers that exit the cerebellar cortex synapse in the dentate nuclei (DN) before reaching extracerebellar structures such as cerebral cortex. Although the DN have a central position in the anatomy of the cerebello-cerebral circuits, the functional neuroanatomy of human DN remains largely unmapped. Neuroimaging research has redefined broad categories of functional division in the human brain showing that primary processing, attentional (task positive) processing, and default-mode (task negative) processing are three central poles of neural macro-scale functional organization. This new macro-scale understanding of the range and poles of brain function has revealed that a broad spectrum of human neural processing categories (primary, task positive, task negative) is represented not only in the cerebral cortex, but also in the thalamus, striatum, and cerebellar cortex. Whether functional organization in DN obeys a similar set of macroscale divisions, and whether DN are yet another compartment of representation of a broad spectrum of human neural processing categories, remains unknown. Here we show for the first time that human DN is optimally divided into three functional territories as indexed by high spatio-temporal resolution resting-state MRI in 60 healthy adolescents, and that these three distinct territories contribute uniquely to default-mode, salience-motor, and visual brain networks. These conclusions are supported by novel analytical strategies in human studies of DN organization, including 64-channel MRI imaging, data-driven methods, and replication in an independent sample. Our findings provide a systems neuroscience substrate for cerebellar output to influence multiple broad categories of neural control - namely default- mode, attentional, and multiple unimodal streams of information processing including motor and visual. They also provide a validated data-driven mapping of functions in human DN, crucial for the design of methodology and interpretation of results in future neuroimaging studies of brain function and dysfunction.
Production and use of triploid zebrafish for surrogate reproduction
Authors: Franěk Roman , Tichopád Tomáš , Fučíková Michaela , Steinbach Christoph , Pšenička Martin 
Published: April 2019

AbstractWe report for first time comparison of two approaches for zebrafish triploid production using cold shock and heat shock treatment. Subsequently, produced triploid zebrafish were used as a recipients for intraperitoneal transplantation of ovarian and testicular cells originating from vas:EGFP strain in order to verify their suitability for surrogate reproduction. Heat shock treatment was far more effective evaluated as success rate of triploid production and viability in comparison to cold shock. Triploids were produced with up to 100% efficiency in particular females. As expected, all triploids were males. Subsequently, germ cells transplantation revealed that triploids are suitable surrogate hosts. Production of donor-derived sperm was achieved in 23% and 16% of triploids transplanted by testicular and ovarian cells, respectively. Success of the transplantation was confirmed by positive GFP signal detected in gonads of dissected fish and stripped sperm. Germline transmission was confirmed by fertilization tests followed by PCR analysis of embryos. Reproductive success of germline chimera triploids evaluated as fertilization rate and progeny development was comparable to control groups.
Whole-genome fingerprint of the DNA methylome during chemically induced differentiation of the human AML cell line HL-60/S4
Authors: Antwi Enoch Boasiako , Olins Ada , Teif Vladimir B , Bieg Matthias , Bauer Tobias , Gu Zuguang , Brors Benedikt , Eils Roland , Olins Donald , Ishaque Naveed 
Published: April 2019

AbstractBackgroundMyeloid differentiation gives rise to a plethora of immune cells in the human body. This differentiation leaves strong signatures in the epigenome through each differentiated state of genetically identical cells. The leukemic HL-60/S4 promyelocytic cell can be easily differentiated from its undifferentiated promyelocyte state into neutrophil-and macrophage-like cell states, making it an excellent system for studying myeloid differentiation. In this study, we present the underlying genome and epigenome architecture of HL-60/S4 through its undifferentiated and differentiated cell states.ResultsWe performed whole genome bisulphite sequencing of HL-60/S4 cells and their differentiated counterparts. With the support of karyotyping, we show that HL-60/S4 maintains a stable genome throughout differentiation. Analysis of differential CpG methylation reveals that most methylation changes occur in the macrophage-like state. Differential methylation of promoters was associated with immune related terms. Key immune genes, CEBPA, GFI1, MAFB and GATA1 showed differential expression and methylation. However, we observed strongest enrichment of methylation changes in enhancers and CTCF binding sites, implying that methylation plays a major role in large scale transcriptional reprogramming and chromatin reorganisation during differentiation. Correlation of differential expression and distal methylation with support from chromatin capture experiments allowed us to identify putative proximal and long-range enhancers for a number of immune cell differentiation genes, including CEBPA and CCNF. Integrating expression data, we present a model of HL-60/S4 differentiation in relation to the wider scope of myeloid differentiation.ConclusionsFor the first time, we elucidate the genome and CpG methylation landscape of HL-60/S4 during differentiation. We identify all differentially methylated regions and positions. We link these to immune function and to important factors in myeloid differentiation. We demonstrate that methylation plays a more significant role in modulating transcription via enhancer reprogramming, rather than by promoter regulation. We identify novel regulatory regions of key components in myeloid differentiation that are regulated by differential methylation. This study contributes another layer of “omics” characterisation of the HL-60/S4 cell line, making it an excellent model system for studying rapid in vitro cell differentiation.Summary statementEpigenomics plays a major role in cell identity and differentiation. We present the DNA methylation landscape of leukemic cells during in-vitro differentiation, to add another ‘omics layer to better understand the mechanisms behind differentiation.
Amygdala controls saccade and gaze physically, motivationally, and socially
Authors: Maeda Kazutaka , Inoue Ken-ichi , Kunimatsu Jun , Takada Masahiko , Hikosaka Okihide 
Published: April 2019

AbstractThe amygdala is uniquely sensitive to emotional events. However, it is not understood whether and how the amygdala uses such emotional signals to control behavior, especially eye movements. We therefore injected muscimol (GABAAagonist) into the central nucleus of amygdala (CeA) in monkeys. This unilateral temporary inactivation suppressed saccades to contralateral but not ipsilateral targets, resulting in longer latencies, hypometric amplitudes, and slower velocity. During free viewing of movies, gaze was distributed mostly in the ipsilateral hemifield. Moreover, CeA inactivation disrupted the tendency of gaze toward social interaction images, which were normally focused on continuously. Conversely, optogenetic stimulation of CeA facilitated saccades to the contralateral side. These findings suggest that CeA controls spatially selective gaze and attention in emotional contexts, and provide a new framework for understanding psychiatric disorders related to amygdala dysfunction.HighlightsCentral amygdala facilitates contralateral saccades selectively.Saccade facilitation is related to motivational goals and social interaction.The amygdala thus controls goal-directed behavior based on emotional contexts.
Morpho-anatomical observations on Phyllanthus of Southwestern Bangladesh with two new records for Bangladesh
Authors: Tuhin Md. Sajjad Hossain , Limon Md. Sharif Hasan 
Published: April 2019

AbstractAn extensive floristic survey was done to annotate Phyllanthus of southwestern Bangladesh from 2015 to 2018. In total, 2189 individuals of Phyllanthus were counted and identified as eight different species (five herbs, two trees and a shrub). All species were examined following both morphological and anatomical methods, based on taxonomic notes. The listed species werePhyllanthus acidus, Phyllanthus amarus, Phyllanthus debilis, Phyllanthus emblica, Phyllanthus niruri, Phyllanthus urinaria, Phyllanthus reticulatusandPhyllanthus virgatus. Among them,Phyllanthus amarusandPhyllanthus debiliswere listed for the first time from Bangladesh during this study period.
A suite of rare microbes interacts with a
dominant, heritable, fungal endophyte to influence
plant trait expression
Authors: Harrison Joshua G. , Beltran Lyra P. , Buerkle C. Alex , Cook Daniel , Gardner Dale R. , Parchman Thomas L. , Poulson Simon R. , Forister Matthew L. 
Published: April 2019

Abstract
Endophytes are microbes that live, for at
least a portion of their life history, within
plant tissues. Endophyte assemblages are often
composed of a few abundant taxa and many
infrequently-observed, rare taxa. The ways in
which most endophytes affect host phenotype are
unknown; however, certain dominant endophytes can
influence plants in ecologically meaningful
ways–including by affecting growth and
contributing to immune responses. In contrast, the
effects of rare endophytes have been unexplored,
and how rare and common endophytes might interact
is also unknown. Here, we manipulate both the
suite of rare foliar endophytes (including both
fungi and bacteria) and Alternaria
fulva–a dominant, vertically-
transmitted fungus–within the fabaceous forb
Astragalus
lentiginosus. We report that rare,
low-biomass endophytes affected host size and
foliar %N, but only when the dominant fungal
endophyte (A. fulva)
was not present. A.
fulva also reduced plant size and
%N, but these deleterious effects on the host
could be offset by a striking antagonism we
observed between this heritable fungus and a
foliar pathogen. These results are unusual in that
they are derived from experimental manipulation in
a non-crop or non-grass system and demonstrate
that interactions among taxa determine the net
effect of endophytic assemblages on their hosts.
We suggest that the myriad infrequently-observed
endophytes within plant leaves may be more than a
collection of uninfluential, commensal organisms,
but instead have meaningful ecological
roles.
Evaluation of the possible association of Body Mass Index and four metabolic gene polymorphisms with longevity in an Italian cohort: a role forAPOE, eNOS, andFTOgene polymorphisms
Authors: Santovito Alfredo , Galli Gabriella , Ruberto Stefano 
Published: April 2019

ABSTRACTBackgroundlongevity is considered the result of interactions between environmental and genetic factors.Aimwe investigated the possible association of body mass index and the frequencies ofAPOE, ACE, eNOS, andFTOgene polymorphisms with longevity.Subjects and Method1,100 healthy volunteers aged 10-100 were recruited. We genotyped subjects forAPOE, ACE, eNOS, andFTOgene polymorphisms. Data about height and weight were also collected. The sample was split in four age groups: 1-24, 25-49, 50-85 and 86-100.Resultssignificant differences were found in BMI values between age groups, with exception of 1-24 with respect to 86-100. A significant decrease of theAPO E4, eNOS 393andFTO Aand allele frequencies was observed in the 86-100 age group with respect to younger groups. ForACEgene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed subdividing the sample in two main age groups: 1-85 and 86-100.Conclusionthis study provides evidences for a role ofAPOE, eNOS, andFTOgene polymorphisms in longevity. It has been estimated that the number of centenarians worldwide will double each decade until 2100, making population data about gene polymorphisms relevant for further studies about longevity.
Experimental manipulation of selfish genetic elements links genes to microbial community function
Authors: Quistad Steven D. , Doulcier Guilhem , Rainey Paul B. 
Published: April 2019

AbstractMicrobial communities underpin earth’s biological and geochemical processes, but their complexity hampers understanding. Motivated by the challenge of diversity and the need to forge ways of capturing dynamical behaviour connecting genes to function, biologically independent experimental communities comprising hundreds of microbial genera were established from garden compost and propagated on nitrogen-limited minimal medium with cellulose (paper) as sole carbon source. After one year of bi-weekly transfer, communities retained hundreds of genera. To connect genes to function we used a simple experimental manipulation that involved periodic collection of selfish genetic elements (SGEs) from separate communities, followed by pooling and redistribution across communities. The treatment was predicted to promote amplification and dissemination of SGEs and thus horizontal gene transfer (HGT). Confirmation came from comparative metagenomics, which showed substantive movement of ecologically significant genes whose dynamic across space and time could be followed. Enrichment of genes implicated in nitrogen metabolism, and particularly ammonification, prompted biochemical assays that revealed a measurable impact on community function. Our simple experimental strategy offers a conceptually new approach for unravelling dynamical processes affecting microbial community function.
Directional and frequency characteristics of auditory neurons in Culex male mosquitoes
Authors: Lapshin Dmitry N. , Vorontsov Dmitry D. 
Published: April 2019

AbstractThe paired auditory organ of mosquito, the Johnston’s organ (JO), being the receiver of particle velocity component of sound, is directional by its structure. However, to date almost no direct physiological measurements of its directionality was done. In addition, the recent finding on the grouping of the JO auditory neurons into the antiphase pairs demanded confirmation by different methods. Using the vector superposition of the signals produced by two orthogonally oriented speakers, we measured the directional characteristics of individual units as well as their relations in physiologically distinguishable groups – pairs or triplets. The feedback stimulation method allowed to discriminate responses of the two simultaneously recorded units, and to show that they indeed responded in antiphase. We also show that ratios between the individual tuning frequencies in pairs and triplets are non-random and follow the principle of harmonic synchronization, remarkably similar to the one known from the observations of mosquito behavior. Units of different tuning and sensitivity are evenly distributed around the axis of the JO, providing the mosquito with the ability to produce complex auditory behaviors.Summary statementAuditory neurons of mosquito are grouped into pairs or triplets, each unit tuned to a specific frequency. Within the pair units respond to opposite directions of the sound. Units of different tuning and sensitivity are evenly distributed around the axis of the Johnston’s organ.
Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder
Authors: Li Ningfei , Baldermann Juan Carlos , Kibleur Astrid , Treu Svenja , Akram Harith , Elias Gavin J.B. , Boutet Alexandre , Lozano Andres M. , Al-Fatly Bassam , Strange Bryan , Barcia Juan , Zrinzo Ludvic , Joyce Eileen , Chabardes Stephan , Visser-Vandewalle Veerle , Polosan Mircea , Kuhn Jens , Kühn Andrea A. , Horn Andreas 
Published: April 2019

AbstractMultiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.
Quantification of translation uncovers the functions of the alternative transcriptome
Authors: Calviello Lorenzo , Hirsekorn Antje , Ohler Uwe 
Published: April 2019

AbstractAt the center of the gene expression cascade, translation is fundamental in defining the fate of much of the transcribed genome. RNA sequencing enables the quantification of complex transcript mixtures, often detecting several splice isoforms of unknown functions for one gene. We have developed ORFquant, a new approach to annotate and quantify translation at the single open reading frame (ORF) level, using information from Ribo-seq data. Relying on a novel approach for transcript filtering, we quantify translation on thousands of ORFs, showing the power of Ribo-seq in revealing alternative ORFs on multiple isoforms per gene. While we find that one ORF represents the dominant translation product for most genes, we also detect genes with translated ORFs on multiple transcript isoforms, including targets of RNA surveillance mechanisms. Assessing the translation output across human cell lines reveals the extent of gene-specific differences in protein production, which are supported by steady-state protein abundance estimates. Computational analysis of Ribo-seq data with ORFquant (available at https://github.com/lcalviell/ORFquant) provides a window into the heterogeneous functions of complex transcriptomes.