bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropathy and neural plasticity in the subcutaneous white adipose depot
Authors: Blaszkiewicz Magdalena , Willows Jake W. , Dubois Amanda L. , Waible Stephen , Johnson Cory P. , DiBello Kristen , Lyons Lila L. , Breeding William P. , Tilbury Karissa B. , Michael Merilla , Harrison Benjamin , Townsend Kristy L. 
Published: November 2018

AbstractThe difficulty in obtaining as well as maintaining weight loss, together with the loss of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ and metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and less neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature. These findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with exercise, cold exposure or neurotrophic factor treatment, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health.
Metabolism-Induced Oxidative Stress and DNA Damage Selectively Trigger Genome Instability in Polyploid Cells
Authors: Thomson Gregory J. , Hernon Claire , Nicanor Austriaco O.P. , Shapiro Rebecca S. , Belenky Peter , Bennett Richard J. 
Published: November 2018

AbstractUnderstanding the forces impacting genome stability is important for diverse processes such as tumorigenesis and reproductive biology. The pathogenic yeastCandida albicansdisplays unusual genome dynamics in which tetraploid cells, but not diploid cells, become unstable when grown on a glucose-rich ‘pre-sporulation’ medium. Here, we reveal thatC. albicanspolyploid cells are metabolically hyperactive on this medium as evidenced by increased expression of metabolic genes as well as higher rates of fermentation and oxidative respiration. These cells also show elevated levels of reactive oxygen species (ROS), activate the ROS-responsive transcription factor Cap1, and accrue DNA double-strand breaks. Suppression of ROS levels reduced oxidative stress, DNA damage and chromosome instability. These studies reveal how metabolic flux can generate endogenous ROS, triggering DNA damage and genome instability in polyploid, but not diploid, cells. We discuss parallels with metabolism-induced instability in cancer cells and propose that ROS-induced DNA damage could have facilitated ploidy cycling in eukaryotes prior to the evolution of meiosis.
Determining targeting specificity of nuclear-encoded organelle proteins with the self-assembling split-fluorescent protein toolkit
Authors: Sharma Mayank , Kretschmer Carola , Lampe Christina , Stuttmann Johannes , Klösgen Ralf Bernd 
Published: November 2018

AbstractA large number of nuclear-encoded proteins are targeted to the organelles of endosymbiotic origin, namely mitochondria and plastids. To determine the targeting specificity of these proteins, fluorescent protein tagging is a popular approach. However, ectopic expression of fluorescent protein fusions commonly results in considerable background signals and often suffers from the large size and robust folding of the reporter protein, which may perturb membrane transport. Among the alternative approaches that have been developed in recent years, the self-assembling split-fluorescent protein (sasplit-FP) technology appears particularly promising to analyze protein targeting specificityin vivo. Here, we have improved this technology with respect to sensitivity and systematically evaluated its utilization to determine protein targeting to plastids and mitochondria. Furthermore, to facilitate high throughput screening of candidate proteins we have developed aGolden Gate-based vector toolkit, named PlaMiNGo (Plastid and/orMitochondria targeted proteinsN-terminally fused toGFP11 tags viaGolden Gatecloning). As a result of these improvements, dual targeting could be detected for a number of proteins, which had earlier been characterized as being targeted to a single organelle only. These results were independently confirmed with a plant phenotype complementation approach thus demonstrating the sensitivity and robustness of thesasplit-FP-based method to analyze the targeting specificity of nuclear-encoded proteins.HighlightSeveral mono-specific proteins showed dual targeting to plastids and mitochondria with the self-assembling split-GFP system. AGolden Gate-based vector toolkit was constructed to facilitate easy cloning and subsequent determination of protein targeting specificity.
Dynamic properties of internal noise probed by modulating binocular rivalry
Authors: Baker Daniel H. , Richard Bruno 
Published: November 2018

AbstractNeural systems are inherently noisy, and this noise can affect our perception from moment to moment. This is particularly apparent in binocular rivalry, where our perception of competing stimuli shown to the left and right eyes alternates over time in a seemingly random fashion. We investigated internal noise using binocular rivalry by modulating rivalling stimuli using dynamic sequences of external noise of various rates and amplitudes. As well as measuring the effect on dominance durations, we repeated each external noise sequence twice, and assessed the consistency of percepts across repetitions. External noise modulations with standard deviations above 4% contrast increased consistency scores above baseline, and were most effective at 1/8Hz. A computational model of rivalry in which internal noise has a 1/f (pink) temporal amplitude spectrum, and a standard deviation of 16%, provided the best account of our data, and was able to correctly predict perception in additional conditions. Our novel technique provides detailed estimates of the dynamic properties of internal noise during binocular rivalry, and by extension the stochastic processes that drive our perception and other types of spontaneous brain activity.Significance statementAlthough our perception of the world appears constant, sensory representations are variable because of the ‘noisy’ nature of biological neurons. Here we used a binocular rivalry paradigm, in which conflicting images are shown to the two eyes, to probe the properties of this internal variability. Using a novel paradigm in which the contrasts of rivalling stimuli are modulated by two independent external noise streams, we infer the amplitude and character of this internal noise. The temporal amplitude spectrum of the noise has a 1/f spectrum, similar to that of natural visual input, and consistent with the idea that the visual system evolved to match its environment.
AncientYersinia pestisgenomes from across Western Europe reveal early diversification during the First Pandemic (541–750)
Authors: Keller Marcel , Spyrou Maria A. , Scheib Christiana L. , Kröpelin Andreas , Haas-Gebhard Brigitte , Päffgen Bernd , Haberstroh Jochen , i Lacomba Albert Ribera , Raynaud Claude , Cessford Craig , Stadler Peter , Nägele Kathrin , Neumann Gunnar U. , Bates Jessica S. , Trautmann Bernd , Inskip Sarah , Peters Joris , Robb John E. , Kivisild Toomas , McCormick Michael , Bos Kirsten I. , Harbeck Michaela , Herbig Alexander , Krause Johannes 
Published: November 2018

AbstractThe first historically documented pandemic caused byYersinia pestisstarted as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although palaeogenomic studies have previously identified the causative agent asY. pestis, little is known about the bacterium’s spread, diversity and genetic history over the course of the pandemic.To elucidate the microevolution of the bacterium during this time period, we screened human remains from 20 sites in Austria, Britain, Germany, France and Spain forY. pestisDNA and reconstructed six new genomes. We present a novel methodological approach assessing SNPs in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis reveals the existence of previously undocumentedY. pestisdiversity during the 6th–7thcenturies, and provides evidence for the presence of multiple distinctY. pestisstrains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as southern France and Spain, and that southern Germany seems to have been affected by at least two distinctY. pestisstrains. Four of the reported strains form a polytomy similar to others seen across theY. pestisphylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45 kb genomic region in the most recent First Pandemic strain affecting two virulence factors, intriguingly overlapping with a deletion found in 17th–18th-century genomes of the Second Pandemic.Significance StatementThe first historically reported pandemic attributed toYersinia pestisstarted with the Justinianic Plague (541–544) and continued for around 200 years as the so-called First Pandemic. To date, only oneY. pestisstrain from this pandemic has been reconstructed using ancient DNA. In this study, we present six new genomes from Britain, France, Germany and Spain, demonstrating the geographic range of plague during the First pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemic (17thto 18thcentury) that includes the same two virulence factors, thus providing an example of potential convergent evolution ofY. pestisduring large scale epidemics.
Intelligible speech synthesis from neural decoding of spoken sentences
Authors: Anumanchipalli Gopala K. , Chartier Josh , Chang Edward F. 
Published: November 2018

AbstractThe ability to read out, or decode, mental content from brain activity has significant practical and scientific implications1. For example, technology that translates cortical activity into speech would be transformative for people unable to communicate as a result of neurological impairment2,3,4. Decoding speech from neural activity is challenging because speaking requires extremely precise and dynamic control of multiple vocal tract articulators on the order of milliseconds. Here, we designed a neural decoder that explicitly leverages the continuous kinematic and sound representations encoded in cortical activity5,6to generate fluent and intelligible speech. A recurrent neural network first decoded vocal tract physiological signals from direct cortical recordings, and then transformed them to acoustic speech output. Robust decoding performance was achieved with as little as 25 minutes of training data. Naïve listeners were able to accurately identify these decoded sentences. Additionally, speech decoding was not only effective for audibly produced speech, but also when participants silently mimed speech. These results advance the development of speech neuroprosthetic technology to restore spoken communication in patients with disabling neurological disorders.
Epigenetics of floral homeotic genes in relation to sexual dimorphism in the dioecious plantMercurialis annua
Authors: Khadka Janardan , Yadav Narendra Singh , Guy Micha , Grafi Gideon , Golan-Goldhirsh Avi 
Published: November 2018

AbstractIn plants, dioecy characterizes species carrying male and female flowers on separate plants and occurs in about 6% of angiosperms. To date, the molecular mechanism(s) underlying sexual dimorphism is essentially unknown. The ability of gender-reversal by hormone application suggests that epigenetics might play an important role in sexual dimorphism. Proteome analysis of nuclei derived from flower buds of females, males and feminized males of the dioecious plantMercurialis annuarevealed differentially expressed proteins related to nucleic acid binding proteins, hydrolases and transcription factors, including floral homeotic genes. Further analysis showed that class B genes are mainly expressed in male flowers, while class D genes, as well asSUPERMAN-like genes, were mainly expressed in female flowers. Cytokinin-induced feminization of male plants was associated with down-regulation of male-specific genes concomitantly with up-regulation of female-specific genes. No correlation could be found between the expression of class B and D genes and their DNA methylation or chromatin conformation. Thus, our results ruled out epigenetic control over floral identity genes as the major determinants regulating sexual dimorphisms. Rather, determination of sex inM. annuamight be controlled upstream of floral identity genes by a gender-specific factor that affects hormonal homeostasis.HighlightsSex determination inMercurialis annuais not related to epigenetics of floral homeotic genes but appears to be modulated by an unknown gender-specific regulator(s) that affects hormonal homeostasis.
Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells
Authors: Sugiyarto G. , Prossor D. , Dadas O. , Elliott T. , James E. 
Published: November 2018

AbstractRegulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ producing GSW11- specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour growth. Here we show that GSW11-specific T cells are in fact induced in Treg-replete, CT26-bearing mice, where they make up the majority of tumour infiltrating CD8+ lymphocytes, but exhibit a dysfunctional ‘exhausted’ phenotype. This dysfunctional phenotype is induced early in the anti-tumour response in draining lymph nodes, spleens and tumours and is significantly more pronounced in GSW11-specific T cells compared to other tumour-specific T cell responses. Depletion of Tregs prior to tumour challenge significantly reduces the induction of exhaustion in GSW11-specific T cells and correlates with altered T cell receptor (TcR) usage. Moreover, the avidity of GSW11- specific TcRs that expanded in the absence of Tregs was significantly lower compared to TcRs of cytotoxic T lymphocyte (CTL) populations that were diminished in protective anti-tumour responses. This indicates that Tregs suppress the induction of protective anti-tumour T cell responses and may signify that the induction of low avidity T cells, while being more susceptible to exhaustion are the most efficacious in tumour rejection.
The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains
Authors: Luperchio TR , Sauria MEG , Hoskins VE , Wong X , DeBoy E , Gaillard M-C , Tsang P , Pekrun K , Ach RA , Yamada NA , Taylor J , Reddy KL 
Published: November 2018

AbstractThree-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.
Assessing the potential for assisted gene flow using past introduction of Norway spruce in Southern Sweden: Local adaptation and genetic basis of quantitative traits in trees
Authors: Milesi Pascal , Berlin Mats , Chen Jun , Orsucci Marion , Li Lili , Jansson Gunnar , Karlsson Bo , Lascoux Martin 
Published: November 2018

AbstractNorway spruce (Picea abies) is a dominant conifer species of major economic importance in Northern Europe. Extensive breeding programs were established to improve phenotypic traits of interest. In southern Sweden seeds used to create progeny tests were collected on about 3000 trees of outstanding phenotype (“plus” trees) across the region. Some were of local origin but many were recent introductions from the rest of the natural range. The mixed origin of the trees together with partial sequencing of the exome of >1,500 of these trees and phenotypic data retrieved from the Swedish breeding program offered us a unique opportunity to dissect the genetic basis of local adaptation of three quantitative traits (height,diameterandbudburst). Through a combination of multivariate analyses and genome-wide association studies, we showed that there was a very strong effect of geographical origin on growth (height and diameter) and phenology (budburst) with trees from southern origins outperforming local provenances. Association studies also indicated that growth traits were highly polygenic and budburst somewhat less. Hence, our results suggest that assisted gene flow and genomic selection approaches could help alleviating the effect of climate change onP. abiesbreeding programs in Sweden.
The impact of ischemic stroke on connectivity gradients
Authors: Bayrak Şeyma , Khalil Ahmed A. , Villringer Kersten , Fiebach Jochen B. , Villringer Arno , Margulies Daniel S. , Ovadia-Caro Smadar 
Published: November 2018

AbstractUnderstanding the relationship between localized anatomical damage, reorganization, and functional deficits is a major challenge in stroke research. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, thereby affecting a whole network of interconnected regions. Recent advances suggest an alternative to discrete functional networks by describing a connectivity space based on a low-dimensional embedding of the full connectivity matrix. The dimensions of this space, described as connectivity gradients, capture the similarity of areas’ connections along a continuous space. Here, we defined a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes resulted in dimension-specific alterations in functional connectivity over the first week after symptoms onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of change in functional connectivity was determined by the distance from the lesion along these connectivity gradients regardless of the anatomical distance from the lesion. Together, these results provide a novel framework to study reorganization after stroke and suggest that, rather than only impacting on anatomically proximate areas, the indirect effects of ischemic strokes spread along the brain relative to the space defined by its connectivity.
Rapid Whole Cell Imaging Reveals A Calcium-APPL1-Dynein Nexus That Regulates Cohort Trafficking of Stimulated EGF Receptors
Authors: York H M , Patil A , Moorthi U K , Kaur A , Bhowmik A , Hyde G J , Gandhi H , Gaus K , Arumugam S 
Published: November 2018

ABSTRACTMulticellular life processes such as proliferation and differentiation depend on cell surface signaling receptors that bind ligands generally referred to as growth factors. Recently, it has emerged that the endosomal system provides rich signal processing capabilities for responses elicited by these factors [1-3]. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors of the receptor tyrosine kinase family. EGFRs, once activated by EGF, are robustly trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated [4-8]. However, the details of the mechanisms regulating the movements of stimulated EGFR in time and space, i.e., towards the PNR, are not known. What endosomal regulators provide specificity to EGFR? Do modifications to the receptor upon stimulation regulate its trafficking? To understand the events leading to EGFR translocation, and especially the early endosomal dynamics that immediately follow EGFR internalization, requires the real-time, long-term, whole-cell imaging of multiple elements. Here, exploiting the advantages of lattice light-sheet microscopy [9], we show that the binding of EGF by its receptor, EGFR, triggers a transient calcium increase that peaks by 30 s, causing the desorption of APPL1 from pre-existing endosomes within one minute, the rebinding of liberated APPL1 to EGFR within three minutes, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within five minutes. The novel, cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGFR receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking, and have evolved behaviors whose predictability is better suited to signaling [10, 11]. Work presented here demonstrates that our whole cell imaging approach can be a powerful tool in revealing critical transient interactions in key cellular processes such as receptor trafficking.