bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer’s disease model
Authors: Lee Youngsun , Choi Yoori , Park Eun-Joo , Kwon Seokjun , Kim Hyun , Lee Jae Young , Lee Dong Soo 
Published: January 2020

AbstractDrainage of parenchymal waste through the lymphatic system maintains brain homeostasis. Age-related changes of glymphatic-lymphatic clearance lead to the accumulation beta-amyloid (Aβ) in dementia models. In this study, focused ultrasound treatment in combination with microbubbles (FUS-MB) improved Aβ drainage in early dementia model mice, 5XFAD. FUS-MB enhanced solute Aβ clearance from brain, but not plaques, to cerebrospinal fluid (CSF) space and then deep cervical lymph node (dCLN). dCLN ligation exaggerated memory impairment and progress of plaque formation and also the beneficial effects of FUS-MB upon Aβ removal through CSF-lymphatic routes. In this ligation model, FUS-MB improved memory despite accumulation of Aβ in CSF. In conclusion, FUS-MB enhances glymphatic-lymphatic clearance of Aβ mainly by increasing brain-to-CSF Aβ drainage. We suggest that FUS-MB can delay dementia progress in early period and benefits of FUS-MB depend on the effect of Aβ disposal through CSF-lymphatics.
Changing and stable chromatin accessibility supports transcriptional overhaul during neural stem cell activation
Authors: Maybury-Lewis Sun Y. , Brown Abigail K. , Yeary Mitchell , Sloutskin Anna , Dhakal Shleshma , McCarthy-Sinclair Brendan , Juven-Gershon Tamar , Webb Ashley E. 
Published: January 2020

AbstractAdult neural stem cells are largely quiescent, and require transcriptional reprogramming to reenter the cell cycle and undergo neurogenesis. However, the precise mechanisms that underlie the rapid transcriptional overhaul during NSC activation remain undefined. Here, we identify the genome-wide chromatin accessibility differences between primary neural stem and progenitor cells in quiescent and activated states. We show that these distinct cellular states exhibit both shared and unique chromatin profiles, which are both associated with gene regulation. Interestingly, we find that accessible chromatin states specific to quiescent or activated cells are active enhancers bound by pro-neurogenic and quiescence factors, ASCL1 and NFI. In contrast, shared sites are gene promoters harboring constitutively accessible chromatin enriched for particular core promoter elements that are functionally associated with translation and metabolic functions. Together, our findings reveal how accessible chromatin states regulate a transcriptional overhaul and drive the switch between quiescence and proliferation in NSC activation.
Bayesian copy number detection and association in large-scale studies
Authors: Cristiano Stephen , McKean David , Carey Jacob , Bracci Paige , Brennan Paul , Chou Michael , Du Mengmeng , Gallinger Steven , Goggins Michael G. , Hassan Manal , Hung Rayjean , Kurtz Robert , Li Donghui , Lu Lingeng , Neale Rachel , Olson Sara , Petersen Gloria , Rabe Kari , Fu Jack , Risch Harvey , Rosner Gary , Ruczinski Ingo , Klein Alison P. , Scharpf Robert B. 
Published: January 2020

AbstractGermline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging. We developed an approach called CNPBayes to identify latent batch effects, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease. We demonstrate this approach in a Pancreatic Cancer Case Control study of 7,598 participants where the major sources of technical variation were not captured by study site and varied across the genome. Candidate associations aided by this approach include deletions of 8q24 near regulatory elements of the tumor oncogeneMYCand of Tumor Supressor Candidate 3 (TUSC3). This study provides a robust Bayesian inferential framework for estimating copy number and evaluating the role of copy number in heritable diseases.
Acetylation-mediated phase control of the nucleolus regulates cellular acetyl-CoA responses
Authors: Houston Ryan , Sekine Shiori , Calderon Michael J. , Seifuddin Fayaz , Wang Guanghui , Kawagishi Hiroyuki , Malide Daniela A. , Li Yuesheng , Gucek Marjan , Pirooznia Mehdi , Nelson Alissa J. , Stokes Matthew P. , Stewart-Ornstein Jacob , Wendell Stacy G. , Watkins Simon C. , Finkel Toren , Sekine Yusuke 
Published: January 2020

SummaryThe metabolite acetyl-CoA serves as an essential element for a wide range of cellular functions including ATP production, lipid synthesis and protein acetylation. Intracellular acetyl-CoA concentrations are associated with nutrient availability, but the mechanisms by which a cell responds to fluctuations in acetyl-CoA levels remain elusive. Here, we generate a cell system to selectively manipulate the nucleo-cytoplasmic levels of acetyl-CoA using CRISPR-mediated gene editing and acetate supplementation of the culture media. Using this system and quantitative omics analyses, we demonstrate that acetyl-CoA depletion alters the integrity of the nucleolus, impairing ribosomal RNA synthesis and evoking the ribosomal protein-dependent activation of p53. This nucleolar remodeling appears to be mediated through the class IIa HDAC deacetylases regulating the phase state of the nucleolus. Our findings highlight acetylation-mediated control of the nucleolus as an important hub linking acetyl-CoA fluctuations to cellular stress responses.
Calsyntenin-3 directly interacts with neurexins to orchestrate excitatory synapse development in the hippocampus
Authors: Kim Hyeonho , Kim Dongwook , Kim Jinhu , Lee Hee-Yoon , Park Dongseok , Kang Hyeyeon , Matsuda Keiko , Sterky Fredrik H. , Yuzaki Michisuke , Kim Jin Young , Choi Se-Young , Ko Jaewon , Um Ji Won 
Published: January 2020

AbstractCalsyntenin-3 (Clstn3) is a postsynaptic adhesion molecule that induces presynaptic differentiation via presynaptic neurexins (Nrxns), but whether Nrxns directly bind to Clstn3 has been a matter of debate. Here, we show that β-Nrxns directly interact via their LNS domain with Clstn3 and Clstn3 cadherin domains. Expression of splice site 4 (SS4) insert-positive β-Nrxn variants, but not insert-negative variants, reversed the impaired Clstn3 synaptogenic activity observed in Nrxn-deficient neurons. Consistently, Clstn3 selectively formed complexes with SS4-positive Nrxnsin vivo. Neuron-specific Clstn3 deletion caused significant reductions in number of excitatory synaptic inputs, and moderate impairment of light-induced anxiety-like behaviors in mice. Moreover, expression of Clstn3 cadherin domains in CA1 neurons of Clstn3 conditional knockout mice rescued structural deficits in excitatory synapses, especially within the stratum radiatum layer. Collectively, our results suggest that Clstn3 links to SS4-positive Nrxns to induce presynaptic differentiation and orchestrate excitatory synapse development in specific hippocampal neural circuits.
Flexible contextual modulation of naturalistic texture perception in peripheral vision
Authors: Herrera-Esposito Daniel , Coen-Cagli Ruben , Gomez-Sena Leonel 
Published: January 2020

AbstractPeripheral vision comprises most of our visual field, and is essential in guiding visual behavior. Its characteristic capabilities and limitations, which distinguish it from foveal vision, have been explained by the most influential theory of peripheral vision as the product of representing the visual input using summary-statistics. Despite its success, this account may provide a limited understanding of peripheral vision, because it neglects processes of perceptual grouping and segmentation. To test this hypothesis, we studied how contextual modulation, namely the modulation of the perception of a stimulus by its surrounds, interacts with segmentation in human peripheral vision. We used naturalistic textures, which are directly related to summary-statistics representations. We show that segmentation cues affect contextual modulation, and that this is not captured by our implementation of the summary-statistics model. We then characterize the effects of different texture statistics on contextual modulation, providing guidance for extending the model, as well as for probing neural mechanisms of peripheral vision.
Sir2 mitigates an intrinsic imbalance in origin licensing efficiency between early and late replicating euchromatin
Authors: Hoggard Timothy , Müller Carolin A. , Nieduszynski Conrad A. , Weinreich Michael , Fox Catherine A. 
Published: January 2020

AbstractA eukaryotic chromosome relies on the function of multiple spatially distributed DNA replication origins for its stable inheritance. The location of an origin is determined by the chromosomal position of an MCM complex, the inactive form of the DNA replicative helicase that is assembled on chromosomal DNA in G1-phase (a.k.a. origin licensing). While the biochemistry of origin licensing is understood, the mechanisms that promote an adequate spatial distribution of MCM complexes across chromosomes are not. We have elucidated a role for the Sir2 histone deacetylase in establishing the normal distribution of MCM complexes acrossSaccharomyces cerevisiaechromosomes. In the absence of Sir2, MCM complexes accumulated within both early-replicating euchromatin and telomeric heterochromatin, and replication activity within these regions was enhanced. Concomitantly, the duplication of several regions of late-replicating euchromatin were delayed. Thus, Sir2-mediated attenuation of origin licensing established the normal spatial distribution of origins across yeast chromosomes required for normal genome duplication.Significance statementIn eukaryotes, multiple DNA replication origins, the sites where new DNA synthesis begins during the process of cell division, must be adequately distributed across chromosomes to maintain normal cell proliferation and genome stability. This study describes a repressive chromatin-mediated mechanism that acts at the level of individual origins to attenuate the efficiency of origin formation. This attenuation is essential for achieving the normal spatial distribution of origins across the chromosomes of the eukaryotic microbeSaccharomyces cerevisiae. While the importance of chromosomal origin distribution to cellular fitness is now widely acknowledged, this study is the first to define a specific chromatin modification that establishes the normal spatial distribution of origins across a eukaryotic genome.
Proteomic changes in bacteria caused by exposure to environmental conditions can be detected by Matrix-Assisted Laser Desorption/Ionization – Time of Flight (MALDI-ToF) Mass Spectrometry
Authors: Chac Denise , Kordahi Melissa , Brettner Leandra , Verma Arushi , McCleary Paul , Crebs Kelly , Yee Cara , DePaolo R. William 
Published: January 2020

ABSTRACTIn the past decade, matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectrometry (MS) has become a timely and cost-effective alternative to bacterial identification. The MALDI-ToF MS technique analyzes the total protein of culturable microorganisms at the species level and produces a mass spectra based on peptides which is compared to a database of identified profiles. Consequently, unique signatures of each microorganism are produced allowing identification at the species and, more importantly, strain level. Our present study proposes that the MALDI-ToF MS can be further used to screen functional and metabolic differences. While other studies applied the MALDI-ToF technique to identify subgroups within species, we investigated how various environmental factors could alter the unique bacterial signatures. We found that genetic and phenotypic differences between microorganisms belonging to the same species can be reflected in peptide-mass fingerprints generated by MALDI-ToF MS. These results suggest that MALDI-ToF MS can screen intra-species phenotypic differences of several microorganisms.
Captive-reared migratory monarch butterflies show natural orientation when released in the wild
Authors: Wilcox Alana A. E. , Newman Amy E. M. , Raine Nigel E. , Norris D. Ryan 
Published: January 2020

AbstractEastern North American migratory monarch butterflies (Danaus plexippus) have faced sharp declines over the last two decades. Although captive rearing has been used as an important tool for engaging the public and supplementing conservation efforts, a recent study that tested monarchs in a flight simulator suggested that captive-reared monarchs lose their capacity to orient southward during fall migration to their Mexican overwintering sites. We raised offspring of wild-caught monarchs on swamp milkweed (Asclepias incarnata) and, after eclosion, individuals were either tested in a flight simulator or radio-tracked in the wild using array of over 100 automated telemetry towers. While only 33% (7/39) of monarchs tested in the flight simulator showed strong southeast to southwest orientation, 97% (28/29) of the radio-tracked individuals were detected by automated towers south or southeast of the release site, up to 200 km away. Our results suggest that, though captive rearing of monarch butterflies may cause temporary disorientation, proper orientation is likely re-established after exposure to natural skylight cues.
Differential processing and habituation in distinct spatial frequency channels in V1 of a mouse model of fragile X syndrome
Authors: Pak Alexandr , Kissinger Samuel T. , Chubykin Alexander A. 
Published: January 2020

AbstractExtraction of both common and unique features across different visual inputs is crucial for animal survival. Regularities in the visual input lead to learning of the general principles governing an environment, whereas unique features are important for novelty detection. Low and high spatial frequencies (SF) represent two different channels of visual perception, which may be playing different roles in the processing of global pattern and local details. Alterations in the processing of these different SF channels may lead to impaired visual perception. Excessive detail-oriented processing and reduced habituation to sensory stimuli are some of the hallmarks of altered sensory perception in autism. However, the underlying neural mechanisms of these impairments are not understood. To gain insight into the pathophysiology of these impairments, we investigated the low and high SF channels in V1 of Fmr1 KO mice, the mouse model of Fragile X syndrome (FX). We first provide behavioral evidence for reduced habituation of both pupillary baseline and surprise responses in FX mice. Using silicon probe recordings, we demonstrate excessive processing of high SF stimuli in the late stages of visual responses in V1 of FX mice. We then show a reduced adaptation during a visual oddball paradigm in neurons preferring low but not high SF. Overall, our findings suggest that altered processing in distinct SF channels might contribute to altered visual perception and learning in FX and autism.
2019-20 Wuhan coronavirus outbreak: Intense surveillance is vital for preventing sustained transmission in new locations
Authors: Thompson R.N. 
Published: January 2020

ABSTRACTThe outbreak of pneumonia originating in Wuhan, China, has generated 830 confirmed cases, including 26 deaths, as of 24 January 2020. The virus (2019-nCoV) has spread elsewhere in China and to other countries, including South Korea, Thailand, Japan and USA. Fortunately, there has not yet been evidence of sustained human-to-human transmission outside of China. Here we assess the risk of sustained transmission whenever the coronavirus arrives in other countries. Data describing the times from symptom onset to hospitalisation for 47 patients infected in the current outbreak are used to generate an estimate for the probability that an imported case is followed by sustained human-to-human transmission. Under the assumptions that the imported case is representative of the patients in China, and that the 2019-nCoV is similarly transmissible to the SARS coronavirus, the probability that an imported case is followed by sustained human-to-human transmission is 0.37. However, if the mean time from symptom onset to hospitalisation can be halved by intense surveillance, then the probability that an imported case leads to sustained transmission is only 0.005. This emphasises the importance of current surveillance efforts in countries around the world, to ensure that the ongoing outbreak will not become a large global epidemic.
Single generation exposure to a captive diet: a primer for domestication selection in a salmonid fish?
Authors: Islam Shahinur S. , Yates Matthew C. , Fraser Dylan J. 
Published: January 2020

AbstractMillions of wild animals in captivity are reared on diets that differ in their uptake and composition from natural conditions. Few studies have investigated whether such novel diets elicit unintentional domestication selection in captive rearing and supplementation programs. In highly fecund salmonid fishes, natural and captive mortality is highest in the first few months of exogenous feeding. This high early mortality might be a potent driver of unintentional selection because wild fish normally forage on live prey whereas they are fed almost exclusively pellet feed in captivity: fish that do not adapt pellet feed well under captive conditions experience reduced growth and/or die. We tested this hypothesis by generating a large number of families from F1captive and wild fish originating from the same three populations and then rearing them each on pellet and natural, live, drifting feed for three months at the beginning of exogenous feeding. We found that captive fish of every population grew faster than wild fish in all diet treatments. Populations exhibited an idiosyncratic response to diet treatment, with two populations exhibiting faster growth on a pellet diet versus the natural diet but another population exhibiting similar growth in both diet treatments. Fish exposed to a natural diet also exhibited higher survival relative to those given a pellet diet. Captive and wild fish did not differ in survival, regardless of population of origin. Overall, we found evidence that rapid domestication selection associated with a single generation exposure to a novel captive diet generates genetically-based changes to individual fitness (e.g., growth and survival) in a wild fish.
Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China
Authors: Wu Fan , Zhao Su , Yu Bin , Chen Yan-Mei , Wang Wen , Hu Yi , Song Zhi-Gang , Tao Zhao-Wu , Tian Jun-Hua , Pei Yuan-Yuan , Yuan Ming-Li , Zhang Yu-Ling , Dai Fa-Hui , Liu Yi , Wang Qi-Min , Zheng Jiao-Jiao , Xu Lin , Holmes Edward C. , Zhang Yong-Zhen 
Published: January 2020

Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1–3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th2019. Next generation metagenomic RNA sequencing4identified a novel RNA virus from the familyCoronaviridaedesigned WH-Human-1 coronavirus (WHCV).Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genusBetacoronavirus, subgenusSarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.
MHC*IMP – Imputation of Alleles for Genes in the Major Histocompatibility Complex
Authors: Squire David McG. , Motyer Allan , Ahn Richard , Nititham Joanne , Huang Zhi-Ming , Oksenberg Jorge R. , Foerster John , Liao Wilson , Leslie Stephen 
Published: January 2020

AbstractWe report the development of MHC*IMP, a method for imputing non-classical HLA and other genes in the human Major Histocompatibility Complex (MHC). We created a reference panel for 25 genes in the MHC using allele calls from Whole Genome Sequencing data, combined with SNP data for the same individuals. We used this to construct an allele imputation model, MHC*IMP, for each gene. Cross-validation showed that MHC*IMP performs very well, with allele prediction accuracy 93% or greater for all but two of the genes, and greater than 95% for all but four.
Metastable attractors explain the variable timing of stable behavioral action sequences
Authors: Recanatesi Stefano , Pereira Ulises , Murakami Masayoshi , Mainen Zachary , Mazzucato Luca 
Published: January 2020

ABSTRACTNatural animal behavior displays rich lexical and temporal dynamics, even in a stable environment. The timing of self-initiated actions shows large variability even when they are executed in reliable, well-learned sequences. To elucidate the neural mechanism underlying this mix of reliability and stochasticity, we trained rats to perform a stereotyped sequence of self-initiated actions and recorded neural ensemble activity in secondary motor cortex (M2), known to reflect trial-by-trial action timing fluctuations. Using hidden Markov models, we established a dictionary between ensemble activity patterns and actions. We then showed that metastable attractors, with a reliable sequential structure yet high transition timing variability, could be produced by coupling a high-dimensional recurrent network and a low-dimensional feedforward one. Transitions between attractors in our model were generated by correlated variability arising from the feedback loop between the two networks. This mechanism predicted aligned, low-dimensional noise correlations that were empirically verified in M2 ensembles. Our work establishes a novel framework for investigating the circuit origins of self-initiated behavior based on correlated variability.
New distribution records and range extensions of mosquitoes in British Columbia and the Yukon Territory
Authors: Peach Daniel AH. , Poirier Lisa M. 
Published: January 2020

AbstractWe report the first records ofAedes euedesHoward, Dyar, and Knab, andCoquillettidia perturbans(Walker) from Canada’s Yukon Territory, and the first record ofAe. decticusHoward, Dyar, and Knab from British Columbia. We also report range extensions in northern BC for the western treehole mosquito,Aedes sierrensis(Ludlow), the common house mosquito,Culex pipiensL., and the cool weather mosquitoCuliseta incidens(Thomson).