bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective gating of retinal information by arousal
Authors: Liang Liang , Fratzl Alex , Mansour Omar El , Reggiani Jasmine D.S. , Chen Chinfei , Andermann Mark L. 
Published: March 2020

SummaryHow sensory information is processed by the brain can depend on behavioral state. In the visual thalamus and cortex, arousal/locomotion is associated with changes in the magnitude of responses to visual stimuli. Here, we asked whether such modulation of visual responses might already occur at an earlier stage in this visual pathway. We measured neural activity of retinal axons using wide-field and two-photon calcium imaging in awake mouse thalamus across arousal states associated with different pupil sizes. Surprisingly, visual responses to drifting gratings in retinal axonal boutons were robustly modulated by arousal level, in a manner that varied across stimulus dimensions and across functionally distinct subsets of boutons. At low and intermediate spatial frequencies, the majority of boutons were suppressed by arousal. In contrast, at high spatial frequencies, the proportions of boutons showing enhancement or suppression were more similar, particularly for boutons tuned to regions of visual space ahead of the mouse. Arousal-related modulation also varied with a bouton’s sensitivity to luminance changes and direction of motion, with greater response suppression in boutons tuned to luminance decrements vs. increments, and in boutons preferring motion along directions or axes of optic flow. Together, our results suggest that differential filtering of distinct visual information channels by arousal state occurs at very early stages of visual processing, before the information is transmitted to neurons in visual thalamus. Such early filtering may provide an efficient means of optimizing central visual processing and perception of state-relevant visual stimuli.
A Clock-Driven Neural Network Critical for Arousal
Authors: Bell Benjamin J. , Liu Qiang , Kim Dong Won , Lee Sang Soo , Liu Qili , Blum Ian D. , Wang Annette A. , Bedont Joseph L. , Chang Anna J. , Issa Habon , Cohen Jeremiah Y. , Blackshaw Seth , Wu Mark N. 
Published: March 2020

SummaryThe daily cycling of sleep and arousal states is among the most prominent biological rhythms under circadian control. While much is known about the core circadian clock1,2, how this clock tunes sleep and arousal remains poorly understood3. InDrosophila, we previously characterized WIDE AWAKE (WAKE), a clock-output molecule that promotes sleep at night4,5. Here, we show that the function of WAKE in regulating circadian-dependent neural excitability and arousal is conserved in mice.mWake+cells are found in the suprachiasmatic nucleus (SCN) and dorsomedial hypothalamus (DMH).mWakeDMHneurons drive wakefulness and exhibit rhythmic spiking, with greater firing during the night vs the day. Loss of mWAKE leads to increased spiking ofmWake+SCN and DMH neurons and prominent behavioural arousal, specifically during the night. Single-cell sequencing, imaging, and patch-clamp experiments reveal thatmWakeDMHneurons constitute a glutamatergic/GABAergic population that projects widely, receives neuromodulatory input, and acts on neuromodulatory neurons. Strikingly, broad chemogenetic silencing ofmWake+cells leads to profound loss of behavioural responsiveness and low amplitude, low frequency electroencephalography waveforms. These findings suggest that the genetic mechanisms regulating circadian control of sleep and arousal are conserved across >500 million years of evolution and define a clock-regulated neural network critical for arousal.
RNA sequencing reveals interacting key determinants of osteoarthritis acting in subchondral bone and articular cartilage
Authors: Tuerlings Margo , van Hoolwerff Marcella , Houtman Evelyn , Suchiman Eka (H.E.D.) , Lakenberg Nico , Mei Hailiang , van der Linden Enrike (H.M.J.) , Nelissen Rob (R.G.H.H.) , Ramos Yolande (Y.F.M.) , de Almeida Rodrigo Coutinho , Meulenbelt Ingrid 
Published: March 2020

ABSTRACTObjectiveThe aim of this study was to identify key determinants of the interactive osteoarthritis (OA) pathophysiological processes of subchondral bone and cartilage.MethodsWe performed RNA sequencing on macroscopically preserved and lesioned OA subchondral bone of patients that underwent joint replacement surgery due to OA (N=24 pairs; 6 hips, 18 knees, RAAK-study). Unsupervised hierarchical clustering and differential expression analyses were performed. Results were combined with previously identified, differentially expressed genes in cartilage (partly overlapping samples) as well as with recently identified OA risk genes.ResultsWe identified 1569 genes significantly differentially expressed between lesioned and preserved subchondral bone, includingCNTNAP2(FC=2.4, FDR=3.36×10−5) andSTMN2(FC=9.6, FDR=3.36×10−3). Among the identified genes, 305 were also differentially expressed and with same direction of effects in cartilage, includingIL11andCHADL, recently acknowledged OA susceptibility genes. Upon differential expression analysis stratifying for joint site, we identified 509 genes exclusively differentially expressed in subchondral bone of the knee, such asKLF11andWNT4. These exclusive knee genes were enriched for involvement in epigenetic processes, characterized by for instanceHIST1H3JandHIST1H3H.ConclusionTo our knowledge, we are the first to report on differential gene expression patterns of paired OA subchondral bone tissue using RNA sequencing. Among the most consistently differentially expressed genes with OA pathophysiology in both bone and cartilage wereIL11andCHADL.As these genes were recently also identified as robust OA risk genes they classify as attractive druggable targets acting on two OA disease relevant tissues.
Large-scale Proteomic and Phosphoproteomic Analysis of Maize Seedling Leaves During De-etiolation
Authors: Gao Zhi-Fang , Shen Zhuo , Chao Qing , Yan Zhen , Ge Xuan-Liang , Lu Tiancong , Zheng Haiyan , Qian Chun-Rong , Wang Bai-Chen 
Published: March 2020

AbstractDe-etiolation consists of a series of developmental and physiological changes that a plant undergoes in response to light. During this process light, an important environmental signal, triggers the inhibition of mesocotyl elongation and the production of photosynthetically active chloroplasts, and etiolated leaves transition from the “sink” stage to the “source” stage. De-etiolation has been extensively studied in maize (Zea mays L). However, little is known about how this transition is regulated. In this study, we describe a quantitative proteomic and phosphoproteomic atlas of the de-etiolation process in maize. We identified 16,420 proteins and quantified 14,168. In addition, 8,746 phosphorylation sites within 3,110 proteins were identified. From the proteomic and phosphoproteomic data combined, we identified a total of 17,436 proteins, 27.6% of which are annotated protein coding genes in theZea_maysAGPv3.28 database. Only 6% of proteins significantly changed in abundance during de-etiolation. In contrast, the phosphorylation levels of more than 25% of phosphoproteins significantly changed; these included proteins involved in gene expression and homeostatic pathways and rate-limiting enzymes involved in photosynthesis light and carbon reactions. Based on phosphoproteomic analysis, 34% (1,057) of all phosphoproteins identified in this study contained more than three phosphorylation sites, and 37 proteins contained more than 16 phosphorylation sites, which shows that multi-phosphorylation is ubiquitous during the de-etiolation process. Our results suggest that plants might preferentially regulate the level of PTMs rather than protein abundance for adapting to changing environments. The study of PTMs could thus better reveal the regulation of de-etiolation.
Different Proteins Mediate Step-wise Chromosome Architectures inThermoplasma acidophilumandPyrobaculum calidifontis
Authors: Maruyama Hugo , Prieto Eloise I. , Nambu Takayuki , Mashimo Chiho , Kashiwagi Kosuke , Okinaga Toshinori , Atomi Haruyuki , Takeyasu Kunio 
Published: March 2020

AbstractArchaeal species encode a variety of distinct lineage-specific chromosomal proteins. We have previously shown that inThermococcus kodakarensis, histone, Alba, and TrmBL2 play distinct roles in chromosome organization. Although our understanding of individual archaeal chromosomal proteins has been advancing, how archaeal chromosomes are folded into higher-order structures and how they are regulated are largely unknown. Here, we investigated the primary and higher-order structures of archaeal chromosomes from different archaeal lineages. Atomic force microscopy of chromosome spreads out ofThermoplasma acidophilumandPyrobaculum calidifontiscells revealed 10-nm fibers and 30–40-nm globular structures, suggesting the occurrence of higher-order chromosomal folding. Our results also indicated that chromosome compaction occurs toward the stationary phase. Micrococcal nuclease digestion indicated that fundamental structural units of the chromosome exist inT. acidophilumandT. kodakarensisbut not inP. calidifontisorSulfolobus solfataricus. In vitro reconstitution showed that, inT. acidophilum,the bacterial HU protein homolog HTa formed a 6-nm fiber by wrapping DNA, and that Alba was responsible for the formation of the 10-nm fiber by binding along the DNA without wrapping. Remarkably, Alba could form different higher-order complexes with histone or HTa on DNA in vitro. Mass spectrometry detected HTa in theT. acidophilumchromosome but not in other species. A putative transcriptional regulator of the AsnC/Lrp family (Pcal_1183) was detected on theP. calidifontischromosome, but not on that of other species studied. Putative membrane-associated proteins were detected in the chromosomes of the three archaeal species studied, includingT. acidophilum,P. calidifontis, andT. kodakarensis. Collectively, our data show that Archaea use different combinations of proteins to achieve chromosomal architecture and functional regulation.
Human and macaque pairs employ different coordination strategies in a transparent decision game
Authors: Möller Sebastian , Unakafov Anton M. , Fischer Julia , Gail Alexander , Treue Stefan , Kagan Igor 
Published: March 2020

AbstractMany real-world decisions in social contexts are made while observing a partner’s actions. To study dynamic interactions during such decisions, we developed a setup where two agents seated face-to-face engage in game-theoretical tasks on a shared transparent touchscreen display (“transparent games”). We compared human and macaque pairs in a transparent version of the coordination game “Bach-or-Stravinsky”, which entails a conflict about which of two individually-preferred opposing options to choose to achieve coordination. Most human pairs developed coordinated behavior and adopted dynamic turn-taking to equalize the payoffs. All macaque pairs converged on simpler, static coordination. Remarkably, two animals learned to coordinate dynamically after training with a human confederate. This pair selected the faster agent’s preferred option, exhibiting turn-taking behavior that was captured by modeling the visibility of the partner’s action before one’s own movement. Such competitive turn-taking was unlike the prosocial turn-taking in humans, who equally often initiated switches to and from their preferred option. Thus, the dynamic coordination is not restricted to humans, but can occur on the background of different social attitudes and cognitive capacities in rhesus monkeys. Overall, our results illustrate how action visibility promotes emergence and maintenance of coordination when agents can observe and time their mutual actions.
Mapping the influence of the gut microbiota on small molecules in the brain through mass spectrometry imaging
Authors: Hulme Heather , Meikle Lynsey M. , Strittmatter Nicole , Swales John , Hamm Gregory , Brown Sheila L. , Milling Simon , MacDonald Andrew S. , Goodwin Richard J.A. , Burchmore Richard , Wall Daniel M. 
Published: March 2020

AbstractBackgroundThe gut microbiota is known to influence virtually all facets of human health. Recent work has highlighted a potential role for the gut microbiota in neurological health through the microbiome-gut-brain axis. Microbes can influence the brain both directly and indirectly; through neurotransmitter production, induction of host immunomodulators, or through the release or induction of other microbial or host molecules.MethodsHere we used mass spectrometry imaging (MSI), a label-free imaging tool, to map the molecular changes that occur in the murine gut and brain in germ-free, antibiotic-treated and control mice.ResultsWe determined the spatial distribution and relative quantification of neurotransmitters and their precursors across brain and gut sections in response to the microbiome. Using untargeted MSI of small molecules, we detected a significant change in the levels of four identified metabolites in the brains of germ-free animals compared to controls; vitamin B5, 3-hydroxy-3-methylglutaric acid, 3-methyl-4-(trimethylammonio)butanoate and 4-(trimethylammonio)pentanoate. However, antibiotic treatment induced no significant changes in these metabolites in the brain after one week of treatment.ConclusionsThis work exemplifies the utility of MSI as a tool in determining the spatial distribution and quantification of bacterial and host metabolites in the gut and brain whilst also offering the potential for discovery of novel mediators of microbiome-gut-brain axis communication.
Cytoplasmic incompatibility between Old and New World populations of a tramp ant
Authors: Ün Çiğdem , Schultner Eva , Manzano-Marín Alejandro , Flórez Laura V. , Seifert Bernhard , Heinze Jürgen , Oettler Jan 
Published: March 2020

AbstractAs we enter the Anthropocene, the evolutionary dynamics of species will change drastically, and as yet unpredictably, due to human activity. Already today, increases in global human traffic have resulted in the rapid spread of species to new areas, leading to the formation of geographically isolated populations. These go on to evolve in allopatry, which can lead to reproductive isolation, and potentially, the formation of new species. Surprisingly, little is known about such eco-evolutionary processes in ants, even though numerous invasive ant species are globally distributed in geographically isolated populations. Here, we describe the first case of cytoplasmic incompatibility (CI) between populations of a cosmotropic distributed tramp ant with Asian roots,Cardiocondyla obscurior,which has acquired a novelWolbachiastrain in the New World. Our study uncovers the first symbiont-induced mechanism of reproductive isolation in ants, providing a novel perspective on the biology of globally distributed ants.
Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling
Authors: Dodig-Crnković Tea , Hong Mun-Gwan , Thomas Cecilia Engel , Häussler Ragna S. , Bendes Annika , Dale Matilda , Edfors Fredrik , Forsström Björn , Magnusson Patrik K.E. , Schuppe-Koistinen Ina , Odeberg Jacob , Fagerberg Linn , Gummesson Anders , Bergström Göran , Uhlén Mathias , Schwenk Jochen M 
Published: March 2020

AbstractBackgroundPrecision medicine approaches aim to tackle diseases on an individual level through molecular profiling. Despite the growing knowledge about diseases and the reported diversity of molecular phenotypes, the descriptions of human health on an individual level have been far less elaborate.MethodsTo provide insights into the longitudinal protein signatures of well-being, we profiled blood plasma collected over one year from 101 clinically healthy individuals using multiplexed antibody assays. After applying an antibody validation scheme, we utilized > 700 protein profiles for in-depth analyses of the individuals’ short-term health trajectories.FindingsWe found signatures of circulating proteomes to be highly individual-specific. Considering technical and longitudinal variability, we observed both stable and fluctuating proteins in the circulation, as well as networks of proteins that covaried over time. For each participant, there were unique protein profiles and some of these could be explained by associations to genetic variants.InterpretationThis study demonstrates that there was noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. Longitudinal profiling of circulating proteomes has the potential to enable a more personal hence precise assessment of health states, and thereby provide a valuable component of precision medicine approaches.FundingThis work was supported by the Erling Persson Foundation for the KTH Centre for Precision Medicine and the Swedish Heart and Lung Foundation for the SCAPIS project. We also acknowledge the Knut and Alice Wallenberg Foundation for funding the Human Protein Atlas project, Science for Life Laboratory for Plasma Profiling Facility, and the Swedish Research Council (Grant no 2017-00641).
MMS2plot: an R package for visualizing multiple MS/MS spectra for groups of modified and non-modified peptides
Authors: Ming Liya , Zou Yang , Zhao Yiming , Zhang Luna , He Ningning , Chen Zhen , Li Shawn S-C. , Li Lei 
Published: March 2020

ABSTRACTA large number of post-translational modifications (PTMs) in proteins are buried in the unassigned mass spectrometric (MS) spectra in shot-gun proteomics datasets. Because the modified peptide fragments are low in abundance relative to the corresponding non-modified versions, it is critical to develop tools that allow facile evaluation of assignment of PTMs based on the MS/MS spectra. Such tools would preferably have the ability to allow comparison of fragment ion spectra and retention time between the modified and unmodified peptide pairs or group. Herein, we describe MMS2plot, an R package for visualizing peptide-spectrum matches (PSMs) for multiple peptides. MMS2plot features a batch mode and generates the output images in vector graphics file format that facilitate evaluation and publication of the PSM assignment. We expect MMS2plot to play an important role in PTM discovery from large-scale proteomics datasets generated by LC (liquid chromatography)-MS/MS. The MMS2plot package is freely available athttps://github.com/lileir/MMS2plotunder the GPL-3 license.
A pancreas specificPtf1a-driven Cre mouse line causes paternally transmitted germline recombination
Authors: Kabacaoglu Derya , Lesina Marina , Algül Hana 
Published: March 2020

AbstractCre-loxP recombination system is a commonly used tool to achieve site-specific genetic manipulation in genome. For multiple Cre driver mouse lines, parental transmissions of recombined flox alleles are reported.Ptf1a-driven Cre lines are widely used to achieve genetic manipulation in a pancreas specific manner. Herein, we report germline recombination in breedings whenCreallele is retained paternally inPtf1atm1(cre)Hnak. The germline recombination frequency changed depending on the target allele. Therefore, unless the reporter allele is on the target gene, the reporter activity is to be validated. Overall, we highlight that allPtf1a-driven Cre mouse lines should be genotyped for possible germline recombination and we advise the maternal transmission of theCreto progeny.
Leptin Receptors in RIP-Cre25Mgnneurons Mediate Anti-Dyslipidemia Effects of Leptin in Insulin-Deficient Male Mice
Authors: Singha Ashish , Palavicini Juan Pablo , Pan Meixia , Sandoval Darleen , Han Xianlin , Fujikawa Teppei 
Published: March 2020

AbstractLeptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of metabolism including glucose and lipid metabolism, with and without insulin. It is evident that central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms including restoration of dyslipidemia. However, the specific neurons that regulate these glucose-lowering and anti-dyslipidemia effects of leptin remain unidentified. Here we report that leptin receptors (LEPRs) in neurons expressing Cre recombinase driven by a short fragment of a promoter region ofIns2gene (RIP-Cre25Mgnneurons) are required for central leptin signaling to reverse hyperglycemia and dyslipidemia in insulin-deficient mice. Ablation of LEPRs in RIP-Cre25Mgnneurons completely blocks glucose-lowering effects of leptin in insulin-deficient mice. Further investigations reveal that insulin-deficient mice lacking LEPRs in RIP-Cre25Mgnneurons (RIP-CreΔLEPRmice) exhibit greater lipid levels in blood and liver compared to wild-type controls, and that leptin injection into the brain does not suppress dyslipidemia in insulin-deficient RIP-CreΔLEPRmice. Leptin administration into the brain combined with acipimox, which lowers blood lipids by suppressing triglyceride lipase activity, can restore normal glycemia in insulin-deficient RIP-CreΔLEPRmice, suggesting that excess circulating lipids are a driving-force of hyperglycemia in insulin-deficient RIP-CreΔLEPRmice. Collectively, our data demonstrate that LEPRs in RIP-Cre25Mgnneurons significantly contribute to glucose-lowering effects of leptin in an insulin-independent manner by suppression of dyslipidemia.
Genome-wide Screens Identify Lineage- and Tumor Specific-Genes Modulating MHC-I and MHC-II Immunosurveillance in Human Lymphomas
Authors: Dersh Devin , Phelan James D. , Gumina Megan E. , Wang Boya , Arbuckle Jesse H. , Holly Jaroslav , Kishton Rigel J. , Markowitz Tovah E. , Seedhom Mina O. , Fridlyand Nathan , Wright George W. , Huang Da Wei , Ceribelli Michele , Thomas Craig J. , Lack Justin B. , Restifo Nicholas P. , Kristie Thomas M. , Staudt Louis M. , Yewdell Jonathan W. 
Published: March 2020

SummaryTumors frequently subvert MHC class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance. To better define the regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of novel genes that positively and negatively modulate MHC-I cell surface levels. Identified genes cluster in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Many genes exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors display genetic alterations in multiple regulators. We establish that the HSP90 co-chaperone SUGT1 is a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhances DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.