bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achieving stable dynamics in neural circuits
Authors: Kozachkov Leo , Lundqvist Mikael , Slotine Jean-Jacques , Miller Earl K. 
Published: January 2020

1AbstractThe brain consists of many interconnected networks with time-varying, partially autonomous activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable, reproducible state (or sequence of states) for its computations to make sense. We approached this problem from a control-theory perspective by applying contraction analysis to recurrent neural networks. This allowed us to find mechanisms for achieving stability in multiple connected networks with biologically realistic dynamics, including synaptic plasticity and time-varying inputs. These mechanisms included inhibitory Hebbian plasticity, excitatory anti-Hebbian plasticity, synaptic sparsity and excitatory-inhibitory balance. Our findings shed light on how stable computations might be achieved despite biological complexity.
Complete connectomic reconstruction of olfactory projection neurons in the fly brain
Authors: Bates A.S. , Schlegel P. , Roberts R.J.V. , Drummond N. , Tamimi I.F.M. , Turnbull R. , Zhao X. , Marin E.C. , Popovici P.D. , Dhawan S. , Jamasb A. , Javier A. , Li F. , Rubin G.M. , Waddell S. , Bock D.D. , Costa M. , Jefferis G.S.X.E. 
Published: January 2020

AbstractNervous systems contain sensory neurons, local neurons, projection neurons and motor neurons. To understand how these building blocks form whole circuits, we must distil these broad classes into neuronal cell types and describe their network connectivity. Using an electron micrograph dataset for an entireDrosophila melanogasterbrain, we reconstruct the first complete inventory of olfactory projections connecting the antennal lobe, the insect analogue of the mammalian olfactory bulb, to higher-order brain regions in an adult animal brain. We then connect this inventory to extant data in the literature, providing synaptic-resolution ‘holotypes’ both for heavily investigated and previously unknown cell types. Projection neurons are approximately twice as numerous as reported by light level studies; cell types are stereotyped, but not identical, in cell and synapse numbers between brain hemispheres. The lateral horn, the insect analogue of the mammalian cortical amygdala, is the main target for this olfactory information and has been shown to guide innate behaviour. Here, we find new connectivity motifs, including: axo-axonic connectivity between projection neurons; feedback and lateral inhibition of these axons by local neurons; and the convergence of different inputs, including non-olfactory inputs and memory-related feedback onto lateral horn neurons. This differs from the configuration of the second most prominent target for olfactory projection neurons: the mushroom body calyx, the insect analogue of the mammalian piriform cortex and a centre for associative memory. Our work provides a complete neuroanatomical platform for future studies of the adultDrosophilaolfactory system.HighlightsFirst complete parts list for second-order neurons of an adult olfactory systemQuantification of left-right stereotypy in cell and synapse numberAxo-axonic connections form hierarchical communities in the lateral hornLocal neurons and memory-related feedback target projection neuron axons
Creeping yeast: a simple, cheap, and robust protocol for the identification of mating type inSaccharomyces cerevisiae
Authors: Arras Samantha D. M. , Hibbard Taylor R. , Mitsugi-McHattie Lucy , Woods Matthew A. , Johnson Charlotte E. , Munkacsi Andrew , Denmat Sylvie Hermann-Le , Ganley Austen R. D. 
Published: January 2020

AbstractSaccharomyces cerevisiaeis an exceptional genetic system, with genetic crosses facilitated by its ability to be maintained in haploid and diploid forms. Such crosses are straightforward if the mating type/ploidy of the strains are known. Several techniques can be used to determine mating type (or ploidy), but all have limitations. Here we validate a simple, cheap and robust method to rapidly identifyS. cerevisiaemating types. When cells of opposite mating type are mixed in liquid media, they “creep” up the culture vessel sides, a phenotype that can be easily detected visually. In contrast, mixtures of the same mating type or with a diploid simply settle out. The phenotype is robust to different media, cell densities, temperatures and strains, and is observable for several days. Microscopy suggests that cell aggregation during mating is responsible for the phenotype. Yeast knockout collection analysis identified 107 genes required for the creeping phenotype, with these being enriched for mating-specific genes. Surprisingly, the RIM101 signalling pathway was strongly represented. We propose that RIM101 signalling regulates aggregation as part of a wider, previously-unrecognized role in mating. The simplicity and robustness of this method makes it ideal for routine verification ofS. cerevisiaemating type, with future studies required to verify its molecular basis.
Single-nucleus RNA-Seq reveals a new type of brown adipocyte regulating thermogenesis
Authors: Sun Wenfei , Dong Hua , Balaz Miroslav , Slyper Michal , Drokhlyansky Eugene , Colleluori Georgia , Giordano Antonio , Kovanicova Zuzana , Stefanicka Patrik , Ding Lianggong , Rudofsky Gottfried , Ukropec Jozef , Cinti Saverio , Regev Aviv , Wolfrum Christian 
Published: January 2020

AbstractAdipose tissue usually is classified as either white, brown or beige/brite, based on whether it functions as an energy storage or thermogenic organ(Cannon and Nedergaard, 2004; Rosen and Spiegelman, 2014). It serves as an important regulator of systemic metabolism, exemplified by the fact that dysfunctional adipose tissue in obesity leads to a host of secondary metabolic complications such as diabetes, cardiovascular diseases and cancer(Hajer et al., 2008; Lauby-Secretan et al., 2016). In addition, adipose tissue is an important endocrine organ, which regulates the function of other metabolic tissues through paracrine and endocrine signals(Scheele and Wolfrum, 2019; Scherer, 2006). Work in recent years has demonstrated that tissue heterogeneity is an important factor regulating the functionality of various organs(Cao et al., 2017; Ginhoux et al., 2016; Park et al., 2018). Here we used single nucleus analysis in mice and men to deconvolute adipocyte heterogeneity. We are able to identify a novel subpopulation of adipocytes whose abundance is low in mice (2-8%) and which is increased under higher ambient temperatures. Interestingly, this population is abundant in humans who live close to thermoneutrality. We demonstrate that this novel adipocyte subtype functions as a paracrine cell regulating the activity of brown adipocytes through acetate-mediated regulation of thermogenesis. These findings could explain, why human brown adipose tissue is substantially less active than mouse tissue and targeting this pathway in humans might be utilized to restore thermogenic activity of this tissue.
Genome-wide discovery of SLE genetic risk variant allelic enhancer activity
Authors: Lu Xiaoming , Chen Xiaoting , Forney Carmy , Donmez Omer , Miller Daniel , Parameswaran Sreeja , Hong Ted , Huang Yongbo , Pujato Mario , Cazares Tareian , Miraldi Emily R. , Ray John P. , de Boer Carl G. , Harley John B. , Weirauch Matthew T. , Kottyan Leah C. 
Published: January 2020

AbstractGenome-wide association studies of Systemic Lupus Erythematosus (SLE) nominate 3,073 genetic variants at 91 risk loci. To systematically screen these variants for allelic transcriptional enhancer activity, we constructed a massively parallel reporter assay (MPRA) library comprising 12,396 DNA oligonucleotides containing the genomic context around every allele of each SLE variant. Transfection into the Epstein-Barr virus-transformed B cell line GM12878 revealed 482 variants with enhancer activity, with 51 variants showing genotype-dependent (allelic) enhancer activity at 27 risk loci. Comparison of MPRA results in GM12878 and Jurkat T cell lines highlights shared and unique allelic transcriptional regulatory mechanisms at SLE risk loci. In-depth analysis of allelic transcription factor (TF) binding at and around allelic variants identifies one class of TFs whose DNA-binding motif tends to be directly altered by the risk variant and a second, larger class of TFs that bind allelically without direct alteration of their motif by the variant. Collectively, our approach provides a blueprint for the discovery of allelic gene regulation at risk loci for any disease and offers insight into the transcriptional regulatory mechanisms underlying SLE.
Middle-level IM-MS and CIU experiments for improved therapeutic immunoglobulin isotype fingerprinting
Authors: Botzanowski Thomas , Hernandez-Alba Oscar , Malissard Martine , Wagner-Rousset Elsa , Deslignière Evolène , Colas Olivier , Haeuw Jean-François , Beck Alain , Cianférani Sarah 
Published: January 2020

ABSTRACTCurrently approved therapeutic monoclonal antibodies (mAbs) are based on immunoglobulin G (IgG) 1, 2 or 4 isotypes, which differ in their specific inter-chains disulfide bridge connectivities. Different analytical techniques have been reported for mAb isotyping, among which native ion mobility mass spectrometry (IM-MS) and collision induced unfolding (CIU) experiments. However, mAb isotyping by these approaches is based on detection of subtle differences and thus remains challenging at the intactlevel. We report here on middle-level (after IdeS digestion) IM-MS and CIU approaches to afford better differentiation of mAb isotypes. Our method provides simultaneously CIU patterns of F(ab’)2and Fc domains within a single run. Middle-level CIU patterns of F(ab’)2 domains enable more reliable classification of mAb isotypes compared to intact level CIU, while CIU fingerprints of Fc domains are overall less informative for mAb isotyping. F(ab’)2regions can thus be considered as diagnostic domains providing specific CIU signatures for mAb isotyping. Benefits of middle-level IM-MS and CIU approaches are further illustrated on the hybrid IgG2/IgG4 eculizumab. While classical analytical techniques led to controversial results, middle-level CIU uniquely allowed to face the challenge of eculizumab « hybridicity », highlighting that its F(ab’)2and Fc CIU patterns corresponds to an IgG2 and an IgG4, respectively. Altogether, the middle-level CIU approach is more clear-cut, accurate and straightforward for canonical but also more complex, engineered next generation mAb formats isotyping. Middle-level CIU thus constitutes a real breakthrough for therapeutic protein analysis, paving the way for its implementation in R&D laboratories.
The effect of statistical normalisation on network propagation scores
Authors: Picart-Armada Sergio , Thompson Wesley K. , Buil Alfonso , Perera-Lluna Alexandre 
Published: January 2020

AbstractMotivationNetwork diffusion and label propagation are fundamental tools in computational biology, with applications like gene-disease association, protein function prediction and module discovery. More recently, several publications have introduced a permutation analysis after the propagation process, due to concerns that network topology can bias diffusion scores. This opens the question of the statistical properties and the presence of bias of such diffusion processes in each of its applications. In this work, we characterised some common null models behind the permutation analysis and the statistical properties of the diffusion scores. We benchmarked seven diffusion scores on three case studies: synthetic signals on a yeast interactome, simulated differential gene expression on a protein-protein interaction network and prospective gene set prediction on another interaction network. For clarity, all the datasets were based on binary labels, but we also present theoretical results for quantitative labels.ResultsDiffusion scores starting from binary labels were affected by the label codification, and exhibited a problem-dependent topological bias that could be removed by the statistical normalisation. Parametric and non-parametric normalisation addressed both points by being codification-independent and by equalising the bias. We identified and quantified two sources of bias -mean value and variance- that yielded performance differences when normalising the scores. We provided closed formulae for both and showed how the null covariance is related to the spectral properties of the graph. Despite none of the proposed scores systematically outperformed the others, normalisation was preferred when the sought positive labels were not aligned with the bias. We conclude that the decision on bias removal should be problem and data-driven, i.e. based on a quantitative analysis of the bias and its relation to the positive entities.AvailabilityThe code is publicly available athttps://github.com/b2slab/diffuBenchContactsergi.picart@upc.edu
Characterising open chromatin identifies novel cis-regulatory elements important for paraxial mesoderm formation and axis extension
Authors: Mok Gi Fay , Folkes Leighton , Weldon Shannon , Maniou Eirini , Martinez-Heredia Victor , Godden Alice , Williams Ruth , Wheeler Grant N. , Moxon Simon , Münsterberg Andrea E. 
Published: January 2020

SUMMARYThe development of multicellular organisms is exquisitely regulated through differential gene activity, which governs cell differentiation programs. However, many details of spatiotemporal control of gene regulation are still poorly understood. We used the accessibility of chick embryos to examine genome-wide signatures characterizing the progressive differentiation of paraxial mesoderm along the head-to-tail axis. Paraxial mesoderm becomes organized into repetitive units, termed somites, the hallmark of the segmented vertebrate body plan. New somite pairs form periodically as the axis extends at the posterior end. This process generates a developmental gradient within a single embryo, with anterior somites more advanced in their differentiation compared to posterior somites. Following somite formation, cell rearrangements generate compartments, comprising lineages of the musculoskeletal system, including cartilage of the vertebral column and ribs, and skeletal muscle cells of the trunk and limbs. To examine how paraxial mesoderm becomes regionalized and patterned to eventually generate these discrete lineages, we investigated dynamic changes of the transcriptome and of chromatin accessibility using RNA-seq and ATAC-seq across a spatiotemporal series along the embryonic axis. Footprint analysis uncovers differential coverage of binding sites for a number of key transcription factors known to be involved in axial patterning and differentiation, including HOX genes. Furthermore, associating accessible chromatin with nearby expressed genes identifies candidatecis-regulatoryelements (CRE). As exemplars we use TCF15 and MEOX1, which are crucial for somite formation and differentiation, to experimentally validate CREsin vivousing fluorescent reporters. Time-lapse microscopy reveals CRE spatiotemporal activity and mutation analysis uncovers necessary upstream regulators. The CRE for MEOX1 is conserved and recognized in Xenopus. In addition, a human element is active in chicken.In vivoepigenome editing of TCF15 and MEOX1 CREs disrupts gene expression regulation and recapitulates phenotypic abnormalities of anterior-posterior axis extension.
Barley shoot biomass responds strongly to N:P stoichiometry and intraspecific competition, whereas roots only alter their foraging
Authors: Kumar Amit , van Duijnen Richard , Delory Benjamin M. , Reichel Rüdiger , Brüggemann Nicolas , Temperton Vicky M. 
Published: January 2020

AbstractBackground and AimsPlants respond to various environmental stimuli, and root systems are highly responsive to the availability and distribution of nutrients in the soil. Root system responses to the limitation of either nitrogen (N) or phosphorus (P) are well documented, but how the early root system responds to (co-) limitation of one (N or P) or both (N and P) in a stoichiometric framework is not well known despite its relevance in agriculture. In addition, how plant-plant competition (here intra-specific) alters plant responses to N:P stoichiometry is understudied. Therefore, we aimed to investigate the effects of N:P stoichiometry and competition on root system responses and overall plant performance.MethodsPlants (Hordeum vulgareL.) were grown in rhizoboxes for 24 days in the presence or absence of competition (three vs. one plant per rhizobox), and fertilized with different combinations of N:P (low N+low P, low N+high P, high N+low P, and high N+high P).Key ResultsShoot biomass was highest when both N and P were provided in high amounts. In competition, shoot biomass decreased on average by 22%. Interestingly, N:P stoichiometry and competition had no clear effect on root biomass. However, we found distinct root responses in relation to biomass allocation across depths. Specific root length depended on the identity of limiting nutrient (N or P) and presence/absence of competition. Plants rooted deeper when N was the most limiting compared to shallower rooting when P was the most limiting nutrient.ConclusionsOverall, our study sheds light on the early plant responses to plant-plant competition and stoichiometric availability of two macronutrients most limiting plant performance. With low N and P availability during early growth, higher investments in root system development can significantly trade off with aboveground productivity, and strong intra-specific competition can further strengthen such effects.
Use of Transabdominal Ultrasound for the Detection of Intra-Peritoneal Tumor Engraftment and Growth in Mouse Xenografts of Epithelial Ovarian Cancer
Authors: Chambers Laura M. , Esakov Emily , Braley Chad , AlHilli Mariam , Michener Chad , Reizes Ofer 
Published: January 2020

AbstractObjectiveTo evaluate intraperitoneal (IP) tumor engraftment, metastasis and growth in a pre-clinical murine epithelial ovarian cancer (EOC) model using both transabdominal ultrasound (TAUS) and bioluminescencein vivoimaging system (IVIS).MethodsTen female C57Bl/6J mice at six weeks of age were included in this study. Five mice underwent IP injection of 5×106ID8-luc cells (+ D-luciferin) and the remaining five mice underwent IP injection of ID8-VEGF cells. Monitoring of tumor growth and ascites was performed weekly starting at seven days post-injection until study endpoint. ID8-luc mice were monitored using both TAUS and IVIS, and ID8-VEGF mice underwent TAUS monitoring only. Individual tumor implant dimension and total tumor volume were calculated. Average luminescent intensity was calculated and reported per mouse abdomen. Tumor detection was confirmed by gross evaluation and histopathology. All data are presented as mean +/- standard deviation.ResultsOverall, tumors were successfully detected in all ten mice using TAUS and IVIS, and tumor detection correlated with terminal endpoint histology/ H&E staining. For TAUS, the smallest confirmed tumor measurements were at seven days post-injection with mean long axis of 2.23mm and mean tumor volume of 4.17mm3. However, IVIS imaging was able to detect tumor growth at 14 days post-injection.ConclusionsTAUS is highly discriminatory for monitoring EOC in pre-clinical murine model, allowing for detection of tumor dimension as small as 2 mm and as early as seven days post-injection compared to IVUS. In addition, TAUS provides relevant information for ascites development and detection of multiple small metastatic tumor implants. TAUS provides an accurate and reliable method to detect and monitor IP EOC growth in mouse xenografts.
Application of Pedimap — a pedigree visualization tool — to facilitate the decisioning of rice breeding in Sri Lanka
Authors: Rathnayake P.G.R.G. , Sahibdeen S.M. , Udawela U.A.K.S. , Weebadde C.K. , Weerakoon W.M.W. , Sooriyapathirana S.D.S.S. 
Published: January 2020

ABSTRACTThe development of rice cultivars with desirable traits is essential. The decision-making is a crucial step in rice breeding programs. The breeders can make efficient and pragmatic decisions if an organized pedigree visualization platform is available for the material of the rice breeding germplasm. The staple food in Sri Lanka is rice, and there is a great demand for improved varieties with high yield and other promising traits. In the present study, the available data of all the rice varieties released by Rice Research and Development Institute, Sri Lanka, and the related landraces and genotypes were arranged in Pedimap, a pedigree visualization tool. Pedimap can showcase pedigree relationships, phenotypic, and molecular data. The Identity by Descent (IBD) probabilities were calculated using FlexQTL software and included in the Pedimap database. The parentage selection based on the variations of phenotypic traits, selection of marker alleles for molecular breeding, and detection of the founders of genetic effects can be swiftly conducted using Pedimap. However, the power of harnessing the value of Pedimap for making breeding decisions relies on the availability of data for the traits, markers, and genomic sequences. Thus, it is imperative to characterize the breeding germplasms using standard phenomic and genomic characterization procedures before organized into Pedimap. Thereby, the worldwide breeding programs can benefit from each other to produce improved varieties to meet global challenges.