bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primate neuronal connections are sparse as compared to mouse
Authors: Wildenberg G.A. , Rosen M.R. , Lundell J. , Paukner D. , Freedman D.J. , Kasthuri N. 
Published: September 2020

SummaryThe mouse and macaque primary visual cortices are foundational models of cortical functioning, particularly at the level of single neurons. Therefore, detailing differences in how individual neurons connect across these species would inform models of cortical functioning and of how brains evolve. However, existing comparisons are limited, measuring synapse density without regard to where synapses are made or on what types of neurons. We use large volume electron microscopy to address this gap, reconstructing a total of 7735 synapses across 160 total neurons (146 excitatory, 14 inhibitory) from adult Rhesus macaque and mouse Layer 2/3 of primary visual cortex (V1). We find that primate connections are broadly sparse: primate excitatory and inhibitory neurons received 3-5 times fewer spine and somatic synapses with lower ratios of excitatory to inhibitory synapses than mouse equivalents. However, despite reductions in absolute synapse number, patterns of axonal innervation were preserved: inhibitory axons sparsely innervated neighboring excitatory neurons in macaque and mouse at similar rates and proportions. On the output side, most excitatory axons in mice myelinated close to the soma (81%) while most primate axons (68%) did not. Interestingly, primate axons, but not mouse axons, that myelinated had 3.3 fold more axon initial segment synapses than axons that did not myelinate, suggesting differential inhibitory control of long distance output in primate brains. Finally, we discover that when artificial recurrent neural networks (RNNs) are constrained by the metabolic cost of creating and maintaining synapses, increasing the number of nodes (e.g. neurons) as networks optimize for a cognitive task, reduces the number of connections per node, similar to primate neurons as compared to mice.One Sentence SummaryUsing large volume serial electron microscopy, we show that primate cortical neural networks are sparser than mouse and using recursive neural nets, we show that energetic costs of synaptic maintenance could underlie this difference.
Widespread methylation quantitative trait loci and their role in schizophrenia risk
Authors: Perzel Mandell Kira A. , Eagles Nicholas J. , Wilton Richard , Price Amanda J. , Semick Stephen A. , Collado-Torres Leonardo , Tao Ran , Han Shizhong , Szalay Alexander S. , Hyde Thomas M. , Kleinman Joel E. , Weinberger Daniel R. , Jaffe Andrew E. 
Published: September 2020

AbstractDNA methylation (DNAm) regulates gene expression and may represent gene-environment interactions. Using whole genome bisulfite sequencing, we surveyed DNAm in a large sample (n=344) of human brain tissues. We identify widespread genetic influence on local methylation levels throughout the genome, with 76% of SNPs and 38% of CpGs being part of methylation quantitative trait loci (meQTLs). These associations can further be clustered into regions that are differentially methylated by a given SNP, highlighting putative functional regions that explain much of the heritability associated with risk loci. Furthermore, some CpH sites associated with genetic variation. We have established a comprehensive, single base resolution view of association between genetic variation and genomic methylation, and implicate schizophrenia GWAS-associated variants as influencing the epigenetic plasticity of the brain.One-sentence summaryMost genetic variants associated with DNA methylation levels, and implicated schizophrenia GWAS variants in the human brain.
Human FcRn expression and Type I Interferon signaling control Echovirus 11 pathogenesis in mice
Authors: Wells Alexandra I. , Grimes Kalena A. , Kim Kenneth , Branche Emilie , Bakkenist Christopher J. , DePas William H. , Shresta Sujan , Coyne Carolyn B. 
Published: September 2020

AbstractNeonatal echovirus infections are characterized by severe hepatitis and neurological complications that can be fatal. Here, we show that expression of the human homologue of the neonatal Fc receptor (hFcRn), the primary receptor for echoviruses, and ablation of type I interferon (IFN) signaling are key host determinants involved in echovirus pathogenesis. We show that expression of hFcRn alone is insufficient to confer susceptibility to echovirus infections in mice. However, expression of hFcRn in mice deficient in type I interferon (IFN) signaling, hFcRn-IFNAR−/−, recapitulate the echovirus pathogenesis observed in humans. Luminex-based multianalyte profiling from E11 infected hFcRn-IFNAR−/−mice revealed a robust systemic immune response to infection, including the induction of type I IFNs. Furthermore, similar to the severe hepatitis observed in humans, E11 infection in hFcRn-IFNAR−/−mice caused profound liver damage. Our findings define the host factors involved in echovirus pathogenesis and establishin vivomodels that recapitulate echovirus disease.
A single-mode associates global patterns of brain network structure and behavior across the human lifespan
Authors: McPherson Brent , Pestilli Franco 
Published: September 2020

AbstractMultiple human behaviors improve early in life, peaking in young adulthood, and declining thereafter. Several properties of brain structure and function progress similarly across the lifespan. Cognitive and neuroscience research has approached aging primarily using associations between a few behaviors, brain functions, and structures. Because of this, the multivariate, global factors relating brain and behavior across the lifespan are not well understood. We investigated the global patterns of associations between 334 behavioral and clinical measures and 376 brain structural connections in 594 individuals across the lifespan. A single-axis associated changes in multiple behavioral domains and brain structural connections (r=0.5808). Individual variability within the single association axis well predicted the age of the subject (r=0.6275). Representational similarity analysis evidenced global patterns of interactions across multiple brain network systems and behavioral domains. Results show that global processes of human aging can be well captured by a multivariate data fusion approach. [147]Data availabilityThe source data are provided by the Cambridge Aging Neuroscience Projecthttps://camcan-archive.mrc-cbu.cam.ac.uk/. Brain data derived as part of this project and used as features for all the analyses are available on brainlife.io/pubs:Code availabilityCode is available on github athttps://github.com/bcmcpher/cca_agingand as web services reproducing the analyes at
Temporal evolution of single-cell transcriptomes ofDrosophilaolfactory projection neurons
Authors: Xie Qijing , Brbic Maria , Horns Felix , Kolluru Sai Saroja , Jones Bob , Li Jiefu , Reddy Anay , Xie Anthony , Kohani Sayeh , Li Zhuoran , McLaughlin Colleen , Li Tongchao , Xu Chuanyun , Vacek David , Luginbuhl David J. , Leskovec Jure , Quake Stephen R. , Luo Liqun , Li Hongjie 
Published: September 2020

AbstractNeurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological features. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes ofDrosophilaolfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage—neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.
Song type variations of Louisiana Waterthrush (Parkesia motacilla) and their geographic distributions
Authors: Silcock W. Ross , Schwartz Shari L. , Carlini John U. , Dinsmore Stephen J. 
Published: September 2020

AbstractLouisiana Waterthrush(Parkesia motacilla)is a familiar singer in the Western Hemisphere familyParulidae, yet apparent geographic variations in its song and potentially related causal mechanisms have not received detailed examination in previously published studies. Here, we analyzed song pattern variations of 651 Louisiana Waterthrush singers in audio spectrogram recordings obtained from our field work and publicly accessible bioacoustics archives. Visual and auditory assessment of the introductory note sequence of each song identified three distinct song types (A, B, and C) and 88.3% of the songs were assigned to one of these types. Linear Discriminant Analysis and Random Forest methods were used to verify the assignments and showed strong agreement (>90%) for Type A with slightly less agreement on Types B and C. User error rates (proportion of the Linear Discriminant Analysis classifications that were incorrect) were <10% for Types A and B, but 26% for Type C, while producer error rates (proportion of the song type for which the Linear Discriminant Analysis was incorrect) were >25% for Types A and C, but <5% for Type B. Our findings confirmed in a subset of 87 individuals that most between-individual variation was in the number of notes and note sequence duration while most within-individual variation resulted from the percent of downstrokes. The location of each singer was plotted on a map of the breeding range and results indicated the song types have large-scale discrete geographic distributions that co-occur in some regions but not range-wide. Evaluation of the distributions provided tentative support for a hypothesis that two of the song types may independently exhibit congruence with the geographic extent of Pleistocene glacial boundaries and the third song type may be distinguished by a lack of congruence, but further investigation is needed to elucidate whether the song variations represent subpopulations with three separate evolutionary histories.
Overview of the expression of key regeneration genes in embryo development and matured tissues in Axolotl (Ambystoma mexicanum)
Authors: Shah Harshil , Caballero Juan 
Published: September 2020

ABSTRACTThe axolotl is a Mexican endangered species with the capability to perform tissue regeneration in amputated extremities. Being an important research model, the complete genome of the Axolotl was sequenced in 2018 for the first time, revealing an enormous genome: the largest of any animal ever sequenced, and about 10 times larger than the human genome, a new landmark achievement in biology research.In this report, we collected 70 known genes that play an important role in tissue regeneration and searched for their expression during embryo development, regeneration, and in 6 adult tissues: the heart, liver, gills, front leg, rear leg, and tail. We observe those 70 genes expression levels in the 3 conditions and approximately 3 genes seem to be expressed exclusively in regeneration.This report displays a few insights on how this marvelous species can modulate its regenerative capabilities. There is still much more to explore with the Axolotl. Further research into their regenerative capabilities could provide researchers with the perspicacity to possibly accomplish human limb regeneration.
Performance of a point of care test for detecting IgM and IgG antibodies against SARS-CoV-2 and seroprevalence in blood donors and health care workers in Panama
Authors: Villarreal Alcibiades , Rangel Giselle , Zhang Xu , Wong Digna , Britton Gabrielle , Fernandez Patricia L. , Pérez Ambar , Oviedo Diana , Restrepo Carlos , Carreirra María B. , Sambrano Dilcia , Eskildsen Gilberto , De La Guardia Carolina , Zaldivar Yamitzel , Franco Danilo , López-Vergès Sandra , Zhang Dexi , Fan Fanjing , Wang Baojun , Sáez-Llorens Xavier , DeAntonio Rodrigo , Torres-Atencio Ivonne , Ortega-Barria Eduardo , Kosagisharaf Rao , Lleonart Ricardo , Chong Li , Goodridge Amador ,   COVID-19 serology collaborator group
Published: September 2020

ABSTRACTNovel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, which has reached 28 million cases worldwide in eight months. The serological detection of antibodies against the virus will play a pivotal role in complementing molecular tests to improve diagnostic accuracy, contact tracing, vaccine efficacy testing and seroprevalence surveillance. Here, we aimed first to evaluate a lateral flow assay’s ability to identify specific IgM and IgG antibodies against SARS-CoV-2 and second, to report the seroprevalence of these antibodies among health care workers and healthy volunteer blood donors in Panama. We recruited study participants between April 30thand July 7th, 2020. For the test validation and performance evaluation, we analyzed serum samples from participants with clinical symptoms and confirmed positive RT-PCR for SARS-CoV-2, participants with other confirmed infectious diseases, and a set of pre-pandemic serum samples. We used two by two table analysis to determine the test sensitivity and specificity as well as the kappa agreement value with a 95% confidence interval. Then, we used the lateral flow assay to determine seroprevalence among serum samples from COVID-19 patients, potentially exposed health care workers, and healthy volunteer donors. Our results show this assay reached a positive percent agreement of 97.2% (95% CI 84.2-100.0%) for detecting both IgM and IgG. The assay showed akappaof 0.898 (95%CI 0.811-0.985) and 0.918 (95% CI 0.839-0.997) for IgM and IgG, respectively. The evaluation of serum samples from hospitalized COVID-19 patients indicates a correlation between test sensitivity and the number of days since symptom onset; the highest positive percent agreement (87% (95% CI 67.0-96.3%)) was observed at ≥15 days post-symptom onset. We found an overall antibody seroprevalence of 11.6% (95% CI 8.5-15.8%) among both health care workers and healthy blood donors. Our findings suggest this lateral flow assay could contribute significantly to implementing seroprevalence testing in locations with active community transmission of SARS-CoV-2.
Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway
Authors: Ishihama Nobuaki , Choi Seung-won , Noutoshi Yoshiteru , Saska Ivana , Asai Shuta , Takizawa Kaori , He Sheng Yang , Osada Hiroyuki , Shirasu Ken 
Published: September 2020

AbstractSalicylic acid (SA) and its structural analogs are nonsteroidal anti-inflammatory drugs (NSAIDs) that target mammalian cyclooxygenases. In plants, SA acts as a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identified a number of NSAIDs that enhance bacterial effector-induced cell death. Among them, the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent immune responses in plants. TNX treatment reduces NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. Surprisingly, however, cysteine modification associated with NPR1 oligomerizationviaintermolecular disulfide bonds is not affected by either SA or TNX. Therefore, oxicam-type NSAIDs highlight importance of SA effects on the cytosolic redox status, but not on cysteine modification or oligomerization of NPR1.
Chromosome-level genome ofPoropuntius huangchuchieniprovides a diploid progenitor-like reference genome for the allotetraploidCyprinus carpio
Authors: Chen Lin , Li Bijun , Chen Baohua , Li Chengyu , Zhou Zhixiong , Zhou Tao , Yang Weidi , Xu Peng 
Published: September 2020

ABSTRACTThe diploidPoropuntius huangchuchieniin the cyprinid family, which is distributed in the Mekong and Red River basins, is one of the most closely related diploid progenitor-like species of allotetraploid common carp. Therefore, theP. huangchuchienigenome is essential for polyploidy evolution studies in Cyprinidae. Here, we report a chromosome-level genome assembly ofP. huangchuchieniby integrating Oxford Nanopore and Hi-C technology. The assembled genome size was 1021.38 Mb, 895.66 Mb of which was anchored onto 25 chromosomes with a N50 of 32.93 Mb. The genome contained 486.28 Mb repetitive elements and 24,099 protein-coding genes. Approximately 95.9% of the complete BUSCOs were detected, suggesting a high completeness of the genome. Evolutionary analysis revealed thatP. huangchuchienidiverged fromCyprinus carpioat approximately 12 Mya. Genome comparison betweenP. huangchuchieniand the B subgenome ofC. carpioprovided insights into chromosomal rearrangements during the allotetraploid speciation. With the complete gene set, 17,474 orthologous genes were identified betweenP. huangchuchieniandC. carpio, providing a broad view of the gene component in the allotetraploid genome, which is critical for future genomic and genetic analyses. The high-quality genomic dataset created forP. huangchuchieniprovides a diploid progenitor-like reference for the evolution and adaptation of allotetraploid carps.
WSB1 Regulates c-Myc Expression Through β-catenin Signaling and Forms a Feedforward Circuit Promoting the Development of Cancer
Authors: Gao Xiaomeng , Gong Yanling , You Jieqiong , Yuan Meng , Zhu Haiying , Fang Liang , Zhu Hong , Ying Meidan , He Qiaojun , Yang Bo , Cao Ji 
Published: September 2020

AbstractThe dysregulation of transcription factors is widely associated with tumorigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can directly transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies based on its regulatory mechanism hold great potential for cancer therapy. In this study, we found that WSB1, a direct target gene of c-Myc, can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. Luciferase-based promoter activity assays and RNA sequencing results confirmed that WSB1 promoted c-Myc expression through the β-catenin pathway. Mechanistically, WSB1 affected β-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-catenin and subsequently transactivated c-Myc. Of interest, the promoting effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, co-expression of WSB1 and c-Myc strongly enhanced the initiation and progression of tumours bothin vitroandin vivo. Thus, our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.
High-throughput measurements of intra-cellular and secreted cytokine from single spheroids using anchored microfluidic droplets
Authors: Saint-Sardos Adrien , Sart Sebastien , Lippera Kevin , Brient-Litzler Elodie , Michelin Sebastien , Amselem Gabriel , Baroud Charles N. 
Published: September 2020

AbstractWhile many single-cell approaches have been developed to measure secretion from anchorage-independent cells, these protocols cannot be applied to adherent cells, especially when these cells requires to be cultured in 3D formats. Here we demonstrate a platform to measure the secretions from individual spheroids of human mesenchymal stem cells, cultured within microfluidic droplets. The platform allows us to quantify the secretion from hundreds of individual spheroids in each device, by using a secondary droplet to bring functionalized micro-beads into proximity with each spheroid. We focus on vascular endothelial growth factor (VEGF) and measure a distribution of secretion levels that presents broad heterogeneity within the population of spheroids. Moreover, the intra-cellular level of VEGF-A on each spheroid, measured through immuno-staining, correlates well with the extra-cellular measurement, indicating that the heterogeneities observed at the spheroids level result from variations at the scale of individual cells. Finally, we model the molecular accumulation within the droplets and find that physical confinement is crucial for measurements of protein secretions. The model predicts the time to achieve a measurement, which scales with droplet volume. Therefore these first measurements of secretions from individual spheroids provide several new biological insights.
Genomic region associated with pod color variation in pea (Pisum sativum)
Authors: Shirasawa Kenta , Sasaki Kazuhiro , Hirakawa Hideki , Isobe Sachiko 
Published: September 2020

SUMMARYPea (Pisum sativum) was chosen as the research material by Gregor Mendel to discover the laws of inheritance. Out of seven traits studied by Mendel, genes controlling three traits including pod shape, pod color, and flower position have not been identified to date. With the aim to identify the genomic region controlling pod color, we determined the genome sequence of a pea line with yellow pods. Genome sequence reads obtained using a nanopore sequencing technology were assembled into 117,981 contigs that spanned 3.3 Gb in length and showed an N50 value of 51.2 kb. Using single nucleotide polymorphisms (SNPs) detected in a pea mapping population, these contigs were genetically anchored to the publicly available pseudomolecule sequences of the pea genome. Subsequent genetic and association analyses identified a genomic region responsible for pea pod color. At this genomic location, genes encoding 3’ exoribonucleases were selected as potential candidates controlling pod color, based on DNA sequencing and transcriptome analysis of green and yellow pod lines. The results presented in this study are expected to accelerate pan-genome studies in pea and facilitate the identification of the gene controlling one of the traits studied by Mendel.