bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired KDM2B-mediated PRC1 recruitment to chromatin causes neural stem cell senescence and ASD/ID-like behavioral deficits
Authors: Gao Yuen , Duque-Wilckens Natalia , Aljazi Mohammad B , Moeser Adam J , Mias George I , Robison Alfred J , Zhang Yi , He Jin 
Published: September 2021

AbstractAutism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental diseases associated with various genetic mutations. Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with human ASD/ID. However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID pathogenesis remain undetermined. Here we show Kdm2b, one of the genes located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the developing mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell cycle arrest, NSC premature senescence, and leading to the loss of NSC populations in the brain. Importantly, the Kdm2b mutation is sufficient to induce ASD/ID-like social and memory deficits in adult mice. Thus, our study reveals a critical role of an epigenetic factor KDM2B in normal brain development, a causality between the Kdm2b mutation and genesis of ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation and NSC senescence to the12q24.31 microdeletion-associated ASD/ID.
Morphometric Analysis of Lungfish Endocasts Elucidates Early Dipnoan Palaeoneurological Evolution
Authors: Clement Alice M. , Challands T. J. , Cloutier Richard , Houle Laurent , Ahlberg Per E. , Collin Shaun P. , Long John A. 
Published: September 2021

ABSTRACTLungfish (Dipnoi) are lobe-finned fish (Sarcopterygii) that have persisted for over 400 million years from the Devonian Period to present day. They are the extant sister group to tetrapods and thus have the ability to provide unique insight into the condition of the earliest tetrapods as well as their own evolutionary history. The evolution of their dermal skull and dentition is relatively well understood, but this is not the case for the central nervous system. While the brain itself has very poor preservation potential and is not currently known in any fossil lungfish, substantial indirect information about it and associated structures such as the inner ears can be obtained from the cranial endocast. However, before the recent development of X-ray tomography as a palaeontological tool, these endocasts could not be studied non-destructively, and few detailed studies were undertaken. Here we describe and illustrate the endocasts of six Palaeozoic lungfishes (Iowadipterus halli, Gogodipterus paddyensis, Pillararhynchus longi, Griphognathus whitei, Orlovichthys limnatis, andRhinodipterus ulrichi) from tomographic scans. We combine these with six previously described lungfish endocasts (4 fossil and 2 recent taxa), also based on tomographic studies, into a 12-taxon data set for multivariate morphometric analysis using 17 variables. We find that the olfactory region appears to be more highly plastic than the hindbrain, and undergoes significant elongation in several taxa. Further, while the semicircular canals covary as an integrated module, the utriculus and sacculus of the inner ear instead vary independently of each other. The functional and phylogenetic implications of our findings are discussed.
A model of preferential pairing between epithelial and dendritic cells in thymic antigen transfer
Authors: Vobořil Matouš , Březina Jiří , Brabec Tomáš , Dobeš Jan , Ballek Ondřej , Dobešová Martina , Manning Jasper , Blumberg Richard S. , Filipp Dominik 
Published: September 2021

AbstractMedullary thymic epithelial cells (mTECs) which produce and present self-antigens are essential for the establishment of central tolerance. Since mTEC numbers are limited, their function is complemented by thymic dendritic cells (DCs), which transfer mTEC-produced self-antigens via cooperative antigen transfer (CAT). While CAT is required for effective T cell selection, many aspects remain enigmatic. Given the recently described heterogeneity of mTECs and DCs, it is unclear whether the antigen acquisition from a particular TEC subset is mediated by preferential pairing with specific subset of DCs. Using several relevant Cre-based mouse models controlling the expression of fluorescent proteins, we found that in regards to CAT, each subset of thymic DCs preferentially targets distinct mTEC subset(s) and importantly, XCR1+ activated DCs represented the most potent subset in CAT. Interestingly, one thymic DC can acquire antigen repetitively and of these, monocyte-derived DCs (moDC) were determined to be the most efficient in repetitive CAT. moDCs also represented the most potent DC subset in the acquisition of antigen from other DCs. These findings suggest a preferential pairing model for the distribution of mTEC-derived antigens among distinct populations of thymic DCs.
BioCAT: a novel tool to search biosynthetic gene clusters producing nonribosomal peptides with a known structure
Authors: Konanov D.N. , Krivonos D.V. , Ilina E.N. , Babenko V.V. 
Published: September 2021

AbstractMotivationNonribosomal peptides are a class of secondary metabolites synthesized by multimodular enzymes named nonribosomal peptide synthetases and mainly produced by bacteria and fungi. It has been shown that non-ribosomal peptides have a huge structural and functional diversity including antimicrobial activity, therefore, they are of increasing interest for modern biotechnology. Methods such as NMR and LC-MS/MS allow to determine a peptide structure precisely, but it is often not a trivial task to find natural producers of them. Today, the search is usually performed manually, mostly with tools such as antiSMASH or Prism. However, there are cases when potential producers should be found among hundreds of strains, for instance, when analyzing metagenomes data. Thus, the development of automated approaches is a high-priority task for further nonribosomal peptides research.ResultsWe developed BioCAT, a two-side approach to find biosynthetic gene clusters which may produce a given nonribosomal peptide when the structure of interesting nonribosomal peptide has already been found. Formally, BioCAT unites the antiSMASH software and the rBAN retrosynthesis tool but some improvements were added to both gene cluster and peptide chemical structure analyses. The main feature of the method is an implementation of position specific score matrix to store specificities of nonribosomal peptide synthetase modules, which has increased the alignment quality in comparison with more strict approaches developed earlier. An ensemble model was implemented to calculate the final alignment score. We tested the method on a manually curated nonribosomal peptides producers database and compared it with a competing tool called GARLIC. Finally, we showed the method applicability on several external examples.AvailabilityBioCAT is available on the GitHub repository or via pipContactkonanovdmitriy@gmail.com
Permutational immune analysis reveals architectural similarities between inflammaging, Down syndrome and autoimmunity
Authors: Lambert Katharina , Moo Keagan G. , Arnett Azlann , Goel Gautam , Flynn Kaitlin J. , Speake Cate , Wiedeman Alice E. , Greenbaum Carla J. , Long S. Alice , Partridge Rebecca , Buckner Jane H. , Khor Bernard 
Published: September 2021

AbstractPeople with Down syndrome show cellular and clinical features of dysregulated aging of the immune system, including naïve-memory shift in the T cell compartment and increased incidence of autoimmunity. However, a quantitative understanding of how various immune compartments change with age in Down syndrome remains lacking. Here we performed deep immunophenotyping of a cohort of individuals with Down syndrome across the lifespan, selecting for individuals not affected by autoimmunity. We simultaneously interrogated age- and sex-matched healthy neurotypical controls and people with type 1 diabetes, as a representative autoimmune disease. We built a new analytical software, IMPACD, that enabled us to rapidly identify many features of immune dysregulation in Down syndrome that are recapitulated in other autoimmune diseases. We found significant quantitative and qualitative dysregulation of naïve CD4+and CD8+T cells in Down syndrome and identified IL-6 as a candidate driver of some of these changes, thus extending the consideration of immunopathologic cytokines in Down syndrome beyond interferons. Notably, we successfully used immune cellular composition to generate three quantitative models of aging (i.e. immune clocks) trained on control subjects. All three immune clocks demonstrated significantly advanced immune aging in people with Down syndrome. Notably, one of these clocks, informed by Down syndrome-relevant biology, also showed advanced immune aging in people with type 1 diabetes. Together, our findings demonstrate a novel approach to studying immune aging in Down syndrome which may have implications in the context of other autoimmune diseases.One Sentence SummaryPermutational analysis of immune landscape reveals advanced immune aging in people with Down syndrome and in people with type 1 diabetes.
Plant defense synergies and antagonisms affect performance of specialist herbivores of common milkweed
Authors: Edwards Collin , Ellner Stephen , Agrawal Anurag 
Published: September 2021

AbstractAs a general rule, plants defend against herbivores with multiple traits. The defense synergy hypothesis posits that some traits are more effective when co-expressed with others compared to their independent efficacy. However, this hypothesis has rarely been tested outside of phytochemical mixtures, and seldom under field conditions. We tested for synergies between multiple defense traits of common milkweed(Asclepias syriaca)by assaying the performance of two specialist chewing herbivores on plants in natural populations. We employed regression and a novel application of Random Forests to identify synergies and antagonisms between defense traits. We found the first direct empirical evidence for two previously hypothesized defense synergies in milkweed (latex by secondary metabolites, latex by trichomes), and identified numerous other potential synergies and antagonisms. Our strongest evidence for a defense synergy was between leaf mass per area and low nitrogen content; given that these “leaf economic” traits typically covary in milkweed, a defense synergy could reinforce their co-expression. We report that each of the plant defense traits showed context-dependent effects on herbivores, and increased trait expression could well be beneficial to herbivores for some ranges of observed expression. The novel methods and findings presented here complement more mechanistic approaches to the study of plant defense diversity, and provide some of the best evidence to date that multiple classes of plant defense synergize in their impact on insects. Plant defense synergies against highly specialized herbivores, as shown here, are consistent with ongoing reciprocal evolution between these antagonists.
Model-based characterization of the selectivity of neurons in primary visual cortex
Authors: Bartsch Felix , Cumming Bruce G. , Butts Daniel A. 
Published: September 2021

AbstractTo understand the complexity of stimulus selectivity in primary visual cortex (V1), models constructed to match observed responses to complex time-varying stimuli, instead of to explain responses to simple parametric stimuli, are increasingly used. While such models often can more accurately reflect the computations performed by V1 neurons in more natural visual environments, they do not by themselves provide insight into established measures of V1 neural selectivity such as receptive field size, spatial frequency tuning and phase invariance. Here, we suggest a series of analyses that can be directly applied to encoding models to link complex encoding models to more interpretable aspects of stimulus selectivity, applied to nonlinear models of V1 neurons recorded in awake macaque in response to random bar stimuli. In linking model properties to more classical measurements, we demonstrate several novel aspects of V1 selectivity not available to simpler experimental measurements. For example, we find that individual spatiotemporal elements of the V1 models often have a smaller spatial scale than the overall neuron sensitivity, and that this results in non-trivial tuning to spatial frequencies. Additionally, our proposed measures of nonlinear integration suggest that more classical classifications of V1 neurons into simple versus complex cells are spatial-frequency dependent. In total, rather than obfuscate classical characterizations of V1 neurons, model-based characterizations offer a means to more fully understand their selectivity, and provide a means to link their classical tuning properties to their roles in more complex, natural, visual processing.Significance statementVisual neurons are increasingly being studied with more complex, natural visual stimuli, with increasingly complex models necessary to characterize their response properties. Here, we describe a battery of analyses that relate these more complex models to classical characterizations. Using such model-based characterizations of V1 neurons furthermore yields several new insights into V1 processing not possible to capture in more classical means to measure their visual selectivity.
Mechanisms of loading and release of the 9-1-1 checkpoint clamp
Authors: Castaneda Juan C. , Schrecker Marina , Remus Dirk , Hite Richard K. 
Published: September 2021

Abstract5’ single-stranded/double-stranded DNA serve as loading sites for the checkpoint clamp, 9-1-1, which mediates activation of the apical checkpoint kinase, ATRMec1. However, the basis for 9-1-1’s recruitment to 5’ junctions is unclear. Here, we present structures of the yeast checkpoint clamp loader, Rad24-RFC, in complex with 9-1-1 and a 5’ junction and in a post-ATP-hydrolysis state. Unexpectedly, 9-1-1 adopts both closed and planar open states in the presence of Rad24-RFC and DNA. Moreover, Rad24-RFC associates with the DNA junction in the opposite orientation of processivity clamp loaders with Rad24 exclusively coordinating the double-stranded region. ATP hydrolysis stimulates conformational changes in Rad24-RFC, leading to disengagement of DNA-loaded 9-1-1. Together, these structures explain 9-1-1’s recruitment to 5’ junctions and reveal new principles of sliding clamp loading.
High-quality genome assembly of Cinnamomum burmannii (chvar. Borneol) provides insights into the natural borneol biosynthesis
Authors: Li Fangping , Huang Shilin , Mei Yu , Wu Bingqi , Hou Zhuangwei , Zhan Penglin , Cai Shike , Liu Qingmei , Hou Zhihao , Zhao Junliang , Wang Jihua 
Published: September 2021

AbstractCinnamomum burmannii (chvar. Borneol) is a well-known medicinal and industrial plant cultivated in the Lingnan region of China. It is the key source from organism of natural borneol (D-borneol), one of the precious and widely used Chinese herbal medicines with a variety of medicinal effects. Here, we report a high-quality chromosome-scale genome assembly of C. burmannii (chvar. Borneol) using Pacbio single-molecule sequencing and Hi-C technology. The assembled genome size was 1.14 GB with a scaffold N50 of 94.30 Mb, while 98.77% of the assembled sequences were anchored on 12 pseudochromosomes including 41549 protein-coding genes. Genomic evolution analysis revealed C. burmannii and C. micranthum shared two Lauraceae unique ancestral whole-genome duplication (WGD) events. Likewise, comparative genomic analysis showed strong collinearity between these two species. Besides, the analysis for Long Terminal Repeat Retrotransposons (LTR-RTs) indicated the outbreak of LTR-RTs insertion made a great contribution to the size difference of genomes between C. burmannii and C. micranthum. Furthermore, the candidate genes in pathway associated with natural borneol synthesis were identified on the genome and their differential expressions were analyzed in various biological tissues. We considered that several of genes in Mevalonate (MVA) Methylerythritol Phosphate (MEP) pathways or in downstream pathway have the potential to be the key factors in the biosynthesis of D-borneol. We also constructed the genome database (CAMD; http://www.cinnamomumdatabase.com/) of Cinnamomum species for a better data utilization in the future. All these results will enrich the genomic data of Lauraceae plants and facilitate genetic improvement of this commercially important plant.
Mapping vegetation types in Antarctic Peninsula and South Shetlands islands using Sentinel-2 images and Google Earth Engine cloud computing
Authors: Lima da Fonseca Eliana , Casagrande dos Santos Edvan , Ribeiro de Figueiredo Anderson , Simões Jefferson Cardia 
Published: September 2021

AbstractThe Antarctic vegetation maps are usually made using very high-resolution images collected by orbital sensors or unmanned aerial vehicles, generating isolated maps with information valid only for the time of image acquisition. In the context of global environmental change, mapping the current Antarctic vegetation distribution on a regular basis is necessary for a better understanding of the changes in this fragile environment. This work aimed to generate validated vegetation maps for the North Antarctic Peninsula and South Shetlands Islands based on Sentinel-2 images using cloud processing. Sentinel-2 imagery level 1C, acquired between 2016 and 2021 (January-April), were used. Land pixels were masked with the minimum value composite image for the “water vapor” band. The NDVI maximum value composite image was sliced, and its classes were associated with the occurrence of algae (0.15 – 0.20), lichens (0.20 – 0.50), and mosses (0.50 – 0.80). The vegetation map was validated by comparing it with those from the literature. The present study showed that Sentinel-2 images allow building a vegetation type distribution map for Antarctica Peninsula and South Shetlands Islands.
Characterization of the microbiota associated with 12-week-old bovine fetuses exposed to divergent in utero nutrition
Authors: Amat Samat , Holman Devin B. , Schmidt Kaycie , McCarthy Kacie L. , Dorsam Sheri T. , Ward Alison K. , Borowicz Pawel P. , Reynolds Lawrence P. , Caton Joel S. , Sedivec Kevin K. , Dahlen Carl R. 
Published: September 2021

ABSTRACTA recent study reported the existence of a diverse microbiota in 5-to-7-month-old calf fetuses, suggesting that colonization of the bovine gut with so-called “pioneer” microbiota may begin during mid-gestation. In the present study, we investigated 1) the presence of microbiota in bovine fetuses at early gestation (12 weeks), and 2) whether the fetal microbiota is influenced by the maternal rate of gain or dietary supplementation with vitamins and minerals (VTM) during early gestation. Amniotic and allantoic fluids, and intestinal and placental (cotyledon) tissue samples obtained from fetuses (n = 33) on day 83 of gestation were processed for the assessment of fetal microbiota using 16S rRNA gene sequencing. The sequencing results revealed that a diverse and complex microbial community was present in each of these fetal compartments evaluated. Allantoic and amniotic fluids, and fetal intestinal and placenta microbiota each had distinctly different (0.047 ≥ R2 ≥ 0.019, P ≤ 0.031) microbial community structures. Allantoic fluid had a greater (P < 0.05) microbial richness (number of OTUs) (Mean 122) compared to amniotic fluid (84), intestine (63) and placenta (66). Microbial diversity (Shannon index) was similar for the intestinal and placental samples, and both were less diverse compared with fetal fluid microbiota (P < 0.05). Thirty-nine different archaeal and bacterial phyla were detected across all fetal samples, with Proteobacteria (55%), Firmicutes (16.2%), Acidobacteriota (13.6%) and Bacteroidota (5%) predominating. Among the 20 most relatively abundant bacterial genera, Acidovorax, Acinetobacter, Brucella, Corynebacterium, Enterococcus, Exiguobacterium and Stenotrophomonas differed by fetal sample type (P < 0.05). A total of 55 taxa were shared among the four different microbial communities. qPCR of bacteria in the intestine and placenta samples as well as scanning electron microscopy imaging of fetal fluids provided additional evidence for the presence of a microbiota in these samples. Minor effects of maternal rate of gain and VTM supplementation, and their interactions on microbial richness and composition were detected. Overall, the results of this study indicate that colonization with pioneer microbiota may occur during early gestation in bovine fetuses, and that that the maternal nutritional regime during gestation may influence the early fetal microbiota.
GABA and IA Independently Regulate rNST Responses to Afferent Input
Authors: Chen Z. , Terman D.H. , Travers S.P. , Travers J.B. 
Published: September 2021

AbstractTaste responses in the rostral nucleus of the solitary tract (rNST) influence motivated ingestive behavior via ascending pathways, and consummatory reflex behavior via local, brainstem connections. Modifications to the afferent signal within the rNST include changes in gain (the overall rate of neuron activity) and changes in gustatory tuning (the degree to which individual neurons respond to divergent gustatory qualities). These alterations of the sensory signal derive from both synaptic interactions within the nucleus and the constitutive cellular membrane properties of rNST neurons. GABA neurons are well represented within the rNST, as is expression of KV4.3, a channel for a rapidly inactivating outward K+ current (IA). GABAergic synapses suppress rNST responses to afferent input and previous studies showed that this suppression is greater in cells expressing IA, suggesting a possible interaction. Here, we examine the potential interaction between GABAergic inhibition and IA channels in a series of patch clamp experiments. Optogenetic release of GABA suppressed rNST responses to afferent (electrical) stimulation and this effect was greater in cells with IA, confirming an earlier report. We further observed that the composite inhibitory postsynaptic potential was larger in IA positive cells, suggesting one mechanism for the greater afferent suppression. Blocking IA with the channel blocker AmmTX3, enhanced the response to afferent stimulation, suggesting a suppressive role for this channel in regulating afferent input at rest. However, pharmacologic blockade of IA did not suppress GABAergic inhibition, indicating that IA and GABA independently regulate excitatory afferent input.