bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell transcriptome analysis reveals mesenchymal stem cells in cavernous hemangioma
Authors: Ji Fulong , Liu Yong , Shi Jinsong , Liu Chunxiang , Fu Siqi , Wang Heng , Ren Bingbing , Mi Dong , Gao Shan , Sun Daqing 
Published: September 2021

AbstractA cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin and formation remain unknown. In the present study, we characterized the cellular heterogeneity of cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of this study is the discovery of mesenchymal stem cells (MSCs) that cause tumour formation in cavernous hemangioma and we propose that these MSCs may be abnormally differentiated or incompletely differentiated from epiblast stem cells.Other new findings include the responsive ACKR1 positive endothelial cell (ACKR1+EC) and BTNL9 positive endothelial cell (BTNL9+EC) and the BTNL9-caused checkpoint blockade enhanced by the CXCL12-CXCR4 signalling. The activated CD8+T and NK cells may highly express CCL5 for their infiltration in cavernous hemangiomas, independent on the tumor cell-derived CCL5-IFNG-CXCL9 pathway. The highly co-expression of CXCR4 and GZMB suggested that plasmacytoid dendritic cells (pDCs) function for anti-tumour as CD8+T cells in cavernous hemangiomas. The oxidised low-density lipoprotein (oxLDL) in the TME of cavernous hemangiomas may play an important role as a signalling molecular in the immune responses. Notably, we propose that oxLDL induces the oxLDL-OLR1-NLRP3 pathway by over-expression of OLR1 in M1-like macrophages, whereas oxLDL induces the oxLDL-SRs-C1q (SRs are genes encoding scavenger receptors of oxLDL except OLR1) pathway by over-expression of other scavenger receptors in M2-like macrophages.The present study revealed the origin of cavernous hemangiomas and discovered marker genes, cell types and molecular mechanisms associated with the origin, formation, progression, diagnosis or therapy of cavernous hemangiomas. The information from the present study makes important contributions to the understanding of cavernous hemangioma formation and progression and facilitates the development of gold standard for molecular diagnosis and effective drugs for treatment.
Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility
Authors: Tworig Joshua M. , Coate Chandler , Feller Marla B. 
Published: September 2021

AbstractNeural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia which exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.
SYNAPTIC DYSFUNCTION UNDERLIES ALTERATIONS IN THE INITIATION OF GOAL-DIRECTED BEHAVIORS: IMPLICATIONS FOR HIV-1 ASSOCIATED APATHY
Authors: McLaurin Kristen A. , Cranston Michael N. , Li Hailong , Mactutus Charles F. , Harrod Steven B. , Booze Rosemarie M. 
Published: September 2021

ABSTRACTIndividuals living with human immunodeficiency virus type 1 (HIV-1) exhibit an increased prevalence of neuropsychiatric comorbities (e.g., apathy) relative to their seronegative counterparts. Given the profound functional consequences associated with apathy, conceptualizing the multidimensional neuropsychiatric syndrome, and associated neural mechanisms, following chronic HIV-1 viral protein exposure remains a critical need. HIV-1 associated apathy was examined by quantifying goal-directed behaviors, indexed using voluntary wheel running, during the diurnal and nocturnal cycle. Apathetic behaviors in the HIV-1 Tg rat were characterized by a profound decrease in the number of running bouts during both the diurnal and nocturnal cycle, supporting a prominent deficit in the self-initiation of spontaneous behaviors. Additionally, HIV-1 Tg animals exhibited a decreased reinforcing efficacy of voluntary wheel running during the nocturnal cycle. Following the completion of voluntary wheel running, synaptic dysfunction in medium spiny neurons (MSNs) of the nucleus accumbens (NAc) was examined as a potential neural mechanism underlying HIV-1 associated apathy. HIV-1 Tg animals displayed prominent synaptic dysfunction in MSNs of the NAc, characterized by decreased synaptic connectivity and a population shift towards an immature dendritic spine phenotype relative to control animals. Synaptic dysfunction accounted for 42.0% to 68.5% of the variance in the number of running bouts affording a key neural mechanism underlying the self-initiation of spontaneous behaviors. The establishment of a fundamental neural mechanism underlying apathy affords a key target for the development of novel therapeutics and cure strategies for affective alterations associated with HIV-1.
Prey identity affects fitness of a generalist consumer in a brown food web
Authors: Khadempour Lily , Quijano Leslie Rivas , terHorst Casey 
Published: September 2021

AbstractThe use of ever-advancing sequencing technologies has revealed incredible biodiversity at the microbial scale, and yet we know little about the ecological interactions in these communities. For example, in the phytotelmic community found in the purple pitcher plant, Sarrecenia purpurea, ecologists typically consider the bacteria as a functionally homogenous group. In this food web, bacteria decompose detritus and are consumed by protozoa that are considered generalist consumers. Here we tested whether a generalist consumer benefits from all bacteria equally. We isolated and identified 22 strains of bacteria, belonging to six genera, from S. purpurea plants. We grew the protozoa, Tetrahymena sp. with single isolates and strain mixtures of bacteria and measured Tetrahymena fitness. We found that different bacterial strains had different effects on protozoan fitness, both in isolation and in mixture. Our results demonstrate that not accounting for composition of prey communities may affect the predicted outcome of predator-prey interactions.
Bone Structural, Biomechanical and Histomorphometric Characteristics of the Postcranial Skeleton of the Marsh Rice Rat (Oryzomys palustris)
Authors: Castillo E. J. , Croft S. , Jiron J.M , Aguirre J.I. 
Published: September 2021

AbstractINTRODUCTIONThe rice rat (Oryzomys palustris) is a non-conventional laboratory rodent species used to model some human bone disorders. However, no studies have been conducted to characterize the postcranial skeleton. Therefore, we aimed to investigate age- and gender-related features of the appendicular skeleton of this species.METHODSWe used femurs and tibiae from 94 rats of both genders aged 4-28 wks. Bone mineral content (BMC), bone mineral density (BMD), and biomechanical properties were determined in femurs. In addition, bone histomorphometry of tibiae was conducted to assess bone cells activities and bone turnover over time.RESULTSBodyweight, bone length, total metaphysis BMC/BMD, cortical BMC/BMD, cortical thickness, and cortical area progressively augmented with age. Whereas the increase in these parameters plateaued at age 16-22 wks in female rats, they continued to rise to age 28 wks in male rats. Furthermore, bone strength parameters increased with age, with few differences between genders. We also observed a rapid decrease in longitudinal growth between ages 4-16 wks. Whereas young rats had a greater bone formation rate and bone turnover, older rice rats had greater bone volume and trabecular thickness, with no differences between genders.CONCLUSIONS1) Sexual dimorphism in the rice rat becomes grossly evident at age 16 wks; 2) the age-related increases in bone mass, structural cortical parameters, and in some biomechanical property parameters plateau at an older age in male than in female rats; and 3) bone growth and remodeling significantly decreased with age indistinctive of the gender.
Complex genetic patterns and distribution limits mediated by native congeners of the worldwide invasive red-eared slider turtle
Authors: Espindola Sayra , Vázquez-Domínguez Ella , Nakamura Miguel , Osorio-Olvera Luis , Martínez-Meyer Enrique , Myers Edward A. , Overcast Isaac , Reid Brendan N. , Burbrink Frank T. 
Published: September 2021

AbstractNon-native (invasive) species offer a unique opportunity to study the geographic distribution and range limits of species, wherein the evolutionary change driven by interspecific interactions between native and non-native closely related species is a key component. The red-eared slider turtle, Trachemys scripta elegans (TSE), has been introduced and successfully established worldwide. It can coexist with its native congeners T. cataspila, T. venusta and T. taylori in Mexico. We performed comprehensive fieldwork, executed a battery of genetic analyses and applied a novel species distribution modeling approach to evaluate their historical lineage relationships and contemporary population genetic patterns. Our findings support the historical common ancestry between native TSE and non-native (TSEalien), while also highlighting the genetic differentiation of the exotic lineage. Genetic patterns are associated with their range size/endemism gradient, the microendemic T. taylori showed significant reduced genetic diversity and high differentiation, whereas TSEalien showed the highest diversity and signals of population size expansion. Counter to our expectations, lower naturally occurring distribution overlap and little admixture patterns were found between and its congeners, exhibiting reduced gene flow and clear genetic separation across neighboring species despite having zones of contact. We demonstrate that these native Trachemys species have distinct climatic niche suitability, likely preventing establishment of and displacement by the non-native TSE. Additionally, we found major niche overlap between TSEalien and native species worldwide, supporting our prediction that sites with closer ecological optima to the invasive species have higher establishment risk than those that are closer to the niche-center of the native species.
Using hypertemporal Sentinel-1 data to predict forest growing stock volume
Authors: Ge Shaojia , Tomppo Erkki , Rauste Yrjö , McRoberts Ronald E. , Praks Jaan , Gu Hong , Su Weimin , Antropov Oleg 
Published: September 2021

AbstractIn this study, we assess the potential of long time series of Sentinel-1 SAR data to predict forest growing stock volume and evaluate the temporal dynamics of the predictions. The boreal coniferous forests study site is located near the Hyytiälä forest station in central Finland and covers an area of 2,500 km2 with nearly 17,000 stands. We considered several prediction approaches (linear, support vector and random forests regression) and fine-tuned them to predict growing stock volume in several evaluation scenarios. The analyses used 96 Sentinel-1 images acquired over three years. Different approaches for aggregating SAR images and choosing feature (predictor) variables were evaluated. Our results demonstrate considerable decrease in RMSEs of growing stock volume as the number of images increases. While prediction accuracy using individual Sentinel-1 images varied from 85 to 91 m3/ha RMSE (relative RMSE 50-53%), RMSE with combined images decreased to 75.6 m3/ha (relative RMSE 44%). Feature extraction and dimension reduction techniques facilitated achieving the near-optimal prediction accuracy using only 8-10 images. When using assemblages of eight consecutive images, the GSV was predicted with the greatest accuracy when initial acquisitions started between September and January.HighlightsTime series of 96 Sentinel-1 images is analysed over study area with 17,762 forest stands.Rigorous evaluation of tools for SAR feature selection and GSV prediction.Improved periodic seasonality using assemblages of consecutive Sentinel-1 images.Analysis of combining images acquired in “frozen” and “dry summer” conditions.Competitive estimates using calculation of prediction errors with stand-area weighting.
Global anti-tumor immunity after localized, bioengineered Treg depletion
Authors: Majedi Fatemeh S. , Hasani-Sadrabadi Mohammad Mahdi , Thauland Timothy J. , Keswani Sundeep G. , Li Song , Bouchard Louis-S. , Butte Manish J. 
Published: September 2021

AbstractOver 90% of deaths from cancer occur due to solid tumors, occurring at a rate of ∼1,500 deaths per day in the US, highlighting a profound and unmet need for new therapies. Solid tumors evade clearance by T cells due to a variety of immunosuppressive properties of the tumor microenvironment. However, this immunosuppression cannot be easily blocked on a global level because systemic activation of the immune system elicits a host of complications. An ideal therapy for solid tumors would act locally to activate the immune response without evoking global adverse effects. Here we present a biodegradable, macroporous scaffold that is implanted adjacent to the tumor and suppresses the main obstacle to cancer immunosurveillance: intratumoral regulatory T cells. The scaffold also promotes the recruitment and activation of T cell effectors into the tumor, resulting in clearance of otherwise aggressive and fatal tumors in mice. Unexpectedly, the local depletion of Tregs results in an “immunological abscopal effect” acting on distant tumors. We demonstrate that this versatile platform can also deliver tumor-antigen-specific T cells directly to the peri-tumoral environment, bypassing difficulties in intravenous delivery including the environmental barriers imposed by the tumor’s vasculature. By orchestrating multiple local immunomodulatory treatments, this scaffold offers a general approach to engineer T-cell responses to solid tumors without systemic toxicities.
Tight association between microbial eukaryote andImiterviralescommunities in the Pacific Arctic Ocean
Authors: Xia Jun , Kameyama Sohiko , Prodinger Florian , Yoshida Takashi , Cho Kyoung-Ho , Jung Jinyoung , Kang Sung-Ho , Yang Eun-Jin , Ogata Hiroyuki , Endo Hisashi 
Published: September 2021

SummaryViruses are important regulatory factors of marine microbial community including microeukaryotes. However, little is known about their role in the northern Chukchi Sea of the Arctic basin, which remains oligotrophic conditions in summer. To elucidate linkages of microbial eukaryotic community with viruses as well as environmental variables, we investigated the community structures of microeukaryotes (3–144 µm and 0.2–3 µm size fractions) andImitervirales(0.2–3 µm size fraction), a major group of viruses infecting marine microeukaryotes. Surface water samples were collected at 21 ocean stations located in the northeastern Chukchi Sea (NECS), an adjacent area outside the Beaufort Gyre (Adjacent Sea; AS), and two melt ponds on sea ice in the summer of 2018. At the ocean stations, nutrient concentrations were low in most of the locations expect at the shelf in the AS. The community variations were significantly correlated between eukaryotes andImitervirales, even within the NECS characterized by relatively homogeneous environmental conditions. The association of the eukaryotic community with the viral community was stronger than that with geographical and physicochemical environmental factors. These results suggest thatImiterviralesare actively infecting their hosts even in cold and oligotrophic sea water in the Arctic Ocean.
Hybrid ssDNA repair templates enable high yield genome engineering in primary cells for disease modeling and cell therapy manufacturing
Authors: Shy Brian R. , Vykunta Vivasvan , Ha Alvin , Roth Theodore L. , Talbot Alexis , Nguyen David N. , Chen Yan Yi , Blaeschke Franziska , Vedova Shane , Mamedov Murad R. , Chung Jing-Yi , Li Hong , Wolf Jeffrey , Martin Thomas G. , Ye Lumeng , Eyquem Justin , Esensten Jonathan H. , Marson Alexander 
Published: September 2021

AbstractCRISPR-Cas9 offers unprecedented opportunities to modify genome sequences in primary human cells to study disease variants and reprogram cell functions for next-generation cellular therapies. CRISPR has several potential advantages over widely used retroviral vectors including: 1) site-specific transgene insertion via homology directed repair (HDR), and 2) reductions in the cost and complexity of genome modification. Despite rapid progress with ex vivo CRISPR genome engineering, many novel research and clinical applications would be enabled by methods to further improve knock-in efficiency and the absolute yield of live knock-in cells, especially with large HDR templates (HDRT). We recently reported that Cas9 target sequences (CTS) could be introduced into double-stranded DNA (dsDNA) HDRTs to improve knock-in, but yields and efficiencies were limited by toxicity at high HDRT concentrations. Here we developed a novel system that takes advantage of lower toxicity with single-stranded DNA (ssDNA). We designed hybrid ssDNA HDRTs that incorporate CTS sites and were able to boost knock-in percentages by >5-fold and live cell yields by >7-fold relative to dsDNA HDRTs with CTS. Knock-in efficiency and yield with ssCTS HDRTs were increased further with small molecule inhibitor combinations to improve HDR. We demonstrate application of these methods across a variety of target loci, knock-in constructs, and primary human cell types to reach ultra-high HDR efficiencies (>80-90%) which we use for pathogenic gene variant modeling and universal gene replacement strategies for IL2RA and CTLA4 mutations associated with mendelian immune disorders. Finally, we develop a GMP-compatible method for fully non-viral CAR-T cell manufacturing, demonstrating knock-in efficiencies of 46-62% and generating yields of >1.5 x 109 CAR+ T cells, well above current doses for adoptive cellular therapies. Taken together, we present a comprehensive non-viral approach to model disease associated mutations and re-write targeted genome sequences to program immune cell therapies at a scale compatible with future clinical application.
Genomic prediction of growth in a commercially, recreationally, and culturally important marine resource, the Australian snapper (Chrysophrys auratus)
Authors: Sandoval-Castillo Jonathan , Beheregaray Luciano B. , Wellenreuther Maren 
Published: September 2021

AbstractGrowth is one of the most important traits of an organism. For exploited species, this trait has ecological and evolutionary consequences as well as economical and conservation significance. Rapid changes in growth rate associated with anthropogenic stressors have been reported for several marine fishes, but little is known about the genetic basis of growth traits in teleosts. We used reduced genome representation data and genome-wide association approaches to identify growth-related genetic variation in the commercially, recreationally, and culturally important Australian snapper (Chrysophrys auratus, Sparidae). Based on 17,490 high-quality SNPs and 363 individuals representing extreme growth phenotypes from 15,000 fish of the same age and reared under identical conditions in a sea pen, we identified 100 unique candidates that were annotated to 51 proteins. We documented a complex polygenic nature of growth in the species that included several loci with small effects and a few loci with larger effects. Overall heritability was high (75.7%), reflected in the high accuracy of the genomic prediction for the phenotype (small vs large). Although the SNPs were distributed across the genome, most candidates (60%) clustered on chromosome 16, which also explains the largest proportion of heritability (16.4%). This study demonstrates that reduced genome representation SNPs and the right bioinformatic tools provide a cost-efficient approach to identify growth-related loci and to describe genomic architectures of complex quantitative traits. Our results help to inform captive aquaculture breeding programmes and are of relevance to monitor growth-related evolutionary shifts in wild populations in response to anthropogenic pressures.
Powerful, efficient QTL mapping inDrosophila melanogasterusing bulked phenotyping and pooled sequencing
Authors: Macdonald Stuart J. , Cloud-Richardson Kristen M. , Sims-West Dylan J. , Long Anthony D. 
Published: September 2021

AbstractDespite the value of Recombinant Inbred Lines (RILs) for the dissection of complex traits, large panels can be difficult to maintain, distribute, and phenotype. An attractive alternative to RILs for many traits leverages selecting phenotypically-extreme individuals from a segregating population, and subjecting pools of selected and control individuals to sequencing. Under a bulked or extreme segregant analysis paradigm, genomic regions contributing to trait variation are revealed as frequency differences between pools. Here we describe such an extreme quantitative trait locus, or X-QTL mapping strategy that builds on an existing multiparental population, the DSPR (DrosophilaSynthetic Population Resource), and involves phenotyping and genotyping a population derived by mixing hundreds of DSPR RILs. Simulations demonstrate that challenging, yet experimentally tractable X-QTL designs (>=4 replicates, >=5000 individuals/replicate, and a selection intensity of 5-10%) yield at least the same power as traditional RIL-based QTL mapping, and can localize variants with sub-centimorgan resolution. We empirically demonstrate the effectiveness of the approach using a 4-fold replicated X-QTL experiment that identifies 7 QTL for caffeine resistance. Two mapped X-QTL factors replicate loci previously identified in RILs, 6/7 are associated with excellent candidate genes, and RNAi knock-downs support the involvement of 4 genes in the genetic control of trait variation. For many traits of interest to drosophilists a bulked phenotyping/genotyping X-QTL design has considerable advantages.