Major Subpopulations Research Articles

Single-Cell Sequencing of Immune Cells in Human Aortic Dissection Tissue Provides Insights Into Immune Cell Heterogeneity.

BackgroundInflammation plays an important role in the progression of sporadic aortic dissection (AD). Immune cells, especially macrophages, infiltrate the aorta and secrete inflammatory cytokines and matrix metalloproteinases to cause degradation of the extracellular matrix, thereby contributing to the pathogenesis of AD. However, the cellular heterogeneity within these immune cells has not been fully characterized.MethodsWe used single-cell RNA sequencing to profile the transcriptomes of all immune cells in AD tissue and normal aorta. Using magnetic-activated cell sorting gating on CD45, we obtained a higher resolution identification of the immune cell subsets in the aorta.ResultsWe observed significant differences in the proportion of major immune cell subpopulations between AD and normal aorta tissues. Macrophages accounted for a higher percentage in the normal aorta, while the proportions of T cells, B cells and natural killer (NK) cells were all increased in AD tissues. Macrophage clusters that expanded in AD tissues originated primarily from circulating monocytes and expressed genes encoding proinflammatory cytokines and molecules involved in tissue repair. T and NK cells in AD tissues exhibited enhanced cytotoxic properties. A cluster of CD4+ T cells that had expanded in AD tissues was Th17-like and might contribute to the pathogenesis of AD. Cell–cell interaction analysis highlighted the increased communication between macrophages and T cells, which primarily regulated the costimulation of T cells.ConclusionsOur study provides a comprehensive characterization of immune cells in the dissected aorta with an emphasis on the role of macrophages and T cells. The information from our study improves our understanding of immune mechanisms in AD formation and helps to identify additional useful targets for early diagnosis or therapy of AD.

Encoding of Environmental Cues in Central Amygdala Neurons during Foraging.

To successfully forage in an environment filled with rewards and threats, animals need to rely on familiar structures of their environment that signal food availability. The central amygdala (CeA) is known to mediate a panoply of consummatory and defensive behaviors, yet how specific activity patterns within CeA subpopulations guide optimal choices is not completely understood. In a paradigm of appetitive conditioning in which mice freely forage for food across a continuum of cues, we found that two major subpopulations of CeA neurons, Somatostatin-positive (CeASst) and protein kinase Cδ-positive (CeAPKCδ) neurons, can assign motivational properties to environmental cues. Although the proportion of food responsive cells was higher within CeASst than CeAPKCδ neurons, only the activities of CeAPKCδ, but not CeASst, neurons were required for learning of contextual food cues. Our findings point to a model in which CeAPKCδ neurons may incorporate stimulus salience together with sensory features of the environment to encode memory of the goal location.SIGNIFICANCE STATEMENT The CeA has a very important role in the formation of memories that associate sensory information with aversive or rewarding representation. Here, we used a conditioned place preference paradigm, where freely moving mice learn to associate external cues with food availability, to investigate the roles of CeA neuron subpopulations. We found that CeASst and CeAPKCδ neurons encoded environmental cues during foraging but only the activities of CeAPKCδ neurons were required for learning of contextual food cues.

Genetic diversity of Malagasy baobabs: implications for conservation

Assessing the genetic diversity of species and populations is critical for evaluating extinction vulnerability and provides important information for identifying populations of concern and/or those that should be targeted for breeding material. Baobabs (Adansonia L.) are botanical icons for conservation, with increasing attention regarding their threatened status from both scientists and non-scientists alike. Baobabs are of particular interest especially in Madagascar, where six of the eight species are endemic, and three are listed as Endangered or Critically Endangered by the International Union for Conservation of Nature (IUCN). Although A. madagascariensis Baill., A. rubrostipa Jum. & H. Perrier and A. za Baill. are more widespread and classified by IUCN as Least Concern, they show regional variation, which may reflect hidden genetic diversity or even the existence of cryptic species. Here we assess the genetic diversity of the Malagasy baobabs to serve as a basis for future conservation and management planning. Our study used a targeted sequence capture approach (hybrid enrichment) to obtain hundreds of low-copy nuclear loci with phased alleles to assess genetic diversity in the six species and their major regional subpopulations. We discuss the implications of proper delineation of species taxonomy for management issues associated with conservation. We hope such genetic information will guide more targeted population genetic assessments and inform conservation and management efforts, including identification of isolated or disjunct populations that may warrant targeted actions.

Clinicopathological Manifestations and Immune Phenotypes in Adult-Onset Immunodeficiency with Anti-interferon-γ Autoantibodies.

Anti-interferon (IFN)-γ autoantibodies (anti-IFN-γ Abs) is an emerging adult-onset immunodeficiency syndrome. Immune dysfunction in this distinct disorder remains to be clarified. We prospectively collected blood samples of 20 patients with anti-IFN-γ Abs and 40 healthy normal subjects. The percentages of lymphocyte subpopulations, most relevant to T, B, and NK cells, and the percentages of stimulated lymphocytes with cytokine production were assessed using eight-color flow cytometry. The results were adjusted to age and absolute lymphocyte counts. Most (85%) patients presented nontuberculous mycobacterial infection. Skin lesions were predominantly manifested by neutrophilic dermatoses. The involved lymph nodes had granulomatous inflammation, except 22.2% showing atypical lymphoid hyperplasia without granuloma formation. The percentages of CD4 + T cells and nonactivated subpopulations (recent thymic emigrants and naïve subtypes) decreased significantly with increased expression of activation markers and polarization to differentiated cells. The percentage of NK cells increased, but that of two major NK subpopulations, CD161 + CD56bright and CD161 + CD56 + CD16 + subsets, decreased. Increased CD161dim, CD161 + CD56 - CD16 + , and CD57 + NK cell subsets coupled with the decreased expression of NKp30 and NKp46 indicate reconfiguration of the NK cell population and acquisition of adaptive features. Intracellular cytokine production of the lymphocyte subpopulations was significantly low in the patients compared with the control group. We conclude that the immune system in patients with anti-IFN-γ Abs could be exhausted in T cells and be adaptive in NK cells, contributing to the distinct clinicopathologic features.

The Splenic Marginal Zone in Children Is Characterized by a Subpopulation of CD27-Negative, Lowly IGHV-Mutated B Cells.

Young children and older adults suffer from enhanced susceptibility to infections with blood-borne pathogens. An essential step towards immunity is the establishment of a splenic marginal zone (sMZ), which is immature at below 2 years of age. At approximately 5 years of age, an adult level of protection is reached but wanes again in older adults. Although the infant sMZ is thought to contain mostly naïve B cells, memory B cells are recruited to and recirculate from the sMZ throughout life, and class-switched sMZ B cells dominate in older adults. For a better resolution of naïve versus memory B-cell subset accumulation in the sMZ, we performed a single cell-based gene expression analysis of (CD21highIgMhigh) sMZ B cells among five healthy donors (age 3 to 48 years) and validated the sMZ B-cell subset composition by flow cytometry of 147 spleen biopsies (age 0 to 82 years). We identified a major sMZ B-cell subpopulation, which is abundant at birth but decreases with age. These cells lack CD27 expression but carry a weak-to-intermediate memory B-cell signature. These CD27neg sMZ B cells are either IGHV-unmutated or carry only a few IGHV mutations early in life but show average memory B-cell IGHV mutation frequencies (>3%) in adults. The activation and proliferation potential of CD27neg sMZ B cells is significantly above that of non-sMZ B cells already in children. Our study suggests that the human sMZ B-cell pool changes with age, encompassing a major population of lowly Ig-mutated CD27neg but antigen-experienced B cells early in life.

Quantitative In-Depth Transcriptome Analysis Implicates Peritoneal Macrophages as Important Players in the Complement and Coagulation Systems.

To obtain a more detailed picture of macrophage (MΦ) biology, in the current study, we analyzed the transcriptome of mouse peritoneal MΦs by RNA-seq and PCR-based transcriptomics. The results show that peritoneal MΦs, based on mRNA content, under non-inflammatory conditions produce large amounts of a number of antimicrobial proteins such as lysozyme and several complement components. They were also found to be potent producers of several chemokines, including platelet factor 4 (PF4), Ccl6, Ccl9, Cxcl13, and Ccl24, and to express high levels of both TGF-β1 and TGF-β2. The liver is considered to be the main producer of most complement and coagulation components. However, we can now show that MΦs are also important sources of such compounds including C1qA, C1qB, C1qC, properdin, C4a, factor H, ficolin, and coagulation factor FV. In addition, FX, FVII, and complement factor B were expressed by the MΦs, altogether indicating that MΦs are important local players in both the complement and coagulation systems. For comparison, we analyzed human peripheral blood monocytes. We show that the human monocytes shared many characteristics with the mouse peritoneal MΦs but that there were also many major differences. Similar to the mouse peritoneal MΦs, the most highly expressed transcript in the monocytes was lysozyme, and high levels of both properdin and ficolin were observed. However, with regard to connective tissue components, such as fibronectin, lubricin, syndecan 3, and extracellular matrix protein 1, which were highly expressed by the peritoneal MΦs, the monocytes almost totally lacked transcripts. In contrast, monocytes expressed high levels of MHC Class II, whereas the peritoneal MΦs showed very low levels of these antigen-presenting molecules. Altogether, the present study provides a novel view of the phenotype of the major MΦ subpopulation in the mouse peritoneum and the large peritoneal MΦs and places the transcriptome profile of the peritoneal MΦs in a broader context, including a comparison of the peritoneal MΦ transcriptome with that of human peripheral blood monocytes and the liver.

Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

The H2O2 inherently released by the mycobacterial minor subpopulation enhances the survival of the major kin subpopulation against rifampicin

Exposure to antibiotics most often generates oxidative stress in bacteria. Oxidative stress survival mechanisms would facilitate the evolution of antibiotic resistance. As part of an effort to understand oxidative stress survival mechanisms in mycobacteria, here we show that the minor subpopulation (SCs; short-sized cells constituting 10% of the population) of Mycobacterium smegmatis significantly increased the survival of its major kin subpopulation (NCs; normal/long-sized cells constituting 90% of the population) in the mid-log-phase (MLP) cultures against the oxidative stress induced by rifampicin and exogenously added H2O2 (positive control). We had earlier shown that the SCs in the MLP cultures inherently and naturally release significantly high levels of H2O2 into the medium. Addition of the SCs' culture supernatant, unlike the supernatant of the dimethylthiourea (H2O2 scavenger) exposed SCs, enhanced the survival of NCs. It indicated that NCs' survival required the H2O2 present in the SCs' supernatant. This H2O2 transcriptionally induced high levels of catalase-peroxidase (KatG) in the NCs. The naturally high KatG levels in the NCs significantly neutralised the endogenous H2O2 formed upon exposure to rifampicin or H2O2, thereby enhancing the survival of NCs against oxidative stress. The absence of such enhanced survival in the furA-katG and katG knockout (KO) mutants of NCs in the presence of wild-type SCs, confirmed the requirement of the H2O2 present in the SCs' supernatant and NCs' KatG for enhanced oxidative stress survival. The presence of SCs:NCs at 1:9 in the pulmonary tuberculosis patients' sputum alludes to the clinical significance of the finding.

Detrital zircon geochronology of Late Cretaceous successions in the Ganzhou Basin, South China: evidence of a major tectonic transition

Abstract Situated within the southern segment of the South China Block, the Ganzhou Basin formed owing to subduction of the palaeo-Pacific plate beneath the South China Block. Late Cretaceous successions in this basin consist of fluvial and lacustrine facies red beds hosting abundant dinosaur and dinosaur egg fossils. This study reports detrital zircon geochronological data from a crystallized tuff and four sandstones found in the Late Cretaceous Ganzhou Group of the Ganzhou Basin. Age distributions included four major age subpopulations of predominantly Triassic, Devonian–Ordovician, Neoproterozoic and Paleoproterozoic ages. These indicate source material derived from Yanshanian and Triassic granitoids as well as from Kwangsian and Jiangnan orogens. Age signatures generally resemble those recorded in the adjacent Nanxiong Basin but also include distinctive features. Provenance signatures from successive units indicate a tectonic transition from intracontinental extension at c. 120 Ma to compression near the Cretaceous/Paleogene boundary. This tectonic transition was probably driven by continent–continent collision between the Indian and Eurasian plates, as well as by a shift in the subduction direction of the palaeo-Pacific plate beneath the Eurasian plate.

Growth and division mechanisms by which genetic resisters emerge from the rifampicin-surviving population of differentially antibiotic-susceptible mycobacterial subpopulations.

We recently reported the de novo emergence of unusually high numbers of antibiotic resisters from the in vitro cultures of Mycobacterium tuberculosis and Mycobacterium smegmatis surviving in the presence of minimum bactericidal concentration (MBC) of antituberculosis antibiotics. The resisters emerged due to multiple asymmetric divisions of elongated mother cells containing multiple nucleoids and multiple septae. We had earlier found a minor subpopulation of short-sized cells (SCs) and a major subpopulation of normal-sized cells (NCs) (10% and 90%, respectively, of the whole population), with significant difference in antibiotic susceptibility and resister generation frequency, in the in vitro cultures of M. tuberculosis, M. smegmatis, and Mycobacterium xenopi, as well as in pulmonary tuberculosis patients' sputum. However, the mechanisms of growth and division promoting the emergence of antibiotic resisters from these subpopulations remained unknown. Therefore, here, we took up the first-time study to find out the mechanism of growth and division by which antibiotic resisters emerge from the antibiotic-surviving population of the two subpopulations of M. smegmatis. M. smegmatis SCs and NCs were fractionated from mid-log phase cultures using Percoll gradient centrifugation; their purity was checked and exposed to 10×, 2×, and 0.4× MBC of rifampicin for 120 h. The colony-forming units (CFUs) were determined on rifampicin-free plates for the total population and on rifampicin-containing plates for scoring rifampicin resisters. The phenotype and the morphology of the cells at various stages of the exposure were determined using transmission electron microscopy. The dynamic growth and division mechanisms of the cells to emerge as rifampicin resisters were monitored using live-cell time-lapse imaging. The rifampicin resisters were sequenced for mutations in the rifampicin resistance determining region of rpoB gene. Statistical significance was calculated using two-tailed paired t-test, with *P ≤ 0.05 and **P ≤ 0.01. Multinucleated and multiseptated elongated cells emerged from their respective antibiotic-surviving populations. They produced a large number of sibling-daughter cells through multiple asymmetric divisions in short durations, showing abnormally high spurts in CFUs of antibiotic resisters. The CFUs were several-fold higher than that expected from the mass-doubling time of the subpopulations. Despite this commonality, the subpopulations showed specific differences in their response to different multiples of their respective MBC of rifampicin. Mycobacterial subpopulations come out of rifampicin stress by undergoing multiple nucleoid replications, multiple septation for nucleoid segregation, and acquisition of antibiotic target-specific mutations, followed by multiple asymmetric divisions to generate unusually a large number of rifampicin resisters. Because we had earlier shown that SCs and NCs are present in the pulmonary tuberculosis patients' sputum, the present findings have clinical relevance on the mechanism of emergence of antibiotic-resistant strains from mycobacterial subpopulations.

Cross-Tissue Characterization of Heterogeneities of Mesenchymal Stem Cells and Their Differentiation Potentials.

Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative medicine and the treatment of autoimmune disorders. Comparing MSCs from different tissues at the single-cell level is fundamental for optimizing clinical applications. Here we analyzed single-cell RNA-seq data of MSCs from four tissues, namely umbilical cord, bone marrow, synovial tissue, and adipose tissue. We identified three major cell subpopulations, namely osteo-MSCs, chondro-MSCs, and adipo/myo-MSCs, across all MSC samples. MSCs from the umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. MSC subpopulations, with different subtypes and tissue sources, showed pronounced differences in differentiation potentials. After we compared the cell subpopulations and cell status pre-and-post chondrogenesis induction, osteogenesis induction, and adipogenesis induction, respectively, we found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at the single-cell level and subpopulation level, providing better targets for improving induction efficiency.

A Catalog of 204 Offset and Dual Active Galactic Nuclei (AGNs): Increased AGN Activation in Major Mergers and Separations under 4 kpc

Abstract During galaxy mergers, gas and dust are driven toward the centers of merging galaxies, triggering enhanced star formation and supermassive black hole (SMBH) growth. Theory predicts that this heightened activity peaks at SMBH separations <20 kpc; if sufficient material accretes onto one or both of the SMBHs for them to become observable as active galactic nuclei (AGNs) during this phase, they are known as offset and dual AGNs, respectively. To better study these systems, we have built the ACS-AGN Merger Catalog, a large catalog (N = 204) of uniformly selected offset and dual AGN observed by the Hubble Space Telescope at 0.2 < z < 2.5 with separations <20 kpc. Using this catalog, we answer many questions regarding SMBH−galaxy coevolution during mergers. First, we confirm predictions that the AGN fraction peaks at SMBH pair separations <10 kpc; specifically, we find that the fraction increases significantly at pair separations of <4 kpc. Second, we find that AGNs in mergers are preferentially found in major mergers and that the fraction of AGNs found in mergers follows a logarithmic relation, decreasing as merger mass ratio increases. Third, we do not find that mergers (nor the major or minor merger subpopulations) trigger the most luminous AGNs. Finally, we find that nuclear column density, AGN luminosity, and host galaxy star formation rate have no dependence on SMBH pair separation or merger mass ratio in these systems, nor do the distributions of these values differ significantly from that of the overall AGN population.

Immune response in new coronavirus infection COVID-19 in children and adults

Introduction. It is known that COVID-19 occurs more often in adult patients, especially if they have concomitant somatic diseases, children are at less risk of developing it. The aim of this work is to evaluate and compare immune response parameters in new coronavirus infection COVID-19 in children and adults. Materials and methods. The results of the examination of 56 adults 19-55 years old and 57 children 14-18 years old were included in the work. The examination results of COVID-19 patients were compared with similar data in practically healthy individuals of the corresponding age groups. All patients underwent laboratory tests to determine the following parameters: presence of SARS-CoV-2 RNA, general blood test parameters, major lymphocyte subpopulations, level of total immunoglobulins (IgM, IgG, IgA), number of CIC, absorbance and bactericidal activity of leukocytes.Results. The proportion of positive findings for SARS-CoV-2 RNA in different age groups ranged from 13.6% to 25.8%. General and specific patterns of immune response in patients of different age groups were established. Common features were an increase in the number of circulating immune complexes and activated T-lymphocytes. Differences were noted in the level of serum immunoglobulins IgM and IgG, neutrophil uptake activity, the number of monocytes, as well as in the level of different subpopulations of lymphocytes. Discussion. In adults, changes in the adaptive immune response, including the cellular level, are predominantly expressed. In children, there are signs of inefficiency of innate mechanisms of immune responses. Conclusion. The dynamics of the number of examined and positive findings correlate with similar figures in Russia and have a two-wave pattern. Increased number of circulating immune complexes and activated T-lymphocytes is typical for all patients with new coronavirus infection COVID-19 regardless of age, which is a sign of acute infection-inflammatory process development and insufficiently effective elimination of antigen (pathogen).

Genomic investigations provide insights into the mechanisms of resilience to heterogeneous habitats of the Indian Ocean in a pelagic fish

The adaptive genetic variation in response to heterogeneous habitats of the Indian Ocean was investigated in the Indian oil sardine using ddRAD sequencing to understand the subpopulation structure, stock complexity, mechanisms of resilience, and vulnerability in the face of climate change. Samples were collected from different ecoregions of the Indian ocean and ddRAD sequencing was carried out. Population genetic analyses revealed that samples from the Gulf of Oman significantly diverged from other Indian Ocean samples. SNP allele-environment correlation revealed the presence of candidate loci correlated with the environmental variables like annual sea surface temperature, chlorophyll-a, and dissolved oxygen concentration which might represent genomic regions allegedly diverging as a result of local adaptation. Larval dispersal modelling along the southwest coast of India indicated a high dispersal rate. The two major subpopulations (Gulf of Oman and Indian) need to be managed regionally to ensure the preservation of genetic diversity, which is crucial for climatic resilience.

Disaggregating Pacific Islanders and major Asian subpopulations to reveal hidden breast cancer disparities.

80 Background: The Asian American, Native Hawaiian, and Other Pacific Islander (AA/NHPI) population is the fastest growing and most socioeconomically heterogeneous racial/ethnic group in the US. AA/NHPI breast cancer outcomes are often reported as superior to Non-Hispanic Whites (NHW) however evidence suggests aggregating AA/NHPI masks disparities among subpopulations. As NHPI is often ignored as one of five official US races, this study aims to disaggregate AA and NHPI to unmask breast cancer disparities. Methods: An IRB exempt, retrospective cohort study using the National Cancer Database was conducted for women diagnosed with breast cancer in 2004-2016. AA and NHPI patients were compared with the majority NHW group. AA was separated into pertinent geographical origins: East Asian (EA; Chinese, Japanese, Korean), South Asian (SA; Indian, Pakistani), and Southeast Asian (SEA; Filipino, Vietnamese, Laotian, Hmong, Cambodian). Descriptive statistics were used. Logistic and Cox proportional hazard regressions assessed adjusted Odds Ratios (aORs) and adjusted Hazards Ratios (aHR), respectively, with 95% confidence intervals (95%CI). Analyses were adjusted for patient factors (age, insurance, income, rural/urban, education, hospital region, hospital distance, Deyo comorbidity score) and cancer characteristics (grade, stage, metastases, diagnosis year, hormone status). Results: Of 2,073,822 women there were 28,311 EA, 13,259 SA, 21,645 SEA, 5,375 NHPI, and 2,005,232 NHW. The median age was 62 years with median 66 month follow-up. Compared to NHW (9.6%), presentation with late-stage disease (Stage III/IV) was higher in NHPI (12%), SA (12%), and SEA (11%), but not EA (7.5%). On adjusted analysis (Table), EA was the only group with a statistical difference from NHW with aOR=0.85 (95%CI=0.76-0.94). Kaplan-Meier test for overall survival (OS) showed differences between ethnic/racial groups with NHPI having worse OS than AA subpopulations (p<0.0001). On adjusted analysis (Table), all AA subpopulations had lower risk of death compared to NHW: EA (aHR=0.69; 95%CI=0.64-0.74), SA (aHR=0.65; 95CI=0.59-0.71), and SEA (aHR=0.78; 95%CI=0.73-0.84) however the NHPI group had a greater risk of death (aHR=1.14; 95%CI=1.02-1.28). Conclusions: NHPI women with breast cancer have worse outcomes compared to NHW. This is masked by superior AA outcomes when aggregated. The continual improper aggregation of AA with NHPI downplays NHPI cancer disparities. Proper disaggregation of NHPI from AA warrants greater attention.[Table: see text]

Genome‐wide association study for traits related to seedling vigor in rice

AbstractSeedling vigor is a desirable trait in direct‐seeded rice (Oryza sativa L.) to improve plant establishment and enhance weed competition. In this study, a genome‐wide association study (GWAS) on seedling vigor traits was performed on a rice panel of 244 accessions consisting of the five major rice subpopulations (aromatic, aus, tropical japonica, temperate japonica, and indica) using the 7K SNP Cornell‐IR LD Rice Array. A total of seven seedling vigor‐related traits were evaluated under controlled conditions in a growth chamber. All traits had a normal distribution with a wide range of phenotypic variation with CV between 27.6 and 43.9%, except for seedling dry weight, which had a CV of 11.4%. We identified 43 GWAS‐quantitative trait locus (QTL) regions associated with different seedling vigor traits, of which 19 QTL regions were near previously identified genes or QTL regions. These findings confirmed 19 previous QTL and identified 24 potential novel QTL targets for marker‐assisted breeding programs. Additionally, superior donors with high seedling vigor were identified and can be used for rice crop improvement in direct‐seeded systems.

Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice

The aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Unsupervised cluster analysis of the transcriptional profiles from 24,001 aortic cells identified 27 clusters representing 10 cell types: endothelial cells (ECs), fibroblasts, vascular smooth muscle cells (SMCs), immune cells (B cells, T cells, macrophages, and dendritic cells), mesothelial cells, pericytes, and neural cells. After HFD intake, subpopulations of endothelial cells with lipid transport and angiogenesis capacity and extensive expression of contractile genes were defined. In the HFD group, three major SMC subpopulations showed increased expression of extracellular matrix-degradation genes, and a synthetic SMC subcluster was proportionally increased. This increase was accompanied by upregulation of proinflammatory genes. Under HFD conditions, aortic-resident macrophage numbers were increased, and blood-derived macrophages showed the strongest expression of proinflammatory cytokines. Our study elucidates the nature and range of the cellular composition of the ascending aorta and increases understanding of the development and progression of aortic inflammatory disease.

B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease.

Background and ObjectivesTo assess the molecular landscape of B-cell subpopulations across different compartments in patients with neuromyelitis optica spectrum disorder (NMOSD).MethodsWe performed B-cell transcriptomic profiles via single-cell RNA sequencing across CSF, blood, and bone marrow in patients with NMOSD.ResultsAcross the tissue types tested, 4 major subpopulations of B cells with distinct signatures were identified: naive B cells, memory B cells, age-associated B cells, and antibody-secreting cells (ASCs). NMOSD B cells show proinflammatory activity and increased expression of chemokine receptor genes (CXCR3 and CXCR4). Circulating B cells display an increase of antigen presentation markers (CD40 and CD83), as well as activation signatures (FOS, CD69, and JUN). In contrast, the bone marrow B-cell population contains a large ASC fraction with increased oxidative and metabolic activity reflected by COX genes and ATP synthase genes. Typically, NMOSD B cells become hyperresponsive to type I interferon, which facilitates B-cell maturation and anti–aquaporin-4 autoantibody production. The pool of ASCs in blood and CSF were significantly elevated in NMOSD. Both CD19− and CD19+ ASCs could be ablated by tocilizumab, but not rituximab treatment in NMOSD.DiscussionB cells are compartmentally fine tuned toward autoreactivity in NMOSD and become hyperreactive to type I interferon. Inhibition of type I interferon pathway may provide a new therapeutic avenue for NMOSD.

Geography of racial coresidence

Whereas most work on residential race relations in US cities is based on the concept of segregation, our approach studies this issue from a who-lives-with-whom perspective. To this end, we study coresidence profiles – percentages of a given racial subpopulation living in different population zones. Population zones are data-driven divisions of a city based on characteristic racial compositions. We used 1990 and 2010 decennial census block-level data for 61 largest US metropolitan areas to calculate coresidence profiles for four major racial subpopulations in each city at both years. Profiles for each race/year combination were clustered into three archetypes. Cities, where given race profiles belong to the same archetype, have similar coresidence patterns with respect to this race. We present the geographic distributions of co-habitation profiles and show how they changed during the 1990–2010 period. Our results revealed that coresidence profiles depend not only on racial preferences but also on the availability of racial groups; cities in the different geographical regions have different coresidence profiles because they have different shares of White, Black, Hispanic, and Asian subpopulations. Temporal changes in coresidence profiles are linked to the increased share of Hispanic and Asian populations.

Somatostatin contributes to long-term potentiation at excitatory synapses onto hippocampal somatostatinergic interneurons

Somatostatin-expressing interneurons (SOM-INs) are a major subpopulation of GABAergic cells in CA1 hippocampus that receive excitation from pyramidal cells (PCs), and, in turn, provide feedback inhibition onto PC dendrites. Excitatory synapses onto SOM-INs show a Hebbian long-term potentiation (LTP) mediated by type 1a metabotropic glutamate receptors (mGluR1a) that is implicated in hippocampus-dependent learning. The neuropeptide somatostatin (SST) is also critical for hippocampal long-term synaptic plasticity, as well as learning and memory. SST effects on hippocampal PCs are well documented, but its actions on inhibitory interneurons remain largely undetermined. In the present work, we investigate the involvement of SST in long-term potentiation of CA1 SOM-IN excitatory synapses using pharmacological approaches targeting the somatostatinergic system and whole cell recordings in slices from transgenic mice expressing eYFP in SOM-INs. We report that application of exogenous SST14 induces long-term potentiation of excitatory postsynaptic potentials in SOM-INs via somatostatin type 1–5 receptors (SST1-5Rs) but does not affect synapses of PC or parvalbumin-expressing interneurons. Hebbian LTP in SOM-INs was prevented by inhibition of SSTRs and by depletion of SST by cysteamine treatment, suggesting a critical role of endogenous SST in LTP. LTP of SOM-IN excitatory synapses induced by SST14 was independent of NMDAR and mGluR1a, activity-dependent, and prevented by blocking GABAA receptor function. Our results indicate that endogenous SST may contribute to Hebbian LTP at excitatory synapses of SOM-INs by controlling GABAA inhibition, uncovering a novel role for SST in regulating long-term synaptic plasticity in somatostatinergic cells that may be important for hippocampus-dependent memory processes.