Purpose of Review
There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies ...analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.
Recent Findings
The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD.
Summary
A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.
Plant NLRs are modular immune receptors that trigger rapid cell death in response to attempted infection by pathogens. A highly conserved nucleotide-binding domain shared with APAF-1, various ...R-proteins and CED-4 (NB-ARC domain) is proposed to act as a molecular switch, cycling between ADP (repressed) and ATP (active) bound forms. Studies of plant NLR NB-ARC domains have revealed functional similarities to mammalian homologues, and provided insight into potential mechanisms of regulation. However, further advances have been limited by difficulties in obtaining sufficient yields of protein suitable for structural and biochemical techniques. From protein expression screens in Escherichia coli and Sf9 insect cells, we defined suitable conditions to produce the NB-ARC domain from the tomato NLR NRC1. Biophysical analyses of this domain showed it is a folded, soluble protein. Structural studies revealed the NRC1 NB-ARC domain had co-purified with ADP, and confirmed predicted structural similarities between plant NLR NB-ARC domains and their mammalian homologues.
Single-cell RNA-seq can precisely resolve cellular states, but applying this method to low-input samples is challenging. Here, we present Seq-Well, a portable, low-cost platform for massively ...parallel single-cell RNA-seq. Barcoded mRNA capture beads and single cells are sealed in an array of subnanoliter wells using a semipermeable membrane, enabling efficient cell lysis and transcript capture. We use Seq-Well to profile thousands of primary human macrophages exposed to Mycobacterium tuberculosis.
Autism spectrum disorders (ASD) are a group of heterogeneous neurological disorders that are highly variable and are clinically characterized by deficits in social interactions, communication, and ...stereotypical behaviors. Prevalence has risen from 1 in 10,000 in 1972 to 1 in 59 children in the United States in 2014. This rise in prevalence could be due in part to better diagnoses and awareness, however, these together cannot solely account for such a significant rise. While causative connections have not been proven in the majority of cases, many current studies focus on the combined effects of genetics and environment. Strikingly, a distinct picture of immune dysfunction has emerged and been supported by many independent studies over the past decade. Many players in the immune-ASD puzzle may be mechanistically contributing to pathogenesis of these disorders, including skewed cytokine responses, differences in total numbers and frequencies of immune cells and their subsets, neuroinflammation, and adaptive and innate immune dysfunction, as well as altered levels of immunoglobulin and the presence of autoantibodies which have been found in a substantial number of individuals with ASD. This review summarizes the latest research linking ASD, autoimmunity and immune dysfunction, and discusses evidence of a potential autoimmune component of ASD.
Abstract
We present deep
Magellan
/Megacam stellar photometry of four recently discovered faint Milky Way satellites: Sagittarius II (Sgr II), Reticulum II (Ret II), Phoenix II (Phe II), and ...Tucana III (Tuc III). Our photometry reaches ∼2–3 magnitudes deeper than the discovery data, allowing us to revisit the properties of these new objects (e.g., distance, structural properties, luminosity measurements, and signs of tidal disturbance). The satellite color-magnitude diagrams show that they are all old (∼13.5 Gyr) and metal poor (Fe/H ≲ −2.2). Sgr II is particularly interesting, as it sits in an intermediate position between the loci of dwarf galaxies and globular clusters in the size–luminosity plane. The ensemble of its structural parameters is more consistent with a globular cluster classification, indicating that Sgr II is the most extended globular cluster in its luminosity range. The other three satellites land directly on the locus defined by Milky Way ultra-faint dwarf galaxies of similar luminosity. Ret II is the most elongated nearby dwarf galaxy currently known for its luminosity range. Our structural parameters for Phe II and Tuc III suggest that they are both dwarf galaxies. Tuc III is known to be associated with a stellar stream, which is clearly visible in our matched-filter stellar density map. The other satellites do not show any clear evidence of tidal stripping in the form of extensions or distortions. Finally, we also use archival H
i
data to place limits on the gas content of each object.
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, ...immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.
This paper reviews current literature relating to parent and child emotional functioning, specifically their emotion regulatory skills and emotional expression. Included are considerations regarding ...theoretical, methodological, and sampling strengths and weaknesses of existing literature. On the basis of the review, several directions for future research are proposed. First, it is argued that consistency in the measurement of emotion regulation is necessary, including assessment of more refined theoretical conceptualizations of regulatory types, skills, or strategies. Second, it is argued that emotion regulation developmental research examining the post-early childhood period is necessary in order to contribute to a more comprehensive understanding of youths’ emotion regulation. Finally, it is argued that greater examination of paternal influences on child emotional functioning, in addition to maternal influences, is required. Consideration of these issues in future emotion regulation research will ideally contribute to a greater understanding of the mechanisms involved in child and adolescent development of optimal regulatory capacities.
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