Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune ...function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman’s reproductive health, including her risk of acquiring HIV.
•Most African women studied had genital communities with low Lactobacillus abundance•Unlike the gut, high-diversity cervicovaginal communities are pro-inflammatory•Specific bacteria induce cytokine production from genital APCs and epithelial cells
Vaginal colonization by a single bacterium, Lactobacillus, is considered healthy. Kwon and colleagues show that in a cohort of asymptomatic African women, the majority have high-diversity genital bacterial communities that are closely associated with local inflammation. This work suggests specific genital bacteria might increase HIV acquisition risk in women.
When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, ...close temporal dependencies arise between adult speakers’ and listeners’ neural activity. However, it is not known whether similar neural contingencies exist within adult–infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In experiment 1 (n = 17), infants viewed videos of an adult who was singing nursery rhymes with (i) direct gaze (looking forward), (ii) indirect gaze (head and eyes averted by 20°), or (iii) direct-oblique gaze (head averted but eyes orientated forward). In experiment 2 (n = 19), infants viewed the same adult in a live context, singing with direct or indirect gaze. Gaze-related changes in adult–infant neural network connectivity were measured using partial directed coherence. Across both experiments, the adult had a significant (Granger) causal influence on infants’ neural activity, which was stronger during direct and direct-oblique gaze relative to indirect gaze. During live interactions, infants also influenced the adult more during direct than indirect gaze. Further, infants vocalized more frequently during live direct gaze, and individual infants who vocalized longer also elicited stronger synchronization from the adult. These results demonstrate that direct gaze strengthens bidirectional adult–infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning.
This systematic review and meta‐analysis considered evidence of guided play compared to direct instruction or free play to support children's learning and development. Interventions from 39 studies ...were reviewed (published 1977–2020); 17 were included in meta‐analysis (Ntotal = 3893; Mchildage = 1–8 years; Mgirls 49.8%; Methnicity White 41%, African American/Black 28%, Hispanic 19%). Guided play had a greater positive effect than direct instruction on early maths skills (g = 0.24), shape knowledge (g = 0.63), and task switching (g = 0.40); and than free play on spatial vocabulary (g = 0.93). Differences were not identified for other key outcomes. Narrative synthesis highlighted heterogeneity in the conceptualization and implementation of guided play across studies.
Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired ...epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of ...the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Our analysis reveals novel facets of the dedifferentiation response, including acquisition of mesenchymal traits and a Myc module. Furthermore, wound and distal dedifferentiated Schwann cells constitute different populations, with wound cells displaying increased mesenchymal character induced by localized TGFβ signaling. TGFβ promotes invasion and crosstalks with Eph signaling via N-cadherin to drive collective migration of the Schwann cells across the wound. Consistently, Tgfbr2 deletion in Schwann cells resulted in misdirected and delayed reinnervation. Thus, the wound microenvironment is a key determinant of Schwann cell identity, and it promotes nerve repair through integration of multiple concerted signals.
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•Wound Schwann cells have a distinct dedifferentiation program•TGFβ signaling reprograms wound Schwann cells to invasive mesenchymal-like cells•TGFβ crosstalks with Eph signaling to drive collective Schwann cell migration•Loss of TGFβ signaling in Schwann cells delays nerve regeneration
Clements et al. show that the nerve-injury-induced Schwann cell dedifferentiation program is modulated by the wound microenvironment through TGFβ. TGFβ promotes regeneration by reprogramming Schwann cells to invasive, mesenchymal-like cells and crosstalking with Eph signaling to drive collective migration.
The human genome contains hundreds of regions whose patterns of genetic variation indicate recent positive natural selection, yet for most the underlying gene and the advantageous mutation remain ...unknown. We developed a method, composite of multiple signals (CMS), that combines tests for multiple signals of selection and increases resolution by up to 100-fold. By applying CMS to candidate regions from the International Haplotype Map, we localized population-specific selective signals to 55 kilobases (median), identifying known and novel causal variants. CMS can not just identify individual loci but implicates precise variants selected by evolution.
Post Prostatectomy Abdominal Pain Cedermaz, Jonathan R.; Byrne, Elizabeth Z.
Annals of emergency medicine,
December 2022, 2022-12-00, 20221201, Letnik:
80, Številka:
6
Journal Article
Summary Background The use of injectable progestin-only contraceptives has been associated with increased risk of HIV acquisition in observational studies, but the biological mechanisms of this risk ...remain poorly understood. We aimed to assess the effects of progestins on HIV acquisition risk and the immune environment in the female genital tract. Methods In this prospective cohort, we enrolled HIV-negative South African women aged 18–23 years who were not pregnant and were living in Umlazi, South Africa from the Females Rising through Education, Support, and Health (FRESH) study. We tested for HIV-1 twice per week to monitor incident infection. Every 3 months, we collected demographic and behavioural data in addition to blood and cervical samples. The study objective was to characterise host immune determinants of HIV acquisition risk, including those associated with injectable progestin-only contraceptive use. Hazard ratios (HRs) were estimated using Cox proportional hazards methods. Findings Between Nov 19, 2012, and May 31, 2015, we characterised 432 HIV-uninfected South African women from the FRESH study. In this cohort, 152 women used injectable progestin-only contraceptives, 43 used other forms of contraception, and 222 women used no method of long-term contraception. Women using injectable progestin-only contraceptives were at substantially higher risk of acquiring HIV (12·06 per 100 person-years, 95% CI 6·41–20·63) than women using no long-term contraception (3·71 per 100 person-years, 1·36–8·07; adjusted hazard ratio aHR 2·93, 95% CI 1·09–7·868, p=0·0326). HIV-negative injectable progestin-only contraceptive users had 3·92 times the frequency of cervical HIV target cells (CCR5+ CD4 T cells) compared with women using no long-term contraceptive (p=0·0241). Women using no long-term contraceptive in the luteal phase of the menstrual cycle also had a 3·25 times higher frequency of cervical target cells compared with those in the follicular phase (p=0·0488), suggesting that a naturally high progestin state had similar immunological effects to injectable progestin-only contraceptives. Interpretation Injectable progestin-only contraceptive use and high endogenous progesterone are both associated with increased frequency of activated HIV targets cells at the cervix, the site of initial HIV entry in most women, providing a possible biological mechanism underlying increased HIV acquisition in women with high progestin exposure. Funding The Bill and Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases.
Children's self-regulation is associated with their concurrent and long-term school achievement. Theorists have argued the importance of child–adult interactions in the development of children's ...self-regulatory skills. However, empirical findings are mixed and have produced small or modest effect sizes, which could be due to the low ecological validity of the self-regulation measures typically used. In this study, an adult-reported scale, the
Child Self-Regulation in Interaction Scale
(CSIS), was developed to measure preschoolers' behavioral self-regulation in their daily interactions with adults. The psychometric properties of CSIS were also examined. A total of 1015 children and their mothers from multiple regions in China participated in this study. Factor analysis indicated that a three-factor model (namely Inhibition, Updating, and Shifting) was the best fit for the data. The CSIS also had good internal consistency, test–retest reliability, and convergent and criterion validity. Additionally, the three-factor model showed satisfactory gender and longitudinal measurement invariance. The results suggest that the CSIS is a reliable and valid instrument. Children’s self-regulatory behaviors may vary in different contexts. A context-specific measure of self-regulation may have stronger ecological validity by tapping into context-specific behavioral demands and is thus likely to have greater value and utility.
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