BTBR T+tf/J (BTBR) is an inbred strain of mice that displays prominent social deficits and repetitive behaviors analogous to the defining symptoms of autism, along with a complete congenital agenesis of corpus callosum. BTBR is genetically distant from the widely used C57BL/6J (B6) strain, which exhibits high levels of sociability, low repetitive behaviors, and an intact corpus callosum. Emerging evidence implicates compromised inter-hemispherical connectivity in some cases of autism. We investigated the hypothesis that the disconnection of corpus callosum (CC) fiber tracts contribute to behavioral traits in mice that are relevant to the behavioral symptoms of autism. Surgical lesion of the CC in B6 mice at postnatal day 7 had no effect on juvenile play and adult social approach, and did not elevate repetitive self-grooming. No correlations were detected between rostral-caudal extent of the CC lesion and behavioral scores. In addition, LP/J, the strain that is genetically closest to BTBR but has an intact CC, displayed juvenile play deficits and repetitive self-grooming similar to those seen in BTBR. These corroborative results offer evidence against the hypothesis that the corpus callosum disconnection is a primary cause of low sociability and high repetitive behaviors in inbred mice. Our findings indicate that genes mediating other aspects of neurodevelopment, including those whose mutations underlie more subtle disruptions in white matter pathways and connectivity, are more likely to contribute to the aberrant behavioral phenotypes in the BTBR mouse model of autism.

Inbred mouse strains differ greatly in social behaviors, making them a valuable resource to study genetic and non-genetic mechanisms underlying social deficits relevant to autism spectrum disorders. A hallmark symptom of autism is a lack of ability to understand other people’s thoughts and intentions, which leads to impairments in adjusting behaviors in response to ever-changing social situations in daily life. We compared the ability of BTBR T+ tf/J (BTBR), a strain with low sociability, and C57BL/6J (B6), a strain with high sociability, for their abilities to modulate responses to social cues from different partners in the reciprocal social interaction test. Results indicate that BTBR exhibited low sociability toward different partners and displayed minimal ability to modify behaviors toward different partners. In contract, B6 showed high sociability toward different partners and was able to modify social behaviors toward different partners. Consistent results were found in two independent cohorts of different ages, and in both sexes. In the three-chambered test, high sociability in B6 and low sociability in BTBR were independent of strain of the novel mouse. Since social deficits in BTBR could potentially be caused by physical disabilities in detecting social olfactory cues, or in cognitive abilities, we tested BTBR and B6 mice on measures of olfaction and cognition. BTBR mice displayed more sniffing of social odors emitted by soiled bedding than of an odorless novel object, but failed to show a preference for a live novel mouse over a novel object. On olfactory habituation/dishabituation to a sequence of odors, BTBR displayed discrimination abilities across three non-social and two social odors. However, as compared to B6, BTBR displayed less sniff time for both non-social and social odors, and no significant dishabituation between cage odors from two different novel mouse strains, findings that will be important to investigate further. BTBR was generally normal in spatial acquisition on the Morris water maze test, but showed deficits in reversal learning. Time spent freezing on contextual and cued fear conditioning was lower in BTBR than in B6. Our findings suggest that BTBR has poor abilities to modulate its responses to different social partners, which may be analogous to social cognition deficits in autism, adding to the value of this strain as a mouse model of autism.

SignificanceIt is well known that ribosomal RNA processing is directly impacted by the rate of transcription elongation by RNA polymerase I (Pol I). To understand how these processes are orchestrated, we must carefully define transcription elongation properties in vitro and in living cells. Here, we characterize DNA sequence elements that pause and terminate Pol I transcription in vitro. We also establish methods for analyzing Pol I transcription elongation properties in vivo using native elongating transcript sequencing (NETSeq). Our NETSeq data revealed frequent pausing by Pol I and decreased Pol I occupancy at G residues, suggesting unequal rates of nucleotide incorporation by the enzyme. These findings redefine our understanding of Pol I transcription elongation and its heterogeneity in vivo.

Following the outbreak of COVID-19, governments have spent unprecedented sums of money to accommodate people experiencing homelessness, often in underutilized hotels. This intervention contrasts with the policy stasis and "poverty of ambition" that characterized responses to rising homelessness over the past decade in countries such as Australia, the UK, the US, and much of Europe. This is a situation that has prevailed despite rigorous evidence on both the harms of homelessness and the ability of policy to address it. Using Australia as a case study, this policy review examines this sudden change in approach. After detailing various initiatives to respond to COVID-19, we show how these interventions are rationalized by the threat posed to people who are homeless, and the threat posed by homeless populationswho are at high risk of contracting and transmitting the disease-to the health of the non-homeless population. We discuss how these findings contribute to debates about how the framing of homelessness as a problem shapes policy.

Background The deployment of Community Health Workers (CHWs) is widely promoted as a strategy for reducing health inequities in low- and middle-income countries (LMIC). Yet there is limited evidence on whether and how CHW programmes achieve this. This systematic review aimed to synthesise research findings on the following questions: (1) How effective are CHW interventions at reaching the most disadvantaged groups in LMIC contexts? and (2) What evidence exists on whether and how these programmes reduce health inequities in the populations they serve? Methods We searched six academic databases for recent (2014–2020) studies reporting on CHW programme access, utilisation, quality, and effects on health outcomes/behaviours in relation to potential stratifiers of health opportunities and outcomes (e.g., gender, socioeconomic status, place of residence). Quantitative data were extracted, tabulated, and subjected to meta-analysis where appropriate. Qualitative findings were synthesised using thematic analysis. Results One hundred sixty-seven studies met the search criteria, reporting on CHW interventions in 33 LMIC. Quantitative synthesis showed that CHW programmes successfully reach many (although not all) marginalized groups, but that health inequalities often persist in the populations they serve. Qualitative findings suggest that disadvantaged groups experienced barriers to taking up CHW health advice and referrals and point to a range of strategies for improving the reach and impact of CHW programmes in these groups. Ensuring fair working conditions for CHWs and expanding opportunities for advocacy were also revealed as being important for bridging health equity gaps. Conclusion In order to optimise the equity impacts of CHW programmes, we need to move beyond seeing CHWs as a temporary sticking plaster, and instead build meaningful partnerships between CHWs, communities and policy-makers to confront and address the underlying structures of inequity. Trial registration PROSPERO registration number CRD42020177333.