The E3 ubiquitin ligase activity of RING1B is not essential for early mouse development.

Polycomb-repressive complex 1 (PRC1) and PRC2 maintain repression at many developmental genes in mouse embryonic stem cells and are required for early development. However, it is still unclear how they are targeted and how they function. We show that the ability of RING1B, a core component of PRC1, to ubiquitinate histone H2A is dispensable for early mouse embryonic development and much of the gene repression activity of PRC1. Our data support a model in which PRC1 and PRC2 reinforce each other's binding but suggest that the key functions of PRC1 lie beyond the enzymatic capabilities of RING1B.

Breast Milk and Breastfeeding of Infants Born to SARS-CoV-2 Positive Mothers: A Prospective Observational Cohort Study.

OBJECTIVE: There are limited published data on the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from mothers to newborns through breastfeeding or from breast milk. The World Health Organization released guidelines encouraging mothers with suspected or confirmed COVID-19 to breastfeed as the benefits of breastfeeding outweighs the possible risk of transmission. The objective of this study was to determine if SARS-CoV-2 was present in the breast milk of lactating mothers who had a positive SARS-CoV-2 nasopharyngeal swab test prior to delivery, and the clinical outcomes for their newborns. STUDY DESIGN: This was a single-center, observational, prospective cohort study. Maternal-newborn dyads that delivered at New York University Langone Hospital Brooklyn with confirmed maternal SARS-CoV-2 positive screen test at the time of admission were recruited for the study. Breast milk samples were collected during postpartum hospitalization and tested for the presence of SARS-CoV-2 genes N1 and N2 by two-step reverse transcription polymerase chain reaction. Additionally, the clinical characteristics of the maternal newborn dyad, results of nasopharyngeal SARS-CoV-2 testing, and neonatal follow-up data were collected. RESULTS: A total of 19 mothers were included in the study and their infants who were all fed breast milk. Breast milk samples from 18 mothers tested negative for SARS-CoV-2, and 1 was positive for SARS-CoV-2 RNA. The infant who ingested the breast milk that tested positive had a negative nasopharyngeal test for SARS-CoV-2, and had a benign clinical course. There was no evidence of significant clinical infection during the hospital stay or from outpatient neonatal follow-up data for all the infants included in this study. CONCLUSION: In a small cohort of SARS-CoV-2 positive lactating mothers giving birth at our institution, most of their breast milk samples (95%) contained no detectable virus, and there was no evidence of COVID-19 infection in their breast milk-fed neonates. KEY POINTS: · Breast milk may rarely contain detectable SARS-CoV-2 RNA and was not detected in asymptomatic mothers.. · Breast milk with detectable SARS-CoV-2 RNA from a symptomatic mother had no clinical significance for her infant.. · Breast feeding with appropriate infection control instructions appears to be safe in mother with COVID infection..

Treating Children with ASD: The Perspective of Caregivers.

PURPOSE: Treatment of Autism Spectrum Disorders (ASD) is challenging. Parents/caregivers' perspective on the effectiveness of therapies and services available to their children is important but neglected in the literature on ASD.  This study investigated such perspective through questionnaire-guided interviews with a group of parents in the province of Manitoba (Canada). A secondary objective of the study was to explore how health care professionals and specifically pharmacists can assist in providing better care to children with ASD.  Methods: Informed consent was obtained from all participants. Data on diagnoses and prescribed medications were collected from medical charts. Parents/caregivers completed questionnaires during interviews scheduled at their convenience. Specific questions were asked to gather caregivers/parents' perspectives on the effectiveness of medications and non-pharmacological interventions in controlling symptoms experienced by their children.  Information on access to education and health services was also assessed. Common themes were identified using thematic analysis. RESULTS: All children attended school, 88% were males, 50% experienced eating/sleeping difficulties; 69% reported Attention Deficit Hyperactivity Disorder comorbidity. Risperidone was reported to be effective in controlling aggressive behaviours. Methylphenidate and aripiprazole were often discontinued. Melatonin and occupational therapy services were said to be very useful. Access to behavioural therapy was often limited. Parents were concerned about lack of trained professionals in schools, limited understanding of their children's needs, and uncertainty for the future. CONCLUSIONS: Better education and awareness are necessary to help ASD children and their families. Pharmacists should explore opportunities to provide better services. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Short-term outcomes of infants born to mothers with SARS-CoV-2 infection.

OBJECTIVE: The rate of transmission of SARS-CoV-2 from mothers to infants in the peri- and post-natal period remains an area of ongoing investigation. This study aims to determine rates of development of clinically significant COVID-19 disease within 1 month among infants born to symptomatic and asymptomatic SARS-CoV-2 positive mothers. MATERIALS AND METHODS: This was a single-center, retrospective cohort study of all infants born to SARS-CoV-2 positive mothers who were admitted to the Well Baby Nursery (WBN) at New York University Langone Hospital-Brooklyn from 23 March-23 September 2020. Infants born to asymptomatic mothers were allowed to room-in, while infants born to mothers with symptoms of SARS-CoV-2 were isolated and discharged home to an alternate primary caregiver. A phone follow-up program contacted mothers at 2 weeks and 1 month post discharge to inquire about newborn symptoms, maternal symptoms, personal protective equipment (PPE) usage, and any presentations to care. Medical records were also reviewed for clinic and hospital visits to determine if exposed infants developed any symptoms following discharge. RESULTS: Of 1903 deliveries during the study period, 131 mothers (21 symptomatic, 110 asymptomatic) tested positive for SARS-CoV-2 and had infants admitted to the WBN. 57 infants (21 born to symptomatic mothers, 36 born to asymptomatic mothers) were tested prior to discharge, and none were positive. 121 of 133 infants had at least 1 follow up call in the study period. Of these, 31 had symptoms potentially concerning for SARS-CoV-2 infection or Multisystem Inflammatory Syndrome in Children, and 19 presented to medical care for these symptoms. 4 infants had SARS- CoV-2 testing after discharge, and none were positive. 2 infants were admitted to the hospital for fever but neither had a positive SARS-CoV-2 result. 65% of mothers reported always adhering to PPE recommendations. CONCLUSION: Our results suggest that infants born both to symptomatic and asymptomatic mothers are unlikely to develop clinically significant COVID-19 disease in the peri- and post-natal periods.

The X-inactivation trans-activator Rnf12 is negatively regulated by pluripotency factors in embryonic stem cells.

X-inactivation, the molecular mechanism enabling dosage compensation in mammals, is tightly controlled during mouse early embryogenesis. In the morula, X-inactivation is imprinted with exclusive silencing of the paternally inherited X-chromosome. In contrast, in the post-implantation epiblast, X-inactivation affects randomly either the paternal or the maternal X-chromosome. The transition from imprinted to random X-inactivation takes place in the inner cell mass (ICM) of the blastocyst from which embryonic stem (ES) cells are derived. The trigger of X-inactivation, Xist, is specifically downregulated in the pluripotent cells of the ICM, thereby ensuring the reactivation of the inactive paternal X-chromosome and the transient presence of two active X-chromosomes. Moreover, Tsix, a critical cis-repressor of Xist, is upregulated in the ICM and in ES cells where it imposes a particular chromatin state at the Xist promoter that ensures the establishment of random X-inactivation upon differentiation. Recently, we have shown that key transcription factors supporting pluripotency directly repress Xist and activate Tsix and thus couple Xist/Tsix control to pluripotency. In this manuscript, we report that Rnf12, a third X-linked gene critical for the regulation of X-inactivation, is under the control of Nanog, Oct4 and Sox2, the three factors lying at the heart of the pluripotency network. We conclude that in mouse ES cells the pluripotency-associated machinery exerts an exhaustive control of X-inactivation by taking over the regulation of all three major regulators of X-inactivation: Xist, Tsix, and Rnf12.

Situated conceptualization and semantic processing: effects of emotional experience and context availability in semantic categorization and naming tasks.

It has been proposed that much of conceptual knowledge is acquired through situated conceptualization, such that both external (e.g., agents, objects, events) and internal (e.g., emotions, introspections) environments are considered important (Barsalou, 2003). To evaluate this proposal, we characterized two dimensions by which situated conceptualization may be measured and which should have different relevance for abstract and concrete concepts; namely, emotional experience (i.e., the ease with which words evoke emotional experience; Newcombe, Campbell, Siakaluk, & Pexman, 2012) and context availability (i.e., the ease with which words evoke contexts in which their referents may appear; Schwanenflugel & Shoben, 1983). We examined the effects of these two dimensions on abstract and concrete word processing in verbal semantic categorization (VSCT) and naming tasks. In the VSCT, emotional experience facilitated processing of abstract words but inhibited processing of concrete words, whereas context availability facilitated processing of both types of words. In the naming task in which abstract words and concrete words were not blocked by emotional experience, context availability facilitated responding to only the abstract words. In the naming task in which abstract words and concrete words were blocked by emotional experience, emotional experience facilitated responding to only the abstract words, whereas context availability facilitated responding to only the concrete words. These results were observed even with several lexical (e.g., frequency, age of acquisition) and semantic (e.g., concreteness, arousal, valence) variables included in the analyses. As such, the present research suggests that emotional experience and context availability tap into different aspects of situated conceptualization and make unique contributions to the representation and processing of abstract and concrete concepts.