No abstract

Circadian clocks regulate homeostasis and mediate responses to stressors. Lactation is one of the most energetically demanding periods of an adult female's life. Peripartum changes occur in almost every organ so the dam can support neonatal growth through milk production while homeostasis is maintained. How circadian clocks are involved in adaptation to lactation is currently unknown. The abundance and temporal pattern of core clock genes' expression were measured in suprachiasmatic nucleus, liver, and mammary from late pregnant and early lactation mice. Tissue-specific changes in molecular clocks occurred between physiological states. Amplitude and robustness of rhythms increased in suprachiasmatic nucleus and liver. Mammary rhythms of core molecular clock genes were suppressed. Attenuated rhythms appeared to be a physiological adaptation of mammary to lactation, because manipulation of timing of suckling resulting in significant differences in plasma prolactin and corticosterone had no effect on amplitude. Analysis of core clock proteins revealed that the stoichiometric relationship between positive (CLOCK) and negative (PER2) components remained 1:1 in liver but was increased to 4:1 in mammary during physiological transition. Induction of differentiation of mammary epithelial cell line HC11 with dexamethasone, insulin, and prolactin resulted in similar stoichiometric changes among positive and negative clock regulators, and prolactin induced phase shifts in HC11 Arntl expression rhythm. Data support that distinct mechanisms drive periparturient changes in mammary clock. Stoichiometric change in clock regulators occurs with gland differentiation. Suppression of mammary clock gene expression rhythms represents a physiological adaptation to suckling cues. Adaptations in mammary clock are likely needed in part to support suckling demands of neonates.

Pediatric cataract is a leading cause of childhood blindness. This study aimed to determine the genetic cause of pediatric cataract in Australian families by screening known disease-associated genes using massively parallel sequencing technology. We sequenced 51 previously reported pediatric cataract genes in 33 affected individuals with a family history (cases with previously known or published mutations were excluded) using the Ion Torrent Personal Genome Machine. Variants were prioritized for validation if they were predicted to alter the protein sequence and were absent or rare with minor allele frequency <1% in public databases. Confirmed mutations were assessed for segregation with the phenotype in all available family members. All identified novel or previously reported cataract-causing mutations were screened in 326 unrelated Australian controls. We detected 11 novel mutations in GJA3, GJA8, CRYAA, CRYBB2, CRYGS, CRYGA, GCNT2, CRYGA, and MIP; and three previously reported cataract-causing mutations in GJA8, CRYAA, and CRYBB2. The most commonly mutated genes were those coding for gap junctions and crystallin proteins. Including previous reports of pediatric cataract-associated mutations in our Australian cohort, known genes account for >60% of familial pediatric cataract in Australia, indicating that still more causative genes remain to be identified.

On June 2, 2020, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial morbidity and mortality since it was first described in December 2019 (1). Based on epidemiologic data showing spread in congregate settings (2-4), national, state, and local governments instituted significant restrictions on large gatherings to prevent transmission of disease in early March 2020. This and other nonpharmaceutical interventions (NPIs) have shown initial success in slowing the pandemic across the country (5). This report examines the first 7 weeks (March 1-April 18) of implementation of NPIs in Basic Military Training (BMT) at a U.S. Air Force base. In a population of 10,579 trainees, COVID-19 incidence was limited to five cases (47 per 100,000 persons), three of which were in persons who were contacts of the first patient. Transmission of symptomatic COVID-19 was successfully limited using strategies of quarantine, social distancing, early screening of trainees, rapid isolation of persons with suspected cases, and monitored reentry into training for trainees with positive test results after resolution of symptoms.BMT is the first step in the accession of airmen into the USAF. Approximately 40,000 new airmen are trained each year at Joint Base San Antonio-Lackland (JBSA) in Texas with an average of approximately 800 trainees arriving per week. Approximately 75% of incoming trainees are male, and most are in their late teens or early 20s. These trainees are prescreened for underlying medical conditions and are generally in good overall health. Training involves classroom lectures, small group activities, and field exercises. Each training cohort (flight) consists of 50 persons who live in communal, open-bay quarters and perform all daily and training activities as a group. For accountability and safety purposes, trainees are never alone, performing every activity with at least one fellow trainee. In recent decades, outbreaks of respiratory illnesses caused by pathogens such as adenovirus serotype B14 in 2007 have occurred during BMT, resulting in head-to-toe bunk arrangements, regular cleaning of shared equipment, and active syndromic surveillance for respiratory illness (6).

At the end of 1994 the New South Wales Department of Health identified the need for a specialized unit for people with a brain injury who exhibited aggressive and violent behaviour at such a level that they could not be cared for in standard rehabilitation programmes and who were not mentally ill as defined by the Mental Health Act. An interim unit based on the principles of neurobehavioural rehabilitation was opened in the grounds of Lidcombe Hospital, and in January 1995 the first patient (SA) was admitted. Following intervention weekly aggression decreased from a peak of 159 incidents to zero after ten months. Other maladaptive behaviours also decreased markedly. Simultaneous attempts to improve adaptive behaviours were successful. At 11 months follow-up in the community, these gains were all noted to have been maintained. This article discusses the need for specialized units dealing with severe behavioural problems following head injury, presents the case of SA for illustrative purposes, and addresses some of the more common criticisms of such environments.

Few studies have investigated the impact of alterations in gravity on mammalian transcriptomes. Here, we describe the impact of spaceflight on mammary transcriptome of late pregnant rats and the effect of hypergravity exposure on mammary, liver, and adipose transcriptomes in late pregnancy and at the onset of lactation. RNA was isolated from mammary collected on pregnancy day 20 from rats exposed to spaceflight from days 11 to 20 of gestation. To measure the impact of hypergravity on mammary, liver, and adipose transcriptomes we isolated RNA from tissues collected on P20 and lactation day 1 from rats exposed to hypergravity beginning on pregnancy day 9. Gene expression was measured with Affymetrix GeneChips. Microarray analysis of variance revealed alterations in gravity affected the expression of genes that regulate circadian clocks and activate mechanotransduction pathways. Changes in these systems may explain global gene expression changes in immune response, metabolism, and cell proliferation. Expression of genes that modify chromatin structure and methylation was affected, suggesting adaptation to gravity alterations may proceed through epigenetic change. Altered gravity experiments offer insights into the role of forces omnipresent on Earth that shape genomes in heritable ways. Our study is the first to analyze the impact of alterations in gravity on transcriptomes of pregnant and lactating mammals. Findings provide insight into systems that sense gravity and the way in which they affect phenotype, as well as the possibility of sustaining life beyond Earth's orbit.

BackgroundCataract is a major cause of severe visual impairment in childhood. The purpose of this study was to determine the genetic cause of syndromic congenital cataract in an Australian mother and son.MethodFifty-one genes associated with congenital cataract were sequenced in the proband using a custom Ampliseq library on the Ion Torrent Personal Genome Machine (PGM). Reads were aligned against the human genome (hg19) and variants were annotated. Variants were prioritised for validation by Sanger sequencing if they were novel, rare or previously reported to be associated with paediatric cataract and were predicted to be protein changing. Variants were assessed for segregation with the phenotype in the affected mother.ResultA novel likely pathogenic variant was identified in the transactivation domain of the MAF gene (c.176C > G, p.(Pro59Arg)) in the proband and his affected mother., but was absent in 326 unrelated controls and absent from public variant databases.ConclusionThe MAF variant is the likely cause of the congenital cataract, Asperger syndrome, seizures, hearing loss and facial characteristics in the proband, providinga diagnosis of Aymé-Gripp syndrome for the family.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0414-7) contains supplementary material, which is available to authorized users.

Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified.