Central role for the XRCC1 BRCT I domain in mammalian DNA single-strand break repair

The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G1 but is dispensable for this process during S/G2 and consequently for cell survival following DNA alkylation. Little is known about BRCT I, but this domain has attracted considerable interest because it is the site of a genetic polymorphism that epidemiological studies have associated with altered cancer risk. We report that the BRCT I domain comprises the evolutionarily conserved core of XRCC1 and that this domain is required for efficient SSBR during both G1 and S/G2 cell cycle phases and for cell survival following treatment with methyl methanesulfonate. However, the naturally occurring human polymorphism in BRCT I supported XRCC1-dependent SSBR and cell survival after DNA alkylation equally well. We conclude that while the BRCT I domain is critical for XRCC1 to maintain genetic integrity and cell survival, the polymorphism does not impact significantly on this function and therefore is unlikely to impact significantly on susceptibility to cancer

Status of Women and Gender Equity at CWRU - 2021

The first bi-annual report from the Flora Stone Mather Center reviews the representation of women as well as the intersections of race/ethnicity and gender identities across CWRU executive leadership, faculty, staff, and students.https://commons.case.edu/mathercenter-briefs/1003/thumbnail.jp

WISER: Women in Science and Engineering Roundtable

This brief provides an overview of Case Western Reserve University\u27s Women in Science and Engineering Roundtable, including student evaluation and national metrics about women in STEMhttps://commons.case.edu/mathercenter-briefs/1000/thumbnail.jp

Association of Leptin Gene Markers with Carcass Traits in Beef Cattle

The objective of this study was to evaluate four genetic markers on the leptin gene for association with carcass traits in three crossbred families. Three half-sib families were developed from crossbred sires. Families 1, 2, and 3 comprised 26, 21, and 66 offspring, respectively (n = 113). The genetic background of the sires, dams, and offspring was 1/3 Angus, 1/3 Hereford, 1/3 Simmental. Carcass traits collected were finished weight, hot carcass weight (HCW), marbling score, Quality Grade, Longissimus muscle area (LMA), rib fat, Yield Grade, and percent kidney, pelvic, and heart fat (KPH). The four markers analyzed were located on the exon 2, exon 3, and promoter region of the leptin gene. There was an association of marbling score with leptin exon 3 (P \u3c 0.05), and ability to grade choice with leptin exon 2 (P \u3c 0.05), exon 3 (P \u3c 0.001), and promoter (P \u3c 0.01) in family 2. Family 2 also displayed allelic effects for ability to grade choice (P \u3c 0.01) with leptin exon 3 and promoter. Family 3 showed an association between leptin exon 2 (P \u3c 0.05) and marbling score. No association was detected (P \u3e 0.05) on family 1

Isolated Medial Cuneiform Fractures: A Systematic Search and Qualitative Analysis of Case Studies

Background: Isolated medial cuneiform fracture is a rare but diagnostically challenging condition. Diagnostic delay in these cases may lead to delays in ideal treatment approaches and prolonged symptoms. An understanding of clinical presentation is needed to expedite diagnosis, facilitate decision making, and guide treatment approach. Methods: Case studies/series were searched in four databases until September 2019. Included studies had participants with a history of traumatic closed medial cuneiform fracture. Studies were excluded if the medial cuneiform fractures were open fractures, associated with multitrauma, or associated with dislocation/Lisfranc injury. Three blinded reviewers assessed the methodological quality of the studies, and a qualitative synthesis was performed. Results: Ten studies comprising 15 patients were identified. Mean ± SD patient age was 38.0 ± 12.8 years, with 86.7% of reported participants being men. The overall methodological quality was moderate to high, and reporting of the patient selection criteria was poor overall. The most commonly reported clinical symptoms were localized tenderness (60.0%) and edema (53.3%). Direct blow was the most common inciting trauma (46.2%), followed by axial load (30.8%) and avulsion injuries (23.1%). Baseline radiographs were occult in 72.7% of patients; magnetic resonance imaging and computed tomography were the most common diagnostic modalities. Mean ± SD diagnostic delay was 64.7 ± 89.6 days. Conservative management was pursued in 54.5% of patients, with reported resolution of symptoms in 3 to 6 months. Surgical intervention occurred in 45.5% of patients and resulted in functional restoration in 3 to 6 months in all but one patient. Conclusions: Initial radiographs for isolated medial cuneiform fractures are frequently occult. Due to expedience and relatively low cost, radiographs are still a viable first-line imaging modality. If clinical concern remains, magnetic resonance imaging may be pursued to minimize diagnostic delay. Conservative management is a viable treatment method, with expected return to full function in 3 to 6 months

Morning vaccination enhances antibody response over afternoon vaccination: A cluster-randomised trial

Objectives Older adults are less able to produce a protective antibody response to vaccinations. One factor that contributes to this is immune ageing. Here we examined whether diurnal variations in immune responses might extend to the antibody response to vaccination. Design We utilised a cluster-randomised trial design. Setting 24 General Practices (GPs) across the West Midlands, UK who were assigned to morning (9–11 am; 15 surgeries) or afternoon (3–5 pm; 9 surgeries) vaccination times for the annual UK influenza vaccination programme. Participants 276 adults (aged 65+ years and without a current infection or immune disorder or taking immunosuppressant medication). Interventions Participants were vaccinated in the morning or afternoon between 2011 and 2013. Main outcome measures The primary outcome was the change in antibody titres to the three vaccine influenza strains from pre-vaccination to one month post-vaccination. Secondary outcomes of serum cytokines and steroid hormone concentrations were analysed at baseline to identify relationships with antibody responses. Results The increase in antibody levels due to vaccination differed between morning and afternoon administration; mean difference (95% CI) for H1N1 A-strain, 293.3 (30.97–555.66) p = .03, B-strain, 15.89 (3.42–28.36) p = .01, but not H3N2 A-strain, 47.0 (−52.43 to 146.46) p = .35; those vaccinated in the morning had a greater antibody response. Cytokines and steroid hormones were not related to antibody responses. No adverse events were reported. Conclusions This simple manipulation in the timing of vaccine administration to favour morning vaccination may be beneficial for the influenza antibody response in older adults, with potential implications for vaccination strategies generally

The radio source counts at 15 GHz and their implications for cm-wave CMB imaging

We present the preliminary results of a new survey of radio sources using the Ryle telescope at 15.2 GHz. This is the highest frequency at which a survey has been done that is relevant to the issue of radio source contamination in CMB experiments. The differential source count of the 66 sources found in 63 sqdeg is 80(S/Jy)^-2 /Jy/sr from about 20 to 500 mJy. Extrapolating this to 34 GHz (where many cm-wave CMB experiments operate) gives an estimated temperature contribution from sources of 9 microK in a CMB image, with a beam corresponding to multipole l=500. A means of source subtraction is evidently necessary, otherwise the signal-to-noise ratio in CMB images will be limited to 4 or 5, becoming worse at higher resolution. We compare the population of sources observed in this new survey to that predicted by extrapolation from lower frequency surveys, finding that source fluxes, and indeed the existence of many sources, cannot be determined by extrapolation.Comment: 4 pages, 3 figures, submitted to MNRA