The pattern of reproduction in the mole-rat Heliophobius from Tanzania : do not refrain during the long rains!

The genus Heliophobius comprises of at least six cryptic, topotypical species in the Heliophobius argentocinereus species complex. The current study investigated the breeding patterns of a wildcaught population from Tanzania where the putative species H. emini resides. Individuals were collected on a monthly basis for an entire calendar year. Assessment of foetus presence, gonadal histology, reproductive tract morphometrics in combination with gonadal steroid (plasma progesterone and oestradiol-17β in females and testosterone in males) measurements and field observations revealed that rainfall is important for the onset of breeding. The results further confirmed that breeding is limited to a single, yearly reproductive event synchonised to the long rainfall pattern. The distinct breeding peak in July is associated with an elevation in gonadal mass, increase in concentrations of reproductive hormones and presence of Graafian follicles and corpora lutea in the ovaries of females. These reproductive parameters coincided with the end of the long rainfall period, whereas presence of young in the maternal burrow system corresponded with the start of the short rainfall of East Africa. These findings confirm Heliophobius has a single breeding opportunity each year, and this species is therefore vulnerable to any changes that may impact their climatically attuned breeding patterns.MKN was sponsored by a student bursary from DAAD in Germany. NCB acknowledges funding from the South African DST/NRF SARChI Chair for Mammal Behavioural Ecology and Physiology, University of Pretoria.http://www.nrcresearchpress.com/journal/cjzhb2017Mammal Research InstituteZoology and Entomolog

“There is nothing that can prevent me from supporting her:” men’s perspectives on their involvement and support of women’s use of topical therapy for cervical precancer treatment in Kenya

Purpose: Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization’s (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Methods: Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Results: Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner’s prior precancer treatment history. The study aimed to assess men’s support of their female partners’ use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. Conclusion: The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO’s 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner’s use of topical therapies, including adherence to abstinence and contraception guidelines

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Gene Expression Changes Associated with the Airway Wall Response to Injury

Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. As only limited data is available in relation to the in vivo characterisation of the molecular features of repair in the airway we sought to characterise the dynamic changes in gene expression that are associated with the early response to physical injury in the airway wall.We profiled gene expression changes in the airway wall using a large animal model of physical injury comprising bronchial brush biopsy in anaesthetised sheep. The experimental design featured sequential studies in the same animals over the course of a week and yielded data relating to the response at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the response included the up-regulation of cell cycle genes at d1 and d3, and the latter pronounced up-regulation of extracellular matrix-related genes at d3 and d7.It is possible to follow the airway wall response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance

CDKN1B mutation and copy number variation are associated with tumor aggressiveness in luminal breast cancer

The CDKN1B gene, encoding for the CDK inhibitor p27kip1, is mutated in defined human cancer subtypes, including breast, prostate carcinomas and small intestine neuroendocrine tumors. Lessons learned from small intestine neuroendocrine tumors suggest that CDKN1B mutations could be subclonal, raising the question of whether a deeper sequencing approach could lead to the identification of higher numbers of patients with mutations. Here, we addressed this question and analyzed human cancer biopsies from breast (n = 396), ovarian (n = 110) and head and neck squamous carcinoma (n = 202) patients, using an ultra-deep sequencing approach. Notwithstanding this effort, the mutation rate of CDKN1B remained substantially aligned with values from the literature, showing that essentially only hormone receptor-positive breast cancer displayed CDKN1B mutations in a relevant number of cases (3%). However, the analysis of copy number variation showed that another fraction of luminal breast cancer displayed loss (8%) or gain (6%) of the CDKN1B gene, further reinforcing the idea that the function of p27kip1 is important in this type of tumor. Intriguingly, an enrichment for CDKN1B alterations was found in samples from premenopausal luminal breast cancer patients (n = 227, 4%) and in circulating cell-free DNA from metastatic luminal breast cancer patients (n = 59, 8.5%), suggesting that CDKN1B alterations could correlate with tumor aggressiveness and/or occur later during disease progression. Notably, many of the identified somatic mutations resulted in p27kip1 protein truncation, leading to loss of most of the protein or of its C-terminal domain. Using a gene-editing approach in a luminal breast cancer cell line, MCF-7, we observed that the expression of p27kip1 truncating mutants that lose the C-terminal domains failed to rescue most of the phenotypes induced by CDKN1B gene knockout, indicating that the functions retained by the C-terminal portion are critical for its role as an oncosuppressor, at least in luminal breast cancer. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Integrin α5β1 Function Is Regulated by XGIPC/kermit2 Mediated Endocytosis during Xenopus laevis Gastrulation

During Xenopus gastrulation α5β1 integrin function is modulated in a temporally and spatially restricted manner, however, the regulatory mechanisms behind this regulation remain uncharacterized. Here we report that XGIPC/kermit2 binds to the cytoplasmic domain of the α5 subunit and regulates the activity of α5β1 integrin. The interaction of kermit2 with α5β1 is essential for fibronectin (FN) matrix assembly during the early stages of gastrulation. We further demonstrate that kermit2 regulates α5β1 integrin endocytosis downstream of activin signaling. Inhibition of kermit2 function impairs cell migration but not adhesion to FN substrates indicating that integrin recycling is essential for mesoderm cell migration. Furthermore, we find that the α5β1 integrin is colocalized with kermit2 and Rab 21 in embryonic and XTC cells. These data support a model where region specific mesoderm induction acts through kermit2 to regulate the temporally and spatially restricted changes in adhesive properties of the α5β1 integrin through receptor endocytosis

Combination of the W boson polarization measurements in top quark decays using ATLAS and CMS data at root s=8 TeV

The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb(-1)for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal (F-0), left-handed (F-L), or right-handed (F-R) polarizations. The resulting combined measurements of the polarization fractions are F-0= 0.693 +/- 0.014 and F-L= 0.315 +/- 0.011. The fractionF(R)is calculated from the unitarity constraint to be F-R=-0.008 +/- 0.007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F-0(F-L) with respect to the most precise single measurement. A limit on anomalous right-handed vector (V-R), and left- and right-handed tensor (g(L), g(R)) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [-0.11,0.16] for V-R, [-0.08,0.05] for g(L), and [-0.04,0.02] for g(R), at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived.Peer reviewe

Measurement of hadronic event shapes in high-p T multijet final states at √s = 13 TeV with the ATLAS detector

A measurement of event-shape variables in proton-proton collisions at large momentum transfer is presented using data collected at s = 13 TeV with the ATLAS detector at the Large Hadron Collider. Six event-shape variables calculated using hadronic jets are studied in inclusive multijet events using data corresponding to an integrated luminosity of 139 fb−1. Measurements are performed in bins of jet multiplicity and in different ranges of the scalar sum of the transverse momenta of the two leading jets, reaching scales beyond 2 TeV. These measurements are compared with predictions from Monte Carlo event generators containing leading-order or next-to-leading order matrix elements matched to parton showers simulated to leading-logarithm accuracy. At low jet multiplicities, shape discrepancies between the measurements and the Monte Carlo predictions are observed. At high jet multiplicities, the shapes are better described but discrepancies in the normalisation are observed. [Figure not available: see fulltext.

A search for the dimuon decay of the Standard Model Higgs boson with the ATLAS detector

A search for the dimuon decay of the Standard Model (SM) Higgs boson is performed using data corresponding to an integrated luminosity of 139 fb(-1) collected with the ATLAS detector in Run 2 pp collisions at root s = 13 TeV at the Large Hadron Collider. The observed (expected) significance over the background-only hypothesis for a Higgs boson with a mass of 125.09 GeV is 2.0 sigma (1.7 sigma). The observed upper limit on the cross section times branching ratio for pp -> H -> mu mu is 2.2 times the SM prediction at 95% confidence level, while the expected limit on a H -> mu mu signal assuming the absence (presence) of a SM signal is 1.1(2.0). The best-fit value of the signal strength parameter, defined as the ratio of the observed signal yield to the one expected in the SM, is mu = 1.2 +/- 0.6. (C) 2020 The Author(s). Published by Elsevier B.V