Non-random chromosome positioning in mammalian sperm nuclei, with migration of the sex chromosomes during late spermatogenesis

Chromosomes are highly organized and compartmentalized in cell nuclei. The analysis of their position is a powerful way to monitor genome organization in different cell types and states. Evidence suggests that the organization of the genome could be functionally important for influencing different cellular and developmental processes, particularly at early stages of development (i.e. fertilization and the consequent entry of the sperm nucleus into the egg). The position of chromosomes in the sperm nucleus might be crucial, because their location could determine the time at which particular chromatin domains are decondensed and remodelled, allowing some epigenetic level of control or influence over subsequent paternal gene expression in the embryo. Here, we analyse genome organization by chromosome position in mammalian sperm nuclei from three breeds of pig, as a model species. We have mapped the preferential position of all chromosomes (bar one) in sperm nuclei in two dimensions and have established that the sex chromosomes are the most internally localized chromosomes in mature sperm. The distribution of two autosomes and chromosomes X and Y in sperm heads was compared in primary and secondary spermatocytes and spermatids in porcine testes. The sex chromosomes were found at the nuclear edge in primary spermatocytes, which correlates with the known position of the XY body and their position in somatic cells, whereas, in spermatids, the sex chromosomes were much more centrally located, mirroring the position of these chromosomes in ejaculated spermatozoa. This study reveals the temporal repositioning of chromosome territories in spermatogenesis

Relative proximity of chromosome territories influences chromosome exchange partners in radiation-induced chromosome rearrangements in primary human bronchial epithelial cells

Copyright © 2013 The Authors. This article is made available through the Brunel Open Access Publishing Fund. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.Copyright © 2013 The Authors. It is well established that chromosomes exist in discrete territories (CTs) in interphase and are positioned in a cell-type specific probabilistic manner. The relative localisation of individual CTs within cell nuclei remains poorly understood, yet many cancers are associated with specific chromosome rearrangements and there is good evidence that relative territorial position influences their frequency of exchange. To examine this further, we characterised the complexity of radiation-induced chromosome exchanges in normal human bronchial epithelial (NHBE) cells by M-FISH analysis of PCC spreads and correlated the exchanges induced with their preferred interphase position, as determined by 1/2-colour 2D-FISH analysis, at the time of irradiation. We found that the frequency and complexity of aberrations induced were reduced in ellipsoid NHBE cells in comparison to previous observations in spherical cells, consistent with aberration complexity being dependent upon the number and proximity of damaged CTs, i.e. lesion proximity. To ask if particular chromosome neighbourhoods could be identified we analysed all radiation-induced pair-wise exchanges using SCHIP (statistics for chromosome interphase positioning) and found that exchanges between chromosomes (1;13), (9;17), (9;18), (12;18) and (16;21) all occurred more often than expected assuming randomness. All of these pairs were also found to be either sharing similar preferred positions in interphase and/or sharing neighbouring territory boundaries. We also analysed a human small cell lung cancer cell line, DMS53, by M-FISH observing the genome to be highly rearranged, yet possessing rearrangements also involving chromosomes (1;13) and (9;17). Our findings show evidence for the occurrence of non-random exchanges that may reflect the territorial organisation of chromosomes in interphase at time of damage and highlight the importance of cellular geometry for the induction of aberrations of varying complexity after exposure to both low and high-LET radiation.Department of Healt

Modified push-off testing of an inclined shear plane in reinforced concrete strengthened with CFRP fabric

This study reports the findings of an experimental investigation into the behaviour of an inclined shear plane in reinforced concrete, such as a diagonal crack in the web of a beam, strengthened with externally bonded Carbon Fibre Reinforced Polymer (CFRP) fabric. A modified push-off test of novel geometry was developed for this study. This test generates a diagonal failure plane subject to combined shear and tension. Both unwrapped and wrapped tests were conducted, allowing the load sharing and load displacement behaviour of the reinforced concrete, and the reinforced concrete with externally bonded CFRP fabric, to be investigated. Fully wrapped and U-wrapped CFRP fabric configurations were tested. Results indicate that for the arrangement tested, concrete, steel and CFRP contributions to resistance are not independent, and that effective anchorage lengths given in the UK and US guidance for U-wrapped CFRP may not be adequate in some cases.The authors wish to gratefully acknowledge the financial support of the UK Engineering and Physical Sciences Research Council (EPSRC) through grant EP/I018972/1 . The authors also wish to extend their sincere thanks to Jan Nilsson, Martin Touhey and the staff of the University of Cambridge Structures Research Lab for their invaluable assistance in carrying out the experimental programme reported above.This is the author accepted manuscript. The final version is available at http://ascelibrary.org/doi/abs/10.1061/%28ASCE%29CC.1943-5614.0000623

The Millimeter Astronomy Legacy Team 90 GHz Survey (MALT90) and ALMA

ALMA will revolutionize our understanding of star formation within our galaxy, but before we can use ALMA we need to know where to look. The Millimeter Astronomy Legacy Team 90 GHz (MALT90) Survey is a large international project to map the molecular line emission of over 2,000 dense clumps in the Galactic plane. MALT90 serves as a pathfinder for ALMA, providing a large public database of dense molecular clumps associated with high-mass star formation. In this proceedings, we describe the survey parameters and share early science highlights from the survey, including (1) a comparison between galactic and extragalactic star formation relations, (2) chemical trends in MALT90 clumps, (3) the distribution of high-mass star formation in the Milky Way, and (4) a discussion of the Brick, the target of successful ALMA Cycle 0 and Cycle 1 proposals

Tracing the Conversion of Gas into Stars in Young Massive Cluster Progenitors

Whilst young massive clusters (YMCs; $M$ $\gtrsim$ 10$^{4}$ M$_{\odot}$, age $\lesssim$ 100 Myr) have been identified in significant numbers, their progenitor gas clouds have eluded detection. Recently, four extreme molecular clouds residing within 200 pc of the Galactic centre have been identified as having the properties thought necessary to form YMCs. Here we utilise far-IR continuum data from the Herschel Infrared Galactic Plane Survey (HiGAL) and millimetre spectral line data from the Millimetre Astronomy Legacy Team 90 GHz Survey (MALT90) to determine their global physical and kinematic structure. We derive their masses, dust temperatures and radii and use virial analysis to conclude that they are all likely gravitationally bound -- confirming that they are likely YMC progenitors. We then compare the density profiles of these clouds to those of the gas and stellar components of the Sagittarius B2 Main and North proto-clusters and the stellar distribution of the Arches YMC. We find that even in these clouds -- the most massive and dense quiescent clouds in the Galaxy -- the gas is not compact enough to form an Arches-like ($M$ = 2x10$^{4}$ M$_{\odot}$, R$_{eff}$ = 0.4 pc) stellar distribution. Further dynamical processes would be required to condense the resultant population, indicating that the mass becomes more centrally concentrated as the (proto)-cluster evolves. These results suggest that YMC formation may proceed hierarchically rather than through monolithic collapse

Factors associated with medication adherence in school-aged children with asthma

Adherence to preventive asthma treatment is poor, particularly in children, yet the factors associated with adherence in this age group are not well understood. Adherence was monitored electronically over 6 months in school-aged children who attended a regional emergency department in New Zealand for an asthma exacerbation and were prescribed twice-daily inhaled corticosteroids. Participants completed questionnaires including assessment of family demographics, asthma responsibility and learning style. Multivariable analysis of factors associated with adherence was conducted. 101 children (mean (range) age 8.9 (6-15) years, 51% male) participated. Median (interquartile range) preventer adherence was 30% (17-48%) of prescribed. Four explanatory factors were identified: female sex (+12% adherence), Asian ethnicity (+19% adherence), living in a smaller household (-3.0% adherence per person in the household), and younger age at diagnosis (+2.7% for every younger year of diagnosis) (all p<0.02). In school-aged children attending the emergency department for asthma, males and non-Asian ethnic groups were at high risk for poor inhaled corticosteroid adherence and may benefit most from intervention. Four factors explained a small proportion of adherence behaviour indicating the difficulty in identifying adherence barriers. Further research is recommended in other similar populations

Group 2 Innate Lymphoid Cells Are Redundant in Experimental Renal Ischemia-Reperfusion Injury.

Acute kidney injury (AKI) can be fatal and is a well-defined risk factor for the development of chronic kidney disease. Group 2 innate lymphoid cells (ILC2s) are innate producers of type-2 cytokines and are critical regulators of homeostasis in peripheral organs. However, our knowledge of their function in the kidney is relatively limited. Recent evidence suggests that increasing ILC2 numbers by systemic administration of recombinant interleukin (IL)-25 or IL-33 protects against renal injury. Whilst ILC2s can be induced to protect against ischemic- or chemical-induced AKI, the impact of ILC2 deficiency or depletion on the severity of renal injury is unknown. Firstly, the phenotype and location of ILC2s in the kidney was assessed under homeostatic conditions. Kidney ILC2s constitutively expressed high levels of IL-5 and were located in close proximity to the renal vasculature. To test the functional role of ILC2s in the kidney, an experimental model of renal ischemia-reperfusion injury (IRI) was used and the severity of injury was assessed in wild-type, ILC2-reduced, ILC2-deficient, and ILC2-depleted mice. Surprisingly, there were no differences in histopathology, collagen deposition or mRNA expression of injury-associated (Lcn2), inflammatory (Cxcl1, Cxcl2, and Tnf) or extracellular matrix (Col1a1, Fn1) factors following IRI in the absence of ILC2s. These data suggest the absence of ILC2s does not alter the severity of renal injury, suggesting possible redundancy. Therefore, other mechanisms of type 2-mediated immune cell activation likely compensate in the absence of ILC2s. Hence, a loss of ILC2s is unlikely to increase susceptibility to, or severity of AKI

Effect of electronic adherence monitoring on adherence and outcomes in chronic conditions: A systematic review and metaanalysis

Introduction Electronic adherence monitoring (EAM) is increasingly used to improve adherence. However, there is limited evidence on the effect of EAM in across chronic conditions and on patient acceptability. We aimed to assess the effect of EAM on adherence and clinical outcomes, across all ages and all chronic conditions, and examine acceptability in this systematic review and meta-analysis. Methods A systematic search of Ovid MEDLINE, EMBASE, Social Work Abstracts, PsycINFO, International Pharmaceutical Abstracts and CINAHL databases was performed from database inception to December 31, 2020. Randomised controlled trials (RCTs) that evaluated the effect of EAM on medication adherence as part of an adherence intervention in chronic conditions were included. Study characteristics, differences in adherence and clinical outcomes between intervention and control were extracted from each study. Estimates were pooled using random-effects meta-analysis, and presented as mean differences, standardised mean differences (SMD) or risk ratios depending on the data. Differences by study-level characteristics were estimated using subgroup meta-analysis to identify intervention characteristics associated with improved adherence. Effects on adherence and clinical outcomes which could not be meta-analysed, and patient acceptability, were synthesised narratively. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed, and Risk of bias (RoB) assessed using the Cochrane Collaboration's RoB tool for RCTs. The review is registered with PROSPERO CRD42017084231. Findings Our search identified 365 studies, of which 47 studies involving 6194 patients were included. Data from 27 studies (n = 2584) were extracted for the adherence outcome. The intervention group (n = 1267) had significantly better adherence compared to control (n = 1317), (SMD = 0.93, CI:0.69 to 1.17, p<0.0001) with high heterogeneity across studies (I2 = 86%). There was a significant difference in effect according to intervention complexity (p = 0.01); EAM only improved adherence when used with a reminder and/or health provider support. Clinical outcomes were measured in 38/47 (81%) of studies; of these data from 14 studies were included in a meta-analysis of clinical outcomes for HIV, hypertension and asthma. In total, 13/47 (28%) studies assessed acceptability; patient perceptions were mixed. Interpretation Patients receiving an EAM intervention had significantly better adherence than those who did not, but improved adherence did not consistently translate into clinical benefits. Acceptability data were mixed. Further research measuring effects on clinical outcomes and patient acceptability are needed