Diffusion tensor magnetic resonance imaging-derived myocardial fiber disarray in hypertensive left ventricular hypertrophy: visualization, quantification and the effect on mechanical function

Left ventricular hypertrophy induced by systemic hypertension is generally regarded a morphological precursor of unfortunate cardiovascular events. Myocardial fiber disarray has been long recognized as a prevalent hallmark of this pathology. In this chapter, ex vivo diffusion tensor magnetic resonance imaging is employed to delineate the regional loss of myocardial organization that is present in the excised heart of a spontaneously hypertensive rat, as opposed to a control. Fiber tracking results are provided that illustrate in great detail the alterations in the integrity of cardiac muscle microstructure due to the disease. A quantitative analysis is also performed. Another contribution of this chapter is the model-based assessment of the role of the myofiber disarray in modulating the mechanical properties of the myocardium. The results of this study improve our understanding of the structural remodeling mechanisms that are associated with hypetensive left ventricular hypertrophy and their role

Sox9 Transcriptionally Represses Spp1 to Prevent Matrix Mineralization in Maturing Heart Valves and Chondrocytes

Sox9 is an SRY-related transcription factor required for expression of cartilaginous genes in the developing skeletal system and heart valve structures. In contrast to positively regulating cartilaginous matrix, Sox9 also negatively regulates matrix mineralization associated with bone formation. While the transcriptional activation of Sox9 target genes during chondrogenesis has been characterized, the mechanisms by which Sox9 represses osteogenic processes are not so clear. Using ChIP-on-chip and luciferase assays we show that Sox9 binds and represses transactivation of the osteogenic glycoprotein Spp1. In addition, Sox9 knockdown in post natal mouse heart valve explants and rib chondrocyte cultures promotes Spp1 expression and matrix mineralization, while attenuating expression of cartilage genes Type II Collagen and Cartilage Link Protein. Further, we show that Spp1 is required for matrix mineralization induced by Sox9 knockdown. These studies provide insights into the molecular mechanisms by which Sox9 prevents pathologic matrix mineralization in tissues that must remain cartilaginous

Fundamental insight into the effect of carbodiimide crosslinking on cellular recognition of collagen-based scaffolds

Research on the development of collagen constructs is extremely important in the field of tissue engineering. Collagen scaffolds for numerous tissue engineering applications are frequently crosslinked with 1-ethyl-3-(3-dimethylaminopropyl-carbodiimide hydrochloride (EDC) in the presence of N-hydroxy-succinimide (NHS). Despite producing scaffolds with good biocompatibility and low cellular toxicity the influence of EDC/NHS crosslinking on the cell interactive properties of collagen has been overlooked. Here we have extensively studied the interaction of model cell lines with collagen I-based materials after crosslinking with different ratios of EDC in relation to the number of carboxylic acid residues on collagen. Divalent cation-dependent cell adhesion, via integrins α$_{1}$β$_{1}$, α$_{2}$β$_{1}$, α$_{10}$β$_{1}$ and α$_{11}$β$_{1}$, were sensitive to EDC crosslinking. With increasing EDC concentration, this was replaced with cation-independent adhesion. These results were replicated using purified recombinant I domains derived from integrin α$_{1}$ and α$_{2}$ subunits. Integrin α$_{2}$β$_{1}$-mediated cell spreading, apoptosis and proliferation were all heavily influenced by EDC crosslinking of collagen. Data from this rigorous study provides an exciting new insight that EDC/NHS crosslinking is utilising the same carboxylic side chain chemistry that is vital for native-like integrin-mediated cell interactions. Due to the ubiquitous usage of EDC/NHS crosslinked collagen for biomaterials fabrication this data is essential to have a full understanding in order to ensure optimized collagen-based material performance.This work was supported by the British Heart Foundation (Grant NH/11/1/28922, RG/15/4/31268, SP/15/7/31561 and RG/09/003/27122) and the ERC Advanced Grant 320598 3D-E. D. V. Bax is funded by the Peoples Programme of the EU 7th Framework Programme (RAE no: PIIF-GA-2013-624904) and was supported by an EPSRC IKC Proof of Concept Award

Pregnancy and childbirth in English prisons : institutional ignominy and the pains of imprisonment

© 2020 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL.With a prison population of approximately 9000 women in England, it is estimated that approximately 600 pregnancies and 100 births occur annually. Despite an extensive literature on the sociology of reproduction, pregnancy and childbirth among women prisoners is under‐researched. This article reports an ethnographic study in three English prisons undertaken in 2015‐2016, including interviews with 22 prisoners, six women released from prison and 10 staff members. Pregnant prisoners experience numerous additional difficulties in prison including the ambiguous status of a pregnant prisoner, physical aspects of pregnancy and the degradation of the handcuffed or chained prisoner during visits to the more public setting of hospital. This article draws on Erving Goffman's concepts of closed institutions, dramaturgy and mortification of self, Crewe et al.'s work on the gendered pains of imprisonment and Crawley's notion of ‘institutional thoughtlessness’, and proposes a new concept of institutional ignominy to understand the embodied situation of the pregnant prisoner.Peer reviewe

SPT0346-52: Negligible AGN Activity in a Compact, Hyper-starburst Galaxy at z = 5.7

We present Chandra ACIS-S and ATCA radio continuum observations of the strongly lensed dusty, star-forming galaxy SPT-S J034640-5204.9 (hereafter SPT0346-52) at $z$ = 5.656. This galaxy has also been observed with ALMA, HST, Spitzer, Herschel, APEX, and the VLT. Previous observations indicate that if the infrared (IR) emission is driven by star formation, then the inferred lensing-corrected star formation rate ($\sim$ 4500 M_{\sun} yr$^{-1}$) and star formation rate surface density $\Sigma_{\rm SFR}$ ($\sim$ 2000 M_{\sun} {yr^{-1}} {kpc^{-2}}) are both exceptionally high. It remained unclear from the previous data, however, whether a central active galactic nucleus (AGN) contributes appreciably to the IR luminosity. The {\it Chandra} upper limit shows that SPT0346-52 is consistent with being star-formation dominated in the X-ray, and any AGN contribution to the IR emission is negligible. The ATCA radio continuum upper limits are also consistent with the FIR-to-radio correlation for star-forming galaxies with no indication of an additional AGN contribution. The observed prodigious intrinsic IR luminosity of (3.6 $\pm$ 0.3) $\times$ 10$^{13}$ L_{\sun} originates almost solely from vigorous star formation activity. With an intrinsic source size of 0.61 $\pm$ 0.03 kpc, SPT0346-52 is confirmed to have one of the highest $\Sigma_{SFR}$ of any known galaxy. This high $\Sigma_{SFR}$, which approaches the Eddington limit for a radiation pressure supported starburst, may be explained by a combination of very high star formation efficiency and gas fraction.Comment: 8 pages, 6 figures, accepted for publication in Ap

The Rest-Frame Submillimeter Spectrum of High-Redshift, Dusty, Star-Forming Galaxies

We present the average rest-frame spectrum of high-redshift dusty, star-forming galaxies from 250-770GHz. This spectrum was constructed by stacking ALMA 3mm spectra of 22 such sources discovered by the South Pole Telescope and spanning z=2.0-5.7. In addition to multiple bright spectral features of 12CO, [CI], and H2O, we also detect several faint transitions of 13CO, HCN, HNC, HCO+, and CN, and use the observed line strengths to characterize the typical properties of the interstellar medium of these high-redshift starburst galaxies. We find that the 13CO brightness in these objects is comparable to that of the only other z>2 star-forming galaxy in which 13CO has been observed. We show that the emission from the high-critical density molecules HCN, HNC, HCO+, and CN is consistent with a warm, dense medium with T_kin ~ 55K and n_H2 >~ 10^5.5 cm^-3. High molecular hydrogen densities are required to reproduce the observed line ratios, and we demonstrate that alternatives to purely collisional excitation are unlikely to be significant for the bulk of these systems. We quantify the average emission from several species with no individually detected transitions, and find emission from the hydride CH and the linear molecule CCH for the first time at high redshift, indicating that these molecules may be powerful probes of interstellar chemistry in high-redshift systems. These observations represent the first constraints on many molecular species with rest-frame transitions from 0.4-1.2mm in star-forming systems at high redshift, and will be invaluable in making effective use of ALMA in full science operations.Comment: 19 pages, 10 figures (2 in appendices); accepted for publication in Ap

The redshift distribution of dusty star forming galaxies from the SPT survey

We use the Atacama Large Millimeter/submillimeter Array (ALMA) in Cycle 1 to determine spectroscopic redshifts of high-redshift dusty star-forming galaxies (DSFGs) selected by their 1.4mm continuum emission in the South Pole Telescope (SPT) survey. We present ALMA 3mm spectral scans between 84-114GHz for 15 galaxies and targeted ALMA 1mm observations for an additional eight sources. Our observations yield 30 new line detections from CO, [CI] , [NII] , H_2O and NH_3. We further present APEX [CII] and CO mid-J observations for seven sources for which only a single line was detected in spectral-scan data from ALMA Cycle 0 or Cycle 1. We combine the new observations with previously published and new mm/submm line and photometric data of the SPT-selected DSFGs to study their redshift distribution. The combined data yield 39 spectroscopic redshifts from molecular lines, a success rate of >85%. Our sample represents the largest data set of its kind today and has the highest spectroscopic completeness among all redshift surveys of high-z DSFGs. The median of the redshift distribution is z=3.9+/-0.4, and the highest-redshift source in our sample is at z=5.8. We discuss how the selection of our sources affects the redshift distribution, focusing on source brightness, selection wavelength, and strong gravitational lensing. We correct for the effect of gravitational lensing and find the redshift distribution for 1.4mm-selected sources with a median redshift of z=3.1+/-0.3. Comparing to redshift distributions selected at shorter wavelengths from the literature, we show that selection wavelength affects the shape of the redshift distribution