Evidence that the T cell antigen receptor may not be involved in cytotoxicity mediated by gamma/delta and alpha/beta thymic cell lines.

After culture in IL-2, thymocytes expressing either TCR-alpha/beta or -gamma/delta acquired the ability to lyse hematopoietic and solid tumor cell targets without deliberate immunization or apparent restriction by the MHC. Moreover, TCR-alpha/beta- and TCR-gamma/delta-bearing thymic cell lines demonstrated an essentially identical spectrum of cytolysis against several tumor cell targets. Cytotoxicity was not inhibited by antibodies against CD3 or CD2 and modulation of the CD3/TCR complex also failed to affect cytotoxicity. Thus, non-MHC-restricted cytotoxicity can be mediated by thymocytes with either TCR-alpha/beta or TCR-gamma/delta, but the TCR may not be responsible for target recognition

UK survey of occupational therapist’s and physiotherapist’s experiences and attitudes towards hip replacement precautions and equipment

Background: Total hip replacement (THR) is one of the most common orthopaedic procedures in the United Kingdom (UK). Historically, people following THR have been provided with hip precautions and equipment such as: raised toilet seats and furniture rises, in order to reduce the risks of dislocation post-operation. The purpose of this study was to determine current practices in the provision of these interventions in the UK for people following primary THR. Methods: A 27-question, self-administered online survey was developed and distributed to UK physiotherapists and occupational therapists involved in the management of people following primary THR (target respondents). The survey included questions regarding the current practices in the provision of equipment and hip precautions for THR patients, and physiotherapist’s and occupational therapist’s attitudes towards these practices. The survey was disseminated through print and web-based/social media channels. Results: 170 health professionals (87 physiotherapists and 83 occupational therapists), responded to the survey. Commonly prescribed equipment in respondent’s health trusts were raised toilet seats (95%), toilet frames and rails (88%), furniture raises (79%), helping hands/grabbers (77%), perching stools (75%) and long-handled shoe horns (75%). Hip precautions were routinely prescribed by 97% of respondents. Hip precautions were most frequently taught in a pre-operative group (52% of respondents). Similarly equipment was most frequently provided pre-operatively (61% respondents), and most commonly by occupational therapists (74% respondents). There was variability in the advice provided on the duration of hip precautions and equipment from up to six weeks post-operatively to life-time usage. Conclusions: Current practice on hip precautions and provision of equipment is not full representative of clinician’s perceptions of best care after THR. Future research is warranted to determine whether and to whom hip precautions and equipment should be prescribed post-THR as opposed to the current ‘blanket’ provision of equipment and movement restriction provided in UK practice

Induction of otic structures by canonical Wnt signalling in medaka

The Wnt family of signalling proteins is known to participate in multiple developmental decisions during embryogenesis. We misexpressed Wnt1 in medaka embryos and observed anterior truncations, similar to those described for ectopic activation of canonical Wnt signalling in other species. Interestingly, when we induced a heat-shock Wnt1 transgenic line exactly at 30% epiboly, we observed multiple ectopic otic vesicles in the truncated embryos. The vesicles then fused, forming a single large ear structure. These “cyclopic ears” filled the complete anterior region of the embryos. The ectopic induction of otic development can be explained by the juxtaposition of hindbrain tissue with anterior ectoderm. Fibroblast growth factor (Fgf) ligands are thought to mediate the otic-inducing properties of the hindbrain. However, signals different from Fgf3 and Fgf8 are necessary to explain the formation of the ectopic ear structures, suggesting that Wnt signalling is involved in the otic induction process in medaka

SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Can a standard dose of eicosapentaenoic acid (EPA) supplementation reduce the symptoms of delayed onset of muscle soreness?

Unaccustomed exercise can result in delayed onset of muscle soreness (DOMS) which can affect athletic performance. Although DOMS is a useful tool to identify muscle damage and remodelling, prolonged symptoms of DOMS may be associated with the over-training syndrome. In order to reduce the symptoms of DOMS numerous management strategies have been attempted with no significant effect on DOMS-associated cytokines surge. The present study aimed to investigate the acute and chronic effects of a 2x180 mg per day dose of eicosapentaenoic acid (EPA) on interleukin-6 (IL-6) mediated inflammatory response and symptoms associated with DOMS. Methods: Seventeen healthy non-smoking females (age 20.4 +/- 2.1 years, height 161.2 +/- 8.3cm and mass 61.48 +/- 7.4kg) were randomly assigned to either placebo (N = 10) or EPA (N = 7). Serum IL-6, isometric and isokinetic (concentric and eccentric) strength, and rating of perceived exertion (RPE) were recorded on four occasions: i-prior to supplementation, ii-immediately after three weeks of supplementation (basal effects), iii-48 hours following a single bout of resistance exercise (acute training response effects), and iv-48 hours following the last of a series of three bouts of resistance exercise (chronic training response effects). Results: There was only a group difference in the degree of change in circulating IL-6 levels. In fact, relative to the first baseline, by the third bout of eccentric workout, the EPA group had 103 +/- 60% increment in IL-6 levels whereas the placebo group only had 80 +/- 26% incremented IL-6 levels (P = 0.020). We also describe a stable multiple linear regression model which included measures of strength and not IL-6 as predictors of RPE scale. Conclusion: The present study suggests that in doubling the standard recommended dose of EPA, whilst this may still not be beneficial at ameliorating the symptoms of DOMS, it counter intuitively appears to enhance the cytokine response to exercise. In a context where previous in vitro work has shown EPA to decrease the effects of inflammatory cytokines, it may in fact be that the doses required in vivo is much larger than current recommended amounts. An attempt to dampen the exercise-induced cytokine flux in fact results in an over-compensatory response of this system

Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training

The purpose of this study was to investigate associations between acute exercise-induced hormone responses and adaptations to high intensity resistance training in a large cohort (n = 56) of young men. Acute post-exercise serum growth hormone (GH), free testosterone (fT), insulin-like growth factor (IGF-1) and cortisol responses were determined following an acute intense leg resistance exercise routine at the midpoint of a 12-week resistance exercise training study. Acute hormonal responses were correlated with gains in lean body mass (LBM), muscle fibre cross-sectional area (CSA) and leg press strength. There were no significant correlations between the exercise-induced elevations (area under the curve—AUC) of GH, fT and IGF-1 and gains in LBM or leg press strength. Significant correlations were found for cortisol, usually assumed to be a hormone indicative of catabolic drive, AUC with change in LBM (r = 0.29, P < 0.05) and type II fibre CSA (r = 0.35, P < 0.01) as well as GH AUC and gain in fibre area (type I: r = 0.36, P = 0.006; type II: r = 0.28, P = 0.04, but not lean mass). No correlations with strength were observed. We report that the acute exercise-induced systemic hormonal responses of cortisol and GH are weakly correlated with resistance training-induced changes in fibre CSA and LBM (cortisol only), but not with changes in strength