MyoD Synergizes with the E-protein HEB Beta to Induce Myogenic Differentiation

The MyoD family of basic helix-loop-helix transcription factors function as heterodimers with members of the E-protein family to induce myogenic gene activation. The E-protein HEB is alternatively spliced to generate alpha and beta isoforms. While the function of these molecules has been studied in other cell types, questions persist regarding the molecular functions of HEB proteins in skeletal muscle. Our data demonstrate that HEB alpha expression remains unchanged in both myoblasts and myotubes, whereas HEB beta is upregulated during the early phases of terminal differentiation. Upon induction of differentiation, a MyoD-HEB beta complex bound the E1 E-box of the myogenin promoter leading to transcriptional activation. Importantly, forced expression of HEB beta with MyoD synergistically lead to precocious myogenin expression in proliferating myoblasts. However, after differentiation, HEB alpha and HEB beta synergized with myogenin, but not MyoD, to activate the myogenin promoter. Specific knockdown of HEB beta by small interfering RNA in myoblasts blocked differentiation and inhibited induction of myogenin transcription. Therefore, HEB alpha and HEB beta play novel and central roles in orchestrating the regulation of myogenic factor activity through myogenic differentiation

Legacies of humanitarian neglect: long term experiences of children who returned from the Lord’s Resistance Army in Uganda

Background: Much has been written about the short-term challenges facing children returning ‘home’ from rebel fighting groups, but little is known about the longer term day to day realities of return. This article presents findings from the first long-term assessment of the social and economic challenges facing an officially registered group of children who passed through an internationally-financed reception centre after a period of time with the Lord’s Resistance Army (LRA). Methods: Records from a reception centre were used to trace a random sample of individuals to their current location. Two hundred and thirty in-depth semi-structured interviews were carried out and 40 follow-up interviews between 2013 and 2016. Interviews were informed by long-term ethnographic research in the region. These interviews were subsequently coded and analysed to describe the long-term day to day realities of return. Results: At the time of interview, 90% of formerly abducted people returned ‘home’ six or more years ago, and 75% returned nine or more years ago. The majority have managed to access family land for farming, but concerns about what they may have done to survive whilst living with the LRA adversely affects their day-to-day lives. However, some important differences were noted: those men and women who spent less time with the LRA are more likely to live on ancestral land with close relatives; and they are more likely to report experiencing stigma and a spiritual affliction called ‘cen’. In contrast, those who spent the longest time with the LRA are less likely to report these problems, they are mainly living in urban locations and tend to manage slightly better. Children born of war are vulnerable to abuse, irrespective of current residence. Conclusions: Research findings question the merits of post-conflict reintegration programmes emphasising immediate family reunifications, without follow-up monitoring, social protection, education and skills training. By overlooking the diverse experiences of those who lived and fought with the LRA, and failing to anticipate or respond to the long term socio-political and economic challenges facing children on their return, reception centre processes not only failed to foster social reintegration, but they also inadvertently exacerbated the vulnerability of returning children

The ALFALFA "Almost Darks" Campaign: Pilot VLA HI Observations of Five High Mass-to-Light Ratio Systems

We present VLA HI spectral line imaging of 5 sources discovered by ALFALFA. These targets are drawn from a larger sample of systems that were not uniquely identified with optical counterparts during ALFALFA processing, and as such have unusually high HI mass to light ratios. These candidate "Almost Dark" objects fall into 4 categories: 1) objects with nearby HI neighbors that are likely of tidal origin; 2) objects that appear to be part of a system of multiple HI sources, but which may not be tidal in origin; 3) objects isolated from nearby ALFALFA HI detections, but located near a gas-poor early-type galaxy; 4) apparently isolated sources, with no object of coincident redshift within ~400 kpc. Roughly 75% of the 200 objects without identified counterparts in the $\alpha$.40 database (Haynes et al. 2011) fall into category 1. This pilot sample contains the first five sources observed as part of a larger effort to characterize HI sources with no readily identifiable optical counterpart at single dish resolution. These objects span a range of HI mass [7.41 < log(M$_{\rm HI}$) < 9.51] and HI mass to B-band luminosity ratios (3 < M$_{\rm HI}$/L$_{\rm B}$ < 9). We compare the HI total intensity and velocity fields to SDSS optical imaging and to archival GALEX UV imaging. Four of the sources with uncertain or no optical counterpart in the ALFALFA data are identified with low surface brightness optical counterparts in SDSS imaging when compared with VLA HI intensity maps, and appear to be galaxies with clear signs of ordered rotation. One source (AGC 208602) is likely tidal in nature. We find no "dark galaxies" in this limited sample. The present observations reveal complex sources with suppressed star formation, highlighting both the observational difficulties and the necessity of synthesis follow-up observations to understand these extreme objects. (abridged)Comment: Astronomical Journal, in pres

Lemurs in Cacao: Presence and Abundance within the Shade Plantations of Northern Madagascar

© 2019 S. Karger AG, Basel. The recognition that much biodiversity exists outside protected areas is driving research to understand how animals survive in anthropogenic landscapes. In Madagascar, cacao (Theobroma cacao) is grown under a mix of native and exotic shade trees, and this study sought to understand whether lemurs were present in these agroecosystems. Between November 2016 and March 2017, discussions with farmers, nocturnal reconnaissance surveys and camera traps were used to confirm the presence of lemurs in the Cokafa and Mangabe plantations near Ambanja, north-west Madagascar. Four species of lemur were encountered in nocturnal surveys: Mirza zaza, Phaner parienti, Microcebussp. and Cheirogaleussp. with encounter rates of 1.2, 0.4, 0.4 and 0.3 individuals/km, respectively. The presence of Lepilemur dorsalis was confirmed by camera trap. This is the first time lemurs have been studied in cacao plantations, and understanding how these threatened animals use anthropogenic landscapes is vital for their conservation

Epidemiology of chronic pain in children and adolescents : a protocol for a systematic review update

Funding This work was supported by an operating grant from the Canadian Institutes of Health Research (FRN167902) awarded to CTC and funding from the Dalhousie Medical Research Foundation (DMRF). CTC is the senior author and is supported by a Tier 1 Canada Research Chair with infrastructure support from the Canada Foundation for Innovation. CLL is supported by an IWK Health Centre Summer Studentship (1025420). PRT is supported by a Research Nova Scotia Scholars Award, a Nova Scotia Graduate Scholarship and an IWK Graduate Studentship Award, and is a trainee member of Pain Child Health (PICH).Peer reviewedPublisher PD

Engineering adenoviral vectors with improved GBM selectivity

Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of the many human adenoviral serotypes described to date, adenovirus 5 (HAdV-C5) has been the most utilised clinically and experimentally. However, the use of Ad5 as an anti-cancer agent may be hampered by naturally high seroprevalence rates to HAdV-C5 coupled with the infection of healthy cells via native receptors. To explore whether alternative natural adenoviral tropisms are better suited to GBM therapeutics, we pseudotyped an HAdV-C5-based platform using the fibre knob protein from alternative serotypes. We demonstrate that the adenoviral entry receptor coxsackie, adenovirus receptor (CAR) and CD46 are highly expressed by both GBM and healthy brain tissue, whereas Desmoglein 2 (DSG2) is expressed at a low level in GBM. We demonstrate that adenoviral pseudotypes, engaging CAR, CD46 and DSG2, effectively transduce GBM cells. However, the presence of these receptors on non-transformed cells presents the possibility of off-target effects and therapeutic transgene expression in healthy cells. To enhance the specificity of transgene expression to GBM, we assessed the potential for tumour-specific promoters hTERT and survivin to drive reporter gene expression selectively in GBM cell lines. We demonstrate tight GBM-specific transgene expression using these constructs, indicating that the combination of pseudotyping and tumour-specific promoter approaches may enable the development of efficacious therapies better suited to GBM

A two-year participatory intervention project with owners to reduce lameness and limb abnormalities in working horses in Jaipur, India

Participatory methods are increasingly used in international human development, but scientific evaluation of their efficacy versus a control group is rare. Working horses support families in impoverished communities. Lameness and limb abnormalities are highly prevalent in these animals and a cause for welfare concern. We aimed to stimulate and evaluate improvements in lameness and limb abnormalities in horses whose owners took part in a 2-year participatory intervention project to reduce lameness (PI) versus a control group (C) in Jaipur, India.In total, 439 owners of 862 horses participated in the study. PI group owners from 21 communities were encouraged to meet regularly to discuss management and work practices influencing lameness and poor welfare and to track their own progress in improving these. Lameness examinations (41 parameters) were conducted at the start of the study (Baseline), and after 1 year and 2 years. Results were compared with control horses from a further 21 communities outside the intervention. Of the 149 horses assessed on all three occasions, PI horses showed significantly (P<0.05) greater improvement than C horses in 20 parameters, most notably overall lameness score, measures of sole pain and range of movement on limb flexion. Control horses showed slight but significantly greater improvements in four parameters, including frog quality in fore and hindlimbs.This participatory intervention succeeded in improving lameness and some limb abnormalities in working horses, by encouraging changes in management and work practices which were feasible within owners’ socioeconomic and environmental constraints. Demonstration of the potentially sustainable improvements achieved here should encourage further development of participatory intervention approaches to benefit humans and animals in other contexts

Prefracture functional level evaluated by the New Mobility Score predicts in-hospital outcome after hip fracture surgery

BACKGROUND AND PURPOSE: Clinicians need valid and easily applicable predictors of outcome in patients with hip fracture. Adjusting for previously established predictors, we determined the predictive value of the New Mobility score (NMS) for in-hospital outcome in patients with hip fracture. PATIENTS AND METHODS: We studied 280 patients with a median age of 81 (interquartile range 72-86) years who were admitted from their own homes to a special hip fracture unit. Main outcome was the regain of independence in basic mobility, defined as. independence in getting in and out of bed, sitting down and standing up from a chair, and walking with an appropriate walking aid. The Cumulated Ambulation score was used to evaluate basic mobility. Predictor variables were NMS functional level before fracture, age, sex, fracture type, and mental and health status. RESULTS: Except for sex, all predictor variables were statistically significant in univariate testing. In multiple logistic regression analysis, only age, NMS functional level before fracture, and fracture type were significant. Thus, patients with a low prefracture NMS and/or an intertrochanteric fracture would be 18 and 4 times more likely not to regain independence in basic mobility during the hospital stay, respectively, than patients with a high prefracture level and a cervical fracture, respectively. The model was statistically stable and correctly classified 84% of cases. INTERPRETATION: The NMS functional level before fracture, age, and fracture type facilitate prediction of the in-hospital rehabilitation potential after hip fracture surgery

What Happened to Children Who Returned from the Lord’s Resistance Army in Uganda?

Abstract In northern Uganda, more than 50,000 people were recruited by the Lord’s Resistance Army (LRA) between the late 1980s and 2004, mostly by force. Around half of those taken were children (under 18 years old). A large number were never seen by their families again, but more than 20,000 returned through aid-financed reception centres. Endeavours were made to reunite them with their relatives, who were mostly living in insecure displacement camps. Relatively few were subsequently visited, even after the fighting ended in 2006. Thousands of vulnerable children were largely left to their own devices. This article draws on research carried out in 2004–06 and from 2012 to 2018, and compares findings with other publications on reintegration in the region. It argues that implementing best-practice guidelines for relocating displaced children with their immediate relatives had negative consequences. The majority of children who passed through a reception centre are now settled as young adults on ancestral land, where they are commonly abused because of their LRA past. With few exceptions, it is only those who spent a long period with the LRA and who are not living on ancestral land who have managed to avoid such experiences.</jats:p

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring