Identification of a Novel 0.7-kb Polyadenylated Transcript in the LAT Promoter Region of HSV-1 That Is Strain Specific and May Contribute to Virulence

AbstractHerpes Simplex virus expresses latency-associated transcripts (LATs) the function of which remains obscure despite increasing knowledge of their structure and expression. Upstream of the LAT coding region is a region of the genome that is poorly characterized although it lies in an area that is responsible for modulation of reactivation efficiency in two different animal models. Transcript mapping with strains 17, McKrae, KOS, and F has revealed strain differences in this region of the viral genome. Strain 17 and McKrae expressed a novel polyadenylated 0.7-kb transcript that is absent from KOS and F. This transcript is expressed in the LAT direction and has the kinetics of a true late gene during the lytic cycle of infection. A deletion mutant, 17ΔBsa, which does not express the 0.7-kb RNA, is less virulent than the parental strain 17. A rescuant with F sequence (17ΔBsa/RF) shows virulence similar to F, whereas a rescuant with strain 17 sequence (17ΔBsa/R17) is similar to strain 17. Virulence is altered by deletion or substitution in the region encoding the 0.7-kb transcript (BsaI-BsaI); however, reactivation in the mouse explant cocultivation assay or the adrenergically induced rabbit reactivation model remained unchanged. The importance of this region for virulence is discussed

Effect of floor type on the performance, physiological and behavioural responses of finishing beef steers

peer-reviewedBackground:The study objective was to investigate the effect of bare concrete slats (Control), two types of mats [(Easyfix mats (mat 1) and Irish Custom Extruder mats (mat 2)] fitted on top of concrete slats, and wood-chip to simulate deep bedding (wood-chip placed on top of a plastic membrane overlying the concrete slats) on performance, physiological and behavioral responses of finishing beef steers. One-hundred and forty-four finishing steers (503 kg; standard deviation 51.8 kg) were randomly assigned according to their breed (124 Continental cross and 20 Holstein–Friesian) and body weight to one of four treatments for 148 days. All steers were subjected to the same weighing, blood sampling (jugular venipuncture), dirt and hoof scoring pre study (day 0) and on days 23, 45, 65, 86, 107, 128 and 148 of the study. Cameras were fitted over each pen for 72 h recording over five periods and subsequent 10 min sampling scans were analysed. Results: Live weight gain and carcass characteristics were similar among treatments. The number of lesions on the hooves of the animals was greater (P < 0.05) on mats 1 and 2 and wood-chip treatments compared with the animals on the slats. Dirt scores were similar for the mat and slat treatments while the wood-chip treatment had greater dirt scores. Animals housed on either slats or wood-chip had similar lying times. The percent of animals lying was greater for animals housed on mat 1 and mat 2 compared with those housed on concrete slats and wood chips. Physiological variables showed no significant difference among treatments. Conclusions: In this exploratory study, the performance or welfare of steers was not adversely affected by slats, differing mat types or wood-chip as underfoot material

Effects of unilateral isokinetic eccentric training (and detraining) on musculoskeletal characteristics in older people

Introduction: Reductions in lower-limb strength and muscle mass are common in ageing, with a concomitant reduction in aerobic capacity also limiting exercise tolerance. However, eccentric-only exercise has a lower cardiovascular demand (Vallejo et al., 2006) and higher loading potential that may improve exercise tolerance whilst providing a high musculoskeletal adaptive stimulus. Therefore, the present study examined the impact of a 6-week seated isokinetic eccentric training programme and 8 weeks of detraining on lower-limb strength and muscle architectural characteristics in older people. Methods: Maximal eccentric lower-limb force, and vastus lateralis (VL) thickness, pennation angle and fascicle length were measured in 12 participants (age = 67.0 ± 6.3 y, mass = 80.6 ± 16.0 kg, height = 1.6 ± 0.1 m) before (on two occasions separated by 1 week to determine reliability) and after the 6-week training programme using isokinetic dynamometry and real-time ultrasonography. All measures were then re-examined 8 weeks later to quantify detraining (i.e. regression) effects. Training was performed twice-weekly on a BTE Eccentron that simulated downhill walking using an alternating unilateral leg press motion and consisted of 5 min (week 1) or 10 min (weeks 2-6) of isokinetic eccentric contractions performed at 50%MVC at a rate of 40 ‘steps’ per minute. Strength was reassessed every 2 weeks to ensure subjects’ training intensities remained at 50%MVC, with rate of perceived exertion (RPE) recorded after each training session. Results: A significant (P < 0.05) increase in lower-limb eccentric strength (58.8 ± 39.9%), VL muscle thickness (9.8 ± 5.4%), pennation angle (4.4 ± 5.7%) and fascicle length (5.4 ± 4.3%) was detected immediately after the 6-week training programme. RPE remained consistently low throughout the programme (3.3-4.1 out of 10), despite the increased duration and absolute intensity of training. Eight weeks later, lower-limb eccentric strength (50.4 ± 38.0%), VL muscle thickness (6.1 ± 5.5%) and fascicle length (5.8 ± 7.5%) remained significantly greater than pre-training levels, while pennation angle (1.0 ± 6.7%) returned to baseline. Discussion: The substantial increases in strength and muscle size achieved whilst training with low RPE have important clinical and practical implications for exercise prescription in older people, with the practical application and functional outcomes of the exercise regime well-suited to the specific physical needs and challenges of older people. Furthermore, the limited regression detected eight weeks after the completion of the training programme is indicative that eccentric strength training provides prolonged musculoskeletal functional benefits

Strong peoples - strong country: Indigenous heritage monitoring framework summary report

The report titled 'Monitoring Indigenous Heritage within the Reef 2050 Integrated Monitoring and Reporting Program: Final report of the Indigenous Heritage Expert Group' can be viewed through this repository at http://hdl.handle.net/11017/3535This is a summary report of the Strong peoples – Strong country framework, which details information on the framework. The methodology and processes of the expert group are found in, Monitoring Indigenous Heritage within the Reef 2050 Integrated Monitoring and Reporting Program: Final report of the Indigenous Heritage Expert Group (Jarvis, Hill, Buissereth et al. 2019). This summary presents the key elements of the Indigenous heritage monitoring framework for the Great Barrier Reef: Strong peoples – Strong country. It's been extracted from the Indigenous Heritage Expert Group report, which outlines a proposed design for monitoring of the Indigenous heritage theme under the Reef 2050 Integrated Monitoring and Reporting Program

Monitoring the Indigenous heritage within the Reef 2050 Integrated Monitoring and Reporting Program: final report of the Indigenous Heritage Expert Group

An accessible copy of this report is not yet available from this repository, please contact [email protected] for more information

Mothers behaving badly: chaotic hedonism and the crisis of neoliberal social reproduction

This article focuses on the significance of the plethora of representations of mothers ‘behaving badly’ in contemporary anglophone media texts, including the films Bad Moms, Fun Mom Dinner and Bad Mom’s Christmas, the book and online cartoons Hurrah for Gin and the recent TV comedy dramas Motherland, The Let Down and Catastrophe. All these media texts include representations of, first, mothers in the midst of highly chaotic everyday spaces where any smooth routine of domesticity is conspicuous by its absence; and second, mothers behaving hedonistically, usually through drinking and partying, behaviour that is more conventionally associated with men or women without children. After identifying the social type of the mother behaving badly (MBB), the article locates and analyses it in relation to several different social and cultural contexts. These contexts are: a neoliberal crisis in social reproduction marked by inequality and overwork; the continual if contested role of women as ‘foundation parents’; and the negotiation of longer-term discourses of female hedonism. The title gestures towards a popular British sitcom of the 1990s, Men Behaving Badly, which popularized the idea of the ‘new lad’; and this article suggests that the new lad’s counterpart, the ladette, is mutating into the mother behaving badly, or the ‘lad mom’. Asking what work this figure does now, in a later neoliberal context, it argues that the mother behaving badly is simultaneously indicative of a widening and liberating range of maternal subject positions and symptomatic of a profound contemporary crisis in social reproduction. By focusing on the classed and racialised dynamics of the MBB – by examining who exactly is permitted to be hedonistic, and how – and by considering the MBB’s limited and partial imagining of progressive social change, the article concludes by emphasizing the urgency of creating more connections between such discourses and ‘parents behaving politically’

A clinical study of kuru patients with long incubation periods at the end of the epidemic in Papua New Guinea

Kuru is so far the principal human epidemic prion disease. While its incidence has steadily declined since the cessation of its route of transmission, endocannibalism, in Papua New Guinea in the 1950s, the arrival of variant Creutzfeldt–Jakob disease (vCJD), also thought to be transmitted by dietary prion exposure, has given kuru a new global relevance. We investigated all suspected cases of kuru from July 1996 to June 2004 and identified 11 kuru patients. There were four females and seven males, with an age range of 46–63 years at the onset of disease, in marked contrast to the age and sex distribution when kuru was first investigated 50 years ago. We obtained detailed histories of residence and exposure to mortuary feasts and performed serial neurological examination and genetic studies where possible. All patients were born a significant period before the mortuary practice of transumption ceased and their estimated incubation periods in some cases exceeded 50 years. The principal clinical features of kuru in the studied patients showed the same progressive cerebellar syndrome that had been previously described. Two patients showed marked cognitive impairment well before preterminal stages, in contrast to earlier clinical descriptions. In these patients, the mean clinical duration of 17 months was longer than the overall average in kuru but similar to that previously reported for the same age group, and this may relate to the effects of both patient age and PRNP codon 129 genotype. Importantly, no evidence for lymphoreticular colonization with prions, seen uniformly in vCJD, was observed in a patient with kuru at tonsil biopsy

An expanded allosteric network in PTP1B by multitemperature crystallography, fragment screening, and covalent tethering

Abstract: Allostery is an inherent feature of proteins, but it remains challenging to reveal the mechanisms by which allosteric signals propagate. A clearer understanding of this intrinsic circuitry would afford new opportunities to modulate protein function. Here, we have identified allosteric sites in protein tyrosine phosphatase 1B (PTP1B) by combining multiple-temperature X-ray crystallography experiments and structure determination from hundreds of individual small- molecule fragment soaks. New modeling approaches reveal ’hidden’ low-occupancy conformational states for protein and ligands. Our results converge on allosteric sites that are conformationally coupled to the active-site WPD loop and are hotspots for fragment binding. Targeting one of these sites with covalently tethered molecules or mutations allosterically inhibits enzyme activity. Overall, this work demonstrates how the ensemble nature of macromolecular structure, revealed here by multitemperature crystallography, can elucidate allosteric mechanisms and open new doors for long-range control of protein function

The personal is political: reframing individual acts of kindness as social solidarity in social work practice

This paper develops the theoretical position proposed by Zygmunt Bauman (2009), that one of the greatest contemporary ‘social evils’ or injustices we face in society, is the total marketization and individualisation of our lived experience. Bauman (2009) along with Harvey (2005) argues that the last forty years of social, political, and economic reform under the zeitgeist of neoliberalism have transferred the burden of care from the state to the individual. This paper will explore the position that the dominant neoliberal culture within social work, in the form of ‘new managerialism’ has reconstituted social work institutionally as one where interventions now focus on minimum statutory interventions emphasising; risk management, resource allocation, audit culture, and the promotion of self-care through a case work methodology. The discussion will analyse these macro social, political and economic discourses using an ethnographic approach based upon Michael Burawoy’s Global Ethnographic (GE) methodology (Burawoy et al, 2010). Despite the current landscape the research highlights the importance of the personal reframed as the political, and the nuanced ways in which acts of defiance and resistance against the prevailing orthodoxies have been adopted by social workers on the front line

Opening the Woods: Towards a Quantification of Neolithic Clearance Around the Somerset Levels and Moors

Environmental reconstructions from pollen records collected within archaeological landscapes have traditionally taken a broadly narrative approach, with few attempts made at hypothesis testing or formal assessment of uncertainty. This disjuncture between the traditional interpretive approach to palynological data and the requirement for detailed, locally specific reconstructions of the landscapes in which people lived has arguably hindered closer integration of palaeoecological and archaeological datasets in recent decades. Here we implement a fundamentally different method for reconstructing past land cover from pollen records to the landscapes of and around the Somerset Levels and Moors — the Multiple Scenario Approach (MSA) — to reconstruct land cover for a series of 200-year timeslices covering the period 4200–2000 cal BC. Modelling of both archaeological and sediment chronologies enables integration of reconstructed changes in land cover with archaeological evidence of contemporary Neolithic human activity. The MSA reconstructions are presented as a series of land cover maps and as graphs of quantitative measures of woodland clearance tracked over time. Our reconstructions provide a more nuanced understanding of the scale and timing of Neolithic clearance than has previously been available from narrative based interpretations of pollen data. While the archaeological record tends to promote a view of long-term continuity in terms of the persistent building of wooden structures in the wetlands, our new interpretation of the palynological data contributes a more dynamic and varying narrative. Our case study demonstrates the potential for further integration of archaeological and palynological datasets, enabling us to get closer to the landscapes in which people lived