Polymorphisms in the bovine HSP90AB1 gene are associated with heat tolerance in Thai indigenous cattle

Heat shock proteins act as molecular chaperones that have preferentially been transcribed in response to severe perturbations of the cellular homeostasis such as heat stress. Here the traits respiration rate (RR), rectal temperature (RT), pack cell volume (PCV) and the individual heat tolerance coefficient (HTC) were recorded as physiological responses on heat stress (environmental temperatures) in Bos taurus (crossbred Holstein Friesian; HF) and B. indicus (Thai native cattle: White Lamphun; WL and Mountain cattle; MT) animals (n = 47) in Thailand. Polymorphisms of the heat shock protein 90-kDa beta gene (HSP90AB1) were evaluated by comparative sequencing. Nine single nucleotide polymorphisms (SNP) were identified, i.e. three in exons 10 and 11, five in introns 8, 9, 10 and 11, and one in the 3′UTR. The exon 11 SNP g.5082C>T led to a missense mutation (alanine to valine). During the period of extreme heat (in the afternoon) RR and RT were elevated in each of the three breeds, whereas the PCV decreased. Mountain cattle and White Lamphun heifers recorded significantly better physiologic parameters (p < 0.05) in all traits considered, including or particularly HTC than Holstein Friesian heifers. The association analysis revealed that the T allele at SNP g.4338T>C within intron 3 improved the heat tolerance (p < 0.05). Allele T was exclusively found in White Lamphun animals and to 84% in Mountain cattle. Holstein Friesian heifers revealed an allele frequency of only 18%. Polymorphisms within HSP90AB1 were not causative for the physiological responses; however, we propose that they should at least be used as genetic markers to select appropriate breeds for hot climates

Duck (Anas platyrhynchos) linkage mapping by AFLP fingerprinting

Amplified fragment length polymorphism (AFLP) with multicolored fluorescent molecular markers was used to analyze duck (Anas platyrhynchos) genomic DNA and to construct the first AFLP genetic linkage map. These markers were developed and genotyped in 766 F2 individuals from six families from a cross between two different selected duck lines, brown Tsaiya and Pekin. Two hundred and ninety-six polymorphic bands (64% of all bands) were detected using 18 pairs of fluorescent TaqI/EcoRI primer combinations. Each primer set produced a range of 7 to 29 fragments in the reactions, and generated on average 16.4 polymorphic bands. The AFLP linkage map included 260 co-dominant markers distributed in 32 linkage groups. Twenty-one co-dominant markers were not linked with any other marker. Each linkage group contained three to 63 molecular markers and their size ranged between 19.0 cM and 171.9 cM. This AFLP linkage map provides important information for establishing a duck chromosome map, for mapping quantitative trait loci (QTL mapping) and for breeding applications

Imaging the Fano Lattice to 'Hidden Order' Transition in URu2Si2

Within a Kondo lattice, the strong hybridization between electrons localized in real space (r-space) and those delocalized in momentum-space (k-space) generates exotic electronic states called 'heavy fermions'. In URu2Si2 these effects begin at temperatures around 55K but they are suddenly altered by an unidentified electronic phase transition at To = 17.5 K. Whether this is conventional ordering of the k-space states, or a change in the hybridization of the r-space states at each U atom, is unknown. Here we use spectroscopic imaging scanning tunnelling microscopy (SI-STM) to image the evolution of URuSi2 electronic structure simultaneously in r-space and k-space. Above To, the 'Fano lattice' electronic structure predicted for Kondo screening of a magnetic lattice is revealed. Below To, a partial energy gap without any associated density-wave signatures emerges from this Fano lattice. Heavy-quasiparticle interference imaging within this gap reveals its cause as the rapid splitting below To of a light k-space band into two new heavy fermion bands. Thus, the URu2Si2 'hidden order' state emerges directly from the Fano lattice electronic structure and exhibits characteristics, not of a conventional density wave, but of sudden alterations in both the hybridization at each U atom and the associated heavy fermion states.Comment: Main Article + Supplementary Informatio

From 'trading zones' to 'buffer zones': Art and metaphor in the communication of psychiatric genetics to publics

Psychiatric genetics has a difficult relationship with the public given its unshakeable connection to eugenics. Drawing from a five-year public engagement programme that emerged from an internationally renowned psychiatric genetics centre, we propose the concept of the Buffer Zone to consider how an exchange of viewpoints between groups of people – including psychiatric geneticists and lay publics - who are often uneasy in one another’s company can be facilitated through the use of art and metaphor. The artwork at the exhibitions provided the necessary socio-cultural context for scientific endeavours, whilst also enabled public groups to be part of, and remain in, the conversation. Crucial to stress is that this mitigation was not to protect the science; it was to protect the discussion

Soil Microbial Responses to Elevated CO2 and O3 in a Nitrogen-Aggrading Agroecosystem

Climate change factors such as elevated atmospheric carbon dioxide (CO2) and ozone (O3) can exert significant impacts on soil microbes and the ecosystem level processes they mediate. However, the underlying mechanisms by which soil microbes respond to these environmental changes remain poorly understood. The prevailing hypothesis, which states that CO2- or O3-induced changes in carbon (C) availability dominate microbial responses, is primarily based on results from nitrogen (N)-limiting forests and grasslands. It remains largely unexplored how soil microbes respond to elevated CO2 and O3 in N-rich or N-aggrading systems, which severely hinders our ability to predict the long-term soil C dynamics in agroecosystems. Using a long-term field study conducted in a no-till wheat-soybean rotation system with open-top chambers, we showed that elevated CO2 but not O3 had a potent influence on soil microbes. Elevated CO2 (1.5×ambient) significantly increased, while O3 (1.4×ambient) reduced, aboveground (and presumably belowground) plant residue C and N inputs to soil. However, only elevated CO2 significantly affected soil microbial biomass, activities (namely heterotrophic respiration) and community composition. The enhancement of microbial biomass and activities by elevated CO2 largely occurred in the third and fourth years of the experiment and coincided with increased soil N availability, likely due to CO2-stimulation of symbiotic N2 fixation in soybean. Fungal biomass and the fungi∶bacteria ratio decreased under both ambient and elevated CO2 by the third year and also coincided with increased soil N availability; but they were significantly higher under elevated than ambient CO2. These results suggest that more attention should be directed towards assessing the impact of N availability on microbial activities and decomposition in projections of soil organic C balance in N-rich systems under future CO2 scenarios

Feasibility of a randomised controlled trial of remotely delivered problem-solving cognitive behaviour therapy versus usual care for young people with depression and repeat self-harm: lessons learnt (e-DASH)

BackgroundSelf-harm and depression are strong risk factors for repeat self-harm and suicide. We aimed to investigate the feasibility of a randomised controlled trial (RCT) of remotely delivered problem-solving cognitive behaviour therapy (PSCBT) plus treatment as usual (TAU) versus TAU in young people with repeat self-harm and depression.MethodsSingle-blind multi-centre RCT with an internal pilot, pre-set stop-go criteria and qualitative semi-structured interviews. Eligible participants (aged 16–30 years) were recruited from 9 adult or child and adolescent self-harm and crisis services; had ≥ 2 lifetime self-harm episodes, one in the preceding 96 h; and Beck Depression Inventory-II (BDI-II) score ≥ 17. Participants were randomised (1:1) to either TAU or TAU and 10–12 sessions of PSCBT delivered by mobile phone or video-calling.ResultsTwenty-two participants were recruited (11 in each arm), 10 (46%) completed follow-up at 6 months, 9 (82%) started the PSCBT and 4 (36%) completed it. The study did not meet three of its four stop-go criteria, reflecting considerable barriers to recruitment and retention. Participants had severe depression symptoms: with mean BDI-II 38.9 in the PSCBT and 37.2 in TAU groups, respectively. Three (14%) unblindings occurred for immediate safety concerns. Barriers to recruitment and retention included lack of agency for participants, severity of depression, recency of crisis with burden for participants and clinicians who diagnosed depression according to pervasiveness.ConclusionsRCTs of PSCBT for young people with depression and self-harm are not feasible using recruitment through mental health services that conduct assessments following self-harm presentations. Clinician assessment following self-harm presentation mainly identifies those with severe rather than mild-moderate depression

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Protocol for a randomized controlled clinical trial investigating the effectiveness of Fast muscle Activation and Stepping Training (FAST) for improving balance and mobility in sub-acute stroke

BACKGROUND: Following stroke, many people have difficulty activating their paretic muscles quickly and with sufficient power to regain their balance by taking quick and effective steps. Reduced dynamic balance and mobility following stroke, or ‘walking balance’, is associated with reduced self-efficacy and restrictions in daily living activities, community integration, and quality of life. Targeted training of movement speeds required to effectively regain balance has been largely overlooked in post-stroke rehabilitation. The Fast muscle Activation and Stepping Training (FAST) program incorporates fast functional movements known to produce bursts of muscle activation essential for stepping and regaining standing balance effectively. The purpose of this study is to: 1) compare the effectiveness of an outpatient FAST program to an active control outpatient physiotherapy intervention in improving walking balance following stroke, and 2) explore potential mechanisms associated with improvements in walking balance. METHODS/DESIGN: This will be an assessor-blinded, parallel group randomized controlled trial design. Sixty participants (30 per group) who have sustained a stroke within the previous six months will be randomly assigned with stratification for lower limb motor recovery to receive twelve 45-minute 1:1 physiotherapy intervention sessions over 6 – 10 weeks in an outpatient setting of either: 1) FAST intervention - systematic and progressive practice of fast squatting and stepping exercises, or 2) active control - conventional physiotherapy directed at improving balance and mobility that includes no targeted fast movement training. The same blinded research physiotherapist will assess outcomes at three time points: 1) baseline (prior to intervention), 2) follow up (within one week post-intervention); and 3) retention (one month post-intervention). The primary outcome is dynamic balance assessed using the Community Balance and Mobility Scale. We will also assess fast and self-selected walking speed, balance self-efficacy, and the ability to respond to internal and external perturbations to balance and associated changes in postural muscle activation. DISCUSSION: The targeted training of fast functional movements in the FAST program is expected to improve walking balance following stroke compared to the active control intervention. Unique to this study is the investigation of potential mechanisms associated with improvements in walking balance. TRIAL REGISTRATION: NCT01573585 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12883-014-0187-y) contains supplementary material, which is available to authorized users