Molecular responses to abiotic stress and the development of drought tolerance in plants

Water availability is a major limiting factor in the yield of agricultural crops in marginal rainfall areas. One solution is the development of crops that are drought tolerant, either through traditional breeding or genetic engineering. To permit a targeted approach to developing drought tolerance, the molecular basis of drought tolerance must first be elucidated. Previously in our group, a forward genetics screen was undertaken to identify mutants, in the model plant species Arabidopsis thaliana, with an altered response to high light stress (Rossel et al, 2006). This study describes the positional cloning of one of these mutations, namely alx8 (altered APX.2 expression 8). The location of the alx8 mutation was identified as a known stress response regulator, SALJ (At5g63980). This alx8 mutation appears to cause a loss of function of the SALl protein, as the reported SALJ null mutant,fiyl-1 (Xiong et al, 2001), and the SALJ T-DNA insertion line, salk_020882, were found to have similar phenotypes to alx8. DespitefryJ-J being reported as drought sensitive (Xiong et al, 2001), here it is shown that this mutant, as well as alx8 and salk_020882, are drought tolerant in soil based experiments. This drought tolerance was investigated by the characterisation of the morphological, physiological and molecular changes resulting from the alx8 mutation. It was established that alx8 's drought tolerance was not due to a change in cuticular water loss or a decreased number of stomata. Likewise, alx8's drought tolerance was not due to its delayed growth and development. The stomatal dynamics of alx8 were investigated by a number of methods. Previously, alx8 was shown to have an increased water use efficiency (WUE) in a light response curve, but in this study the carbon isotope ratio indicated no change in WUE. However, stomatal function is altered in alx8, as it is shown that the response of stomata to light and high C02 is delayed in alx8 delayed in alx8. Furthermore, double mutants, of alx8 with ostl-2, abil-1 and abi2-1, all of which have impaired stomatal control, were drought tolerant. This indicates that SALJ is involved in the regulation of stomatal signalling pathways. Microarray analysis of alx8 revealed the constitutive up-regulation of 5413 genes involved in a wide range of functions including a number of stress response genes. Other expression changes were genes involved in the regulation of flowering, and growth and development. There were also large changes in the metabolic profile of alx8 including increased accumulation of sugars and polyamines and decreased accumulation of proline. This increased sugar content corresponded with a decrease in transitory starch accumulation in alx8. Despite increased levels of the stress hormone Abscisic Acid (ABA) in alx8, the production of ABA-deficient and ABA-independent double mutants indicated that the delayed development, altered leaf morphology and drought tolerance of alx8 are not ABA-dependent. This is supported by few ABA induced genes being up-regulated in alx8. Hence, SAL1 is a key regulator of stress signalling pathways in Arabiodpsis whose modification in alx8 causes a number of morphological, molecular and physiological changes, and results in drought tolerance

Morphogenesis underlying the development of the everted teleost telencephalon

Background: Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Results: Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Conclusion: Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic neuroepithelium. This may have significant bearing on understanding the eventual organization of the adult fish telencephalon

Weight loss for obese prostate cancer patients on androgen deprivation therapy

PURPOSE: Excess fat mass (FM) contributes to poor prostate cancer (PCa) prognosis and comorbidity. However, FM gain is a common side effect of androgen deprivation therapy (ADT). We examined the efficacy of a 12-wk weight loss intervention to reduce FM and maintain lean mass (LM) in ADT-treated obese PCa patients. METHODS: Fourteen ADT-treated obese PCa patients (72 ± 9 yr, 39.7% ± 5.4% body fat) were recruited for a self-controlled prospective study, with 11 completing the 6-wk control period, followed by a 12-wk intervention comprising 300 min·wk-1 of exercise including supervised resistance training and home-based aerobic exercise, and dietitian consultations advising a daily energy deficit (2100-4200 kJ) and protein supplementation. Body composition was assessed by dual x-ray absorptiometry. Secondary outcomes included muscle strength (one-repetition maximum), cardiorespiratory fitness (maximal oxygen consumption), and blood biomarkers. RESULTS: There were no significant changes during the control period. Patients attended 89% of supervised exercise sessions and 100% of dietitian consultations. No changes in physical activity or energy intake were observed. During the intervention, patients experienced significant reductions in weight (-2.8 ± 3.2 kg, P = 0.016), FM (-2.8 ± 2.6 kg, P \u3c 0.001), and trunk FM (-1.8 ± 1.4 kg, P \u3c 0.001), with LM preserved (-0.05 ± 1.6 kg, P = 0.805). Muscle strength (4.6%-24.7%, P \u3c 0.010) and maximal oxygen consumption (3.5 ± 4.7 mL·min-1·kg-1, P = 0.041) significantly improved. Leptin significantly decreased (-2.2 (-2.7 to 0.5) ng·mL-1, P = 0.016) with no other changes in blood biomarkers such as testosterone and lipids (P = 0.051-0.765); however, C-reactive protein (rs = -0.670, P = 0.024) and triglycerides (r = -0.667, P = 0.025) were associated with individual changes in LM. CONCLUSIONS: This study shows preliminary efficacy for an exercise and nutrition weight loss intervention to reduce FM, maintain LM, and improve muscle strength and cardiorespiratory fitness in ADT-treated obese PCa patients. The change in body composition may affect blood biomarkers associated with obesity and PCa progression; however, further research is required

Maintaining weight loss in obese men with prostate cancer following a supervised exercise and nutrition program—A pilot study

Supervised exercise and nutrition programs can mitigate or reverse androgen deprivation therapy (ADT) induced fat mass (FM) gain, lean mass (LM) loss, and impaired physical function. It is unclear whether these benefits are retained following transition to self-management. This study examined the effect of a home-based weight maintenance program on body composition and physical function in obese men with prostate cancer (PCa) on ADT following a 12-week supervised weight loss intervention. Eleven obese PCa patients (74 ± 5 years, 40.0 ± 4.9% body fat) on ADT ( \u3e 6 months) com-pleted a 12-week self-managed home-based weight maintenance program consisting of 150 min/week of aerobic and resistance training while maintaining a healthy balanced diet. Body composition (DXA), muscle strength (1RM), and cardiorespiratory fitness (400 m walk) were assessed. Significant reductions in weight (−2.8 ± 3.2 kg) and FM (−2.8 ± 2.6 kg), preservation of LM (−0.05 ± 1.6 kg), and improvements in muscle strength and VO2max were achieved across the supervised intervention. Across the home-based program, no significant changes were observed in weight (−0.6 ± 2.8 kg, p = 0.508), FM (0.2 ± 1.4 kg, p = 0.619), LM (−0.8 ± 1.6 kg, p = 0.146), muscle strength (−0.2 to 4.1%, p = 0.086–0.745), or estimated VO2max (0.3 ± 2.1 mL/min/kg, p = 0.649). Self-managed, home-based exercise and nutrition programs are a viable strategy to promote maintenance of body composition and physical function following a supervised intervention in obese PCa patients on ADT

Interdisciplinary dialogues in music, health and wellbeing: Difficulties, challenges and pitfalls

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Health and well-being harms experienced by adult victims of interpersonal violence a scoping review protocol

Objective: The purpose of this scoping review is to identify the extent of research exploring the health and wellbeing harms experienced by adult victims of different types of interpersonal violence. Introduction: Interpersonal violence is defined as violence between individuals, it can take many forms and may be physical, sexual, psychological, coercive or deprivational in nature. Health and wellbeing harms from being subject to interpersonal violence are common and often endure. Interpersonal violence may cause physical injury, often has mental health impacts and is associated with greater risk for long-term medical conditions. Though a substantial body of research of health and wellbeing harms of different types of interpersonal violence exists, to date this has not been collated and mapped, this scoping review will address this gap. Inclusion criteria: Peer-reviewed primary and secondary research studies, from 2000 to 2019 (in English) that address the negative effects of interpersonal violence on the health and wellbeing of adult victims will be included. Studies of group violence, military veterans and violence as acts of war will be excluded. Methods: Six electronic databases (MEDLINE, CENTRAL, CINAHL, Embase, PsycINFO, SocINDEX) and web sources of specialist grey literature will be searched. Screening and data extraction will be assessed by independent researcher verification processes. Relevant studies and their characteristics will be summarised using a pre-designed data extraction form. Further data synthesis will be undertaken to produce a coherent and comprehensive map of research in the field, identify gaps and inform priorities for future directions of research and innovation

Using the behaviour change wheel and person-based approach to develop a digital self-management intervention for patients with adrenal insufficiency: the Support AI study protocol

Introduction: Most patients with Adrenal insufficiency (AI) require lifelong glucocorticoid replacement. They need to increase glucocorticoids during physical illness or major stressful situations and require parenteral hydrocortisone in the event of an adrenal crisis. Patients with AI have impaired quality of life and high mortality; approximately 1 in 6-12 patients are hospitalised at least once/year from a potentially preventable adrenal crisis. Adoption of self-management behaviours are crucial; these include adherence to medication, following “sick day rules” and associated behaviours that aid prevention and treatment of adrenal crisis such as symptom monitoring, having extra tablets, carrying a medical-alert ID and injection kit, and self-injecting when necessary. Current patient education is ineffective at supporting self-management behaviour change or reducing adrenal crisis-related hospitalisations. This research study aims to gain an in-depth understanding of the barriers and enablers to self-management for patients with AI and to develop an evidence-based digital self-management behaviour change intervention. / Methods: The study is conducted in accordance with the MRC Framework for developing complex interventions. Underpinned by the Behaviour Change Wheel (BCW), the Theoretical Domains Framework (TDF), and the Person-Based Approach, this research will be conducted in two phases: Phase 1 will involve a sequential qualitative/quantitative mixed-methods study involving focus group interviews followed by a cross-sectional survey with patients with AI recruited from patient advocacy groups and endocrine clinics in the UK. Phase 2 will develop the Support AI, a website-based digital behaviour change intervention (DBCI) informed by Phase 1 findings to support self-management for patients with AI. The most appropriate behaviour change techniques (BCTs) will be selected utilising a nominal group technique with an Expert Panel of 10-15 key stakeholders. The design of the Support AI website will be guided by the Person-Based Approach using an Agile iterative “think-aloud” technique with 12-15 participants over 3 usability testing iterations. / Conclusion: A theory- and evidence-based digital behaviour change intervention will be developed which will be tested in a feasibility randomised trial following completion of this study. The projected benefit includes cost-effective health care service (reduced hospitalisations and demand for specialist services) and improved health outcomes and quality of life for patients with AI

Single-cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium

The endometrium is a dynamic tissue that exhibits remarkable resilience to repeated episodes of differentiation, breakdown, regeneration, and remodeling. Endometrial physiology relies on a complex interplay between the stromal and epithelial compartments with the former containing a mixture of fibroblasts, vascular, and immune cells. There is evidence for rare populations of putative mesenchymal progenitor cells located in the perivascular niche of human endometrium, but the existence of an equivalent cell population in mouse is unclear. We used the Pdgfrb‐BAC‐eGFP transgenic reporter mouse in combination with bulk and single‐cell RNA sequencing to redefine the endometrial mesenchyme. In contrast to previous reports we show that CD146 is expressed in both PDGFRβ + perivascular cells and CD31 + endothelial cells. Bulk RNAseq revealed cells in the perivascular niche which express the high levels of Pdgfrb as well as genes previously identified in pericytes and/or vascular smooth muscle cells (Acta2, Myh11, Olfr78, Cspg4, Rgs4, Rgs5, Kcnj8, and Abcc9). scRNA‐seq identified five subpopulations of cells including closely related pericytes/vascular smooth muscle cells and three subpopulations of fibroblasts. All three fibroblast populations were PDGFRα+/CD34 + but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively. Immunohistochemistry was used to investigate the spatial distribution of these populations revealing F1/NGFR + cells in most abundance beside epithelial cells. We provide the first definitive analysis of mesenchymal cells in the adult mouse endometrium identifying five subpopulations providing a platform for comparisons between mesenchymal cells in endometrium and other adult tissues which are prone to fibrosis