Arabinose and protocatechuate catabolism genes are important for growth of Rhizobium leguminosarum biovar viciae in the pea rhizosphere

Background and aims: To form nitrogen-fixing nodules on pea roots, Rhizobium leguminosarum biovar viciae must be competitive in the rhizosphere. Our aim was to identify genes important for rhizosphere fitness. Methods: Signature-tagged mutants were screened using microarrays to identify mutants reduced for growth in pea rhizospheres. Candidate mutants were assessed relative to controls for growth in minimal medium, growth in pea rhizospheres and for infection of peas in mixed inoculants. Mutated genes were identified by DNA sequencing and confirmed by transduction. Results: Of 5508 signature-tagged mutants, microarrays implicated 50 as having decreased rhizosphere fitness. Growth tests identified six mutants with rhizosphere-specific phenotypes. The mutation in one of the genes (araE) was in an arabinose catabolism operon and blocked growth on arabinose. The mutation in another gene (pcaM), encoding a predicted solute binding protein for protocatechuate and hydroxybenzoate uptake, decreased growth on protocatechuate. Both mutants were decreased for nodule infection competitiveness with mixed inoculants, but nodulated peas normally when inoculated alone. Other mutants with similar phenotypes had mutations predicted to affect secondary metabolism. Conclusions: Catabolism of arabinose and protocatechuate in the pea rhizosphere is important for competitiveness of R.l. viciae. Other genes predicted to be involved in secondary metabolism are also important

Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice

Background: Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus. Results: Mouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1−/−) mice. Conclusions: These data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation

A synthesis of past, current and future research for protection and management of papyrus (Cyperus papyrus L.) wetlands in Africa

Papyrus wetlands (dominated by the giant sedge Cyperus papyrus L.) occur throughout eastern, central and southern Africa and are important for biodiversity, for water quality and quantity regulation and for the livelihoods of millions of people. To draw attention to the importance of papyrus wetlands, a special session entitled ‘‘The ecology of livelihoods in papyrus wetlands’’ was organized at the 9th INTECOL Wetlands Conference in Orlando, Florida in June 2012. Papers from the session, combined with additional contributions, were collected in a special issue of Wetlands Ecology and Management. The current paper reviews ecological and hydrological characteristics of papyrus wetlands, summarizes their ecosystem services and sustainable use, provides an overview of papyrus research to date, and looks at policy development for papyrus wetlands. Based on this review, the paper provides a synthesis of research and policy priorities for papyrus wetlands and introduces the contributions in the special issue. Main conclusions are that (1) there is a need for better estimates of the area covered by papyrus wetlands. Limited evidence suggests that the loss of papyrus wetlands is rapid in some areas; (2) there is a need for a better understanding and modelling of the regulating services of papyrus wetlands to support trade-off analysis and improve economic valuation; (3) research on papyrus wetlands should include assessment of all ecosystem services (provisioning, regulating, habitat, cultural) so that trade-offs can be determined as the basis for sustainable management strategies (‘wise use’); (4) more research on the governance, institutional and socio-economic aspects of papyrus wetlands is needed to assist African governments in dealing with the challenges of conserving wetlands in the face of growing food security needs and climate change. The papers in the special issue address a number of these issues

Modern Clinical Research on LSD

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Design strategies to improve patient motivation during robot-aided rehabilitation

BACKGROUND: Motivation is an important factor in rehabilitation and frequently used as a determinant of rehabilitation outcome. Several factors can influence patient motivation and so improve exercise adherence. This paper presents the design of two robot devices for use in the rehabilitation of upper limb movements, that can motivate patients during the execution of the assigned motor tasks by enhancing the gaming aspects of rehabilitation. In addition, a regular review of the obtained performance can reinforce in patients' minds the importance of exercising and encourage them to continue, so improving their motivation and consequently adherence to the program. In view of this, we also developed an evaluation metric that could characterize the rate of improvement and quantify the changes in the obtained performance. METHODS: Two groups (G1, n = 8 and G2, n = 12) of patients with chronic stroke were enrolled in a 3-week rehabilitation program including standard physical therapy (45 min. daily) plus treatment by means of robot devices (40 min., twice daily) respectively for wrist (G1) and elbow-shoulder movements (G2). Both groups were evaluated by means of standard clinical assessment scales and the new robot measured evaluation metric. Patients' motivation was assessed in 9/12 G2 patients by means of the Intrinsic Motivation Inventory (IMI) questionnaire. RESULTS: Both groups reduced their motor deficit and showed a significant improvement in clinical scales and the robot measured parameters. The IMI assessed in G2 patients showed high scores for interest, usefulness and importance subscales and low values for tension and pain subscales. CONCLUSION: Thanks to the design features of the two robot devices the therapist could easily adapt training to the individual by selecting different difficulty levels of the motor task tailored to each patient's disability. The gaming aspects incorporated in the two rehabilitation robots helped maintain patients' interest high during execution of the assigned tasks by providing feedback on performance. The evaluation metric gave a precise measure of patients' performance and thus provides a tool to help therapists promote patient motivation and hence adherence to the training program

Upper extremity impairments in women with or without lymphedema following breast cancer treatment

Breast-cancer-related lymphedema affects ∼25% of breast cancer (BC) survivors and may impact use of the upper limb during activity. The purpose of this study is to compare upper extremity (UE) impairment and activity between women with and without lymphedema after BC treatment. 144 women post BC treatment completed demographic, symptom, and Disability of Arm-Shoulder-Hand (DASH) questionnaires. Objective measures included Purdue pegboard, finger-tapper, Semmes-Weinstein monofilaments, vibration perception threshold, strength, range of motion (ROM), and volume. Women with lymphedema had more lymph nodes removed (p < .001), more UE symptoms (p < .001), higher BMI (p = .041), and higher DASH scores (greater limitation) (p < .001). For all participants there was less strength (elbow flexion, wrist flexion, grip), less shoulder ROM, and decreased sensation at the medial upper arm (p < .05) in the affected UE. These differences were greater in women with lymphedema, particularly in shoulder abduction ROM (p < .05). Women with lymphedema had bilaterally less elbow flexion strength and shoulder ROM (p < .05). Past diagnosis of lymphedema, grip strength, shoulder abduction ROM, and number of comorbidities contributed to the variance in DASH scores (R 2 of 0.463, p < .001). UE impairments are found in women following treatment for BC. Women with lymphedema have greater UE impairment and limitation in activities than women without. Many of these impairments are amenable to prevention measures or treatment, so early detection by health care providers is essential

Potential of a suite of robot/computer-assisted motivating systems for personalized, home-based, stroke rehabilitation

BACKGROUND: There is a need to improve semi-autonomous stroke therapy in home environments often characterized by low supervision of clinical experts and low extrinsic motivation. Our distributed device approach to this problem consists of an integrated suite of low-cost robotic/computer-assistive technologies driven by a novel universal access software framework called UniTherapy. Our design strategy for personalizing the therapy, providing extrinsic motivation and outcome assessment is presented and evaluated. METHODS: Three studies were conducted to evaluate the potential of the suite. A conventional force-reflecting joystick, a modified joystick therapy platform (TheraJoy), and a steering wheel platform (TheraDrive) were tested separately with the UniTherapy software. Stroke subjects with hemiparesis and able-bodied subjects completed tracking activities with the devices in different positions. We quantify motor performance across subject groups and across device platforms and muscle activation across devices at two positions in the arm workspace. RESULTS: Trends in the assessment metrics were consistent across devices with able-bodied and high functioning strokes subjects being significantly more accurate and quicker in their motor performance than low functioning subjects. Muscle activation patterns were different for shoulder and elbow across different devices and locations. CONCLUSION: The Robot/CAMR suite has potential for stroke rehabilitation. By manipulating hardware and software variables, we can create personalized therapy environments that engage patients, address their therapy need, and track their progress. A larger longitudinal study is still needed to evaluate these systems in under-supervised environments such as the home

VKORC1 Pharmacogenetics and Pharmacoproteomics in Patients on Warfarin Anticoagulant Therapy: Transthyretin Precursor as a Potential Biomarker

Recognizing specific protein changes in response to drug administration in humans has the potential for the development of personalized medicine. Such changes can be identified by pharmacoproteomics approach based on proteomic technologies. It can also be helpful in matching a particular target-based therapy to a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism. Warfarin is a commonly prescribed oral anticoagulant in patients with prosthetic valve disease, venous thromboembolism and stroke.We used a combined pharmacogenetics and iTRAQ-coupled LC-MS/MS pharmacoproteomics approach to analyze plasma protein profiles of 53 patients, and identified significantly upregulated level of transthyretin precursor in patients receiving low dose of warfarin but not in those on high dose of warfarin. In addition, real-time RT-PCR, western blotting, human IL-6 ELISA assay were done for the results validation.This combined pharmacogenomics and pharmacoproteomics approach may be applied for other target-based therapies, in matching a particular marker in a subgroup of patients, in addition to the profile of genetic polymorphism