Practical actions to strengthen capacity for deep-water research in Africa

While Africa's deep marine biodiversity offers economic prospects it also supports crucial ecosystem services and sustainable development is dependent on knowledge of these systems. Building understanding of deep-water ecosystems is key, but there are substantial discrepancies in countries' abilities to achieve this. Coinciding with the 2024 Ocean Decade Conference, the Challenger 150 African Network of Deep-water Researchers is pleased to release a report on “Practical Actions to Strengthen Capacity for Deep-water Research in Africa”. Through a series of online workshops, the ANDR brought together 98 individuals from 19 African nations to discuss challenges for deep-water research in Africa, identify solutions to overcome these and propose practical actions going forward

Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway

Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A2A receptors immunoreactivity. Moreover, activation of accumbens A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Patient and public involvement in designing and conducting doctoral research: the whys and the hows

YesPublic and patient involvement (PPI) has been shown to have a positive impact on health and social care research. However, adequate examples describing how to operationalise effective PPI, especially in doctoral studies, are lacking. Hence, doctoral researchers new to research, or those with limited experience, can be discouraged from facilitating PPI in their research. This paper aims to describe and discuss in detail the approaches used by four doctoral researchers to incorporate PPI at different stages of their research studies from study design to disseminating findings. We aim to inform other doctoral researchers about the challenges and limitations relating to PPI that we faced. Through these, we share pragmatic recommendations for facilitating PPI during doctoral studies. The description of four case studies demonstrated that PPI could be incorporated at various stages during doctoral research. This has had a beneficial impact on our research study progression, researcher self-esteem and lastly, helped alleviate researcher isolation during doctoral studies.Supported by Research Design Service Yorkshire and the Humber (RDSYH), the National Institute for Health Research (NIHR) Yorkshire and Humber Patient Safety Translational Research Centre (NIHR Yorkshire and Humber PSTRC). This paper presents independent research funded by NIHR under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0317-20010).Research Development Fund Publication Prize Award winner, July 2019

Optical Dissection of Neural Circuits Responsible for Drosophila Larval Locomotion with Halorhodopsin

Halorhodopsin (NpHR), a light-driven microbial chloride pump, enables silencing of neuronal function with superb temporal and spatial resolution. Here, we generated a transgenic line of Drosophila that drives expression of NpHR under control of the Gal4/UAS system. Then, we used it to dissect the functional properties of neural circuits that regulate larval peristalsis, a continuous wave of muscular contraction from posterior to anterior segments. We first demonstrate the effectiveness of NpHR by showing that global and continuous NpHR-mediated optical inhibition of motor neurons or sensory feedback neurons induce the same behavioral responses in crawling larvae to those elicited when the function of these neurons are inhibited by Shibirets, namely complete paralyses or slowed locomotion, respectively. We then applied transient and/or focused light stimuli to inhibit the activity of motor neurons in a more temporally and spatially restricted manner and studied the effects of the optical inhibition on peristalsis. When a brief light stimulus (1–10 sec) was applied to a crawling larva, the wave of muscular contraction stopped transiently but resumed from the halted position when the light was turned off. Similarly, when a focused light stimulus was applied to inhibit motor neurons in one or a few segments which were about to be activated in a dissected larva undergoing fictive locomotion, the propagation of muscular constriction paused during the light stimulus but resumed from the halted position when the inhibition (>5 sec) was removed. These results suggest that (1) Firing of motor neurons at the forefront of the wave is required for the wave to proceed to more anterior segments, and (2) The information about the phase of the wave, namely which segment is active at a given time, can be memorized in the neural circuits for several seconds

Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans

Psychotropic medication use among nursing home residents in Austria: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The use of psychotropic medications and their adverse effects in frail elderly has been debated extensively. However, recent data from European studies show that these drugs are still frequently prescribed in nursing home residents. In Austria, prevalence data are lacking. We aimed to determine the prevalence of psychotropic medication prescription in Austrian nursing homes and to explore characteristics associated with their prescription.</p> <p>Methods</p> <p>Cross-sectional study and association analysis in forty-eight out of 50 nursing homes with 1844 out of a total of 2005 residents in a defined urban-rural region in Austria. Prescribed medication was retrieved from residents' charts. Psychotropic medications were coded according to the Anatomical Therapeutic Chemical Classification 2005. Cluster-adjusted multiple logistic regression analysis was performed to investigate institutional and residents' characteristics associated with prescription.</p> <p>Results</p> <p>Residents' mean age was 81; 73% of residents were female. Mean cluster-adjusted prevalence of residents with at least one psychotropic medication was 74.6% (95% confidence interval, CI, 72.0–77.2). A total of 45.9% (95% CI 42.7–49.1) had at least one prescription of an antipsychotic medication. Two third of all antipsychotic medications were prescribed for bedtime use only. Anxiolytics were prescribed in 22.2% (95% CI 20.0–24.5), hypnotics in 13.3% (95% CI 11.3–15.4), and antidepressants in 36.8% (95% CI 34.1–39.6) of residents. None of the institutional characteristics and only few residents' characteristics were significantly associated with psychotropic medication prescription. Permanent restlessness was positively associated with psychotropic medication prescription (AOR 1.54, 95% CI 1.32–1.79) whereas cognitive impairment was inversely associated (AOR 0.70, 95% CI 0.56–0.88).</p> <p>Conclusion</p> <p>Frequency of psychotropic medication prescription is high in Austrian nursing homes compared to recent published data from other countries. Interventions should aim at reduction and optimisation of prescriptions.</p

Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy

High Throughput Screening (HTS) is a successful strategy for finding hits and leads that have the opportunity to be converted into drugs. In this paper we highlight novel computational methods used to select compounds to build a new screening file at Pfizer and the analytical methods we used to assess their quality. We also introduce the novel concept of molecular redundancy to help decide on the density of compounds required in any region of chemical space in order to be confident of running successful HTS campaigns

Systematic Screening of Drosophila Deficiency Mutations for Embryonic Phenotypes and Orphan Receptor Ligands

This paper defines a collection of Drosophila deletion mutations (deficiencies) that can be systematically screened for embryonic phenotypes, orphan receptor ligands, and genes affecting protein localization. It reports the results of deficiency screens we have conducted that have revealed new axon guidance phenotypes in the central nervous system and neuromuscular system and permitted a quantitative assessment of the number of potential genes involved in regulating guidance of specific motor axon branches. Deficiency “kits” that cover the genome with a minimum number of lines have been established to facilitate gene mapping. These kits cannot be systematically analyzed for phenotypes, however, since embryos homozygous for many deficiencies in these kits fail to develop due to the loss of key gene products encoded within the deficiency. To create new kits that can be screened for phenotype, we have examined the development of the nervous system in embryos homozygous for more than 700 distinct deficiency mutations. A kit of ∼400 deficiency lines for which homozygotes have a recognizable nervous system and intact body walls encompasses >80% of the genome. Here we show examples of screens of this kit for orphan receptor ligands and neuronal antigen expression. It can also be used to find genes involved in expression, patterning, and subcellular localization of any protein that can be visualized by antibody staining. A subset kit of 233 deficiency lines, for which homozygotes develop relatively normally to late stage 16, covers ∼50% of the genome. We have screened it for axon guidance phenotypes, and we present examples of new phenotypes we have identified. The subset kit can be used to screen for phenotypes affecting all embryonic organs. In the future, these deficiency kits will allow Drosophila researchers to rapidly and efficiently execute genome-wide anatomical screens that require examination of individual embryos at high magnification