Rab11-dependent recycling of calcium channels is mediated by auxiliary subunit α2δ-1 but not α2δ-3

N-type voltage-gated calcium channels (CaV2.2) are predominantly expressed at presynaptic terminals, and their function is regulated by auxiliary α2δ and β subunits. All four mammalian α2δ subunits enhance calcium currents through CaV1 and CaV2 channels, and this increase is attributed, in part, to increased CaV expression at the plasma membrane. In the present study we provide evidence that α2δ-1, like α2δ-2, is recycled to the plasma membrane through a Rab11a-dependent endosomal recycling pathway. Using a dominant-negative Rab11a mutant, Rab11a(S25N), we show that α2δ-1 increases plasma membrane CaV2.2 expression by increasing the rate and extent of net forward CaV2.2 trafficking in a Rab11a-dependent manner. Dominant-negative Rab11a also reduces the ability of α2δ-1 to increase CaV2.2 expression on the cell-surface of hippocampal neurites. In contrast, α2δ-3 does not enhance rapid forward CaV2.2 trafficking, regardless of whether Rab11a(S25N) is present. In addition, whole-cell CaV2.2 currents are reduced by co-expression of Rab11a(S25N) in the presence of α2δ-1, but not α2δ-3. Taken together these data suggest that α2δ subtypes participate in distinct trafficking pathways which in turn influence the localisation and function of CaV2.2

What Do Toilets Have to Do With It? Health, the Environment, and the Working Poor in Rural South Texas Colonias

This paper develops and tests an environmental health ecological framework between the quality of infrastructure, utilities and resident’s practices to health problems reported in three Nueces County, Texas colonias. Populated by predominantly low-income, minority families, these peri-urban settlements are characterized by substandard housing, lacking traditional sewage systems, potable drinking water and pluvial drainage. It was hypothesized that those without indoor toilets, pluvial drainage and regular garbage collection would be more likely to report health problems. The study found that keeping trash for over a week was statistically related to gastrointestinal illness and eye infections. Having indoor toilets in conjunction with substandard septic tanks was statistically related to gastrointestinal illness, respiratory problems and skin infections. The lack of pluvial drainage was statistically significantly, while not related to a particular disease. The argument is made that flooding problems may have contributed to the sanitation problems. Specifically, drainage problems affect the septic tanks and cause backflow to the indoor toilets. Although a small sample, the findings show that people who live in colonias are at risk for disease because structural measures to improve sanitation are not available

rLOAD: does sex mediate the effect of acute antiplatelet loading on stroke outcome.

BackgroundBiologic sex can influence response to pharmacologic therapy. The purpose of this proof-of-concept study was to evaluate the medicating effects of estrogen in the efficacy of acute antiplatelet loading therapy on stroke outcome in the rabbit small clot embolic model.MethodsFemale and male (20/group) New Zealand White rabbits were embolized to produce embolic stroke by injecting small blood clots into the middle cerebral artery via an internal carotid artery catheter. Two hours after embolization, rabbits were treated with standard dose antiplatelet loading (aspirin 10 mg/kg plus clopidogrel 10 mg/kg). Primary outcome measures were platelet inhibition, behavioral outcome P 50 (the weight of microclots (mg) that produces neurologic dysfunction in 50% of a group of animals), and effect of endogenous estrogen on outcome.ResultsFor the first time in a non-rodent model of stroke, it was found that higher endogenous estrogen levels resulted in significantly better behavioral outcome in female subjects (r s -0.70, p < 0.011). Platelet inhibition in response to collagen, arachidonic acid, and adenosine diphosphate (ADP) was not significantly different in females with higher vs. lower estrogen levels.ConclusionsBehavioral outcomes are improved with females with higher endogenous estrogen levels treated with standard dose antiplatelet loading. This is the first non-rodent study to demonstrate that higher endogenous estrogen levels in female rabbits appear to be neuroprotective in ischemic stroke. This research supports the further study of the effect of endogenous estrogen levels on outcome with standard dose antiplatelet loading in stroke patients not eligible for revascularization therapies

Taking the Leap: Exploring a Theory of Program Innovation

Innovation in Extension is often referred to as something tangible, such as a new resource or technique or new concepts. However, these things result from a program innovation process. In this article, we elaborate a grounded theory of how this process unfolds in the context of Extension. Through analysis of data from a national survey of practitioners from innovative programs, a panel presentation, and interviews with faculty at the University of Minnesota, we describe seven factors that influence what prompts innovation and how the process tends to unfold. We synthesize a capitals-based conceptual model and discuss implications for diagnosing and strengthening program innovation

Inferring common cognitive mechanisms from brain blood-flow lateralization data: a new methodology for fTCD analysis

Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV) lateralization data, obtained with functional TransCranial Doppler (fTCD) ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralization Index (LI) for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG) at two difficulty levels. In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG, and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training. CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated. The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques

The diagnostic validity and reliability of an internet-based clinical assessment program for mental disorders

BACKGROUND: Internet-based assessment has the potential to assist with the diagnosis of mental health disorders and overcome the barriers associated with traditional services (eg, cost, stigma, distance). Further to existing online screening programs available, there is an opportunity to deliver more comprehensive and accurate diagnostic tools to supplement the assessment and treatment of mental health disorders. OBJECTIVE: The aim was to evaluate the diagnostic criterion validity and test-retest reliability of the electronic Psychological Assessment System (e-PASS), an online, self-report, multidisorder, clinical assessment and referral system. METHODS: Participants were 616 adults residing in Australia, recruited online, and representing prospective e-PASS users. Following e-PASS completion, 158 participants underwent a telephone-administered structured clinical interview and 39 participants repeated the e-PASS within 25 days of initial completion. RESULTS: With structured clinical interview results serving as the gold standard, diagnostic agreement with the e-PASS varied considerably from fair (eg, generalized anxiety disorder: &kappa;=.37) to strong (eg, panic disorder: &kappa;=.62). Although the e-PASS\u27 sensitivity also varied (0.43-0.86) the specificity was generally high (0.68-1.00). The e-PASS sensitivity generally improved when reducing the e-PASS threshold to a subclinical result. Test-retest reliability ranged from moderate (eg, specific phobia: &kappa;=.54) to substantial (eg, bulimia nervosa: &kappa;=.87). CONCLUSIONS: The e-PASS produces reliable diagnostic results and performs generally well in excluding mental disorders, although at the expense of sensitivity. For screening purposes, the e-PASS subclinical result generally appears better than a clinical result as a diagnostic indicator. Further development and evaluation is needed to support the use of online diagnostic assessment programs for mental disorders. <br /

A dynamical systems approach to optimizing irrigation strategy under the influence of land-atmosphere feedbacks.

The soil-moisture feedback describes how precipitation amount, timing and intensity react to spatial anomalies in surface moisture. For heterogeneous moisture distributions with moist/dry patches on the scale of 10− 50km, numerical studies supported by observations indicate a negative soil-moisture feedback, where it rains more over dry patches (Imamovic, 2018; Rieck et al., 2014). The circulation established by the heterogeneous soil-moisture patches not only modifies the spatial rain distribution but allows for more water to be extracted from the atmosphere, thereby increasing the domain mean precipitation. We here suggest that the negative soil-moisture feedback can be exploited when irrigating agricultural land: if farmers cooperate by following a spatially heterogeneous irrigation pattern, they can increase both their collective time-mean precipitation and thus the total water available for growing crops. However, the spatially non-local nature of the feedback allows individual farmers to exploit this strategy, thereby saving their own resources; a typical ‘tragedy of commons’ situation. We formulate this setup in terms of an optimisation problem and study its parameter phase space, both analytically and numerically, in order to understand optimal rules and the consequences of the players’ choice to cooperate vs. compete. Different constraints in terms of water availability (reservoir) and average soil moisture as defined by the evaporation timescale are explored. Reducing the details of the land-atmosphere interaction into simple feedback parameters helps to elucidate the complex interactions between the precipitation, soil moisture and the human intervention by irrigation. Taking into account the negative soil-moisture feedback in irrigation models opens up new strategies to optimise water management and thereby increase crop yield

In-situ Plasma Studies using a Direct Current Microplasma in a Scanning Electron Microscope

Microplasmas can be used for a wide range of technological applications and to improve our understanding of fundamental physics. Scanning electron microscopy, on the other hand, provides insights into the sample morphology and chemistry of materials from the mm-down to the nm-scale. Combining both would provide direct insight into plasma-sample interactions in real-time and at high spatial resolution. Up till now, very few attempts in this direction have been made, and significant challenges remain. This work presents a stable direct current glow discharge microplasma setup built inside a scanning electron microscope. The experimental setup is capable of real-time in-situ imaging of the sample evolution during plasma operation and it demonstrates localized sputtering and sample oxidation. Further, the experimental parameters such as varying gas mixtures, electrode polarity, and field strength are explored and experimental $V$-$I$ curves under various conditions are provided. These results demonstrate the capabilities of this setup in potential investigations of plasma physics, plasma-surface interactions, and materials science and its practical applications. The presented setup shows the potential to have several technological applications, e.g., to locally modify the sample surface (e.g., local oxidation and ion implantation for nanotechnology applications) on the $\mu$m-scale.Comment: LG, DC, and RDM contributed equally to this work. The videos mentioned in the manuscript can be found in the Zenodo repository linked in the pape

My Road Ahead study protocol: A randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer

Background: There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone. Methods/design: This study utilises a RCT design with three groups receiving: 1) the 6-module My Road Ahead intervention alone; 2) the My Road Ahead intervention plus a moderated online forum; and 3) the moderated online forum alone. It is expected that 150 men with localised prostate cancer will be recruited into the RCT. Online measures will assess men’s psychological distress as well as sexual and relationship adjustment at baseline, post-intervention, 3 month follow-up and 6 month follow-up. The study is being conducted in Australia and participants will be recruited from April 2012 to Feb 2014. The primary aim of this study is to evaluate the efficacy of My Road Ahead in reducing psychological distress. Discussion: To our knowledge, My Road Ahead is the first self-directed online psychological intervention developed for men who have been treated for localised prostate cancer. The RCT will assess the efficacy of this intervention in improving psychological well-being, sexual satisfaction, relationship satisfaction and overall quality of life. If successful, this intervention could provide much needed support to men receiving treatment for localised prostate cancer in a highly accessible manner