Matching cell type to function in cortical circuits

In this issue of Neuron, Pinto and Dan (2015) performed single-cell calcium imaging in the mouse dorsomedial prefrontal cortex to reveal correlated, cell-type-specific responses in three major GABA-ergic interneuron subtypes during a goal-directed sensory discrimination task

Enhancing service requirements of technical product-service systems

Due to the integration of product and services as a new business model, product reliability and strategies for cost reduction at the early design stage have become important factors for many manufacturing firms. It is, therefore, critical at this phase to analyse the risk involved with Service Requirements noncompliance in order to help designers make informed decisions; as these decisions have a large impact on the Product Life Cycle (PLC). An investigation has been performed into how Service Requirements are analysed in a service orientated business to achieve reduced Life Cycle Cost (LCC) and improvements of existing Service Requirements. Weibull distribution and Monte Carlo principle have been proposed to do so; as they are considered as the most widely used in product reliability studies in the industry sector. A generic methodology for risk evaluation of failure to deliver a new product against Service Requirements is presented in this paper. This is part of the ongoing research project which aims to, apart from comparing current and targeted Service Requirements, it also facilitates an optimisation of them at the minimum risk of nonconformity

FPGA-based multi-sensor relative navigation in space: Preliminary analysis in the framework of the I3DS H2020 project

The Horizon 2020 Integrated 3D Sensors (I3DS) project brings together the following entities throughout Europe: THALES ALENIA SPACE - France / Italy / UK / Spain, SINTEF (Norway), TERMA (Denmark), COSINE (Netherlands), PIAP Space (Poland), HERTZ Systems (Poland), and Cranfield University (UK). I3DS is co-funded under the Horizon 2020 EU research and development program and is part of the Strategic Research Cluster on Space Robotics Technologies. The ambition of I3DS is to produce a standardised modular Inspector Sensor Suite (INSES) for autonomous orbital and planetary applications for future space missions. Orbital applications encompass activities such as on-orbit servicing and repair, space rendezvous and docking, collision avoidance and active debris removal (ADR). Simultaneous localisation and surface mapping (SLAM) for planetary exploration and general navigation in an unknown environment for scientific purposes can be considered in planetary applications. These envisaged space applications can be tackled by exploiting the flexibility, high performance and long product life of FPGAs. Conventional FPGAs are subject to Single Event Upsets (SEU) due to space radiation, causing their failure. Therefore, space-graded FPGAs, such as those developed by Xilinx, are targeted within the I3DS project. Currently, the main use of the FPGA within the development of this robust end-to-end multi-sensor suite is for navigation and data preprocessing. The aim of this paper is to assess the capabilities of FPGAs to carry out complex operations, such as running navigation algorithms for space applications. The motivation for the development of the on-board software architecture is as follows: raw data, acquired from the various sensors – including, among others, a High Resolution camera, a stereo camera and a LiDAR – is pre-processed to ensure the provision of robust and optimised inputs to 3D navigation algorithms. Noise reduction and conversion into suitable formats for the successful application of navigation algorithms are therefore the main aims of the data pre-processing. Some techniques adopted in this phase include outlier rejection and data dimensionality reduction for large point clouds, e.g. from LiDAR, and geometric and radiometric correction of the images from the cameras. The pre-processed data will then feed state-of-the-art relative navigation algorithms. Some of the proposed navigation algorithms include Generalised Iterative Closest Point (GICP) for dense 3D point clouds, relative positioning with fiducial markers, and visual odometry. The system environment for the preliminary operation is a test-bench setup formed by a standard desktop computer and a non-space-graded FGA (Xilinx UltraZed-EG FPGA). The choice of FPGA was based on the similarity of this board to other spacegraded ones also provided by Xilinx. Experimental tests on the algorithms are being performed in the framework of the validation campaign for the I3DS project. Preliminary results indicate that the data pre-processing can be efficiently carried out on the FPGA board

Cortical fosGFP expression reveals broad receptive field excitatory neurons targeted by POm

Neighboring cortical excitatory neurons show considerable heterogeneity in their responses to sensory stimulation. We hypothesized that a subset of layer 2 excitatory neurons in the juvenile (P18 to 27) mouse whisker somatosensory cortex, distinguished by expression of the activity-dependent fosGFP reporter gene, would be preferentially activated by whisker stimulation. In fact, two-photon targeted, dual whole-cell recordings showed that principal whisker stimulation elicits similar amplitude synaptic responses in fosGFP-expressing and fosGFP(-) neurons. FosGFP(+) neurons instead displayed shorter latency and larger amplitude subthreshold responses to surround whisker stimulation. Using optogenetic stimulation, we determined that these neurons are targeted by axons from the posteromedial nucleus (POm), a paralemniscal thalamic nucleus associated with broad receptive fields and widespread cortical projections. We conclude that fosGFP expression discriminates between single- and multi-whisker receptive field layer 2 pyramidal neurons

Therapeutic Exercise and Pain Neurophysiology Education in Female Patients with Fibromyalgia Syndrome: A Feasibility Study

Background: We compared the effects of therapeutic exercise (TE) combined with pain neurophysiology education (PNE) to those of TE in isolation on pain intensity, general fibromyalgia impact, mechanical pain sensitivity, pain catastrophizing, psychological distress and quality of life in women with fibromyalgia syndrome (FMS). Methods: A feasibility study with a 3 month follow-up was designed. Thirty-two patients with FMS were randomly assigned to PNE + TE group (n = 16) or to TE group (n = 16). Both groups received 30 sessions of TE (3 per week), and the PNE + TE group received eight face-to-face educational sessions. The measuring instruments used were the visual analogue scale, a standard pressure algometer, the Revised Fibromyalgia Impact Questionnaire, the Pain Catastrophizing Scale, the Hospital Anxiety and Depression Scale and the Health Assessment Questionnaire. Results: The PNE + TE group showed a statistically significant decrease on pain intensity compared to TE group at short term (p = 0.015). No between-groups differences were found for mechanical pain sensitivity, general fibromyalgia impact, pain catastrophizing, psychological distress or quality of life (p > 0.05). Conclusions: The combination of PNE and TE was more effective than TE for reducing pain intensity in the short-term. No differences were found for psychological distress, pain catastrophizing and quality of life after the intervention or at 3 months of follow-up

Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors $\textit{in vivo}$. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.This study was funded by DFG collaborative research grant SFB958 (projects A09 to K.P. and G.R.L., A01 to V.H. and Z02 to J.S.). Additional support was provided by a senior ERC grant (grant number 294678 to G.R.L.) and by the NeuroCure Cluster of Excellence (to V.H., G.R.L. and J.F.A.P.). K.P. was supported by a Cecile-Vogt Fellowship (MDC). S.P. was supported by a Marie Curie Fellowship from the European Union (grant number 253663 Touch in situ). C.P. received a Ph.D. fellowship from the University of Cagliari. J.F.A.P. was funded by a European Research Council (ERC) starting grant (ERC-2010-StG-260590), the DFG (FOR 1341, FOR 2143), the Berlin Institute of Health (BIH) and the European Union (FP7, 3x3Dimaging 323945). R.K. was supported by an ERC Advanced Investigator grant (294293-PAIN PLASTICITY). D.H. was funded by the Berlin Institute of Health (BIH). E.St.J.S., L.E. and M.M. were supported by an Alexander von Humboldt Fellowship

Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis

Altres ajuts: Cancer Prevention and Research Institute of Texas (CPRIT), Core Facility Support Award (CPRIT-RP180672, R1313, 1R01GM138781-01); NIH (CA125123, RR024574); Eunice Kennedy Shriver National Institute of Child Health & Human Development of the NIH (P50HD103555); BCM start-up funds; Albert and Margaret Alkek Foundation; McNair Medical Institute; Robert and Janice McNair Foundation; BCM Seed Funding (1P20CA221731-01A1); National Institute of General Medical Sciences (R01 GM120033); Cynthia and Antony Petrello Endowment; Mark A. Wallace Endowment; McKnight Foundation; Dana Foundation; BCM Computational and Integrative Biomedical Research Center seed grant.Neural stem cells, the source of newborn neurons in the adult hippocampus, are intimately involved in learning and memory, mood, and stress response. Despite considerable progress in understanding the biology of neural stem cells and neurogenesis, regulating the neural stem cell population precisely has remained elusive because we have lacked the specific targets to stimulate their proliferation and neurogenesis. The orphan nuclear receptor TLX/NR2E1 governs neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is not well understood because its endogenous ligand is not known. Here, we identify oleic acid (18:1ω9 monounsaturated fatty acid) as such a ligand. We first show that oleic acid is critical for neural stem cell survival. Next, we demonstrate that it binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes, which in turn increases neural stem cell mitotic activity and drives hippocampal neurogenesis in mice. Interestingly, oleic acid-activated TLX strongly up-regulates cell cycle genes while only modestly up-regulating neurogenic genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation and drive the progeny toward neuronal lineage. Oleic acid thus serves as a metabolic regulator of TLX activity that can be used to selectively target neural stem cells, paving the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis

Infection status and risk factors of HIV, HBV, HCV, and syphilis among drug users in Guangdong, China - a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>China has witnessed a remarkable increase in sexually transmitted infections (STIs) and HIV. The study is to assess the prevalence of HIV, HBV, HCV and syphilis and related risk factors among drug users in mandatory detoxification center Qingyuan, Guangdong, China.</p> <p>Method</p> <p>A cross-sectional study on drug use behaviors, sex behaviors, and presence of antibodies to HIV, HCV, Treponema pallidum, and surface antigen of HBV (HBsAg) was conducted among drug users recruited from 3 detoxification centers in Qingyuan, Guangdong, China. Risk factors for each of four infections were analyzed with logistic regression model.</p> <p>Results</p> <p>A total of 740 subjects were recruited, the median age was 31 years old (range 24-38). The seroprevalence rates of HIV, HBsAg, HCV and syphilis were 4.6%, 19.3%, 71.6% and 12.6%, respectively. Risk factors for HIV were intravenous drug use and co-infection with syphilis. Having a regular sexual partner who was a drug user was considered to be a risk factor for HBV. Intravenous drug use was a risk factor for HCV. However, the consistent use of condoms with commercial sex partners was protective for HCV infection. Compared to drug users living in urban area, those living in rural areas were more likely to be infected with syphilis, and there was an association between commercial sex and syphilis.</p> <p>Conclusion</p> <p>The prevalence of HIV, HBV, HCV and syphilis were high among drug users in detoxification centers in Qingyuan, thus, risk reduction programs for the drug user population is urgently required.</p

Fatores de risco cardiovascular em pessoas semabrigo e na população geral da cidade do Porto, Portugal

We described the distribution of risk factors for cardiovascular disease among homeless people living in the city of Porto, Portugal. Comparisons were made between subsamples of homeless people recruited in different settings and between the overall homeless sample group and a sample of the general population. All "houseless" individuals attending one of two homeless hostels or two institutions providing meal programs on specific days were invited to participate and were matched with subjects from the general population. We estimated sex, age and education-adjusted prevalence ratios or mean differences. The prevalence of previous illicit drug consumption and imprisonment was almost twice as high among the homeless from institutions providing meal programs. This group also showed lower mean systolic and diastolic blood pressure. Prevalence of smoking was almost 50% higher in the overall homeless group. Mean body mass index and waist circumference were also lower in the homeless group and its members were almost five times less likely to report dyslipidemia. Our findings contribute to defining priorities for interventions directed at this segment of society and to reducing inequalities in this extremely underprivileged populatio

Rapid and Reversible Recruitment of Early Visual Cortex for Touch

The loss of vision has been associated with enhanced performance in non-visual tasks such as tactile discrimination and sound localization. Current evidence suggests that these functional gains are linked to the recruitment of the occipital visual cortex for non-visual processing, but the neurophysiological mechanisms underlying these crossmodal changes remain uncertain. One possible explanation is that visual deprivation is associated with an unmasking of non-visual input into visual cortex.We investigated the effect of sudden, complete and prolonged visual deprivation (five days) in normally sighted adult individuals while they were immersed in an intensive tactile training program. Following the five-day period, blindfolded subjects performed better on a Braille character discrimination task. In the blindfold group, serial fMRI scans revealed an increase in BOLD signal within the occipital cortex in response to tactile stimulation after five days of complete visual deprivation. This increase in signal was no longer present 24 hours after blindfold removal. Finally, reversible disruption of occipital cortex function on the fifth day (by repetitive transcranial magnetic stimulation; rTMS) impaired Braille character recognition ability in the blindfold group but not in non-blindfolded controls. This disruptive effect was no longer evident once the blindfold had been removed for 24 hours.Overall, our findings suggest that sudden and complete visual deprivation in normally sighted individuals can lead to profound, but rapidly reversible, neuroplastic changes by which the occipital cortex becomes engaged in processing of non-visual information. The speed and dynamic nature of the observed changes suggests that normally inhibited or masked functions in the sighted are revealed by visual loss. The unmasking of pre-existing connections and shifts in connectivity represent rapid, early plastic changes, which presumably can lead, if sustained and reinforced, to slower developing, but more permanent structural changes, such as the establishment of new neural connections in the blind