Gain Modulation by Corticostriatal and Thalamostriatal Input Signals during Reward-Conditioned Behavior.

The cortex and thalamus send excitatory projections to the striatum, but little is known about how these inputs, either individually or collectively, regulate striatal dynamics during behavior. The lateral striatum receives overlapping input from the secondary motor cortex (M2), an area involved in licking, and the parafascicular thalamic nucleus (PF). Using neural recordings, together with optogenetic terminal inhibition, we examine the contribution of M2 and PF projections on medium spiny projection neuron (MSN) activity as mice performed an anticipatory licking task. Each input has a similar contribution to striatal activity. By comparing how suppressing single or multiple projections altered striatal activity, we find that cortical and thalamic input signals modulate MSN gain and that this effect is more pronounced in a temporally specific period of the task following the cue presentation. These results demonstrate that cortical and thalamic inputs synergistically regulate striatal output during reward-conditioned behavior

The American Society of Pain and Neuroscience (ASPN) practical guidelines to study design and scientific manuscript preparation in neuromodulation

Background: Healthcare clinical and even policy decisions are progressively made based on research-based evidence. The process by which the appropriate trials are developed and well-written manuscripts by means of evidence-based medicine recommendations has resulted in unprecedented necessity in evidence-based medicine in neuromodulation. Methods: The essential considerations in the planning of neuromodulation research are discussed in the light of available scientific literature as well as the authors\u27 scientific expertise regarding research study design and scientific manuscript preparation. Conclusion: This article should enable the reader to understand how to appropriately design a clinical research study and prepare scientific manuscripts. The high-quality and well-designed studies, when performed and reported effectively, support evidence-based medicine and foster improved patient outcomes

Noninterventional statistical comparison of BTS and CHEST guidelines for size and severity in primary pneumothorax.

Hilar rather than apical interpleural distance more accurately predicts need for intercostal chest drain insertion http://ow.ly/JvKFYThe study was funded by the East Anglian Thoracic Society. M.Z. Nikolić is a Wellcome Trust PhD Programme for Clinicians Fellow at the University of Cambridge. S.J. Marciniak is a Medical Research Council Senior Clinical Fellow. J. Wason is funded by the Cambridge Biomedical Research Centre. Funding information for this article has been deposited with FundRef.This is the final version of the article. It first appeared from the European Respiratory Society via http://dx.doi.org/10.1183/09031936.0011861

Does device matter? Impacts of food-specific inhibition training on food choice, liking and approach bias when delivered by smartphone or computer.

Food-specific inhibition training (FSIT) requires users to inhibit responses to energy-dense (ED) food stimuli within a reaction time game. FSIT reduces choice and liking of ED foods. Research with the public shows larger effects when FSIT is delivered by computer versus smartphone. This pre-registered study is the first to compare computer-FSIT versus smartphone-FSIT in a controlled setting. Three-hundred-and-thirty-one adults were randomised to computer-FSIT, smartphone-FSIT or non-food control training (computer-delivered). In session 1, participants completed baseline measures of impulsive food choice, food approach bias (approach/avoid implicit association test), and food liking ratings, before completing eight minutes of FSIT/control training. In session 2, participants repeated the same training task, followed by the same measures of food choice, approach bias and liking. We hypothesised that FSIT groups would show healthier food choices, lower ED food liking, and reduced ED food approach bias at post-training compared to control. We expected no statistically significant differences between the two FSIT groups. Post-exclusions, data for 259 participants was analysed. Contrary to predictions, there was no evidence of significant group differences on any of the outcome measures. Baseline measures suggest participants already showed high approach to healthy foods, which may explain these null results

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways

A global database for metacommunity ecology, integrating species, traits, environment and space

The use of functional information in the form of species traits plays an important role in explaining biodiversity patterns and responses to environmental changes. Although relationships between species composition, their traits, and the environment have been extensively studied on a case-by-case basis, results are variable, and it remains unclear how generalizable these relationships are across ecosystems, taxa and spatial scales. To address this gap, we collated 80 datasets from trait-based studies into a global database for metaCommunity Ecology: Species, Traits, Environment and Space; “CESTES”. Each dataset includes four matrices: species community abundances or presences/absences across multiple sites, species trait information, environmental variables and spatial coordinates of the sampling sites. The CESTES database is a live database: it will be maintained and expanded in the future as new datasets become available. By its harmonized structure, and the diversity of ecosystem types, taxonomic groups, and spatial scales it covers, the CESTES database provides an important opportunity for synthetic trait-based research in community ecology

Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppression in vivo drove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression also drove response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy