Santanabowles1089

Parvalbumin-expressing interneurons in cortical networks are coupled by gap-junctions, forming a syncytium that supports propagating epileptiform discharges, induced by 4-aminopyridine. It remains unclear, however, whether these propagating events occur under more natural states, without pharmacological blockade. In particular, we investigated whether propagation also happens when extracellular K+ rises, as is known to occur following intense network activity, such as during seizures. We examined how increasing [K+]o affects the likelihood of propagating activity away from a site of focal (200-400µm) optogenetic activation of parvalbumin-expressing interneurons. Activity was recorded using a linear 16-electrode array placed along layer V of primary visual cortex. At baseline levels of [K+]o (3.5mM), induced activity was recorded only within the illuminated area. However, when [K+]o was increased above a threshold level (50th percentile= 8.0mM; interquartile range= 7.5-9.5mM), time-locked, fast-spiking unit acum of parvalbumin(PV)-expressing interneurons, in conditions that are known to exist at times within the brain. Previous work has only shown gap-junction coordination very locally, through directly connected cells, or induced at a distance by pharmacological means. We show that cell-class specific spread is facilitated by raised extracellular K+ This is highly pertinent to what happens at the onset of, and during, seizures, when extracellular K+ can rise rapidly to levels well in excess of the measured threshold for propagation. Ac-DEVD-CHO Our data suggests that interneuronal coupling will be enhanced at this time, and this has clear implications for the behaviour of these cells as seizures progress. Copyright © 2020 Papasavvas et al.The multitude of neuronal subtypes and extensive interconnectivity of the mammalian brain presents a substantial challenge to those seeking to decipher its functions. While the molecular mechanisms of several neuronal functions remain poorly characterized, advances in Next-Generation Sequencing (NGS) and gene-editing technology have begun to close this gap. The Clustered Regularly Interspaced Palindromic Repeats - CRISPR Associated Protein (CRISPR-Cas) system has emerged as a powerful genetic tool capable of manipulating the genome of essentially any organism and cell type, an attribute which has advanced our understanding of complex neurological diseases by enabling the rapid generation of novel, disease-relevant in vitro and transgenic animal models. In this review, we discuss recent developments in the rapidly accelerating field of CRISPR-mediated genome engineering. We begin with an overview of the canonical function of the CRISPR platform, followed by a functional review of its many adaptations, with an emphasis on its applications for genetic interrogation of the normal and diseased nervous system. Additionally, we discuss limitations of the CRISPR editing system and suggest how future modifications to existing platforms may advance our understanding of the brain. Copyright © 2020 Sandoval et al.Gene-poor, repeat-rich regions of the genome are poorly understood and have been understudied due to technical challenges and the misconception that they are degenerating "junk". Yet multiple lines of evidence indicate these regions may be an important source of variation that could drive adaptation and species divergence, particularly through regulation of fertility. The ∼40 Mb Y chromosome of Drosophila melanogaster contains only 16 known protein-coding genes and is highly repetitive and entirely heterochromatic. Most of the genes originated from duplication of autosomal genes and have reduced nonsynonymous substitution rates, suggesting functional constraint. We devised a genetic strategy for recovering and retaining stocks with sterile Y-linked mutations and combined it with CRISPR to create mutants with deletions that disrupt three Y-linked genes. Two genes, PRY and FDY, had no previously identified functions. We found that PRY mutant males are sub-fertile, but FDY mutant males had no detectable fertility defects. FDY, the newest known gene on the Y chromosome, may have fertility effects that are conditional or too subtle to detect. The third gene, CCY, had been predicted but never formally shown to be required for male fertility. CRISPR-targeting and RNAi of CCY caused male sterility. Surprisingly, however, our CCY mutants were sterile even in the presence of an extra wild-type Y chromosome, suggesting that perturbation of the Y chromosome can lead to dominant sterility. Our approach provides an important step toward understanding the complex functions of the Y chromosome and parsing which functions are accomplished by genes versus repeat elements. Copyright © 2020, Genetics.OBJECTIVES In the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location. METHODS Patients were randomised 11111 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects. RESULTS Thinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects. CONCLUSIONS Sprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results. TRIAL REGISTRATION NUMBER NCT01919164. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.In previous years individuals with tattoos were thought to have a higher rate of mental illness and risk taking behaviour. With the widespread adoption of tattoos in Western countries in recent years this negative association has been questioned. An issue which arises, however, is that "tattooing" is a heterogeneous activity that covers a wide spectrum of designs and motivations. To examine the characteristics of individuals presenting to medicolegal autopsy with "expletive tattoos" 19 individuals with tattoos that contained selected obscene words were compared to controls. Fifteen cases (79%) were found where deaths were classified as unnatural - 7 drug/alcohol related, 5 suicides, 2 accidents and 1 homicide. The decedents had an age range of 21-58 years, mean 39.7 years, with a male to female ratio of 141. Compared to controls there was a significantly increased number of unnatural deaths in the group with expletive tattoos (p  less then  0.01), with a tendency to involve males. This study has shown that expletive tattoos in a forensic context may be associated with unnatural and violent deaths, and that the study of particular subgroups of tattooed individuals may be useful in discerning specific trends that are unclear if "tattoos" are treated as a homogeneous phenomenon. Crown All rights reserved.INTRODUCTION Growing researches have shown that obese/overweight and healthy weight individuals exhibit different neural responses to food-related stimuli. Accordingly, researchers proposed several theories to explain these differences. Hereon, meta-analyses were conducted using activation likelihood estimation (ALE) to verify these theories and specify the reason of overeating from two aspects. MATERIALS AND METHODS Pubmed, Web of Science and Neurosynth were searched for the current study and screened according to inclusion criteria. Firstly, neural responses to visual food cues versus non-food images were compared between obese/overweight and healthy weight individuals. Then, neural activation to high-calorie food images versus low-calorie food/non-food visual stimuli was further investigated among the two populations. Coordinates in included studies were recorded and analysed by Ginger ALE software under threshold at uncorrected p less then 0.001 with cluster-level p less then 0.05 (cFWE). RESULTS Eleven and seven studies were found in the first and second set of meta-analysis, respectively. The first meta-analysis showed that obese/overweight have hyper-responsivity in reward area and hypo-responsivity in both gustatory processing and inhibitory control area. The second meta-analysis indicated that the reward responsivity in the obese/overweight individuals was amplified and healthy weight individuals had higher activation in areas associated with gustatory processing in response to high-calorie food images. CONCLUSIONS Our results showed that the obese/overweight exhibit hyper-responsivity in brain regions involved in reward processing for visual food cue which provide strong support for incentive-sensitization theory of obesity and healthy weight individuals showed higher response in inhibitory control region which support the inhibitory control deficit theory of obesity. The native community Shonori is made up of Ashaninka families of the Peruvian Amazon. This paper addresses community health through an assessment and nursing care plan based on the Purnell cultural competency model and the standardized nurse taxonomy (NANDA, NIC, NOC). The assessment is based on 12 domains related to inheritance and biocultural ecology, communication, roles and family organization, risk behaviours, nutrition, pregnancy, death and spirituality rituals, and health care providers and practices. A diagnosis of «Poor health of the community r /t insufficient resources m/b health problems suffered by the community» is detected. The expected results criteria in the care plan are social competence, community health status and control of social risk related to communicable diseases. The interventions consist of promoting community health, analyzing and identifying the health situation and risks, and controlling and protecting from communicable diseases and environmental risks. Interventions of the public water supply network and subsidies for agricultural and housing support, allowed vectors to be reduced, costs of safe water supply to be covered, and food to be bought to improve child nutrition. The use of traditional medicine was enhanced and health and sexual education campaigns were carried out in coordination with the official health system. A follow-up was carried out for 40 days, corroborating the improvement of community health, and the need for a group approach with all actors.