Activity

Overall, we demonstrate that the dynamics of multiple electrophysiological variables exhibit distinct relationships between their spontaneous and evoked activity, a result which carries implications for experimental design and analysis in non-invasive electrophysiology.

Obesity, one of the most common chronic health conditions worldwide, is a multifactorial disease caused by complex genetic and environmental interactions. Several association studies have revealed a considerable number of candidate loci for obesity; however, the genotype-phenotype correlations remain unclear. To date, no comprehensive systematic review has been conducted to investigate the genetic risk factors for obesity among Arabs.

This study aimed to systematically review the genetic polymorphisms that are significantly associated with obesity in Arabs.

We searched four literature databases (PubMed, Science Direct, Scopus, and Google Scholar) from inception until May 2020 to obtain all reported genetic data related to obesity in Arab populations. Quality assessment and data extraction were performed individually by three investigators.

In total, 59 studies comprising a total of 15,488 cases and 9,760 controls were included in the systematic review. A total of 76 variants located within or near 49 genes were reported to be significantly associated with obesity. Among the 76 variants, two were described as unique to Arabs, as they have not been previously reported in other populations, and 19 were reported to be distinctively associated with obesity in Arabs but not in non-Arab populations.

There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients.

There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients.One of the pathological hallmarks of amyotrophic lateral sclerosis (ALS) is mislocalized, cytosolic aggregation of TAR DNA-Binding Protein-43 (TDP-43). Not only TDP-43 per se is a causative gene of ALS but also mislocalization and aggregation of TDP-43 seems to be a common pathological change in both sporadic and familial ALS. The mechanism how nuclear TDP-43 transforms into cytosolic aggregates remains elusive, but recent studies using optogenetics have proposed that aberrant liquid-liquid phase separation (LLPS) of TDP-43 links to the aggregation process, leading to cytosolic distribution. Although LLPS plays an important role in the aggregate formation, there are still several technical problems in the optogenetic technique to be solved to progress further in vivo study. Here we report a chemically oligomerizable TDP-43 system. Oligomerization of TDP-43 was achieved by a small compound AP20187, and oligomerized TDP-43 underwent aggregate formation, followed by cytosolic mislocalization and induction of cell toxicity. The mislocalized TDP-43 co-aggregated with wt-TDP-43, Fused-in-sarcoma (FUS), TIA1 and sequestosome 1 (SQSTM1)/p62, mimicking ALS pathology. The chemically oligomerizable TDP-43 also revealed the roles of the N-terminal domain, RNA-recognition motif, nuclear export signal and low complexity domain in the aggregate formation and mislocalization of TDP-43. The aggregate-prone properties of TDP-43 were enhanced by a familial ALS-causative mutation. In conclusion, the chemically oligomerizable TDP-43 system could be useful to study the mechanisms underlying the droplet-aggregation phase transition and cytosolic mislocalization of TDP-43 in ALS and further study in vivo.Lévy walks describe patterns of intermittent motion with variable step sizes. In complex biological systems, Lévy walks (non-Brownian, superdiffusive random walks) are associated with behaviors such as search patterns of animals foraging for food. Here we show that Lévy walks also describe patterns of oscillatory activity in primate cerebral cortex. We used a combination of empirical observation and modeling to investigate high-frequency (gamma band) local field potential activity in visual motion-processing cortical area MT of marmoset monkeys. We found that gamma activity is organized as localized burst patterns that propagate across the cortical surface with Lévy walk dynamics. SNS-032 solubility dmso Lévy walks are fundamentally different from either global synchronization, or regular propagating waves, because they include large steps that enable activity patterns to move rapidly over cortical modules. The presence of Lévy walk dynamics therefore represents a previously undiscovered mode of brain activity, and implies a novel way for the cortex to compute. We apply a biophysically realistic circuit model to explain that the Lévy walk dynamics arise from critical-state transitions between asynchronous and localized propagating wave states, and that these dynamics yield optimal spatial sampling of the cortical sheet. We hypothesise that Lévy walk dynamics could help the cortex to efficiently process variable inputs, and to find links in patterns of activity among sparsely spiking populations of neurons.Ischemia reperfusion (IR) injury plays a pivotal role in many diseases and leads to collateral damage during surgical interventions. While most studies focus on alleviating its severity in the context of brain, liver, kidney, and cardiac tissue, research as regards to skeletal muscle has not been conducted to the same extent. In the past, myostatin (MSTN), primarily known for supressing muscle growth, has been implicated in inflammatory circuits, and research provided promising results for cardiac IR injury mitigation by inhibiting MSTN cell surface receptor ACVR2B. This generated the question if interrupting MSTN signaling could temper IR injury in skeletal muscle. Examining human specimens from free myocutaneous flap transfer demonstrated increased MSTN signaling and tissue damage in terms of apoptotic activity, cell death, tissue edema, and lipid peroxidation. In subsequent in vivo MstnLn/Ln IR injury models, we identified potential mechanisms linking MSTN deficiency to protective effects, among others, inhibition of p38 MAPK signaling and SERCA2a modulation. Furthermore, transcriptional profiling revealed a putative involvement of NK cells. Collectively, this work establishes a protective role of MSTN deficiency in skeletal muscle IR injury.