Liprater1734

We found that treatment of hSOD1

mice with the KCa3.1 inhibitor, TRAM-34 i) attenuates the pro-inflammatory phenotype of hypothalamic microglia; ii) increases food intake and promotes weight gain; iii) increases the number of healthy POMC (pro-opiomelanocortin) neurons; iv) changes the expression of cannabinoid receptors (CB

R), involved in energy homeostasis.

Using ALS mouse models, we describe defects in the hypothalamic melanocortin system that affect appetite control. These results reveal a new regulatory role for KCa3.1 to counteract weight loss in ALS.

Using ALS mouse models, we describe defects in the hypothalamic melanocortin system that affect appetite control. These results reveal a new regulatory role for KCa3.1 to counteract weight loss in ALS.The brain consists of neural circuits, which are assemblies of various neuron types. For understanding how the brain works, it is essential to identify the functions of each type of neuron and neuronal circuits. Recent advances in our understanding of brain function and its development have been achieved using light to detect neuronal activity. Optical measurement of membrane potentials through voltage imaging is a desirable approach, enabling fast, direct, and simultaneous detection of membrane potentials in a population of neurons. Its high speed and directness can help detect synaptic and action potentials and hyperpolarization, which encode critical information for brain function. Here, we describe in vivo voltage imaging procedures that we have recently established using zebrafish, a powerful animal model in developmental biology and neuroscience. By applying two types of voltage sensors, voltage-sensitive dyes (VSDs, Di-4-ANEPPS) and genetically encoded voltage indicators (GEVIs, ASAP1), spatiotemporal dynamics of voltage signals can be detected in the whole cerebellum and spinal cord in awake fish at single-cell and neuronal population levels. Combining this method with other approaches, such as optogenetics, behavioral analysis, and electrophysiology would facilitate a deeper understanding of the network dynamics of the brain circuitry and its development.

Voltage-gated sodium (Na

) channels are expressed de novo in carcinomas where their activity promotes invasiveness. Sunitinib PDGFR inhibitor Breast and colon cancer cells express the neonatal splice variant of Na

1.5 (nNa

1.5) which has several amino acid substitutions in the domain I voltage-sensor compared to its adult counterpart (aNa

1.5). This study aimed to determine whether nNa

1.5 could be distinguished pharmacologically from aNa

1.5.

Cells expressing either nNa

1.5 or aNa

1.5 were exposed to small-molecule inhibitors, an antibody or natural toxins, and changes in electrophysiological parameters were measured. Stable expression in EBNA cells and transient expression in Xenopus laevis oocytes were used. Currents were recorded by whole-cell patch clamp and two-electrode voltage-clamp, respectively.

Several clinically-used blockers of Na

channels (lidocaine, procaine, phenytoin, mexiletine, ranolazine and riluzole) could not distinguish between nNa

1.5 or aNa

1.5. On the other hand, two tarantula toxins (HaTx and ProTx-II) and a polyclonal antibody (NESOpAb) preferentially inhibited currents elicited by either nNa

1.5 or aNa

1.5 by binding to the spliced region of the channel. Furthermore, the amino acid residue at position 211 (aspartate in aNa

1.5/lysine in nNa

1.5), i.e. the charge reversal in the spliced region of the channel, played a key role in the selectivity especially in the antibody binding.

We conclude that the cancer-related nNa

1.5 channel can be distinguished pharmacologically from its nearest neighbour, aNa

1.5. Thus, it may be possible to design small molecules as anti-metastatic drugs for non-toxic therapy of nNa

1.5-expressing carcinomas.

We conclude that the cancer-related nNaV 1.5 channel can be distinguished pharmacologically from its nearest neighbour, aNaV 1.5. Thus, it may be possible to design small molecules as anti-metastatic drugs for non-toxic therapy of nNaV 1.5-expressing carcinomas.

The stillbirth rate for Australian Aboriginal and Torres Strait Islander infants remains higher than non-Indigenous rates. Risks for stillbirth include maternal factors such as ethnicity, age, geographic location, and physical health. Fetal risk factors include gestational age, birthweight and congenital anomalies. The total stillbirth rate for all babies born at the Townsville University Hospital during the study period was 11 per 1000 births.

To identify Aboriginal and Torres Strait Islander stillbirth rates, risk factors and causes in North Queensland.

A retrospective chart audit was conducted to identify Indigenous women who had experienced stillbirth in the Townsville University Hospital between January 2005 and December 2014.

Thirty-two charts were available for audit. The stillbirth rate for non-Indigenous infants was 10.3 per 1000 births. The stillbirth rate for Indigenous infants was 11.7 per 1000 births. Almost half of the women lived in rural, remote or very remote areas. Maternal risk factionals will support culturally responsive care for women and their families to mitigate stillbirth risk and enhance pregnancy outcomes in non-urban Queensland.The Metabolic Syndrome has become one of the major public health challenges in the world, and adjusting the glucose and lipid to the normal level is crucial for treating the Metabolic Syndrome. Olfactory receptors (ORs) expressed in extra-nasal tissues participate in diverse biological processes, including the regulation of glucose and lipid metabolism. Ectopic ORs can regulate insulin secretion, glucagon secretion, fatty acid oxidation, lipogenesis, thermogenesis, and so forth. Understanding the physiological function and deciphering the olfactory recognition code by suitable ligands make ectopic ORs potential targets for the treatment of the Metabolic Syndrome. Thus, we delineate the roles and mechanisms of ectopic ORs in the regulation of glucose and lipid metabolism, summarize the corresponding natural ligands, and discuss existing problems and therapeutic potential of targeting ORs in the Metabolic Syndrome.Surgical-site infections (SSIs) are among the most difficult-to-manage complications after lower extremity total joint arthroplasty (TJA). While the rates of most implant-related complications have decreased over time due to improvements in prosthetic materials and surgical techniques, the incidence of periprosthetic joint infections (PJIs) continues to increase. They place a tremendous economic burden on healthcare systems that is projected to reach $1.8 billion by the year 2030. A number of perioperative infection mitigation strategies exist that are often implemented concurrently to minimize the risk of these complications. A multicenter randomized controlled trial is underway to evaluate the efficacy of a bundled care program for the prevention of PJIs in lower extremity TJA. This bundle includes five infection-reduction strategies that are used pre-, peri-, and postoperatively, including (1) povidone-iodine skin preparation and nasal decolonization; (2) iodine-alcohol surgical prepping solution; (3) iodophor-impregnated incise drapes; (4) forced-air warming blankets; and (5) negative pressure wound therapy for select patients. The aim of this review is to describe these products and their appropriate usage, review the available literature evaluating their use, and compare them with other commercially available products. Based on the available literature, each of these strategies appear to be important components for SSI-prevention protocols. We believe that implementing all five of these mitigation strategies concurrently will lead to a synergistic effect for infection control following lower extremity TJA.The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.Electroencephalogram (EEG) is a common tool used to understand brain activities. The data are typically obtained by placing electrodes at the surface of the scalp and recording the oscillations of currents passing through the electrodes. These oscillations can sometimes lead to various interpretations, depending on, for example, the subject's health condition, the experiment carried out, the sensitivity of the tools used, or human manipulations. The data obtained over time can be considered a time series. There is evidence in the literature that epilepsy EEG data may be chaotic. Either way, the Embedding Theory in dynamical systems suggests that time series from a complex system could be used to reconstruct its phase space under proper conditions. In this letter, we propose an analysis of epilepsy EEG time series data based on a novel approach dubbed complex geometric structurization. Complex geometric structurization stems from the construction of strange attractors using Embedding Theory from dynamical systems. The complex geometric structures are themselves obtained using a geometry tool, the α-shapes from shape analysis. Initial analyses show a proof of concept in that these complex structures capture the expected changes brain in lobes under consideration. Further, a deeper analysis suggests that these complex structures can be used as biomarkers for seizure changes.The Potjans-Diesmann cortical microcircuit model is a widely used model originally implemented in NEST. Here, we reimplemented the model using NetPyNE, a high-level Python interface to the NEURON simulator, and reproduced the findings of the original publication. We also implemented a method for scaling the network size that preserves first- and second-order statistics, building on existing work on network theory. Our new implementation enabled the use of more detailed neuron models with multicompartmental morphologies and multiple biophysically realistic ion channels. This opens the model to new research, including the study of dendritic processing, the influence of individual channel parameters, the relation to local field potentials, and other multiscale interactions. The scaling method we used provides flexibility to increase or decrease the network size as needed when running these CPU-intensive detailed simulations. Finally, NetPyNE facilitates modifying or extending the model using its declarative language; optimizing model parameters; running efficient, large-scale parallelized simulations; and analyzing the model through built-in methods, including local field potential calculation and information flow measures.