Bergpeters2610

Synaptotagmins belong to a large family of proteins. Although various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1-10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR, qPCR, and in situhybridization, focusing on the family members whose products likely underlie Ca2+ -dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5, and 7). Most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafish syt1, syt2, syt5, and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ -dependent processes in different retinal neurons.

The proton resonance frequency (PRF)-based thermometry uses heating-induced phase variations to reconstruct magnetic resonance (MR) temperature maps. However, the measurements of the phase differences may be corrupted by the presence of fat due to its phase being insensitive to heat. The work aims to reconstruct the PRF-based temperature maps for tissues containing fat.

This work proposes a PRF-based method that eliminates the fat's phase contribution by estimating the temperature-insensitive fat vector. A vector in a complex domain represents a given voxel's magnetization from an acquired, complex MR image. In this method, a circle was fit to a time series of vectors acquired from a heated region during a heating experiment. The circle center served as the fat vector, which was then subtracted from the acquired vectors, leaving only the temperature-sensitive vectors for thermal mapping. This work was verified with the gel phantoms of 10%, 15%, and 20% fat content and the ex vivo phantom of porcine abdomeRF-based method can improve the accuracy of the temperature measurements in tissues with fat, such as breast, abdomen, prostate, and bone marrow.Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP- and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1- and NOS-immunoreactive neurons, respectively, were also co-localized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were co-localized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

Catastrophic health expenditure (CHE) is a reliable measure of the financial unpreparedness of the studied population to meet unexpected health issues. The alarming proportion of patients who incur CHE in the wake of an acute neurological illness like Guillain Barre Syndrome (GBS) is of serious concern in a country like India where a large majority of households are uninsured.

Medical records of patients diagnosed with at a tertiary care centre in Delhi were analysed retrospectively to determine the rate of CHE. Clinical details and other contributory variables were also recorded.

53 patients with a median age of 29years (10.5-46.5) were included in the study. Tow- third of patients were less than 40years of age and 58.5% were male. 90.6% of patients incurred CHE with a median amount INR 273300spent out of pocket.

The enormous magnitude of financial distress and crisis emerging out of an acute neurological illness needs to be addressed with urgency to prevent impoverishment of already weakened households.

The enormous magnitude of financial distress and crisis emerging out of an acute neurological illness needs to be addressed with urgency to prevent impoverishment of already weakened households.Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)‑32‑5p in PAAD cells. miR‑32‑5p mimic and inhibitor were used to transfect the human PAAD AsPC‑1 cell line to determine the role of miR‑32‑5p in cell proliferation and metastasis. The starBase database predicted the binding of miR‑32‑5p to the target gene TBC/LysM‑associated domain containing 1 (TLDC1). Further analyses were performed to assess miR‑32‑5p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR‑32‑5p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR‑32‑5p and TLDC1 was verified using the dual‑luciferase reporter assay. miR‑32‑5p and TLDC1 expression levels were detected by reverse transcription‑quantitative PCR and western blotting, respective, the present study demonstrated that miR‑32‑5p may serve as a tumor‑suppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. DBZ inhibitor cost Therefore, miR‑32‑5p may serve as a potential diagnostic or prognostic marker for PAAD.Pulmonary arterial hypertension (PAH) is a severe vascular disease that adversely affects patient health and can be life threatening. The present study aimed to investigate the detailed role of nuclear paraspeckle assembly transcript 1 (NEAT1) in PAH. Using RT‑qPCR, the expression levels of NEAT1, microRNA (miR)‑34a‑5p, and Krüppel‑like factor 4 (KLF4) were detected in both hypoxia‑treated pulmonary arterial smooth muscle cells (PASMCs) and serum from PAH patients. Then, the interactions among miR‑34a‑5p, NEAT1, and KLF4 were evaluated by dual‑luciferase reporter assay. The detailed role of the NEAT1/miR‑34a‑5p/KLF4 axis in PAH pathogenesis was further explored using MTT, Transwell, and western blot assays. The results revealed that NEAT1 targeted miR‑34a‑5p and miR‑34a‑5p targeted KLF4. In hypoxia‑treated PASMCs and serum from PAH patients, high NEAT1 and KLF4 expression levels and low miR‑34a‑5p expression were observed. The proliferation and migration of hypoxia‑treated PASMCs were reduced by transfection with sh‑NEAT1 or miR‑34a‑5p mimics. The suppressive effects of NEAT1 knockdown on the proliferation and migration of hypoxia‑treated PASMCs were reversed by knock down of miR‑34a‑5p expression and increased KLF4 expression. NEAT1 was not only highly expressed in the serum of PAH patients but its silencing also alleviated PAH by regulating miR‑34a‑5p/KLF4 in vitro. The present study highlighted a potential new therapeutic target and diagnostic biomarker for PAH.Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload‑induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload‑induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload in vitro, followed by co‑treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA‑AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co‑treatment with BAPTA‑AM. Moreover, BAPTA‑AM suppressed iron influx into chondrocytes and inhibited iron overload‑induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism‑related diseases and iron overload‑induced OA progression.The autophagy‑lysosome system allows cells to adapt to environmental changes by regulating the degradation and recycling of cellular components, and to maintain homeostasis by removing aggregated proteins and defective organelles. Cyclin G‑associated kinase (GAK) is involved in the regulation of clathrin‑dependent endocytosis and cell cycle progression. In addition, a single nucleotide polymorphism at the GAK locus has been reported as a risk factor for Parkinson's disease. However, the roles of GAK in the autophagy‑lysosome system are not completely understood, thus the present study aimed to clarify this. In the present study, under genetic disruption or chemical inhibition of GAK, analyzing autophagic flux and observing morphological changes of autophagosomes and autolysosomes revealed that GAK controlled lysosomal dynamics via actomyosin regulation, resulting in a steady progression of autophagy. GAK knockout (KO) in A549 cells impaired autophagosome‑lysosome fusion and autophagic lysosome reformation, which resulted in the accumulation of enlarged autophagosomes and autolysosomes during prolonged starvation.