Kimacosta2247

Anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) is a B cell- and antibody-mediated autoimmune disease which may be regulated by CD40/CD40L signaling pathway. we enrolled anti-NMDARE patients and measured the serum CD40 and CD40L concentrations. The serum concentration of CD40 was decreased, while CD40L was increased in anti-NMDARE patients compared with that of healthy controls. The concentrations of CD40 and CD40L were both elevated in the acute stage of anti-NMDARE and were reduced during remission. Serum CD40L levels were positively correlated with serum CD40 levels. These results revealed that the CD40/CD40L signaling pathway might contribute to the pathogenesis of anti-NMDARE.Whole-brain segmentation is a crucial pre-processing step for many neuroimaging analyses pipelines. Accurate and efficient whole-brain segmentations are important for many neuroimage analysis tasks to provide clinically relevant information. Several recently proposed convolutional neural networks (CNN) perform whole brain segmentation using individual 2D slices or 3D patches as inputs due to graphical processing unit (GPU) memory limitations, and use sliding windows to perform whole brain segmentation during inference. However, these approaches lack global and spatial information about the entire brain and lead to compromised efficiency during both training and testing. We introduce a 3D hemisphere-based CNN for automatic whole-brain segmentation of T1-weighted magnetic resonance images of adult brains. First, we trained a localization network to predict bounding boxes for both hemispheres. Then, we trained a segmentation network to segment one hemisphere, and segment the opposing hemisphere by reflecting it across the mid-sagittal plane. Our network shows high performance both in terms of segmentation efficiency and accuracy (0.84 overall Dice similarity and 6.1 mm overall Hausdorff distance) in segmenting 102 brain structures. On multiple independent test datasets, our method demonstrated a competitive performance in the subcortical segmentation task and a high consistency in volumetric measurements of intra-session scans.Alterations in neuromodulation or synaptic transmission in biophysical attractor network models, as proposed by the dominant dopaminergic and glutamatergic theories of schizophrenia, successfully mimic working memory (WM) deficits in people with schizophrenia (PSZ). Yet, multiple, often opposing alterations in memory circuits can lead to the same behavioral patterns in these network models. Here, we critically revise the computational and experimental literature that links NMDAR hypofunction to WM precision loss in PSZ. We show in network simulations that currently available experimental evidence cannot set apart competing biophysical accounts. Critical points to resolve are the effects of increases vs. decreases in E/I ratio (e.g. through NMDAR blockade) on firing rate tuning and shared noise modulations and possible concomitant deficits in short-term plasticity. We argue that these concerted experimental and computational efforts will lead to a better understanding of the neurobiology underlying cognitive deficits in PSZ.Low-frequency deep brain stimulation (LFS) inhibits neuronal hyperexcitability during epilepsy. Accordingly, the use of LFS as a treatment method for patients with drug-resistant epilepsy has been proposed. However, the LFS antiepileptic mechanisms are not fully understood. Here, the role of metabotropic glutamate receptors group I (mGluR I) in LFS inhibitory action on epileptiform activity (EA) was investigated. EA was induced by increasing the K+ concentration in artificial cerebrospinal fluid (ACSF) up to 12 mM in hippocampal slices of male Wistar rats. LFS (1 Hz, 900 pulses) was delivered to the bundles of Schaffer collaterals at the beginning of EA. The excitability of CA1 pyramidal neurons was assayed by intracellular whole-cell recording. Applying LFS reduced the firing frequency during EA and substantially moved the membrane potential toward repolarization after a high-K+ ACSF washout. In addition, LFS attenuated the EA-generated neuronal hyperexcitability. A blockade of both mGluR 1 and mGluR 5 prevented the inhibitory action of LFS on EA-generated neuronal hyperexcitability. Activation of mGluR I mimicked the LFS effects and had similar inhibitory action on excitability of CA1 pyramidal neurons following EA. However, mGluR I agonist's antiepileptic action was not as strong as LFS. The observed LFS effects were significantly attenuated in the presence of a PKC inhibitor. Altogether, the LFS' inhibitory action on neuronal hyperexcitability following EA relies, in part, on the activity of mGluR I and a PKC-related signaling pathway.

The gut-brain axis has been discussed as a possible factor contributing to ictogenesis and epilepsy. While recent preclinical studies have proposed a link between the antiseizure effect of a ketogenic diet (KD) and alterations to the gut microbiota, there is a knowledge gap about microbial composition as a result of Scn1a genetic deficiency and how this is affected by KD in Dravet syndrome.

A large-scale microbiome analysis using 16S rRNA gene sequencing was performed in fecal samples collected from wildtype and Dravet mice fed either control diet (CD) or KD. find more Microbial alterations associated with the Dravet phenotype or triggered by KD exposure were identified.

The comprehensive microbial analysis revealed pronounced alterations in gut microbiota between wildtype and Dravet mice. The regulation of Chao index indicated a reduced species richness in Dravet mice when compared to wildtype controls. The ratio between Firmicutes and Bacteroidetes phyla was increased in mice with the Dravet genotype, therefore-triggered changes would be essential to confirm the relevance of these findings.

In conclusion, the comprehensive microbial analysis demonstrated pronounced alterations in the gut microbiota with evidence of a gut dysbiosis as a consequence of the Scn1a genetic deficiency. Exposure to KD affected the gut microbiome in Dravet mice. Interestingly, abundance of selected genera correlated with the seizure phenotype of Dravet mice. Future studies investigating the functional relevance of disease-associated and KD-triggered changes would be essential to confirm the relevance of these findings.Exercise responses and injury rates differ between individual hamstrings and this may be linked with their morphology. The aim of this study was to compare muscle length and tendon dimensions between the individual hamstrings at two knee joint angles using free hand three-dimensional ultrasound (3D US). Muscle-tendon length and distal tendon cross-sectional area (CSA), volume, length and echogenicity of biceps femoris long (BFlh) and short (BFsh) head, semimembranosus (SM) and semitendinosus (ST) of 16 individuals were measured using free-hand 3D US at 0° (full extension) and 45° of knee flexion. ST showed the greatest length than all muscles and BFsh the lowest (p 0.05). Freehand 3D US indicated that hamstring muscle length and distal tendon dimensions differ between individual hamstrings. All muscles and tendons lengthened as the knee was extended but this change was similar for all individual hamstrings.

Preferential expression of receptors for TNF-family related apoptosis inducing ligand (TRAIL), DR4 and DR5 makes TRAIL an attractive anti-cancer therapeutic. However, the efficacy of targeting death receptors has not been extensively studied in nasopharyngeal cancer (NPC). Here we investigated TRAIL sensitivity and its underlying mechanism in NPC cell lines, and assessed the potential of TRAIL as a therapeutic option against NPC.

Using two established NPC cell lines, we report the expression of DR4 and DR5, which respond to TRAIL ligation by triggering efficient Type II apoptosis. Mechanistically, early activation of caspase-3 and its membrane recruitment is identified in NPC cell lines, which is associated with, hitherto unreported, interaction with transmembrane and tetratricopeptide repeat containing 2 (TMTC2) in the lipid raft domains. TMTC2 expression is induced upon exposure to TRAIL and involves intracellular increase in peroxynitrite (ONOO

) production. While ONOO

increase is downstream of caspase-8 activation, it is involved in the upregulation of TMTC2, gene knockdown of which abrogated TRAIL-induced apoptotic execution. Bioinformatics analyses also provide evidence for a strong correlation between TMTC2 and DR4 or caspase-3 as well as a significantly better disease-free survival in patients with high TMTC2 expression.

Collectively, redox-dependent execution of NPC cells upon ligation of TRAIL receptors reintroduces the possible therapeutic use of TRAIL in NPC as well as underscores the potential of using TMTC2 as a biomarker of TRAIL sensitivity.

Collectively, redox-dependent execution of NPC cells upon ligation of TRAIL receptors reintroduces the possible therapeutic use of TRAIL in NPC as well as underscores the potential of using TMTC2 as a biomarker of TRAIL sensitivity.Column experiments were conducted to investigate the effects of ion type, ion strength, humic acid (HA), and nanometer alumina (NA) particles on the transport of hexavalent chromium (HC) in saturated porous media. A one-dimensional model is developed to simulate the migration of HC affected by NA particles. link2 The results show that nano-alumina particles would enhance the mobility of HC in saturated porous media. However, the influence of NA on the migration of HC in porous media is complex. When the concentration of NA reaches 30 mg/L, HC has minimum retention parameter and best mobility. The transport of HC also is affected by ion strength and ion type. Higher ionic strength would decrease the retention of HC and enhance its mobility. Compared with sodium ion, calcium ion has larger effects on the transport of HC. Moreover, HA can improve the mobility of HC in saturated porous media, but the corresponding promoting effect decreases with the increase of HA concentration. As nanometer contaminants and HC come into the subsurface environment, findings from this study elucidate the key factors and processes controlling the transport of HC in porous media, which can promote the prediction and assessment of HC in the groundwater system.Oil spill clean-up measures using in situ burning can potentially result in seafloor contamination affecting benthic organisms. To mimic realistic exposure and measure effects, ovigerous Northern shrimp were continuously exposed for two weeks to the water-soluble fraction of oil coated on gravel followed by two weeks in clean seawater. North Sea crude oil (NSC) and field generated in situ burn residue (ISBR) of NSC were used (Low 3 g/kg gravel, Medium 6 g/kg gravel and High 12 g/kg gravel). The concentrations of polyaromatic hydrocarbons (PAHs) in the water resulting from NSC were higher compared to ISBR. link3 No mortality was observed in any treatment and overall moderate sublethal effects were found, mostly after exposure to NSC. Feeding was temporarily reduced at higher concentrations of NSC. PAH levels in hepatopancreas tissue were significantly elevated following exposure and still significantly higher at the end of the experiment in NSCHigh and ISBRHigh compared to control. Mild inflammatory response reactions and tissue ultrastructural alterations in gill tissue were observed in both treatments.