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Furthermore,
disruption did not affect apoptosis in early cortical organoids. After re-expressing wild-type STAMBP, STAMBP
, and STAMBP
(a known pathogenic mutation) within
KO organoids, only STAMBP
rescued the impaired proliferation of
deficient organoids, but not STAMBP
and STAMBP
.
Our findings demonstrate that the clinical phenotype of
mutations is highly variable, and patients with different
mutations show differences in the severity of symptoms. The
missense mutation identified here is a novel pathogenic mutation that impairs the proliferation of NSCs in human brain development.
Our findings demonstrate that the clinical phenotype of STAMBP mutations is highly variable, and patients with different STAMBP mutations show differences in the severity of symptoms. The STAMBP missense mutation identified here is a novel pathogenic mutation that impairs the proliferation of NSCs in human brain development.Pro-opiomelanocortin (POMC)-expressing neurons in the hypothalamic arcuate nucleus (ARC) play key roles in feeding and energy homoeostasis, hence their development is of great research interest. As the process of neurogenesis is accompanied by changes in adhesion, polarity, and migration that resemble aspects of epithelial-to-mesenchymal transitions (EMTs), we have characterised the expression and regulation within the prospective ARC of transcription factors with context-dependent abilities to regulate aspects of EMT. Informed by pseudotime meta-analysis of recent scRNA-seq data, we use immunohistochemistry and multiplex in situ hybridisation to show that SOX2, SRY-Box transcription factor 9 (SOX9), PROX1, Islet1 (ISL1), and SOX11 are sequentially expressed over the course of POMC neurogenesis in the embryonic chick. Through pharmacological studies ex vivo, we demonstrate that while inhibiting either sonic hedgehog (SHH) or Notch signalling reduces the number of SOX9+ neural progenitor cells, these treatments lead, respectively, to lesser and greater numbers of differentiating ISL1+/POMC+ neurons. These results are consistent with a model in which SHH promotes the formation of SOX9+ progenitors, and Notch acts to limit their differentiation. Both pathways are also required to maintain normal levels of proliferation and to suppress apoptosis. Together our findings demonstrate that hypothalamic neurogenesis is accompanied by dynamic expression of transcription factors (TFs) that mediate EMTs, and that SHH and Notch signalling converge to regulate hypothalamic cellular homoeostasis.Obesity and hyperglycemia are risk factors for cognitive decline and for the development of Alzheimer's Disease (AD). Bariatric surgery is an effective treatment for obesity that was shown to improve cognitive decline in obese patients. Bariatric surgery was shown to exert weight loss independent effects on metabolic diseases such as type 2 diabetes. We tested whether sleeve gastrectomy (SG), a common bariatric surgery, can affect the cognitive impairment in lean, normoglycemic female 5xFAD mice, a genetic model for AD. 5xFAD mice and wild-type (WT) littermates underwent SG or sham surgery at the age of 5 months and were tested for metabolic, behavioral, and molecular phenotypes 90 days later. SG led to a reduction in blood glucose levels and total plasma cholesterol levels in 5xFAD mice without inducing weight loss. However, the surgery did not affect the outcomes of long-term spatial memory tests in these mice. Analysis of β-Amyloid plaques corroborated the behavioral studies in showing no effect of surgery on the molecular phenotype of 5xFAD mice. In conclusion, SG leads to an improved metabolic profile in lean female 5xFAD mice without inducing weight loss but does not affect the brain pathology or behavioral phenotype. Our results suggest that the positive effects of bariatric surgery on cognitive decline in obese patients are likely attributed to weight loss and improvement in obesity sequelae, and not to weight loss independent effects of surgery.Type 2 diabetes (T2D) is the most common comorbidity of COVID-19, and both are related to the lack of circulating melatonin. In addition, chronic pain is a common sequela of both COVID-19 and T2D. Using a neuropathic pain model produced by sciatic nerve chronic constriction injury in Zucker diabetic fatty rats, a verified preclinical genetic T2D neuropathy animal model, this study aimed to show that transcutaneous auricular vagal nerve stimulation (taVNS) could elevate plasma melatonin concentration, upregulate the expression of melatonin receptors (MTRs) in the amygdala, and relieve peripheral neuropathic pain. Furthermore, taVNS would restore melatonin levels and relieve pain even in pinealectomized rats. On the contrary, intraperitoneally injected luzindole, a melatonin receptor antagonist, would attenuate the antinociceptive effects of taVNS. In conclusion, the mechanism of the therapeutic effect of taVNS on chronic pain involves the release of extrapineal melatonin and the positive regulation of the expression of central MTRs. This beneficial efficacy should be considered during COVID-19 rehabilitation in individuals with diabetes.
This study aimed to explore the electrophysiological characteristics of resting-state electroencephalography (rsEEG) in patients with visuospatial neglect (VSN) after stroke.
A total of 44 first-event sub-acute strokes after right hemisphere damage (26 with VSN and 18 without VSN) were included. Besides, 18 age-matched healthy participants were used as healthy controls. The resting-state electroencephalography (EEG) of 64 electrodes was recorded to obtain the power of the spectral density of different frequency bands. The global delta/alpha ratio (DAR), DAR over the affected hemispheres (DAR
), DAR over the unaffected hemispheres (DAR
), and the pairwise-derived brain symmetry index (pdBSI; global and four bands) were compared between groups and receiver operating characteristic (ROC) curve analysis was conducted. The Barthel index (BI), Fugl-Meyer motor function assessment (FMA), and Berg balance scale (BBS) were used to assess the functional state of patients. Visuospatial neglect was assessed using atask (
= 0.442,
= 0.024).
rsEEG may be a useful tool for screening for stroke patients with visuospatial neglect, and DAR and parieto-occipital pdBSI
may be useful biomarkers for visuospatial neglect after stroke.
rsEEG may be a useful tool for screening for stroke patients with visuospatial neglect, and DAR and parieto-occipital pdBSIalpha may be useful biomarkers for visuospatial neglect after stroke.Multimodal medical image fusion (MMIF) has been proven to effectively improve the efficiency of disease diagnosis and treatment. However, few works have explored dedicated evaluation methods for MMIF. This paper proposes a novel quality assessment method for MMIF based on the conditional generative adversarial networks. First, with the mean opinion scores (MOS) as the guiding condition, the feature information of the two source images is extracted separately through the dual channel encoder-decoder. The features of different levels in the encoder-decoder are hierarchically input into the self-attention feature block, which is a fusion strategy for self-identifying favorable features. Then, the discriminator is used to improve the fusion objective of the generator. Finally, we calculate the structural similarity index between the fake image and the true image, and the MOS corresponding to the maximum result will be used as the final assessment result of the fused image quality. buy Uprosertib Based on the established MMIF database, the proposed method achieves the state-of-the-art performance among the comparison methods, with excellent agreement with subjective evaluations, indicating that the method is effective in the quality assessment of medical fusion images.In the seed-based method for studying functional connectivity (FC), seed selection is relevant. Here, we propose a new methodological approach for resting-state FC analysis of hand motor networks using the individual hand motor hotspot (hMHS) as seed. Nineteen right-handed healthy volunteers underwent a transcranial magnetic stimulation (TMS) session and resting-state fMRI. For each subject, the hMHS in both hemispheres was identified by TMS with the contralateral abductor pollicis brevis muscle as the target, the site eliciting the highest and most reliable motor-evoked potentials. Seed regions were built on coordinates on the cortex corresponding to the individual left and right hMHSs. For comparison, the left and right Brodmann's area 4 (BA4) masks extracted from a standard atlas were used as seed. The left and right hMHSs showed FC patterns at rest mainly including sensorimotor regions, with a bilateral connectivity only for the left hMHS. The statistical contrast BA4 > hMHS for both hemispheres showed different extension and lateralization of the functionally connected cortical regions. On the contrary, no voxels survived the opposite contrast (hMHS > BA4). This suggests that detection of individual hand motor seeds by TMS allows to identify functionally connected motor networks that are more specific with respect to those obtained starting from the a priori atlas-based identification of the primary motor cortex.Insider threat from individuals operating within an organization presents a significant source of violations of information security. Our previous research has used scalp recorded event-related brain potentials (ERPs) and the Information Security Paradigm (ISP) to identify the neural correlates of decision-making processes related to violations of information security. In the current study, we sought to expand this research by examining the effects of two variables that were drawn from the broader decision-making literature (i.e., the benefactor and delay of a reward) on ERPs measured in the ISP. In the ISP we varied whether Josh-a hypothetical IT specialist-or a significant other was the benefactor of a violation, and whether the benefit of a violation was received after a short or long delay. The choice data revealed that individuals were less likely to endorse an unethical action than a control action. The electrophysiological data revealed ERPs that differentiated ethical scenarios from control scenarios between 200 and 2,000 ms after onset of the decision prompt, distributed over the occipital, central, and lateral frontal regions of the scalp. These ERPs were insensitive to the benefactor and delay of the reward. In contrast, there was slow wave activity over the frontal-polar region that was sensitive to both variables. The current findings provide evidence for separable neural systems that are either generally related to ethical decision-making in the ISP or are sensitive to the benefactor or delay of a reward resulting from an unethical decision.
Sleep disturbance is commonly reported by menopausal women. Stroke risk and poor stroke outcomes in women have usually been attributed to menopause. This study aimed to investigate the mediating effect of sleep duration on relationship between menopause and risk of stroke in natural menopause women.
A cross-sectional study was performed, and participants were recruited through a multistage, stratified, probability proportional to size sampling method in this research. The stroke risk was measured using the risk assessment form for high-risk stroke population. The average sleep duration was calculated by adding up night sleep and afternoon nap duration. Multivariate regression analysis was conducted to identify the association between menopause, sleep duration, and stroke risk. The direct and indirect effects of menopause on stroke risk were analyzed by using the sleep duration in a mediation framework.
Perimenopause, menopause, average sleep duration, and night sleep duration were significantly associated with stroke risk (
< 0.
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