Molecular Dynamic Simulation Model for the Growth of Thin Films in The Structure Zone Model

A two dimensional molecular dynamic (atomistic) simulation model was used to investigate the relationship between the nano-structure and the deposition parameters; namely, substrate temperature, deposition rate, angle of incidence, surface roughness. Qualitative agreements with the predictions of the structure zone model (SZM) and the theoretical results of Srolovitze and coworkers (1988), as well as expectations through changes in the activated processes during film growth due to changes in deposition parameters (Grovenor and coworkers (1984)) are obtained. It is shown that by enhancing the atomic mobility (i.e., increasing the substrate temperature or/and lowering the deposition rate) films of higher density with fewer voids are produced. By increasing the deposition angle, the nano-structure of the film changes from a dense film with few voids, to a nano-structure with columns/boundless inclined with the same angle ( β ) towards the incidence atoms with elongated voids. The angle β increases with increasing the deposition angle (α ), and in agreement with the tangent rule (Dirks and Leamy (1977)). The angle of bundles (or the angle of the formation of the voids between atomic bundles), and columnar structure are caused by shadowing effects. Results showed that β decreases slowly with increasing surface mobility (i.e., increasing the substrate temperature or/and reducing the deposition rate). In general, the model provides almost all predicted results and agrees well with observation

Impairment of cerebrovascular hemodynamics in patients with severe and milder forms of sickle cell disease

In patients with sickle cell disease (SCD), cerebral blood flow (CBF) is elevated to counteract anemia and maintain oxygen supply to the brain. This may exhaust the vasodilating capacity of the vessels, possibly increasing the risk of silent cerebral infarctions (SCI). To further investigate cerebrovascular hemodynamics in SCD patients, we assessed CBF, arterial transit time (ATT), cerebrovascular reactivity of CBF and ATT (CVRCBF and CVRATT) and oxygen delivery in patients with different forms of SCD and matched healthy controls. We analyzed data of 52 patients with severe SCD (HbSS and HbS beta(0)-thal), 20 patients with mild SCD (HbSC and HbS beta(+)-thal) and 10 healthy matched controls (HbAA and HbAS). Time-encoded arterial spin labeling (ASL) scans were performed before and after a vasodilatory challenge using acetazolamide (ACZ). To identify predictors of CBF and ATT after vasodilation, regression analyses were performed. Oxygen delivery was calculated and associated with hemoglobin and fetal hemoglobin (HbF) levels. At baseline, severe SCD patients showed significantly higher CBF and lower ATT compared to both the mild SCD patients and healthy controls. As CBFpostACZ was linearly related to CBFpreACZ, CVRCBF decreased with disease severity. CVRATT was also significantly affected in severe SCD patients compared to mild SCD patients and healthy controls. Considering all groups, women showed higher CBFpostACZ than men (p < 0.01) independent of baseline CBF. Subsequently, post ACZ oxygen delivery was also higher in women (p < 0.05). Baseline, but not post ACZ, GM oxygen delivery increased with HbF levels. Our data showed that baseline CBF and ATT and CVRCBF and CVRATT are most affected in severe SCD patients and to a lesser extent in patients with milder forms of SCD compared to healthy controls. Cerebrovascular vasoreactivity was mainly determined by baseline CBF, sex and HbF levels. The higher vascular reactivity observed in women could be related to their lower SCI prevalence, which remains an area of future work. Beneficial effects of HbF on oxygen delivery reflect changes in oxygen dissociation affinity from hemoglobin and were limited to baseline conditions suggesting that high HbF levels do not protect the brain upon a hemodynamic challenge, despite its positive effect on hemolysis.Neuro Imaging Researc

Supplementation with vitamin D and insulin homeostasis in healthy overweight and obese adults: A randomized clinical trial

Introduction: Hypovitaminosis D which is a frequent problem in overweight and obese individuals, seems to interfere with cells responsible for control of glycemic status. Therefore, the current research intended to study the impact of supplementation with vitamin D on insulin homeostasis among healthy obese and overweight individuals. Methods: The current study was conducted among obese or overweight individuals who had hypovitaminosis D. After separation of participants into two groups, one group received vitamin D pearls (50,000 IU/weekly) for eight weeks, whereas another group received a placebo over the same period. Next, the level of vitamin D, fasting blood sugar (FBS), fasting insulin, Homeostasis Model Assessment 2 for Insulin Resistance (HOMA2-IR), Function of β-cell (HOMA2-β), and Insulin Sensitivity (HOMA2-S) and lipid profile of participants were evaluated. Results: Overall, 67.2 of the participants were female. No considerable difference was observed concerning biochemical parameters among the study groups at baseline. After eight weeks, the mean (SD) level of vitamin D was significantly lower in the placebo group than those in the vitamin D group. (38.6 ± 8.1 vs. 14.9 ± 6.4; P < 0.001). The patients who received vitamin D had significant lower levels of FBS (P < 0.001), fasting insulin (P < 0.001), HOMA2-IR (P < 0.001), and HOMA2-β (P = 0.03), than the placebo group. The HOMA2-S was significantly enhanced in vitamin D group, while it reduced in another group (P < 0.001). However, no considerable decrease was found in triglyceride, cholesterol, high-density lipoprotein or low-density lipoprotein. Conclusion: Supplementation with vitamin D improved sensitivity to insulin and pancreatic function of β cells of healthy overweight and obese adults. © 2021 Asia Oceania Association for the Study of Obesit

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders. [Display omitted] We identified genetic variants of HNRNPC in 13 individuals with intellectual disability and global developmental delay. Through a meta-analysis of multiple cell types, we found that loss of HNRNPC affects alternative splicing, in particular of intellectual disability-associated genes. In vivo assays confirmed that neurodevelopment was affected by aberrant HNRNPC levels