Investigation of defect levels in BaSi2 epitaxial films by photoluminescence and the effect of atomic hydrogen passivation

Photoluminescence (PL) measurements were carried out on 0.5-μm thick BaSi2 epitaxial films grown on Si(111) substrates with various Ba-to-Si deposition rate ratios (R Ba/R Si) in the range of 1.7–5.1. The samples were excited from both the frontside (BaSi2) and the backside (Si substrate), at temperatures in the range of 8–50 K. These measurements have highlighted the existence of localized states within the bandgap that result from defects in the BaSi2 films. The PL intensity is highly dependent on the excitation power, temperature, and R Ba/R Si. Of those studied, the BaSi2 film at R Ba/R Si = 4.0 showed the most intense PL and weak photoresponsivity, whereas the PL intensity was weaker for the other samples. Therefore, we chose this sample for a detailed PL investigation. Based on the results we determined the energy separation between localized states, corresponding to PL peak energies. The difference in PL spectra excited from the BaSi2-side and Si-side is attributed to the difference in kinds of defects emitting PL. The photoresponsivity of the BaSi2 was drastically enhanced by atomic hydrogen passivation, and the PL intensity of the sample decreased accordingly

Detection of local vibrational modes induced by intrinsic defects in undoped BaSi2 light absorber layers using Raman spectroscopy

We fabricate BaSi2 epitaxial films on Si(111) substrates by molecular beam epitaxy and investigate point defects inside the films using Raman spectroscopy with the help of first-principles calculation. Point defects such as Ba substituted for Si antisites, Si vacancies, and Si interstitials are considered as candidates for native point defects in BaSi2. Vibration analysis based on first-principles calculation suggests that local vibrational modes caused by these point defects appear at around 430, 480, and 560 cm−1, respectively, and are in good agreement with Raman peak positions. Comparing calculations with Raman spectra of the films formed with different Ba to Si deposition rate ratios RBa/RSi from 1.0 to 5.1, we conclude that the density of point defects reaches a minimum at RBa/RSi = 2.2. Furthermore, the position of Raman peaks at approximately 490 cm−1 shifts to a lower wavenumber, depending on RBa/RSi and thereby the density of point defects

SC-01RalA IN BIOLOGY AND THERAPY OF MPNST IN CORRELATION TO CANCER STEM CELLS

For the last 20 years, cellular biologists have been focusing on the role of Ras signaling pathway in neurofibromatosis 1(NF1) and its lethal derivation, malignant peripheral nerve sheath tumors (MPNST). While our team has worked on the influence of Ras pathway on responsiveness of MPNST cells to therapy, we introduced a novel cell signaling pathway down-stream of Ras, i.e. Ral pathway, as an important regulator of the biological features of MPNST with potentials for being targeted for treatment of this malignancy. We have also showed that RalA is overactivated in the cancer stem cell (CSC) fraction of MPNST tumors establishing this pathway to harbor potentials for targeting MPNST CSCs. In summary our preliminary data shed light on following facts: 1- RalA signaling pathway is overactivated in differentiated MPNST cells and human tissues. 2- RalA overactivation is a characteristic of MPNST cancer stem cells. 3- RalA inhibition hinders the malignant phenotype of MPNST cells. 4- Disruption of RalA signaling results in loss of viability and invasion of MPNST cells. In this presentation, we further evaluate the mechanism of RalA overactivation and in-vivo potentials of its inhibition as a therapeutic strategy for MPNST

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Population structure of two closely related pelagic cichlids in Lake Victoria, Haplochromis pyrrhocephalus and H. laparogramma

Cichlid fishes in Lake Victoria show spectacular diversification that is thought to be recent. Therefore, by investigating those fishes, we may be able to elucidate recently completed or ongoing speciation processes. We studied the population structures of two closely related pelagic cichlid species, Haplochromis pyrrhocephalus and H. laparogramma, using a mitochondrial DNA locus and 12 nuclear microsatellite loci as putative neutral markers. Ten and two populations of H. pyrrhocephalus and H. laparogramma, respectively, were sampled from the southern part of Lake Victoria. We grouped those 12 populations into four mutually differentiated regional populations, one of which consisted of the two H. laparogramma populations. The levels of differentiation were substantial at the mitochondrial locus (FST = 0.03–0.54), but very low at microsatellite loci (RST = 0.008–0.116). The data from both types of loci indicated that the regional population of H. laparogramma was first separated from those of H. pyrrhocephalus if we set aside one erratic population of H. pyrrhocephalus. The data also suggested recent population expansions of the two species, the time scales for which were estimated to be on the order of 104–105 years. These data suggested that dynamic speciation processes accompanied occasional spawning of new species and population size changes in this lake

Correction: Endothelial Expression of Endothelin Receptor A in the Systemic Capillary Leak Syndrome.

Idiopathic systemic capillary leak syndrome (SCLS) is a rare and potentially fatal vascular disorder characterized by reversible bouts of hypotension and edema resulting from fluid and solute escape into soft tissues. Although spikes in permeability-inducing factors have been linked to acute SCLS flares, whether or not they act on an inherently dysfunctional endothelium is unknown. To assess the contribution of endothelial-intrinsic mechanisms in SCLS, we derived blood-outgrowth endothelial cells (BOEC) from patients and healthy controls and examined gene expression patterns. Ednra, encoding Endothelin receptor A (ETA)-the target of Endothelin 1 (ET-1)-was significantly increased in SCLS BOEC compared to healthy controls. Although vasoconstriction mediated by ET-1 through ETA activation on vascular smooth muscle cells has been well characterized, the expression and function of ETA receptors in endothelial cells (ECs) has not been described. To determine the role of ETA and its ligand ET-1 in SCLS, if any, we examined ET-1 levels in SCLS sera and functional effects of endothelial ETA expression. ETA overexpression in EAhy926 endothelioma cells led to ET-1-induced hyper-permeability through canonical mechanisms. Serum ET-1 levels were elevated in acute SCLS sera compared to remission and healthy control sera, suggesting a possible role for ET-1 and ETA in SCLS pathogenesis. However, although ET-1 alone did not induce hyper-permeability of patient-derived BOEC, an SCLS-related mediator (CXCL10) increased Edrna quantities in BOEC, suggesting a link between SCLS and endothelial ETA expression. These results demonstrate that ET-1 triggers classical mechanisms of vascular barrier dysfunction in ECs through ETA. Further studies of the ET-1-ETA axis in SCLS and in more common plasma leakage syndromes including sepsis and filovirus infection would advance our understanding of vascular integrity mechanisms and potentially uncover new treatment strategies