Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids

International audienceThe amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain unknown. Here we show that lower-to-upper jaw transformation induced by inactivation of the Endothelin1-Dlx5/6 cascade involving Goosecoid results in loss of the tympanic membrane in mouse, but causes duplication of the tympanic membrane in chicken. Detailed anatomical analysis indicates that the relative positions of the primary jaw joint and first pharyngeal pouch led to the coupling of tympanic membrane formation with the lower jaw in mammals, but with the upper jaw in diapsids. We propose that differences in connection and release by various pharyngeal skeletal elements resulted in structural diversity, leading to the acquisition of the tympanic membrane in two distinct manners during amniote evolution

PHB2 Protects Sister-Chromatid Cohesion in Mitosis

SummaryCohesion between sister chromatids is essential for proper chromosome segregation in mitosis. In vertebrate mitotic cells, most cohesin is removed from the chromosome arms [1–4], but centromeric cohesin is protected by shugoshin until the onset of anaphase [5]. However, the mechanism of this protection of centromeric cohesion is not well understood. Here, we demonstrate that prohibitin 2 (PHB2) is involved in the regulation of sister-chromatid cohesion during mitosis in HeLa cells. PHB2 is an evolutionarily conserved protein in eukaryotes and has multiple functions, such as transcriptional regulation and cell viability and development [6–8]. However, its functions in mitosis have not yet been determined. We show that depletion of PHB2 by RNA interference (RNAi) causes premature sister-chromatid separation and defects in chromosome congression accompanied by mitotic arrest by spindle-checkpoint activation. In the absence of PHB2, cohesin is dissociated from centromeres during early mitosis, although the centromeric localization of shugoshin is preserved. Thus, our findings suggest that, in addition to the shugoshin, PHB2 is also required to protect the centromeric cohesion from phosphorylation by Plk1 during early mitosis and that its function is essential for proper mitotic progression

Cherenkov-Phase-Matched Nonlinear Optical Detection and Generation of Terahertz Radiation via GaAs With Metal-Coating

Terahertz (THz) wave detection and emission via Cherenkov-phase-matched nonlinear optical effects at 1.55-μm optical wavelength were demonstrated using a GaAs with metal-coating (M-G-M) and bare GaAs as a reference sample in conjunction with a metallic tapered parallel-plate waveguide (TPPWG). The metal-coated GaAs is superior to the bare wafer both as a THz electro-optic detector and as an emitter. Significant improvements in the detection and emission efficiency were obtained by utilizing a metal-coating due to better confinement and lower loss of the THz waves propagating in the M-G-M compared with bare GaAs

Familial Occurrence of a Congenital Portosystemic Shunt of the Portal Vein

A congenital portosystemic shunt of the portal vein is a very rare vascular anomaly associated with the liver. We report the case of a 5-year-old girl with a patent ductus venosus and her 31-year-old mother with a congenital portosystemic shunt. The child presented with a history of an extremely low birth weight in addition to an atrial septal defect and a patent ductus venosus. At the age of 2, she underwent ligation of the ductus venosus. Her mother was also diagnosed with a congenital vascular anomaly at the age of 16. We have followed up and evaluated her asymptomatic mother for 15 years. To our knowledge, this is the first report describing the occurrence of a congenital portosystemic shunt in both a mother and her child

Clinico–stastical study of outpatients and inpatients in the Matsumoto Dental University Hospital,for the last three years

Summary.The Matsumoto Dental University Hospital is located in the center of Nagano Prefecture and is the core hospital in the area.In this study,we carried out a clinicostatistical survey of outpatients and inpatients for the past 3 years.The number of outpatient and inpatients were 6,545 and 861,respectively,for the study period.The referral rate was 71.8%,which annually increased.The number of hospitalized patients by age was bimodal in their 20s and 70s.Dental diseases were most common in outpatients,followed by temporomandibular joint diseases,mucosal/skin diseases,and inflammatory diseases.Inpatients mostly had dental diseases,jaw deformities,inflammatory diseases,and cystic diseases.Moreover,410 cases used the operating room.Consequently,the number was annually increasing.Therefore,this study suggests that our department is functioning as a regional core hospital.However,building a medical care system that strengthens regional cooperation so that it can meet the various needs is necessary

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