Cv2, functioning as a pro-BMP factor via twisted gastrulation, is required for early development of nephron precursors

AbstractThe fine-tuning of BMP signals is critical for many aspects of complex organogenesis. In this report, we show that the augmentation of BMP signaling by a BMP-binding secreted factor, Crossveinless2 (Cv2), is essential for the early embryonic development of mammalian nephrons. In the Cv2-null mouse, the number of cap condensates (clusters of nephron progenitors, which normally express Cv2) was decreased, and the condensate cells exhibited a reduced level of aggregation. In these Cv2–/– condensates, the level of phosphorylated Smad1 (pSmad1) was substantially lowered. The loss of a Bmp7 allele in the Cv2–/– mouse enhanced the cap condensate defects and further decreased the level of pSmad1 in this tissue. These observations indicated that Cv2 has a pro-BMP function in early nephrogenesis. Interestingly, the renal defects of the Cv2–/– mutant were totally suppressed by a null mutation of Twisted gastrulation (Tsg), which encodes another BMP-binding factor, showing that Cv2 exerts its pro-BMP nephrogenic function Tsg-dependently. By using an embryonic kidney cell line, we presented experimental evidence showing that Cv2 enhances pro-BMP activity of Tsg. These findings revealed the molecular hierarchy between extracellular modifiers that orchestrate local BMP signal peaks in the organogenetic microenvironment

Precise Three-Dimensional Morphology of the Male Anterior Anorectum Reconstructed From Large Serial Histologic Sections: A Cadaveric Study

BACKGROUND: Deep anatomic knowledge of the male anterior anorectum is important to avoid urethral injury and rectal perforation in intersphincteric resection or abdominoperineal resection for very low rectal cancer. However, its structure is difficult to understand, because the anorectum, muscles, and urogenital organs are complicatedly and 3-dimensionally arranged. OBJECTIVE: The purpose of this study was to revisit the anatomic information of the male anterior anorectum for intersphincteric resection and abdominoperineal resection with a focus on the spatial muscular morphology. DESIGN: This was a descriptive cadaveric study. SETTINGS: The study was conducted at Ehime and Kyoto universities. PATIENTS: Tissue specimens from 9 male cadavers were included. MAIN OUTCOME MEASURES: Specimens around the anterior anorectum were serially sectioned in the horizontal, sagittal, or frontal plane; large semiserial histologic sections were created at 250-μm intervals. The series were stained with Elastica van Gieson, and some sections from the series were studied by immunohistochemistry to detect smooth and striated muscles. Two series were digitalized and reconstructed 3-dimensionally. RESULTS: Two regions without a clear anatomic border were elucidated: 1) the anterior region of the external anal sphincter, where the external anal sphincter, bulbospongiosus muscle, and superficial transverse perineal muscle were intertwined; and 2) the rectourethralis muscle, where the smooth muscle of the longitudinal muscle continuously extended to the posteroinferior area of the urethra, which became closest to the anorectum at the prostatic apex level. A tight connection between the striated and smooth muscles was identified at the anterior part of the upper external anal sphincter and anterolateral part of the puborectalis muscle level. LIMITATIONS: This study involved a small sample size of elderly cadavers. CONCLUSIONS: This study clarified the precise spatial relationship between smooth and striated muscles. The detailed anatomic findings will contribute more accurate step-by-step anterior dissection in intersphincteric resection and abdominoperineal resection, especially with the transanal approach, which can magnify the muscle fiber direction and contraction of striated muscle by electrostimulation. MORFOLOGÍA TRIDIMENSIONAL PRECISA DEL ANORRECTO ANTERIOR MASCULINO RECONSTRUIDO A TRAVÉS DE SECCIONES MAYORES HISTOLÓGICAS EN SERIE: UN ESTUDIO CADAVÉRICO: El conocimiento anatómico amplio del anorrecto anterior masculino es importante para evitar lesiones de uretra y perforación de recto en la resección interesfinterica o la resección abdominoperineal para cáncer de recto bajo. Sin embargo, su estructura es difícil de entender porque el anorrecto, los músculos y los órganos urogenitales están aliñados en forma complexa tridimensional. OBJETIVO: Revisar de nuevo el conocimiento anatómico del anorrecto anterior masculino relevante a la resección interesfinterica y la resección abdominoperineal con un enfoque en la morfología muscular espacial. DISEÑO:: Estudio descriptivo cadavérico. ENTORNO: Ehime y la Universidad de Kyoto. SUJETOS: Tejido especímenes de nueve cadáveres masculinos. PUNTOS FINALES DE VALORACIÓN:: Las muestras alrededor del anorrecto anterior se seccionaron en serie en planos horizontal, sagital y coronal. Se crearon mayores secciones histológicas en serie a intervalos de 250 μm. Los especímenes fueron teñidos con Elástica van Gieson, y algunas secciones de la serie se estudiaron mediante inmunohistoquímica para detectar músculos lisos y estriados. Dos series fueron digitalizadas y reconstruidas tridimensionalmente. RESULTADOS: Se demostraron dos regiones sin un borde anatómico definido: (i) la región anterior del esfínter anal externo, donde se entrelazaron el esfínter anal externo, el músculo bulbospongoso y el músculo perineal transverso superficial; y (ii) músculo rectouretral, donde el músculo liso del músculo longitudinal se extiende continuamente a la zona posteroinferior de la uretra, que se acerca más al anorrecto a nivel del ápice prostático. La conexión estrecha entre los músculos estriados y lisos se identificó en la parte anterior del esfínter anal externo superior y la parte anterolateral del nivel del músculo puborrectal. LIMITACIÓN:: Este estudio incluyó una muestra pequeña de cadáveres ancianos. CONCLUSIÓN:: Este estudio aclaró la relación espacial precisa entre los músculos lisos y estriados. Los hallazgos anatómicos detallados ayudarán para una disección anterior paso a paso más precisa en la resección interesfintérica y la resección abdominoperineal, especialmente con el abordaje transanal, que puede magnificar la dirección de las fibras musculares y la contracción del músculo estriado utilizando electroestimulación

Identification of 45 New Neutron-Rich Isotopes Produced by In-Flight Fission of a 238U Beam at 345 MeV/nucleon

A search for new isotopes using in-flight fission of a 345 MeV/nucleon 238U beam has been carried out at the RI Beam Factory at the RIKEN Nishina Center. Fission fragments were analyzed and identified by using the superconducting in-flight separator BigRIPS. We observed 45 new neutron-rich isotopes: 71Mn, 73,74Fe, 76Co, 79Ni, 81,82Cu, 84,85Zn, 87Ga, 90Ge, 95Se, 98Br, 101Kr, 103Rb, 106,107Sr, 108,109Y, 111,112Zr, 114,115Nb, 115,116,117Mo, 119,120Tc, 121,122,123,124Ru, 123,124,125,126Rh, 127,128Pd, 133Cd, 138Sn, 140Sb, 143Te, 145I, 148Xe, and 152Ba

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