Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

Lympho-hematopoiesis is regulated by cytokines; however, it remains unclear how cytokines regulate hematopoietic stem cells (HSCs) to induce production of lymphoid progenitors. Here, we show that in mice whose CXC chemokine ligand 12 (CXCL12) is deleted from half HSC niche cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, HSCs migrate from CXCL12-deficient niches to CXCL12-intact niches. In mice whose CXCL12 is deleted from all Ebf3+/leptin receptor (LepR)+ CAR cells, HSCs are markedly reduced and their ability to generate B cell progenitors is reduced compared with that to generate myeloid progenitors even when transplanted into wild-type mice. Additionally, CXCL12 enables the maintenance of B lineage repopulating ability of HSCs in vitro. These results demonstrate that CAR cell-derived CXCL12 attracts HSCs to CAR cells within bone marrow and plays a critical role in the maintenance of HSCs, especially lymphoid-biased or balanced HSCs. This study suggests an additional mechanism by which cytokines act on HSCs to produce B cells.Nakatani T., Sugiyama T., Omatsu Y., et al. Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells. Nature Communications 14, 6402 (2023); https://doi.org/10.1038/s41467-023-42047-2

A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV)  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To  overcome  the  problem,  neutral  beam  etching  (NBE),  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ) times the imaginary part  of  the  complex  Young's  modulus  (Eds)  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures

A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV)  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To  overcome  the  problem,  neutral  beam  etching  (NBE),  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ) times the imaginary part  of  the  complex  Young's  modulus  (Eds)  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures.Keywords: cantilever, neutral beam etching, surface los

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe