Physician-scientists in the United States at 2020: Trends and concerns

Physician-scientists comprise a unique and valuable part of the biomedical workforce, but for decades there has been concern about the number of physicians actively engaged in research. Reports have outlined the challenges facing physician-scientists, and programs have been initiated to encourage and facilitate research careers for medically trained scientists. Many of these initiatives have demonstrated successful outcomes, but there has not been a recent summary of the impact of the past decade of effort. This report compiles available data from surveys of medical education and physician research participation to assess changes in the physician-scientist workforce from 2011-2020. Several trends are positive: rising enrollments in MD-PhD programs, greater levels of interest in research careers among matriculating medical students, more research experience during medical school and rising numbers of physicians in academic medicine, and an increase in first R01 grants to physician-scientists. However, there are now decreased levels of interest in research careers among graduating medical students, a steady decline in MDs applying for NIH loan repayment program support, an increased age at first R01 grant success for physicians, and fewer physicians reporting research as their primary work activity: all of these indicators create concern for the stability of the career path. Despite a recommendation by the Physician-Scientist Workforce in 2014 to create real-time reporting on NIH grants and grantees to help the public assess trends, this initiative has not been completed. Better information is still needed to fully understand the status of the physician-scientist workforce, and to assess efforts to stabilize this vulnerable career path

Expression profiling of snoRNAs in normal hematopoiesis and AML

Key Points A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.</jats:p

CXCR2- and E-Selectin–induced Neutrophil Arrest during Inflammation In Vivo

The signaling events leading to the activation of integrins and firm arrest of rolling neutrophils in inflamed venules have yet to be elucidated. In vitro assays suggest that both E-selectin and chemokines can trigger arrest of rolling neutrophils, but E-selectin−/− mice have normal levels of adherent neutrophils in inflamed venules. To test whether chemokine-induced neutrophil arrest in vivo can be unmasked by blocking E-selectin, we investigated neutrophil adhesion in inflamed cremaster muscle venules in tumor necrosis factor (TNF)-α–treated CXCR2−/− or wild-type (WT) mice injected with E-selectin blocking monoclonal antibody (mAb) 9A9. To block chemokine receptor signaling, we investigated E-selectin−/− or WT mice treated with pertussis toxin (PTx) intravenously. Neutrophil adhesion was unchanged in CXCR2−/−, E-selectin−/−, PTx-treated WT, or mAb 9A9–treated WT mice. However, TNF-α–induced neutrophil adhesion was almost completely abrogated in E-selectin−/− mice treated with PTx and significantly reduced in CXCR2−/− mice treated with the E-selectin blocking mAb. In thioglycollate-induced peritonitis, PTx treatment blocked neutrophil recruitment into the peritoneum of E-selectin−/− mice, but had only a partial effect in WT animals. These data show that E-selectin– and chemokine-mediated arrest mechanisms are overlapping in this model and identify CXCR2 as an important neutrophil arrest chemokine in vivo

Human T Regulatory Cells Can Use the Perforin Pathway to Cause Autologous Target Cell Death

AbstractCytotoxic T lymphocytes and natural killer cells use the perforin/granzyme pathway to kill virally infected cells and tumor cells. Mutations in genes important for this pathway are associated with several human diseases. CD4+ T regulatory (Treg) cells have emerged as important in the control of immunopathological processes. We have previously shown that human adaptive Treg cells preferentially express granzyme B and can kill allogeneic target cells in a perforin-dependent manner. Here, we demonstrate that activated human CD4+CD25+ natural Treg cells express granzyme A but very little granzyme B. Furthermore, both Treg subtypes display perforin-dependent cytotoxicity against autologous target cells, including activated CD4+ and CD8+ T cells, CD14+ monocytes, and both immature and mature dendritic cells. This cytotoxicity is dependent on CD18 adhesive interactions but is independent of Fas/FasL. Our findings suggest that the perforin/granzyme pathway is one of the mechanisms that Treg cells can use to control immune responses

Computational identification of the normal and perturbed genetic networks involved in myeloid differentiation and acute promyelocytic leukemia

A dissection of the genetic networks and circuitries is described for two form of leukaemia. Integrating transcription factor binding and gene expression profiling, networks are revealed that underly this important human disease

Reversible Luminescent Reaction of Amines with Copper(i) Cyanide

Copper(I) cyanide exposed to various liquid or vapor-phase amines (L) at ambient temperature produces a variety of visible photoluminescence colors via reversible formation of amine adducts. The adducts show phase matches to authentic (CuCN)Ln, n = 0.75–2.0, produced by heating CuCN with liquid amine