A Monocytic Barrier to the Humanization of Immunodeficient Mice.

Mice with severe immunodeficiencies have become very important tools for studying foreign cells in an in vivo environment. Xenotransplants can be used to model cells from many species, although most often, mice are humanized through the transplantation of human cells or tissues to meet the needs of medical research. The development of immunodeficient mice is reviewed leading up to the current state-of-the-art strains, such as the NOD-scid-gamma (NSG) mouse. NSG mice are excellent hosts for human hematopoietic stem cell transplants or immune reconstitution through transfusion of human peripheral blood mononuclear cells. However, barriers to full hematopoietic engraftment still remain; notably, the survival of human cells in the circulation is brief, which limits overall hematological and immune reconstitution. Reports have indicated a critical role for monocytic cells, monocytes, macrophages, and dendritic cells, in the clearance of xenogeneic cells from circulation. Various aspects of the NOD genetic background that affect monocytic cell growth, maturation, and function that are favorable to human cell transplantation are discussed. Important receptors, such as SIRPα, that form a part of the innate immune system and enable the recognition and phagocytosis of foreign cells by monocytic cells are reviewed. The development of humanized mouse models has taken decades of work in creating more immunodeficient mice, genetic modification of these mice to express human genes, and refinement of transplant techniques to optimize engraftment. Future advances may focus on the monocytic cells of the host to find ways for further engraftment and survival of xenogeneic cells.

Recent Advances in the Total Synthesis of the Tetrahydroisoquinoline Alkaloids (2002-2020).

The tetrahydroisoquinoline (THIQ) natural products constitute one of the largest families of alkaloids and exhibit a wide range of structural diversity and biological activity. Ranging from simple THIQ natural products to complex trisTHIQ alkaloids such as the ecteinascidins, the chemical syntheses of these alkaloids and their analogs have been thoroughly investigated due to their intricate structural features and functionalities, as well as their high therapeutic potential. This review describes the general structure and biosynthesis of each family of THIQ alkaloids as well as recent advancements of the total synthesis of these natural products from 2002 to 2020. Recent chemical syntheses that have emerged harnessing novel, creative synthetic design, and modern chemical methodology will be highlighted. This review will hopefully serve as a guide for the unique strategies and tools used in the total synthesis of THIQ alkaloids, as well as address the longstanding challenges in their chemical and biosynthesis.

Gender differences in question-asking at the 2019 American Society of Hematology Annual Meeting.

Attendance at professional conferences is an important component of career development, because conferences are a major forum for presenting new research, interacting with colleagues and networking. An extensive literature documents differences in the professional experiences of women and men, including experiences at professional conferences. We hypothesized that women are less likely than men to ask questions at conferences, thus forgoing opportunities for professional development. To address this issue, we analyzed the question-asking behavior of women and men at the 2019 Annual Meeting and Exposition of the American Society of Hematology. In all, 112 sessions (55% of those eligible) were randomly chosen for coding, yielding data on 577 presentations. Although approximately 50% of moderators and speakers were women, the proportion of questions asked by women was significantly lower compared with the estimated proportion of women attending the conference (23% vs 39%; P < .0001). Women were more likely to ask questions if another woman asked the first question or if the session topic was red cells. These results suggest that although women are represented equally as moderators and speakers, they are less likely to engage in the postpresentation discourse by asking questions. Encouraging women to speak up in professional situations and providing training on question-asking skills can help address this gender gap that potentially contributes to disparities in professional visibility and career advancement for women in hematology.

Vaginal metastasis of gestational trophoblastic neoplasia resulting in hemorrhage: A case report.

Complete molar pregnancies complicate approximately 1 in 1500 pregnancies in the United States and result in gestational trophoblastic neoplasia in about 15-20% of these cases. Vaginal metastasis is the second most common site of metastasis and may present with vaginal bleeding and hemorrhage. This report describes a case of a 19-year-old Hispanic primigravida who presented with hemorrhage from an anterior vaginal wall metastasis two weeks after dilation and curettage for complete molar pregnancy. Hemorrhage resolved after extrusion of the lesion from the anterior vaginal wall. Pathology showed markedly atypical trophoblastic tissue from the lesion. Vaginal involvement of gestational trophoblastic neoplasia can present with life-threatening hemorrhage.

Neural components of altruistic punishment.

Altruistic punishment, which occurs when an individual incurs a cost to punish in response to unfairness or a norm violation, may play a role in perpetuating cooperation. The neural correlates underlying costly punishment have only recently begun to be explored. Here we review the current state of research on the neural basis of altruism from the perspectives of costly punishment, emphasizing the importance of characterizing elementary neural processes underlying a decision to punish. In particular, we emphasize three cognitive processes that contribute to the decision to altruistically punish in most scenarios: inequity aversion, cost-benefit calculation, and social reference frame to distinguish self from others. Overall, we argue for the importance of understanding the neural correlates of altruistic punishment with respect to the core computations necessary to achieve a decision to punish.

Social learning in humans and other animals.

Decisions made by individuals can be influenced by what others think and do. Social learning includes a wide array of behaviors such as imitation, observational learning of novel foraging techniques, peer or parental influences on individual preferences, as well as outright teaching. These processes are believed to underlie an important part of cultural variation among human populations and may also explain intraspecific variation in behavior between geographically distinct populations of animals. Recent neurobiological studies have begun to uncover the neural basis of social learning. Here we review experimental evidence from the past few decades showing that social learning is a widespread set of skills present in multiple animal species. In mammals, the temporoparietal junction, the dorsomedial, and dorsolateral prefrontal cortex, as well as the anterior cingulate gyrus, appear to play critical roles in social learning. Birds, fish, and insects also learn from others, but the underlying neural mechanisms remain poorly understood. We discuss the evolutionary implications of these findings and highlight the importance of emerging animal models that permit precise modification of neural circuit function for elucidating the neural basis of social learning.