NR4A1 and NR4A2 orphan nuclear receptors regulate endothelial-to-hematopoietic transition in mouse hematopoietic stem cell specification.

Hematopoietic stem cells (HSCs) sustain life-long hematopoiesis and emerge during mid-gestation from hemogenic endothelial progenitors via an endothelial-to-hematopoietic transition (EHT). The full scope of molecular mechanisms governing this process remains unclear. The NR4A subfamily of orphan nuclear receptors act as tumor suppressors in myeloid leukemogenesis and have never been implicated in HSC specification.

A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones.

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice.

The evolving hematopoietic niche during development.

Mammalian hematopoietic stem cells (HSCs) emerge from the hemogenic endothelium in the major embryonic arteries. HSCs undergo a complex journey first migrating to the fetal liver (FL) and from there to the fetal bone marrow (FBM), where they mostly remain during adult life. In this process, a pool of adult HSCs is produced, which sustains lifelong hematopoiesis.

Integrating GPT as an Assistant for Low-Cost Virtual Reality Escape-Room Games.

This work explores the integration of generative pretrained transformer (GPT), an AI language model developed by OpenAI, as an assistant in low-cost virtual escape games. The study focuses on the synergy between virtual reality (VR) and GPT, aiming to evaluate its performance in helping solve logical challenges within a specific context in the virtual environment while acting as a personalized assistant through voice interaction. The findings from user evaluations revealed both positive perceptions and limitations of GPT in addressing highly complex challenges, indicating its potential as a valuable tool for providing assistance and guidance in problem-solving situations.

Neurobeachin regulates hematopoietic progenitor differentiation and survival by modulating Notch activity.

Hematopoietic stem cells (HSCs) can generate all blood cells. This ability is exploited in HSC transplantation (HSCT) to treat hematologic disease. A clear understanding of the molecular mechanisms that regulate HSCT is necessary to continue improving transplant protocols.

Use of Ozone as a Substrate Treatment for the Control of Trichoderma in the Production of Pleurotus ostreatus.

Pleurotus ostreatus is one of the most widely cultivated species in the world. It can be produced in many lignocellulosic substrates after carrying out a treatment to eliminate competing microorganisms. The most commonly used is pasteurization by steam or by immersion in hot water.

Haematopoietic stem cell health in sickle cell disease and its implications for stem cell therapies and secondary haematological disorders.

Gene modification of haematopoietic stem cells (HSCs) is a potentially curative approach to sickle cell disease (SCD) and offers hope for patients who are not eligible for allogeneic HSC transplantation. Current approaches require in vitro manipulation of healthy autologous HSC prior to their transplantation. However, the health and integrity of HSCs may be compromised by a variety of disease processes in SCD, and challenges have emerged in the clinical trials of gene therapy.

Murine foetal liver supports limited detectable expansion of life-long haematopoietic progenitors.

Current dogma asserts that the foetal liver (FL) is an expansion niche for recently specified haematopoietic stem cells (HSCs) during ontogeny. Indeed, between embryonic day of development (E)12.5 and E14.

Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis.

Background: Early aggressive hydration is widely recommended for the management of acute pancreatitis, but evidence for this practice is limited.

Methods: At 18 centers, we randomly assigned patients who presented with acute pancreatitis to receive goal-directed aggressive or moderate resuscitation with lactated Ringer's solution. Aggressive fluid resuscitation consisted of a bolus of 20 ml per kilogram of body weight, followed by 3 ml per kilogram per hour.

Inflammatory exposure drives long-lived impairment of hematopoietic stem cell self-renewal activity and accelerated aging.

Hematopoietic stem cells (HSCs) mediate regeneration of the hematopoietic system following injury, such as following infection or inflammation. These challenges impair HSC function, but whether this functional impairment extends beyond the duration of inflammatory exposure is unknown. Unexpectedly, we observed an irreversible depletion of functional HSCs following challenge with inflammation or bacterial infection, with no evidence of any recovery up to 1 year afterward.

Diversity in the bone marrow niche: Classic and novel strategies to uncover niche composition.

Our view on the role and composition of the bone marrow (BM) has dramatically changed over time from a simple nutrient for the bone to a highly complex multicellular tissue that sustains haematopoiesis. Among these cells, multipotent haematopoietic stem cells (HSCs), which are predominantly quiescent, possess unique self-renewal capacity and multilineage differentiation potential and replenish all blood lineages to maintain lifelong haematopoiesis. Adult HSCs reside in specialised BM niches, which support their functions.

Specification of hematopoietic stem cells in mammalian embryos: a rare or frequent event?

Hematopoietic stem cells (HSCs) are the blood-forming stem cells thought to be responsible for supporting the blood system throughout life. Transplantability has long been the flagship assay used to define and characterize HSCs throughout ontogeny. However, it has recently become clear that many cells emerge during ontogeny that lack transplantability yet nevertheless are fated to ultimately contribute to the adult HSC pool.

Vivern-A Virtual Environment for Multiscale Visualization and Modeling of DNA Nanostructures.

DNA nanostructures offer promising applications, particularly in the biomedical domain, as they can be used for targeted drug delivery, construction of nanorobots, or as a basis for molecular motors. One of the most prominent techniques for assembling these structures is DNA origami. Nowadays, desktop applications are used for the in silico design of such structures.

High Visual-Quality Scenes in Low-Cost Virtual Reality With Collisions and Irregular Surfaces.

Mobile phones offer an excellent low-cost alternative for Virtual Reality. However, the hardware constraints of these devices restrict the displayable visual complexity of graphics. Image-based rendering techniques arise as an alternative to solve this problem, but usually, the support of collisions and irregular surfaces (i.

ChemVA: Interactive Visual Analysis of Chemical Compound Similarity in Virtual Screening.

In the modern drug discovery process, medicinal chemists deal with the complexity of analysis of large ensembles of candidate molecules. Computational tools, such as dimensionality reduction (DR) and classification, are commonly used to efficiently process the multidimensional space of features. These underlying calculations often hinder interpretability of results and prevent experts from assessing the impact of individual molecular features on the resulting representations.

Clones assemble! The clonal complexity of blood during ontogeny and disease.

Hematopoietic stem and progenitor cells (HSPCs) govern the daily expansion and turnover of billions of specialized blood cells. Given their clinical utility, much effort has been made toward understanding the dynamics of hematopoietic production from this pool of stem cells. An understanding of hematopoietic stem cell clonal dynamics during blood ontogeny could yield important insights into hematopoietic regulation, especially during aging and repeated exposure to hematopoietic stress-insults that may predispose individuals to the development of hematopoietic disease.

The global clonal complexity of the murine blood system declines throughout life and after serial transplantation.

Although many recent studies describe the emergence and prevalence of "clonal hematopoiesis of indeterminate potential" in aged human populations, a systematic analysis of the numbers of clones supporting steady-state hematopoiesis throughout mammalian life is lacking. Previous efforts relied on transplantation of "barcoded" hematopoietic stem cells (HSCs) to track the contribution of HSC clones to reconstituted blood. However, ex vivo manipulation and transplantation alter HSC function and thus may not reflect the biology of steady-state hematopoiesis.

Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs.

The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach.

Evaluating the impact of the biocontrol agent Trichoderma harzianum ITEM 3636 on indigenous microbial communities from field soils.

Aim: To investigate the impact of inoculating peanut seeds with the biocontrol agent Trichoderma harzianum ITEM 3636 on the structure of bacterial and fungal communities from agricultural soils.

Methods And Results: Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (PCR-DGGE) and next-generation sequencing (NGS) of amplicons (or marker gene amplification metagenomics) were performed to investigate potential changes in the structure of microbial communities from fields located in a peanut-producing area in the province of Córdoba, Argentina. Fields had history of peanut smut (caused by Thecaphora frezii) incidence.

Nfix Promotes Survival of Immature Hematopoietic Cells via Regulation of c-Mpl.

Hematopoietic stem and progenitor cells (HSPCs) are necessary for life-long blood production and replenishment of the hematopoietic system during stress. We recently reported that nuclear factor I/X (Nfix) promotes HSPC survival post-transplant. Here, we report that ectopic expression of Nfix in primary mouse HSPCs extends their ex vivo culture from about 20 to 40 days.

Lifelong haematopoiesis is established by hundreds of precursors throughout mammalian ontogeny.

Current dogma asserts that mammalian lifelong blood production is established by a small number of blood progenitors. However, this model is based on assays that require the disruption, transplantation and/or culture of embryonic tissues. Here, we used the sample-to-sample variance of a multicoloured lineage trace reporter to assess the frequency of emerging lifelong blood progenitors while avoiding the disruption, culture or transplantation of embryos.

Murine hemogenic endothelial precursors display heterogeneous hematopoietic potential ex vivo.

Hematopoietic stem and progenitor cells (HSPCs) sustain life-long hematopoiesis and are first detected in the embryo by transplantation at embryonic day 10.5 (E10.5).

Hematopoietic stem cells under pressure.

Purpose Of Review: Hematopoietic stem cells (HSCs) and progenitors are tasked with maintaining hematopoietic homeostasis in the face of numerous insults and challenges, including infection, inflammation, and exsanguination. HSCs possess the remarkable ability to reconstitute the entire hematopoietic system of an organism whose own hematopoietic system has been ablated. This ability is exploited routinely in the clinic via HSC transplantation (HSCT).

Functional screen identifies regulators of murine hematopoietic stem cell repopulation.

Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA-transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251.