Explore the vast range of titles available.

Analysis of transplantation of single haematopoietic stem cells in mice defines stable lineage-restricted fates in long-term self-renewing multipotent stem cells, including a class of multipotent stem cells that exclusively replenishes the megakaryocyte/platelet lineage. The many fates of stem cells in the blood line Many blood disorders can be treated with haematopoietic (blood-generating) stem cell (HSC) transplants, but such treatment does not always lead to efficient replenishment of all blood lineages. Through single-cell transplantation of HSCs in mice, Sten Eirik Jacobsen and colleagues define lineage-restricted fates of long-term self-renewing cells. They identify a class of HSC that effectively replenishes the megakaryocyte and platelet lineages over other lineages, and other HSCs that are more able to participate in megakaryocyte, erythroid and myeloid lineages despite being able to sustain lymphoid potential. Genetic lineage tracing also shows that platelet-biased HSCs are able to support unperturbed adult haematopoiesis. Rare multipotent haematopoietic stem cells (HSCs) in adult bone marrow with extensive self-renewal potential can efficiently replenish all myeloid and lymphoid blood cells 1 , securing long-term multilineage reconstitution after physiological and clinical challenges such as chemotherapy and haematopoietic transplantations 2 , 3 , 4 . HSC transplantation remains the only curative treatment for many haematological malignancies, but inefficient blood-lineage replenishment remains a major cause of morbidity and mortality 5 , 6 . Single-cell transplantation has uncovered considerable heterogeneity among reconstituting HSCs 7 , 8 , 9 , 10 , 11 , a finding that is supported by studies of unperturbed haematopoiesis 2 , 3 , 4 , 12 and may reflect different propensities for lineage-fate decisions by distinct myeloid-, lymphoid- and platelet-biased HSCs 7 , 8 , 9 , 10 , 13 . Other studies suggested that such lineage bias might reflect generation of unipotent or oligopotent self-renewing progenitors within the phenotypic HSC compartment, and implicated uncoupling of the defining HSC properties of self-renewal and multipotency 11 , 14 . Here we use highly sensitive tracking of progenitors and mature cells of the megakaryocyte/platelet, erythroid, myeloid and B and T cell lineages, produced from singly transplanted HSCs, to reveal a highly organized, predictable and stable framework for lineage-restricted fates of long-term self-renewing HSCs. Most notably, a distinct class of HSCs adopts a fate towards effective and stable replenishment of a megakaryocyte/platelet-lineage tree but not of other blood cell lineages, despite sustained multipotency. No HSCs contribute exclusively to any other single blood-cell lineage. Single multipotent HSCs can also fully restrict towards simultaneous replenishment of megakaryocyte, erythroid and myeloid lineages without executing their sustained lymphoid lineage potential. Genetic lineage-tracing analysis also provides evidence for an important role of platelet-biased HSCs in unperturbed adult haematopoiesis. These findings uncover a limited repertoire of distinct HSC subsets, defined by a predictable and hierarchical propensity to adopt a fate towards replenishment of a restricted set of blood lineages, before loss of self-renewal and multipotency.

Background Platelets and erythrocytes constitute over 95% of all hematopoietic stem cell output. However, the clonal dynamics of HSC contribution to these lineages remains largely unexplored. Results We use lentiviral genetic labeling of mouse hematopoietic stem cells to quantify output from all lineages, nucleate, and anucleate, simultaneously linking these with stem and progenitor cell transcriptomic phenotypes using single-cell RNA-sequencing. We observe dynamic shifts of clonal behaviors through time in same-animal peripheral blood and demonstrate that acute platelet depletion shifts the output of multipotent hematopoietic stem cells to the exclusive production of platelets. Additionally, we observe the emergence of new myeloid-biased clones, which support short- and long-term production of blood cells. Conclusions Our approach enables kinetic studies of multi-lineage output in the peripheral blood and transcriptional heterogeneity of individual hematopoietic stem cells. Our results give a unique insight into hematopoietic stem cell reactivation upon platelet depletion and of clonal dynamics in both steady state and under stress.

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC INS , visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS parameters and significantly reduced fasting glucose ( P  < 0.001), HbA1c ( P  = 0.014) and the prevalence of DM ( P  = 0.003) when disease control was achieved. Both somatostatin analogues and surgery improved ISI Matsuda ( P  < 0.001) and reduced AUC INS ( P  < 0.001) and VAI ( P  < 0.001 and P  = 0.003, respectively). Only in controlled somatostatin analogues-treated patients a significant reduction in insulinogenic index ( P  = 0.010) was observed. ISI Matsuda showed a significant independent correlation with IGF-1 levels (β = −0.258; P  = 0.001) and VAI score (β = −0.430; P  < 0.001). VAI was independently correlated with IGF-1 (β = 0.183; P  = 0.004). Both somatostatin analogues and surgery can safely be used as first-line therapy in acromegaly, without any untoward effects on glucose tolerance. The control of acromegaly is the main determinant of beneficial effects on general features of insulin sensitivity. VAI could represent an additional link between disease control and insulin sensitivity.

Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems. These distinct stem cells use cellularly, molecularly and functionally separate pathways for the replenishment of molecularly distinct megakaryocyte-restricted progenitors: a slower steady-state multipotent pathway and a fast-track emergency-activated platelet-restricted pathway. These findings provide a framework for enhancing platelet replenishment in settings in which slow recovery of platelets remains a major clinical challenge. Jacobsen and colleagues elucidate the nonhierarchical relationship between two types of stem cells: Vwf − hematopoietic stem cells that stably replenish all blood cell lineages without a platelet bias, and Vwf + stem cells that replenish almost exclusively platelets, and demonstrate that the two types utilize cellularly and molecularly distinct progenitor trajectories for replenishment of platelets.

Approaches that are transdisciplinary and participatory can help to address complex socio-ecological issues by integrating multiple disciplinary perspectives while taking into account the different needs and experiences of community members and other stakeholders. Despite this promise, such approaches are rarely applied within the scientific community, as researchers and public actors often lack the training, practice and reference cases required to handle the working relationships and translations of terminology, ideas and values across multiple bodies of knowledge. A case study described in this manuscript depicts a group of researchers, artists and citizens consciously engaged in the construction of a transdisciplinary process as part of a 40-day ‘citizen science’ experiment focussed on assessing soil fertility in the urban area of Milan, Italy. The group drew from recognised scientific approaches, applied agronomic methodologies, artistic practices and technological tools, integrating them into a hybrid process of collective and participatory inquiry. As a quantitative outcome of the experiment, a dataset of bio-chemical parameters was generated, which was enriched by agronomic interpretations but also by artistic and reflective materials. Importantly, the process developed transdisciplinary and participatory skills, as it created a potentially replicable procedure of engagement, analysis and presentation for use in other citizen science settings. This article presents the context, the multiple objectives of the research and the applied approach and its timeline. Described in detail are the process of designing and conducting the experiment by involving an extended research community—including both junior and senior researchers—in progressive steps. Quantitative and qualitative results are provided. The findings are meant to contribute case material and methods to inform the advancement of transdisciplinary research approaches within the scientific community as well as examples of ways to transcend the boundaries of science to include artists and community stakeholders. The aspiration is to inform and inspire concrete application of transdisciplinary and participatory methods in concert to address complex socio-environmental challenges.

Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins.

Anthropogenic ecological crisis constitutes a significant challenge that all within the academy must urgently face, including the Natural Language Processing (NLP) community. While recent years have seen increasing work revolving around climate-centric discourse, crucial environmental and ecological topics outside of climate change remain largely unaddressed, despite their prominent importance. Mainstream NLP tasks, such as sentiment analysis, dominate the scene, but there remains an untouched space in the literature involving the analysis of environmental impacts of certain events and practices. To address this gap, this paper presents EcoVerse, an annotated English Twitter dataset of 3,023 tweets spanning a wide spectrum of environmental topics. We propose a three-level annotation scheme designed for Eco-Relevance Classification, Stance Detection, and introducing an original approach for Environmental Impact Analysis. We detail the data collection, filtering, and labeling process that led to the creation of the dataset. Remarkable Inter-Annotator Agreement indicates that the annotation scheme produces consistent annotations of high quality. Subsequent classification experiments using BERT-based models, including ClimateBERT, are presented. These yield encouraging results, while also indicating room for a model specifically tailored for environmental texts. The dataset is made freely available to stimulate further research.