Physical biomarkers for human hematopoietic stem and progenitor cells

Adhesion of hematopoietic stem and progenitor cells (HSPCs) to the bone marrow niche plays critical roles in the maintenance of the most primitive HSPCs. The interactions of HSPC−niche interactions are clinically relevant in acute myeloid leukemia (AML), because (i) leukemia-initiating cells adhered to the marrow niche are protected from the cytotoxic effect by chemotherapy and (ii) mobilization of HSPCs from healthy donors' bone marrow is crucial for the effective stem cell transplantation. However, although many clinical agents have been developed for the HSPC mobilization, the effects caused by the extrinsic molecular cues were traditionally evaluated based on phenomenological observations. This review highlights the recent interdisciplinary challenges of hematologists, biophysicists and cell biologists towards the design of defined in vitro niche models and the development of physical biomarkers for quantitative indexing of differential effects of clinical agents on human HSPCs

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Post-bureaucracy and the agile absorption of uncertainty through interaction

Eckstein B, Muster J. Postbürokratie und die agile Unsicherheitsabsorption in Interaktionen. Gruppe. Interaktion. Organisation: Zeitschrift für Angewandte Organisationspsychologie. 2021.This article for the GIO-Journal proposes a perspective rooted in functional equivalence for the analysis of post-bureaucratic reforms that partly shift the organizational absorption of uncertainty to formal interactions of their members. Postbureaucracy tries to conceptualize organizational and societal changes throughout the second half of the 20th century. Agile management frameworks that multiply interactions between members of an organization can be treated as a phenomenon of postbureaucratic organizing. Drawing on systems theory this paper examines how postbureaucratic reforms trigger new uncertainties and how they are tackled by agile concepts of management. We will illustrate this by analyzing the agile concepts Scrum and Holacracy and show how relocation triggers new needs for formalization. Doing this we will focus on how interdependencies of communication in systems of interaction are centered in different dimensions. This paper advocates for a perspective on postbureaucracy in terms of functional equivalence to grasp the connection between the renouncement of formalization and the emergence of new needs for formalization.Dieser Beitrag in der Zeitschrift GIO schlägt eine äquivalenzfunktionalistische Perspektive auf postbürokratische Reformen vor, die Teile der Unsicherheitsabsorption von Organisationen in Interaktionssysteme verlagern. Postbürokratie versucht, organisationale und gesellschaftliche Entwicklungen in der zweiten Hälfte des 20. Jahrhunderts auf den Begriff zu bringen. Auch aktuelle agile Managementkonzepte lassen sich der Postbürokratie zuordnen und zeichnen sich unter anderem durch eine Multiplikation von Interaktionen aus. Mithilfe der Theorie sozialer Systeme untersuchen wir wie neue Unsicherheiten in Organisationen durch postbürokratische Reformen entstehen und von agilen Managementkonzepten bearbeitet werden. An den agilen Konzepten Scrum und Holacracy wird gezeigt, dass diese Verlagerung neuen Formalisierungsbedarf produziert. Im Fokus stehen dabei die Zentrierungen kommunikativer Interdependenzen in Interaktionen in der Sach‑, Zeit- und Sozialdimension. Der Beitrag plädiert für eine äquivalenzfunktionalistische Perspektive auf Postbürokratie, die den Zusammenhang von Formalisierungsverzicht in Organisationen und neuen Formalisierungsbedarfen als funktionalen Leistungszusammenhang begreift

Impact of left atrial appendage fibrosis on atrial fibrillation in patients following coronary bypass surgery

Eckstein J, Renner A, Zittermann A, et al. Impact of left atrial appendage fibrosis on atrial fibrillation in patients following coronary bypass surgery. Clinical Cardiology . 2022.OBJECTIVES: We aimed to assess the relationship of left atrial appendage (LAA) fibrosis with atrial fibrillation (AF) and postoperative events in patients receiving coronary artery bypass graft surgery (CABG).; BACKGROUND: Increased atrial fibrosis has been associated with AF and worse outcome following catheter ablation. Only limited data exists focusing on the impact of LAA fibrosis on AF after CABG.; METHODS: LAA tissue from 164 CABG-patients was stained with Masson-Goldner trichrome. The histological landscape was scanned and segmented into superpixels for software analysis (QuPath). A classification algorithm was extensively trained to detect fibrotic superpixels for quantification. In 43 propensity score matched pairs with AF or sinus rhythm (SR), LAA fibrosis was compared. Moreover, subgroups of mitral valve regurgitation (MR) were analyzed as follows: SR, SR+MR, AF and AF+MR. The predictive value of LAA fibrosis postoperative stroke, postoperative AF and mortality was assessed.; RESULTS: Fibrotic remodeling (%) showed no significant difference for the total cohort between the SR and AF group (SR: 30.8±11.4% and AF: 33.8±16.0%, respectively, p=.32). However, significant fibrotic remodeling was observed for SR and AF subgroups (SR: 27.2±12.2% vs. AF: 35.3±13.7%; respectively, p=.049) and between SR and SR+MR subgroups (SR: 27.2±12.2% vs. SR+MR: 34.9±9.1%, respectively, p=.027). LAA fibrosis was not significantly associated with postoperative stroke, postoperative AF or overall mortality (all p>.05).; CONCLUSION: LAA fibrosis may contribute to an individual arrhythmia substrate for AF in patients with AF but also in those with SR and coincidence of MR. LAA fibrosis was not found to be predictive for clinical events in patients after CABG. © 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC

Cell-specific proteome analyses of human bone marrow reveal molecular features of age-dependent functional decline

Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) and five other cell populations that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified is assessed in 59 human subjects from different ages. As the HPCs become older, pathways in central carbon metabolism exhibit features reminiscent of the Warburg effect, where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation reveals a reduced functionality and a bias towards myeloid differentiation. Ageing causes alterations in the bone marrow niche too, and diminishes the functionality of the pathways involved in HPC homing. The data represent a valuable resource for further analyses, and for validation of knowledge gained from animal models