Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in
are reactivated from quiescence in response to nutrition by the insulin signaling ...pathway. It is widely accepted that quiescent stem cells are arrested in G
In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G
or G
G
-G
heterogeneity directs NSC behavior: G
qNSCs reactivate before G
qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G
NSCs to enter quiescence by promoting degradation of Cdc25
and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences
transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.
Making Room for the River Yu, Siyu; Brand, A. D.; Berke, Philip
Journal of the American Planning Association,
10/1/2020, 2020-10-01, Letnik:
86, Številka:
4
Journal Article
Recenzirano
Problem, research strategy, and findings: In this study we analyze plan integration for flood resilience in the city of Nijmegen, the site of the largest Room for the River project in The ...Netherlands. Little is known about the degree to which local and regional plans are coordinated with the national Room for the River program or about the cumulative influence of plans on flood vulnerability. To effectively investigate these issues, we use and build upon the Plan Integration for Resilience Scorecard (PIRS) concept and method, which analyzes the consistency and effects of networks of plans on community vulnerability. We expand the scope to include plans from multiple administrative scales and the focus to include environmental vulnerability. Using a three-phase evaluation process, we demonstrate that Room for the River policies are well integrated in Nijmegen's network of plans, particularly with respect to flood safety and natural protection. However, we also find that policies at different administrative scales lack consistency in some places, some socially vulnerable neighborhoods receive comparatively little policy attention, and local plans often prioritize development over flood resilience, though higher tier plans sometimes make up for these policy gaps. Flood resilience is still finding its way in the Dutch planning system.
Takeaway for practice: The PIRS offers planning practitioners a method to assess how networks of plans influence community vulnerability and, as demonstrated in this analysis, to determine the degree to which plans at multiple administrative scales target the most physically, socially, and environmentally vulnerable geographic areas. It can be used to support the ambitious goals of a program like Room for the River and align them with local development priorities.
Comprehensive national joint replacement registries with well-validated data offer unique opportunities for examining the potential future burden of hip and knee osteoarthritis (OA) at a population ...level. This study aimed to forecast the burden of primary total knee (TKR) and hip replacements (THR) performed for OA in Australia to the year 2030, and to model the impact of contrasting obesity scenarios on TKR burden.
De-identified TKR and THR data for 2003-2013 were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. Population projections and obesity trends were obtained from the Australian Bureau of Statistics, with public and private hospital costs sourced from the National Hospital Cost Data Collection. Procedure rates were projected according to two scenarios: (1) constant rate of surgery from 2013 onwards; and (2) continued growth in surgery rates based on 2003-2013 growth. Sensitivity analyses were used to estimate future TKR burden if: (1) obesity rates continued to increase linearly; or (2) 1-5% of the overweight or obese population attained a normal body mass index.
Based on recent growth, the incidence of TKR and THR for OA is estimated to rise by 276% and 208%, respectively, by 2030. The total cost to the healthcare system would be $AUD5.32 billion, of which $AUD3.54 billion relates to the private sector. Projected growth in obesity rates would result in 24,707 additional TKRs totalling $AUD521 million. A population-level reduction in obesity could result in up to 8062 fewer procedures and cost savings of up to $AUD170 million.
If surgery trends for OA continue, Australia faces an unsustainable joint replacement burden by 2030, with significant healthcare budget and health workforce implications. Strategies to reduce national obesity could produce important TKR savings.
The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac cell types arise is limited. We mapped the origin of the embryonic mouse ...heart at single-cell resolution using a combination of transcriptomic, imaging, and genetic lineage labeling approaches. This mapping provided a transcriptional and anatomic definition of cardiac progenitor types. Furthermore, it revealed a cardiac progenitor pool that is anatomically and transcriptionally distinct from currently known cardiac progenitors. Besides contributing to cardiomyocytes, these cells also represent the earliest progenitor of the epicardium, a source of trophic factors and cells during cardiac development and injury. This study provides detailed insights into the formation of early cardiac cell types, with particular relevance to the development of cell-based cardiac regenerative therapies.
Human influenza A viruses are known to be transmitted via the air from person to person. It is unknown from which anatomical site of the respiratory tract influenza A virus transmission occurs. Here, ...pairs of genetically tagged and untagged influenza A/H1N1, A/H3N2 and A/H5N1 viruses that are transmissible via the air are used to co-infect donor ferrets via the intranasal and intratracheal routes to cause an upper and lower respiratory tract infection, respectively. In all transmission cases, we observe that the viruses in the recipient ferrets are of the same genotype as the viruses inoculated intranasally, demonstrating that they are expelled from the upper respiratory tract of ferrets rather than from trachea or the lower airways. Moreover, influenza A viruses that are transmissible via the air preferentially infect ferret and human nasal respiratory epithelium. These results indicate that virus replication in the upper respiratory tract, the nasal respiratory epithelium in particular, of donors is a driver for transmission of influenza A viruses via the air.
Despite Antiplatelet therapy (APT), cardiovascular patients undergoing revascularisation remain at high risk for thrombotic events. Individual response to APT varies substantially, resulting in ...insufficient protection from thrombotic events due to high on-treatment platelet reactivity (HTPR) in less than or equal to40% of patients. Individual variation in platelet response impairs APT guidance on a single patient level. Unfortunately, little is known about individual platelet response to APT over time, timing for accurate residual platelet reactivity measurement, or the optimal test to monitor residual platelet reactivity. To investigate residual platelet reactivity variability over time in individual patients undergoing carotid endarterectomy (CEA) treated with clopidogrel. Platelet reactivity was determined in patients undergoing CEA in a prospective, single-centre, observational study using the VerifyNow (change in turbidity from ADP-induced binding to fibrinogen-coated beads), the VASP assay (quantification of phosphorylation of vasodilator-stimulated phosphoprotein), and a flow-cytometry-based assay (PACT) at four perioperative time points. Genotyping identified slow (CYP2C19*2 and CYP2C19*3) and fast (CYP2C19*17) metabolisers. Between December 2017 and November 2019, 50 patients undergoing CEA were included. Platelet reactivity measured with the VerifyNow (p = < .001) and VASP (p = .029) changed over time, while the PACT did not. The VerifyNow identified patients changing HTRP status after surgery. The VASP identified patients changing HTPR status after eight weeks (p = .018). CYP2C19 genotyping identified 13 slow metabolisers. In patients undergoing CEA, perioperative platelet reactivity measurements fluctuate over time with little agreement between platelet reactivity assays. Consequently, HTPR status of individual patients measured with the VerifyNow and VASP assay changed over time. Therefore, generally used perioperative platelet reactivity measurements seem unreliable for adjusting perioperative APT strategy.
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