Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition.

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development

New insights into emotion valence and loyalty intentions in relational exchanges

This research examines how emotion valence and future intentions arising from relational exchangeswithaservicefirmdependonaconsumer'slevelofgoalattainmentandlocusofcausality (firm vs. self) of relational outcomes. Drawing on the theories of goal-directed behavior and agency of causation, this study hypothesizes that levels of goal attainment and locus of causality influence the generation of positive emotions (gratitude), negative emotions (grudge and guilt), relational mediators (trust and commitment), and subsequent future intentions to remain loyal to the firm. Based on a controlled experiment with 284 subjects in a consumer-determined relationshipsetting,theresearchfindsthatemotionvalenceandfutureloyaltyintentionsarecontingent upon the fulfillment of relational objectives of individual consumers and the agency of causation for the outcome of the relational exchanges. In doing so, this study delineates the conditioning mechanism that directs how emotion valence influences behavioral intentions. The study contributes to the consumer behavior and services marketing literatures on consumption-based emotionsandhassignificantpracticeimplicationsforrelationalbehaviors

A transit amplifying population underpins the efficient regenerative capacity of the testis

The spermatogonial stem cell (SSC) that supports spermatogenesis throughout adult life resides within the GFRα1-expressing A type undifferentiated spermatogonia. The decision to commit to spermatogenic differentiation coincides with the loss of GFRα1 and reciprocal gain of Ngn3 (Neurog3) expression. Through the analysis of the piRNA factor Miwi2 (Piwil4), we identify a novel population of Ngn3-expressing spermatogonia that are essential for efficient testicular regeneration after injury. Depletion of Miwi2-expressing cells results in a transient impact on testicular homeostasis, with this population behaving strictly as transit amplifying cells under homeostatic conditions. However, upon injury, Miwi2-expressing cells are essential for the efficient regenerative capacity of the testis, and also display facultative stem activity in transplantation assays. In summary, the mouse testis has adopted a regenerative strategy to expand stem cell activity by incorporating a transit-amplifying population to the effective stem cell pool, thus ensuring rapid and efficient tissue repair

Depression, the Family, and Family Therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100166/1/j.1467-8438.1992.tb00921.x.pd

Single-cell transcriptomics identifies CD44 as a marker and regulator of endothelial to haematopoietic transition

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development

Contributions of neuropsychology to the study of ancient literature

The present work introduces the neuropsychological paradigm as a new approach to studying ancient literature. In the first part of the article, an epistemological framework for the proper use of neuropsychology in relation to ancient literature is presented. The article then discusses neuropsychological methods of studying different human experiences and dimensions already addressed by ancient literatures. The experiences of human encounters with gods among ancient cultures are first considered, through the contributions of Julian Jaynes and Eric R. Dodds. The concepts of right and left in the Bible, and that of soul are then discussed. Ecstatic experience in Paul of Tarsus is also presented, with a particular focus on glossolalia. Neuroscientific differences between mindful and unitive meditative practices are then described referring to ancient Buddhist literature, and finally a brief description of dreams in ancient Greek literature is proposed. Neuropsychology variously enables a more profound understanding of themes characterizing human experiences that ancient literature has already explored; these investigations prove that the collaboration of neuroscience and humanistic studies can return fruitful and interesting results

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients

Mathematical applications in criminal justice

No abstract availabl

The construction of police knowledge on gun crime

No abstract availabl