FOG-1 and GATA-1 act sequentially to specify definitive megakaryocytic and erythroid progenitors

During haematopoiesis, megakaryocytes and erythrocytes derive from a common precursor called preMegE. This study reports a role for the transcription factor FOG-1 in specification of preMegEs, while GATA-1 is subsequently required for erythroid-lineage commitment

Influence of C(60) fullerene on the ischemia-reperfusion injury in the skeletal muscle of rat limb: mechanokinetic and biochemical analysis

Influence of the pristine C60 fullerene aqueous colloidal solution (C60FAS) on the ischemia-reperfusion injury in the skeletal muscle of rat limb was studied. Skeletal muscle damage effects were induced by 3 h lasting­ vascular ischemia. The impact of C60FAS was studied after its intramuscular injection immediately after 1 h of reper­fusion at different doses, namely: 1, 2 and 3 mg/kg of body weight. Changes in the mechanokinetic parame­ters of ischemic skeletal muscle contraction at different modes of functioning and biochemical parame­ters of blood were used as markers of ischemic injury, and analyzed in detail under action of C60FAS. The obtained results indicate on great promise of use of C60FAS to reduce the consequences of ischemic muscle trauma

Cluster mutation-periodic quivers and associated Laurent sequences

We consider quivers/skew-symmetric matrices under the action of mutation (in the cluster algebra sense). We classify those which are isomorphic to their own mutation via a cycle permuting all the vertices, and give families of quivers which have higher periodicity. The periodicity means that sequences given by recurrence relations arise in a natural way from the associated cluster algebras. We present a number of interesting new families of non-linear recurrences, necessarily with the Laurent property, of both the real line and the plane, containing integrable maps as special cases. In particular, we show that some of these recurrences can be linearised and, with certain initial conditions, give integer sequences which contain all solutions of some particular Pell equations. We extend our construction to include recurrences with parameters, giving an explanation of some observations made by Gale. Finally, we point out a connection between quivers which arise in our classification and those arising in the context of quiver gauge theories.Comment: The final publication is available at www.springerlink.com. 42 pages, 35 figure

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Éducation inclusive et prévention de la violence

International audienc

ORIGINAL ARTICLE Cytochrome P450 2C9 polymorphism and acenocoumarol therapy

Background: Oral anticoagulants, in Hungary acenocoumarol being the one exclusively used, have a low therapeutic index and a high bleeding complication rate. The cytochrome P450 2C9 enzyme plays an important role in their metabolism. Aim: To investigate the influence of CYP2C9 polymorphism on the occurrence of bleeding complications related to acenocoumarol therapy. Methods: Genotyping of 421 patients (183 men and 238 women, mean age 66.2±11.8 years), who had been taking acenocoumarol for at least 6 months, was performed. Based on patient history and laboratory data, the correlations between genotype and acenocoumarol dose and bleeding complications were retrospectively analysed. Results: In 145 patients bearing alleles with reduced activity (CYP2C9*2 and/or *3), the optimal dose of acenocoumarol was significantly (pWstęp: Doustne leki przeciwzakrzepowe, w tym acenokumarol, który jest jedynym antykoagulantem stosowanym na Węgrzech, charakteryzują się niskim współczynnikiem terapeutycznym i wysokim ryzykiem powikłań krwotocznych. Układ cytochromu P450 (CYP2C9) bierze istotny udział w metabolizmie antykoagulantów doustnych. Cel pracy: Ocena wpływu polimorfizmu CYP2C9 na częstość występowania powikłań krwotocznych związanych ze stosowaniem acenokumarolu. Metodyka: Grupa badana składała się z 421 chorych (183 mężczyzn, 238 kobiet, średni wiek 66,2±11,8 lat), u których stosowano acenokumarol przez okres co najmniej 6 mies. przed przeprowadzeniem niniejszej analizy. Na podstawie wywiadu, danych z historii choroby, badań laboratoryjnych i genetycznych dokonano retrospektywnej oceny zależności pomiędzy genotypem a stosowaną dawką acenokumarolu i występowaniem powikłań krwotocznych. Wyniki: U 145 chorych, u których występowały allele o zmniejszonej aktywności (CYP2C9*2 lub *3) optymalna dawka acenokumarolu była istotnie niższa niż u chorych z dzikim typem allelu (odpowiednio 2,12±0,96 mg/dobę vs 2,90±1,46 mg/dobę, p 6 stwierdzano istotnie częściej u chorych, u których stwierdzano allele o zmniejszonej aktywności (p=0,021). Częstość występowania małych powikłań krwotocznych była istotnie wyższa u chorych, u których stwierdzano allele o zmniejszonej aktywności (OR=1,99; CI=1,20–3,33,