Indium segregation in Gd5(Si, Ge)4 magnetocaloric materials

Chemical substitution is one of the most efficient tools to tune and optimize magnetic and magnetocaloric properties of the giant magnetocaloric materials. In particular, Indium substitutions could be useful both for tuning properties of these interesting intermetallic materials and to unveil their local-scale behavior across the magnetostructural transition via hyperfine techniques. Hence, in order to investigate the effect of Indium additions on the crystal structure, micro-structure, magnetic and magnetocaloric properties, a series of In-containing samples derived from the base Gd5Si1.2Ge2.8 stoichiometry were prepared. The major findings are that while In is insoluble in the 5: 4 phase, it will instead promote the emergence of the impurity 5: 3 phase and segregates into this phase. Hence, In leads to major crystallographic changes, which enhance atomic disorder and disrupt the Si to Ge ratio in the 5: 4 phase. Subsequently, a higher 5: 4 unit cell volume and a lower magnetic ordering temperature are found in the In-substituted samples. Finally, the magnetocaloric properties of the In-substituted samples reveal a detrimental effect on the maximum magnetic entropy change.Work is partially supported by the projects POCI/CTM/61284/2004, PTDC/CTM-NAN/115125/2009, FEDER/POCTI n0155/94 from Fundacão para a Ciência ex Tecnologia (FCT), Portugal. A.M.P. thanks FCT for the Grant No. SFRH/BPD/63150/2009. J H Belo thanks FCT for the Grant SFRH/BD/88440/2012, the project PTDC/FISMAC/ 31302/2017 and his contract DL57/2016 reference SFRH-BPD-87430/2012. Work at IFIMUP is supported by the following funding projects: POCI-01-0145-FEDER-032527, POCI-01–0145-FEDER-029454 and CERN-FIS-PAR-0005-2017. Work at the INMA is supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades through project MAT2017-82970-C2, PID2020-112914RB-I00 and Spanish DGA (grant no. E28−20R). The research at Ames Laboratory is supported by the Materials Sciences and Engineering Division, Office of Basic Energy Sciences of the U.S. Department of Energy (DOE). Ames Laboratory is operated for the U.S DOE by Iowa State University under Contract No. DE-AC02-07CH11358.Peer reviewe

Gross stomach morphology in akodontine rodents (Cricetidae: Sigmodontinae: Akodontini): a reappraisal of its significance in a phylogenetic context

Akodontini, the second largest tribe within sigmodontine rodents, encompasses several stomach morphologies. This is striking because most sigmodontine groups of comparable taxonomic rank are very conservative in this respect. Based on extensive sampling of newly dissected specimens (213 stomachs representing 36 species), as well as published examples, covering almost all akodontine living genera (15 of 16), we undertook a reappraisal of the gross morphology of this organ. We then mapped this information, together with gallbladder occurrence, in a refined multilocus molecular phylogeny of the tribe. We surveyed three different configurations of stomachs in akodontines, according to the degree of development and location of the glandular epithelium; in addition, two minor variations of one of these types were described. Of the five major clades that integrate Akodontini, four are characterized by a single stomach morphology, while one clade exhibits two morphologies. Mapping stomach type on the phylogeny recovered two configurations for the most recent ancestor of Akodontini. A revised survey of gallbladder evidence also revealed overlooked congruencies. The observed stomach diversity and its arrangement in the phylogeny, along with additional morphological characters and the genetic diversity among the main clades, supports the necessity of changes in the current classification of the tribe. Recognition of subtribes or partitioning of Akodontini into several additional tribes of equal rank could be suitable options.Akodontini, la segunda mayor tribu de los roedores sigmodontinos, presenta varias morfologías de estómago. Esto es extraño porque la mayor parte de los grupos comparables de sigmodontinos son muy conservadores en este aspecto. Sobre la base de una extensa muestra de nuevos especímenes diseccionados (213 estómagos representando 36 especies), como así también de ejemplos publicados, abarcando la casi totalidad de los géneros vivientes de akodontinos (15 de 16), efectuamos una re-evaluación de la anatomía gruesa de este órgano. Luego, mapeamos esta información, conjuntamente con la ocurrencia de vesícula biliar, en una filogenia molecular multilocus refinada para la tribu. Detectamos tres configuraciones diferentes de estómagos en akodontinos, de acuerdo con el grado de desarrollo y localización del epitelio glandular; adicionalmente, fueron descriptas dos variantes menores de estos tipos. De los cinco clados principales recobrados en Akodontini, cuatro están caracterizados por una única configuración de morfología del estómago y uno exhibe dos morfologías. Las reconstrucciones de los caracteres asociados al estómago sobre la filogenia concuerdan en recuperar dos configuraciones en el ancestro más reciente de Akodontini. Una revisión de la evidencia de la vesícula biliar también reveló congruencias hasta ahora inadvertidas. La diversidad estomacal observada y su disposición en la filogenia junto con otros caracteres morfológicos, más la diversidad genética entre los clados principales, sugieren la necesidad de cambios en la clasificación vigente de la tribu. El reconocimiento de subtribus o la partición de los Akodontini en varias unidades de rango tribal podrían ser opciones adecuadas.Fil: Pardiñas, Ulises Francisco J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Canõn, Carola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Diversidad y Evolución Austral; ArgentinaFil: Galliari, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Brito, Jorge. Instituto Nacional de Biodiversidad; EcuadorFil: Bernal Hoverud, Nuria. Wildlife Conservation Society; BoliviaFil: Lessa, Gisele. Universidade Federal de Viçosa.; BrasilFil: De Oliveira, Joaõ Alves. Universidade Federal do Rio de Janeiro; Brasi

Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.

Bruton's tyrosine kinase (BTK) is a member of the TEC-family kinases and crucial for the proliferation and differentiation of B-cells. We evaluated the therapeutic potential of a covalent inhibitor (JS25) with nanomolar potency against BTK and with a more desirable selectivity and inhibitory profile compared to the FDA-approved BTK inhibitors ibrutinib and acalabrutinib. Structural prediction of the BTK/JS25 complex revealed sequestration of Tyr551 that leads to BTK's inactivation. JS25 also inhibited the proliferation of myeloid and lymphoid B-cell cancer cell lines. Its therapeutic potential was further tested against ibrutinib in preclinical models of B-cell cancers. JS25 treatment induced a more pronounced cell death in a murine xenograft model of Burkitt's lymphoma, causing a 30-40% reduction of the subcutaneous tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. In a patient model of diffuse large B-cell lymphoma, the drug response of JS25 was higher than that of ibrutinib, leading to a 64% "on-target" efficacy. Finally, in zebrafish patient-derived xenografts of chronic lymphocytic leukemia, JS25 was faster and more effective in decreasing tumor burden, producing superior therapeutic effects compared to ibrutinib. We expect JS25 to become therapeutically relevant as a BTK inhibitor and to find applications in the treatment of hematological cancers and other pathologies with unmet clinical treatment

Association of obesity with 3-month mortality in kidney failure patients with COVID-19

Background: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. Methods: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m2), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. Results: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (Pinteraction = 0.99), but differed by sex (Pinteraction = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. Conclusion: In KFRT patients with COVID-19, on dialysis or a kidney transplant, obesity is associated with an increased risk of mortality at 3 months. This is in contrast to the obesity paradox generally observed in dialysis patients. Additional studies are required to corroborate the sex difference in the association of obesity with mortality