Propagation of hippocampal ripples to the neocortex by way of a subiculum-retrosplenial pathway

Bouts of high frequency activity known as sharp wave ripples (SPW-Rs) facilitate communication between the hippocampus and neocortex. However, the paths and mechanisms by which SPW-Rs broadcast their content are not well understood. Due to its anatomical positioning, the granular retrosplenial cortex (gRSC) may be a bridge for this hippocampo-cortical dialogue. Using silicon probe recordings in awake, head-fixed mice, we show the existence of SPW-R analogues in gRSC and demonstrate their coupling to hippocampal SPW-Rs. gRSC neurons reliably distinguished different subclasses of hippocampal SPW-Rs according to ensemble activity patterns in CA1. We demonstrate that this coupling is brain state-dependent, and delineate a topographically-organized anatomical pathway via VGlut2-expressing, bursty neurons in the subiculum. Optogenetic stimulation or inhibition of bursty subicular cells induced or reduced responses in superficial gRSC, respectively. These results identify a specific path and underlying mechanisms by which the hippocampus can convey neuronal content to the neocortex during SPW-Rs

Biomaterial compuesto de titanio-hidroxiapatita

Fil: Oldani, C. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Grinschpun, L. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Cormin, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Schneiter, M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Salvatierra, N. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Los implantes no cementados requieren el menor tiempo de osteointegración ya que el mismo hueso será su anclaje. Por lo tanto, esta aplicación requiere un material con bioactividad superficial y una estructura porosa importante. Este artículo presenta un compuesto a base de titanio, reforzado con partículas de hidroxiapatita producido mediante técnicas de metalurgia de polvos. Las materias primas fueron mezclas de polvos de hidruro de titanio e hidroxiapatita natural (20% en peso), obtenida a partir de hueso bovino, prensados a 490 MPa en un molde rígido y sinterizados a 1200 º C en vacío y a temperaturas en el rango de 600 a 1000 º C en argón. Las muestras sinterizadas a 1200 º C muestran una variación en volumen (dilatación) debido a una reacción entre los componentes del compuesto. Estas reacciones no aparecen a temperaturas bajas (600 y 800 º C), pero estas muestras exhiben cierta porosidad debido a la escasa sinterización. Los compactos se caracterizaron por metalografía y mediante pruebas biológicas de citotoxicidad. Los mejores resultados metalográficos se obtienen en las muestras sinterizadas a 800 ºC, la que no es citotóxica.Fil: Oldani, C. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Grinschpun, L. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Cormin, R. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Schneiter, M. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Fil: Salvatierra, N. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Departamento de Materiales; Argentina.Ingeniería de los Materiale

The GTPase-activating protein RN-tre controls focal adhesion turnover and cell migration.

SummaryBackgroundIntegrin-mediated adhesion of cells to the extracellular matrix (ECM) relies on the dynamic formation of focal adhesions (FAs), which are biochemical and mechanosensitive platforms composed of a large variety of cytosolic and transmembrane proteins. During migration, there is a constant turnover of ECM contacts that initially form as nascent adhesions at the leading edge, mature into FAs as actomyosin tension builds up, and are then disassembled at the cell rear, thus allowing for cell detachment. Although the mechanisms of FA assembly have largely been defined, the molecular circuitry that regulates their disassembly still remains elusive.ResultsHere, we show that RN-tre, a GTPase-activating protein (GAP) for Rabs including Rab5 and Rab43, is a novel regulator of FA dynamics and cell migration. RN-tre localizes to FAs and to a pool of Rab5-positive vesicles mainly associated with FAs undergoing rapid remodeling. We found that RN-tre inhibits endocytosis of β1, but not β3, integrins and delays the turnover of FAs, ultimately impairing β1-dependent, but not β3-dependent, chemotactic cell migration. All of these effects are mediated by its GAP activity and rely on Rab5.ConclusionsOur findings identify RN-tre as the Rab5-GAP that spatiotemporally controls FA remodeling during chemotactic cell migration

Donor Lymphocyte Infusions After Allogeneic Stem Cell Transplantation in Acute Leukemia: A Survey From the Gruppo Italiano Trapianto Midollo Osseo (GITMO)

We conducted a retrospective multicenter study including pediatric and adult patients with acute leukemia (AL) who received donor lymphocyte infusions (DLIs) after allogeneic hematopoietic stem cell transplantation (HCT) between January 1, 2010 and December 31, 2015, in order to determine the efficacy and toxicity of the immune treatment. Two hundred fifty-two patients, median age 45.1 years (1.6\u201373.4), were enrolled from 34 Italian transplant centers. The underlying disease was acute myeloid leukemia in 180 cases (71%). Donors were HLA identical or 1 locus mismatched sibling (40%), unrelated (40%), or haploidentical (20%). The first DLI was administered at a median time of 258 days (55\u20133,784) after HCT. The main indication for DLI was leukemia relapse (73%), followed by mixed chimerism (17%), and pre-emptive/prophylactic use (10%). Ninety-six patients (38%) received one single infusion, whereas 65 (26%), 42 (17%), and 49 patients (19%) received 2, 3, or 654 infusions, respectively, with a median of 31 days between two subsequent DLIs. Forty percent of evaluable patients received no treatment before the first DLI, whereas radiotherapy, conventional chemotherapy or targeted treatments were administered in 3, 39, and 18%, respectively. In informative patients, a few severe adverse events were reported: grade III\u2013IV graft versus host disease (GVHD) (3%), grade III\u2013IV hematological toxicity (11%), and DLI-related mortality (9%). Forty-six patients (18%) received a second HCT after a median of 232 days (32\u20131,390) from the first DLI. With a median follow-up of 461 days (2\u20133,255) after the first DLI, 1-, 3-, and 5- year overall survival (OS) of the whole group from start of DLI treatment was 55, 39, and 33%, respectively. In multivariate analysis, older recipient age, and transplants from haploidentical donors significantly reduced OS, whereas DLI for mixed chimerism or as pre-emptive/prophylactic treatment compared to DLI for AL relapse and a schedule including more than one DLI significantly prolonged OS. This GITMO survey confirms that DLI administration in absence of overt hematological relapse and multiple infusions are associated with a favorable outcome in AL patients. DLI from haploidentical donors had a poor outcome and may represent an area of further investigation

Commercial fisheries in a mega unregulated floodplain river: assessment of the most favourable hydrological conditions for its preservation

This paper deals with the hydrological variability effects on the primary commercial fish species inhabiting the main channel and the floodplain of the large Paraná River in its middle reaches in Argentina. Analysing more than eight decades (1935–2016) of information on the most frequent and abundant commercial species in conjunction with hydrological levels and temperature, our results show that spring–summer floods of a certain magnitude (c. 6 m) and durations (> 80 days) are crucial for sustaining commercial fisheries. Moreover, the frequency of these floods was modulated by the decadal climatic fluctuations that have occurred over the past 100 years in the Paraná Basin. An insight into the probable incidence of some anthropogenic influences is also provided.Fil: Rabuffetti, Ana Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Espínola, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Abrial, Elie. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Amsler, Mario Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Blettler, Martin Cesar Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Eurich, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Eberle Folmer, Eliana Gisel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentin

Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities

Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country.To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt.Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software.The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health.Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians

Allelic HLA Matching and Pair Origin Are Favorable Prognostic Factors for Unrelated Hematopoietic Stem Cell Transplantation in Neoplastic Hematologic Diseases: An Italian Analysis by the Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade 65II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and 648/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence

Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population