Synaptic plasticity and cognitive function are disrupted in the absence of Lrp4.

Lrp4, the muscle receptor for neuronal Agrin, is expressed in the hippocampus and areas involved in cognition. The function of Lrp4 in the brain, however, is unknown, as Lrp4-/- mice fail to form neuromuscular synapses and die at birth. Lrp4-/- mice, rescued for Lrp4 expression selectively in muscle, survive into adulthood and showed profound deficits in cognitive tasks that assess learning and memory. To learn whether synapses form and function aberrantly, we used electrophysiological and anatomical methods to study hippocampal CA3-CA1 synapses. In the absence of Lrp4, the organization of the hippocampus appeared normal, but the frequency of spontaneous release events and spine density on primary apical dendrites were reduced. CA3 input was unable to adequately depolarize CA1 neurons to induce long-term potentiation. Our studies demonstrate a role for Lrp4 in hippocampal function and suggest that patients with mutations in Lrp4 or auto-antibodies to Lrp4 should be evaluated for neurological deficits

Minimal Stability in Maximal Supergravity

Recently, it has been shown that maximal supergravity allows for non-supersymmetric AdS critical points that are perturbatively stable. We investigate this phenomenon of stability without supersymmetry from the sGoldstino point of view. In particular, we calculate the projection of the mass matrix onto the sGoldstino directions, and derive the necessary conditions for stability. Indeed we find a narrow window allowing for stable SUSY breaking points. As a by-product of our analysis, we find that it seems impossible to perturb supersymmetric critical points into non-supersymmetric ones: there is a minimal amount of SUSY breaking in maximal supergravity.Comment: 27 pages, 1 figure. v2: two typos corrected, published versio

A semi-synthetic molecule derived from dehydroleucodine affects the trypanosoma cruzi cell cycle

Trypanosoma cruzi is a parasite causing Chagas disease, which is endemic in Latin America, but in the last 20 years, it has expanded worldwide. The current treatment is restricted to Nifurtimox and Benznidazole, but both are relatively toxic and have limited efficacy on the patients. The development of new effective therapeutic agents is urgently needed. The sesquiterpene lactones (STLs) are natural compounds purified from native plants of Argentina with multiple pharmacological applications. The STL dehydroleucodine (DhL), has an alpha-methylene group that could react with multiple sulfhydryl group-containing proteins, affecting cellular functions such as proliferation, the activity mitochondrial, leading to the cell death/apoptosis. This study is focused on elucidating the action mechanisms of DhL and its derivative DC-X11, obtained by chemical substitution, on T. cruzi epimastigotes (strain Dm28c). We observed that DhL and DC-X11 have antiproliferative and cytostatic effects on the parasites. By morphological and ultrastructural studies, we observed an increase of parasites with multiple cell nuclei, kinetoplasts, or flagella after the treatment with DC-X11, suggesting an effect on late steps of the cell cycle (i.e., cellular division). These results were confirmed with parasites synchronized with hydroxyurea (HU 20 mM) for 24 h, and then they were treated with the compound. We concluded that the derivative DC-X11 inhibits T. cruzi proliferation by delaying the progression of the cell division. Further studies are necessary to identify the molecular targets affected by DC-X11.Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad Biología de Cuy

Sesquiterpene lactones affect the redox system of trypanosoma cruzi

Chagas disease is caused by Trypanosoma cruzi (T. cruzi) and affects millions of people worldwide, mostly in Latin America. Despite its sanitary importance, there are currently only two drugs available for its treatment: benznidazole and nifurtimox, both exhibiting serious adverse effects on patients. In order to complete its life cycle, T. cruzi faces extreme environmental conditions ?i.e. oxidative stress- as it propagates from an insect vector to a mammalian host, driving the transition from non-infective epimastigote to the infective form trypomastigote. It is known that the antioxidant defense system in the trypanosomatids is different from that in mammalian cells since the parasites have exclusive molecules and reducing enzymes. Because of this, the parasite redox machinery is an attractive target for antiparasitic therapies. The sesquiterpene lactone dehydroleucodine (DhL), is a trypanocidal molecule containing an alpha-methylene group that could react with sulfhydryl groups of key redox enzymes. This study was focused on elucidating the DhL mechanism of action and extended to ten DhL derivatives (DC-X1 to DC-X10) obtained by chemical substitutions on the methylene group. We firstly confirmed an antiproliferative effect of DhL and its chemical derivatives, being DC- X6 one of the most active. The effect of DhL and DC-X6 was blocked by reduced glutathione, suggesting that compounds are reactive to sulfhydryl groups of certain molecules. Moreover, parasites overexpressing reducing enzymes, such as Tc-CPX, showed a protective effect against these STLs. Consistent with these results, both STLs increased ROS concentration in the wild type parasites. These results indicate that STLs induce oxidative stress on the parasites, possibly by affecting some crucial enzymes of the redox system.Fil: Gomez, Jessica Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Departamento de Biología; ArgentinaFil: Guarise, C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; ArgentinaFil: Tello Faral, P.. Instituto Pasteur de Montevideo; UruguayFil: Robello, Carlos. Instituto Pasteur de Montevideo; UruguayFil: Caballero, P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; ArgentinaFil: Cifuente, Diego Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa, M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad de Biología de Cuy

Can anodised zirconium implants stimulate bone formation? Preliminary study in rat model

Mechanical properties and good biocompatibility of zirconium and some of its alloys focus these materials as good candidates for biomedical applications. The attractive in vivo performance of zirconium is mainly due to the presence of a protective oxide layer. In this preliminary study, surface modification of pure zirconium was made by anodisation in acidic media at low potentials, enhancing the barrier protection given by the oxides and the osseointegration. Electrochemical and SEM (scanning electron microscopy) assays were done in commercially pure zirconium cylinders and two surface conditions were compared: pure and zirconium anodised at 30V. The in vivo assays were held in a tibia rat model. The histological features and fluorochrome labelling changes of newly bone formed around implants were evaluated on the non-decalcified sections 63 days after surgery. Electrochemical and SEM assays showed that anodisation treatment would increased the barrier effect over the material and the in vivo assays showed a continuous newly bone formation around the implant with a different amount of osteocytes in their lacunaes depending the region. There was no significant change in bone thickness around both kinds of implants but conversely a significant increase in the mineralization apposition rate was determined for the anodised condition suggesting that anodisation treatment would stimulate and assist to the osseointegration process. We conclude that anodisation treatment at 30 V can stimulate the implant fixation in a rat model and this study would propose the study of zirconium as candidate material for permanent implant.Fil: Katunar, Maria Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Gomez Sanchez, Andrea Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Ballarre, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Baca, Matías. Hospital Interzonal General de Agudos ‘‘Oscar Alende’’. Mar del Plata; ArgentinaFil: Vottola, Carlos. Hospital Interzonal General de Agudos ‘‘Oscar Alende’’; ArgentinaFil: Orellano, Juan C.. Hospital Interzonal General de Agudos ‘‘Oscar Alende’’. Mar del Plata; ArgentinaFil: Schell, Hanna. Universitatsmedizin Berlin; AlemaniaFil: Duffo, Gustavo Sergio. Comision Nacional de Energia Atomica. Gerencia D/area de Energia Nuclear. Unidad de Actividad de Materiales (cac); Argentina. Universidad Nacional de San Martín; ArgentinaFil: Cere, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

A Benchmark White Dwarf-Ultracool Dwarf Wide Field Binary

© 2023 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/We present the discovery and multi-wavelength characterisation of VVV J1438-6158 AB, a new field wide-binary system consisting of a 4.6(+5.5-2.4) Gyr and Teff = 9500+/-125 K DA white dwarf (WD) and a Teff = 2400+/-50 K M8 ultracool dwarf (UCD). The projected separation of the system is a = 1236.73 au (~13.8"), and although along the line-of-sight towards the Scorpius-Centaurus (Sco-Cen) stellar association, VVV J1438-6158 AB is likely to be a field star, from a kinematic 6D probabilistic analysis. We estimated the physical, and dynamical parameters of both components via interpolations with theoretical models and evolutionary tracks, which allowed us to retrieve a mass of 0.62+/-0.18 MSun for the WD, and a mass of 98.5+/-6.2 MJup (~0.094+/-0.006 MSun) for the UCD. The radii of the two components were also estimated at 0.01309+/-0.0003 RSun and 1.22+/-0.05 RJup, respectively. VVV J1438-6158 AB stands out as a benchmark system for comprehending the evolution of WDs and low-mass companions given its status as one of the most widely separated WD+UCD systems known to date, which likely indicates that both components may have evolved independently of each other, and also being characterised by a large mass-ratio (q = 0.15+/-0.04), which likely indicates a formation pathway similar to that of stellar binary systems.Peer reviewe

Technological Aspects of the Production of Fructo and Galacto-Oligosaccharides. Enzymatic Synthesis and Hydrolysis

Fructo- and galacto-oligosaccharides (FOS and GOS) are non-digestible oligosaccharides with prebiotic properties that can be incorporated into a wide number of products. This review details the general outlines for the production of FOS and GOS, both by enzymatic synthesis using disaccharides or other substrates, and by hydrolysis of polysaccharides. Special emphasis is laid on technological aspects, raw materials, properties, and applications

The Role of Gender Inequality and Health Expenditure on the Coverage of Demand for Family Planning Satisfied by Modern Contraceptives: A Multilevel Analysis of Cross-Sectional Studies in 14 LAC Countries

BACKGROUND: Despite international efforts to improve reproductive health indicators, little attention is paid to the contributions of contextual factors to modern contraceptive coverage, especially in the Latin America and the Caribbean (LAC) region. This study aimed to identify the association between country-level Gender Inequality and Health Expenditure with demand for family planning satisfied by modern contraceptive methods (DFPSm) in Latin American sexually active women. METHODS: Our analyses included data from the most recent (post-2010) Demographic and Health Survey or Multiple Indicator Cluster Survey from 14 LAC countries. Descriptive analyses and multilevel logistic regressions were performed. Six individual-level factors were included. The effect of the country-level factors Gender Inequality Index (GII) and Current Health Expenditure on DFPSm was investigated. FINDINGS: DFPSm ranged from 41.8% (95% CI: 40.2-43.5) in Haiti to 85.6% (95% CI: 84.9-86.3) in Colombia, with an overall median coverage of 77.8%. A direct association between the odds of DFPSm and woman\u27s education, wealth index, and the number of children was identified. Women from countries in the highest GII tertile were less likely (OR: 0.32, 95% CI: 0.13-0.76) to have DFPSm than those living in countries in the lowest tertile. INTERPRETATION: Understanding the contribution of country-level factors to modern contraception may allow macro-level actions focused on the population\u27s reproductive needs. In this sense, country-level gender inequalities play an important role, as well as individual factors such as wealth and education. FUNDING: Bill and Melinda Gates Foundation and Associação Brasileira de Saúde Coletiva (ABRASCO)

Integrating NGS-derived mutational profiling in the diagnosis of multiple lung adenocarcinomas

MICROABSTRACT: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8). Accuracy of diagnosis can be significantly improved with integration of NGS data. BACKGROUND: Distinguishing between multiple primary lung cancers (MPLC) and intrapulmonary metastases (IPM) is challenging. The goal of this study was to evaluate how Next Generation Sequencing (NGS) information may be integrated in the diagnostic strategy. PATIENTS AND METHODS: Patients with multiple lung adenocarcinomas were classified using both the comprehensive histologic assessment and NGS. We computed the joint probability of each pair having independent mutations by chance (thus being classified as MPLC). These probabilities were computed using the marginal mutation rates of each mutation, and the known negative dependencies between driver genes and different gene loci. With these NGS-driven data, cases were re-classified as MPLC or IPM. RESULTS: We analyzed 61 patients with a total of 131 tumors. The most frequent mutation was KRAS (57.3%) which occured at a rate higher than expected (p < 0.001) in lung cancer. No mutation was detected in 25/131 tumors (19.1%). Discordant molecular findings between tumor sites were found in 46 patients (75.4%); 11 patients (18.0%) had concordant molecular findings, and 4 patients (6.6%) had concordant molecular findings at 2 of the 3 sites. After integration of the NGS data, the initial diagnosis was confirmed for 41 patients (67.2%), the diagnosis was revised for 12 patients (19.7%) or was considered as non-informative for 8 patients (13.1%). CONCLUSION: Integrating the information of NGS data may significantly improve accuracy of diagnosis and staging