Effect of botulinum neurotoxins from Mendoza of clostridium botulinum strains on cytoskeletal proteins of mammary tumor cells

The botulinum neurotoxin serotype A (BoNT A) produced by Clostridium botulinum, which causes botulism, is used for the treatment of multiple neurological diseases and its therapeutic action against cancer is currently being evaluated. In previous studies, we have shown that BoNT A from autochthonous soil strains (Su) have different properties than the reference A Hall strain. Among these, its molecular structure, its enzymatic activity against brain SNARE proteins and its greater specific toxic activity (AE) stand out. In cells from human mammary carcinoma (MCF-7) treated with BoNTs for 45 min, we found a marked effect on the expression of cytoskeletal proteins. Therefore, in this work, we delve into the study of the action of autochthonous BoNTs A and prototype A Hall on the distribution of actin and tubulin in these cells. Native forms of autochthonous BoNT (Su strains 1935 and 1891, Tupungato) and prototype A Hall were purified by saline precipitation. Their AE values (LD50 / mg protein) were established and their electrophoretic characteristics were evaluated under non-denaturing conditions. 250 LD50 of the BoNTs were incubated to MCF-7 cell cultures for 10 or 25 min. Later, the cells were fixed and processed for indirect immunofluorescence with the use of specific antibodies that recognize tubulin or actin. The samples were visualized by fluorescence microscopy. At the two times evaluated, the three types of BoNTs produced a marked redistribution of the actin cytoskeleton, patch form, on areas coinciding with the plasma membrane. Tubulin was redistributed to multiple areas with high signal density at 10 min of incubation only in the presence of BoNT 1891. At 25 min of incubation, the cells treated with BoNTs 1891 and 1935 showed this effect, while in those incubated with A Hall, the distribution of these proteins was not modified. The notable alterations in the distribution of components of the tumor cell cytoskeleton by BoNT from native strains of Mendoza soils open new perspectives for therapy against solid tumors.Fil: Chapana, Agostina Lucía. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Guarniolo, D.. Universidad Nacional de Cuyo. Facultad de Cs.médicas. Departamento de Patología. Area de Microbiología; ArgentinaFil: Carvelli, Flavia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sosa, E.. Universidad Nacional de Cuyo. Facultad de Cs.médicas. Departamento de Patología. Area de Microbiología; ArgentinaFil: Fernández, R. A.. Universidad Nacional de Cuyo. Facultad de Cs.médicas. Departamento de Patología. Area de Microbiología; ArgentinaFil: Sosa, M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Caballero, P. A.. Universidad Nacional de Cuyo. Facultad de Cs.médicas. Departamento de Patología. Area de Microbiología; ArgentinaIV Reunión Conjunta de Sociedades de Biología de la República ArgentinaArgentinaSociedad de Biología de CuyoSociedad Argentina de BiologíaSociedad de Biología de RosarioSociedad Chilena de Reproducción y DesarrolloAsociación de Biología de TucumánSociedad de Biología de Córdob

Subsurface life can modify volatile cycling on a planetary scale

The past decade of environmental microbiology has revealed that subsurface environments, both marine and continental, harbor one of the largest ecosystems of our planet, with diversity and biomass rivaling those of the surface. In addition, subsurface life has been recently shown to contribute significantly to the planet’s biogeochemistry, with microbial activity potentially playing an important role in controlling the flux and composition of volatiles recycled between the Earth’s surface and interior, which has broad implications for the search for life beyond our planet. Current efforts to discover extraterrestrial life are focused on planetary bodies with largely inhospitable surfaces, such as Mars, Venus, Europa, Titan, and Enceladus. In these locations, subsurface environments might provide niches of habitability, making the study of deep microbial life a priority for future astrobiological missions. Understanding how volatile elements are exchanged between planetary surfaces and interiors and the role of a subsurface biosphere in altering their composition and flux might provide a tractable target for defining planetary habitability and the detection of subsurface life forms.Fil: Giovanelli, D.. Università degli Studi di Napoli Federico II; Italia. Tokyo Institute of Technology; Japón. Rutgers University; Estados Unidos. Consiglio Nazionale delle Ricerche; Italia. Woods Hole Oceanographic Institution; Estados UnidosFil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Cordone, A.. Università degli Studi di Napoli Federico II; ItaliaFil: Covone, G.. Università degli Studi di Napoli Federico II; Italia. Istituto Nazionale di Astrofisica; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Jessen, G.. Universidad Austral de Chile; ChileFil: Lloyd, K.. University of Tennessee; Estados UnidosFil: de Moor, J. M.. Universidad Nacional; Costa RicaFil: Morrison, S. M.. Carnegie Institution For Science; Estados UnidosFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Vitale Brovarone, A.. Alma Mater Studiorum Universit`a Di Bologna; Italia. Sorbonne University; Francia. Museum National d’Histoire Naturelle; Franci

Evolución del banco in vitro de germoplasma de mandioca (Manihot esculenta, Euphorbiaceae) de la Facultad de Ciencias Agrarias de la UNNE y del Instituto de Botánica del Nordeste (CONICET-UNNE) en tiempos prepandémicos y pandémicos por COVID-19

El funcionamiento normal de laboratorios de conservación de germoplasma vegetal involucra la realización de actividades numerosas y diversas, las cuales fueron afectadas por la pandemia causada por coronavirus de 2019 (COVID-19). El objetivo de esta comunicación es realizar una reseña de la evolución del banco de germoplasma in vitro de mandioca presente en la FCA-UNNE e IBONE (CONICET-UNNE) y dar a conocer las prácticas de manejo habituales y los procedimientos realizados para preservar con vida el material vegetal protegiendo la salud del personal involucrado antes y durante la pandemia por COVID-19. Docentes, investigadores, alumnos de grado y posgrado llevaron adelante, durante casi 40 años, la conservación in vitro de 56 cultivares de mandioca provenientes de diferentes países. Previamente a marzo del año 2020, el manejo del banco estaba centrado principalmente en la ejecución de actividades científico-tecnológicas para la conservación del material y la búsqueda de parámetros para establecer un orden de subcultivos. Decretado el Aislamiento Social, Preventivo y Obligatorio en Argentina, se continuó con las actividades de conservación aplicando las prácticas usuales y siguiendo las medidas sanitarias de orden político-institucionales implementadas. Para afrontar los nuevos escenarios sanitarios, se deberán ajustar metodologías que sean eficaces para mantener la viabilidad del material vegetal y prolongar el tiempo de conservación

The Helium and Carbon Isotope Characteristics of the Andean Convergent Margin

Subduction zones represent the interface between Earth’s interior (crust and mantle) and exterior (atmosphere and oceans), where carbon and other volatile elements are actively cycled between Earth reservoirs by plate tectonics. Helium is a sensitive tracer of volatile sources and can be used to deconvolute mantle and crustal sources in arcs; however it is not thought to be recycled into the mantle by subduction processes. In contrast, carbon is readily recycled, mostly in the form of carbon-rich sediments, and can thus be used to understand volatile delivery via subduction. Further, carbon is chemically-reactive and isotope fractionation can be used to determine the main processes controlling volatile movements within arc systems. Here, we report helium isotope and abundance data for 42 deeply-sourced fluid and gas samples from the Central Volcanic Zone (CVZ) and Southern Volcanic Zone (SVZ) of the Andean Convergent Margin (ACM). Data are used to assess the influence of subduction parameters (e.g., crustal thickness, subduction inputs, and convergence rate) on the composition of volatiles in surface volcanic fluid and gas emissions. He isotopes from the CVZ backarc range from 0.1 to 2.6 RA (n = 23), with the highest values in the Puna and the lowest in the Sub-Andean foreland fold-and-thrust belt. Atmosphere-corrected He isotopes from the SVZ range from 0.7 to 5.0 RA (n = 19). Taken together, these data reveal a clear southeastward increase in 3He/4He, with the highest values (in the SVZ) falling below the nominal range associated with pure upper mantle helium (8 ± 1 RA), approaching the mean He isotope value for arc gases of (5.4 ± 1.9 RA). Notably, the lowest values are found in the CVZ, suggesting more significant crustal inputs (i.e., assimilation of 4He) to the helium budget. The crustal thickness in the CVZ (up to 70 km) is significantly larger than in the SVZ, where it is just ∼40 km. We suggest that crustal thickness exerts a primary control on the extent of fluid-crust interaction, as helium and other volatiles rise through the upper plate in the ACM. We also report carbon isotopes from (n = 11) sites in the CVZ, where δ13C varies between −15.3‰ and −1.2‰ [vs. Vienna Pee Dee Belemnite (VPDB)] and CO2/3He values that vary by over two orders of magnitude (6.9 × 108–1.7 × 1011). In the SVZ, carbon isotope ratios are also reported from (n = 13) sites and vary between −17.2‰ and −4.1‰. CO2/3He values vary by over four orders of magnitude (4.7 × 107–1.7 × 1012). Low δ13C and CO2/3He values are consistent with CO2 removal (e.g., calcite precipitation and gas dissolution) in shallow hydrothermal systems. Carbon isotope fractionation modeling suggests that calcite precipitation occurs at temperatures coincident with the upper temperature limit for life (122°C), suggesting that biology may play a role in C-He systematics of arc-related volcanic fluid and gas emissions.Fil: Barry, P. H.. Woods Hole Oceanographic Institution; Estados UnidosFil: De Moor, J. M.. University of New Mexico; Estados Unidos. UNIVERSIDAD NACIONAL DE COSTA RICA (UNA);Fil: Chiodi, Agostina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Aguilera, F.. Universidad Católica del Norte; ChileFil: Hudak, M. R.. Woods Hole Oceanographic Institution; Estados UnidosFil: Bekaert, D. V.. Woods Hole Oceanographic Institution; Estados UnidosFil: Turner, S. J.. University of Massachussets; Estados UnidosFil: Curtice, J.. Woods Hole Oceanographic Institution; Estados UnidosFil: Seltzer, A. M.. Woods Hole Oceanographic Institution; Estados UnidosFil: Jessen, G. L.. Universidad Austral de Chile; ChileFil: Osses, E.. Universidad Austral de Chile; ChileFil: Blamey, J. M.. Universidad de Santiago de Chile; ChileFil: Amenábar, M. J.. Universidad de Santiago de Chile; ChileFil: Selci, M.. University Of Naples Federico Ii; ItaliaFil: Cascone, M.. University Of Naples Federico Ii; ItaliaFil: Bastianoni, A.. University Of Naples Federico Ii; ItaliaFil: Nakagawa, M.. Tokyo Institute Of Technology; JapónFil: Filipovich, Ruben Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Bustos, Emilce. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Schrenk, M. O.. Michigan State University; Estados UnidosFil: Buongiorno, J.. Maryville College; Estados UnidosFil: Ramírez, C. J.. Servicio Geológico Ambiental (segeoam); Costa RicaFil: Rogers, T. J.. University of Tennessee; Estados UnidosFil: Lloyd, K. G.. University of Tennessee; Estados UnidosFil: Giovannelli, D.. Institute Of Marine Biological Resources And Biotechno; Itali

Distinct Methylation Changes at the IGF2-H19 Locus in Congenital Growth Disorders and Cancer

Background: Differentially methylated regions (DMRs) are associated with many imprinted genes. In mice methylation at a DMR upstream of the H19 gene known as the Imprint Control region (IC1) is acquired in the male germline and influences the methylation status of DMRs 100 kb away in the adjacent Insulin-like growth factor 2 (Igf2) gene through long-range interactions. In humans, germline-derived or post-zygotically acquired imprinting defects at IC1 are associated with aberrant activation or repression of IGF2, resulting in the congenital growth disorders Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, respectively. In Wilms tumour and colorectal cancer, biallelic expression of IGF2 has been observed in association with loss of methylation at a DMR in IGF2. This DMR, known as DMR0, has been shown to be methylated on the silent maternal IGF2 allele presumably with a role in repression. The effect of IGF2 DMR0 methylation changes in the aetiology of BWS or SRS is unknown. Methodology/Principal Findings: We analysed the methylation status of the DMR0 in BWS, SRS and Wilms tumour patients by conventional bisulphite sequencing and pyrosequencing. We show here that, contrary to previous reports, the IGF2 DMR0 is actually methylated on the active paternal allele in peripheral blood and kidney. This is similar to the IC

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A facility to Search for Hidden Particles (SHiP) at the CERN SPS

A new general purpose fixed target facility is proposed at the CERN SPS accelerator which is aimed at exploring the domain of hidden particles and make measurements with tau neutrinos. Hidden particles are predicted by a large number of models beyond the Standard Model. The high intensity of the SPS 400~GeV beam allows probing a wide variety of models containing light long-lived exotic particles with masses below ${\cal O}$(10)~GeV/c$^2$, including very weakly interacting low-energy SUSY states. The experimental programme of the proposed facility is capable of being extended in the future, e.g. to include direct searches for Dark Matter and Lepton Flavour Violation

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths