Mechanical Properties of Chaperone BiP, the Master Regulator of the Endoplasmic Reticulum

Immunoglobulin heavy-chain-binding protein (BiP protein) is a 75-kDa Hsp70 monomeric ATPase motor that plays broad and crucial roles maintaining proteostasis inside the cell. Its malfunction has been related with the appearance of many and important health problems such as neurodegenerative diseases, cancer, and heart diseases, among others. In particular, it is involved in many endoplasmic reticulum (ER) processes and functions, such as protein synthesis, folding, and assembly, and also it works in the posttranslational mechanism of protein translocation. However, it is unknown what kind of molecular motor BiP works like, since the mechanochemical mechanism that BiP utilizes to perform its work during posttranslational translocation across the ER is not fully understood. One novel approach to study both structural and catalytic properties of BiP considers that the viscoelastic regime behavior of the enzymes (considering them as a spring) and their mechanical properties are correlated with catalysis and ligand binding. Structurally, BiP is formed by two domains, and to establish a correlation between BiP structure and catalysis and how its conformational and viscoelastic changes are coupled to ligand binding, catalysis, and allosterism (information transmitted between the domains), optical tweezers and nano-rheology techniques have been essential in this regard

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Community-based vicuña (Vicugna vicugna) shearing in the arid Puna of Argentina: Body weight and fiber traits obtained during the chakus

In the Argentine Puna, innovation proposals for the production of vicuña fiber represent a strategic opportunity for local communities. However, the development of these proposals, essential for the addition of local value, is affected by the lack of information on the relationship between fiber quality and processing. Thus, this study aimed to characterize the variability in both the quantity and quality of vicuña fiber obtained by shearing in the Argentine Puna, in the context of sustainable management plans presented by different indigenous communities of the Yavi district, Jujuy province. Samples (n = 150) were taken during shearing in locations at low (4222 masl, n = 4). The following were recorded: sex, age, and body weight (BW, kg) of the animals, fleece weight (FW, g), staple length (SL, mm), mean fiber diameter (MFD, μm), mean diameter of down fibers (DDO, μm), mean diameter of hair (DHA, μm), coarse hair content (CHC, %), proportion of down fibers (PWB, %) and mean fiber curvature (MFC, ◦/mm). In adult vicuñas BW and SL were significantly affected by altitude, FW was affected by sex, and all the other quality variables were affected by the sampling location. Adult vicuñas BW from high locations were lighter than those from low locations (38.6 vs. 41.6 kg, P < 0.01). SL was greater in animals from low locations than in those from high locations (42.4 vs. 38.8 mm, P < 0.05). Average FW was 228 g, with animals from low locations showing more variable FW than those from high locations. Females produced lighter fleece than adult males (216 vs. 244 g, P < 0.01). MFD, DDO and DHA, CHC, PWB and MFC presented averages of 13 μm, 12.6 μm, 53 μm, 0.9 %, 87.0 % and 87◦/mm, respectively. For young vicuñas, the BW and FW were 30.9 kg and 213 g, respectively. Differences among sampling locations were significant for all quality variables studied and could present implications for the textile processing of vicuña fiber.Estación Experimental Agropecuaria BarilocheFil: Sacchero, Diego Mariano. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área de Producción Animal. Laboratorio de Fibras Textiles de Origen Animal; ArgentinaFil: Quiroga Roger, Juan Alfonso. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación y Desarrollo Tecnológico para la Agricultura Familiar Región NOA; ArgentinaFil: Romero, Sandra Raquel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación y Desarrollo Tecnológico para la Agricultura Familiar Región NOA; ArgentinaFil: Maurino, Maria Julia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área de Producción Animal. Laboratorio de Fibras Textiles de Origen Animal; ArgentinaFil: Gonzalez, Ezequiel Bernardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área de Producción Animal. Laboratorio de Fibras Textiles de Origen Animal; Argentin

Mechanical properties of BiP protein determined by nano-rheology

© 2018 The Protein Society Immunoglobulin Binding Protein (BiP) is a chaperone and molecular motor belonging to the Hsp70 family, involved in the regulation of important biological processes such as synthesis, folding and translocation of proteins in the Endoplasmic Reticulum. BiP has two highly conserved domains: the N-terminal Nucleotide-Binding Domain (NBD), and the C-terminal Substrate-Binding Domain (SBD), connected by a hydrophobic linker. ATP binds and it is hydrolyzed to ADP in the NBD, and BiP's extended polypeptide substrates bind in the SBD. Like many molecular motors, BiP function depends on both structural and catalytic properties that may contribute to its performance. One novel approach to study the mechanical properties of BiP considers exploring the changes in the viscoelastic behavior upon ligand binding, using a technique called nano-rheology. This technique is essentially a traditional rheology experiment, in which an oscillatory force is directly applied to the pr

Single molecule force spectroscopy reveals the effect of BiP chaperone on protein folding

BiP (Immunoglobulin Binding Protein) is a member of the Hsp70 chaperones that participates in protein folding in the endoplasmic reticulum. The function of BiP relies on cycles of ATP hydrolysis driving the binding and release of its substrate proteins. It still remains unknown how BiP affects the protein folding pathway and there has been no direct demonstration showing which folding state of the substrate protein is bound by BiP, as previous work has used only peptides. Here, we employ optical tweezers for single molecule force spectroscopy experiments to investigate how BiP affects the folding mechanism of a complete protein and how this effect depends on nucleotides. Using the protein MJ0366 as the substrate for BiP, we performed pulling and relaxing cycles at constant velocity to unfold and refold the substrate. In the absence of BiP, MJ0366 unfolded and refolded in every cycle. However, when BiP was added, the frequency of folding events of MJ0366 significantly decreased, and the loss of folding always occurred after a successful unfolding event. This process was dependent on ATP and ADP, since when either ATP was decreased or ADP was added, the duration of periods without folding events increased. Our results show that the affinity of BiP for the substrate protein increased in these conditions, which correlates with previous studies in bulk. Therefore, we conclude that BiP binds to the unfolded state of MJ0366 and prevents its refolding, and that this effect is dependent on both the type and concentration of nucleotides.Fondo Nacional de Desarrollo Cientifico y Tecnologico (Fondecyt), Chile, 11130263, 1151274, 11110534, 3160645 / Project CONICYT + NERC + Programa de Colaboracion Internacional, PCI-PII20150073 / U-inicia from Vicerrectoria de Investigacion Universidad de Chile / CONICYT-PCHA/MagisterNacional, 2015-22151448 / Aid for short stays for research abroad, International Engagement, Vice-Presidency of Academic Affairs, University of Chile / CONICYT-PCHA/DoctoradoNacional, 2013-21130254, 2014-2115096

Intelligent software and tecnological convergence

La Facultad de Ingeniería de la Universidad Católica de Colombia, conforme al factor calidad y considerando las tendencias de vanguardia en el ámbito de innovación en ingeniería, desarrollo en la segunda parte de esté congreso, el software inteligente y convergencia tecnológica, Raspberry PI dispositivo apuntador utilizando Open CV, Procesar imágenes identificando maleza en cultivos, también plataformas tecnológicas en enseñanza en la automatización industrial, implementación de JAX-RS, arquitectura soportada en sistemas inteligentes con control de aprendizaje interactivo, modelado del efecto de alineación estática en prótesis transtibiales en redes neuronales, desarrollo e implementación robótica industrial, modelos en la predicción de pérdidas de propagación de ondas electromagnéticas por celular, además, sistemas de autocuidado para el monitoreo en la infraestructura tecnológica distribuida, modelado de elementos 3D trabajos basados en redes difusas, lógica modal de comunicación en sistemas multiagentes, sistemas de adquisición de datos en procesos agroindustriales, herramientas diagnostica en ergonomía aplicada en puesto de trabajo uso de música colombiana en estudiantes colombianos con BCI, sin olvidar, el método automático en morfología digital de hojas tropicales en Colombia, simulación de radiopropagación en red LTE en banda de dividendo digital, desarrollo de plataformas con inteligencia artificial, Cloud computing una oportunidad para las mipymes en Colombia, ontología en la construcción de indicadores en un sistema de soporte con identificador de vulnerabilidad, Nano y biotecnología para generar energía, modelo de optimización del programa para intercambio de riñones, adicionalmente, la tendencia en redes y banda ancha, aplicación de algoritmo genético en nuevos productos, control de maleza en la productividad de cultivo, tecnología de la información para la asignación de turnos de enfermería, antenas fractales en nanoestructuradas, y por último, Brokering servicios multiplataforma con accesibilidad de profesores y estudiantes a contenido educativo gratis. (Redacción propia).II. Software Inteligente y Convergencia Tecnológica. Raspberry Pi como dispositivo apuntador utilizando OpenCV e integrales proyectivas. Procesamiento de imágenes para identificación de malezas en cultivos. Plataforma tecnológica para la enseñanza y la simulación de procesos en automatización industrial. Comparación de implementaciones JAX-RS. Arquitectura distribuida soportada en sistemas inteligentes difusos para el seguimiento del aprendizaje en entornos interactivos. Modelado del efecto de la alineación estática de prótesis transtibiales aplicando redes neuronales. Diseño, desarrollo e implementación de la robótica industrial. Modelos para la predicción de pérdidas de propagación de ondas electromagnéticas en interiores en frecuencias de comunicación celular. Sistema de autocuidado basado en un enfoque de multiagentes para el monitoreo y la corrección de problemas en una infraestructura tecnológica distribuida. Modelado de elementos 3D: de Solidworks a Matlab. Construcción de activos de trabajo basados en conocimiento con redes difusas. Lógica modal en la formalización de comunicación en sistemas multiagentes. Sistemas de adquisición de datos en redes convergentes aplicados en procesos de agroindustria. Herramienta diagnóstica para la evaluación ergonómica del puesto de trabajo. El uso de música colombiana para evaluar el sentido de pertenencia en estudiantes colombianos con BCI. Un método automático para la caracterización morfológica digital de hojas tropicales de Colombia. Simulación de radiopropagación para el diseño de una red LTE en la banda del dividendo digital. Marco conceptual para el desarrollo de plataformas de enseñanza y aprendizaje basadas en inteligencia artificial. Cloud computing, una oportunidad para apalancar la cadena de valor de las mipymes en Colombia. Ontología para la construcción de indicadores de un sistema de soporte a las decisiones para la identificación del índice de vulnerabilidad territorial. Nano y biotecnología para la generación de energía (proyectos Universidad Católica). Modelo de optimización del programa de intercambio de riñones con múltiples etapas. Tendencias en redes y servicios de banda ancha. Aplicación de algoritmos genéticos al diseño de nuevos productos. El control de malezas como elemento significativo en la productividad de cultivos. Tecnologías de la información para resolver el problema de asignación de turnos de enfermería. Antenas fractales nanoestructuradas y estudiantes a contenidos educativos gratuitos