Abstract: Botulism is caused by a potent neurotoxin that blocks neuromuscular transmission, resulting in death by asphyxiation. Currently, the therapeutic options are limited and there is no antidote. Here, we harness the structural and trafficking properties of an atoxic derivative of botulinum neurotoxin (BoNT) to transport a function-blocking single-domain antibody into the neuronal cytosol where it can inhibit BoNT serotype A (BoNT/A1) molecular toxicity. Post-symptomatic treatment relieved toxic signs of botulism and rescued mice, guinea pigs, and nonhuman primates after lethal BoNT/A1 challenge. This platform might enable delivery of antibodies and other protein-based therapeutics to previously inaccessible intraneuronal targets. Resumen: El botulismo es causado por una potente neurotoxina que bloquea la transmisión neuromuscular, provocando la muerte por asfixiamiento. Actualmente, las opciones de tratamiento son limitadas y no existe un antídoto. En este artículo aprovechamos las propiedades estructurales y de tráfico neuronal de un derivado atóxico de la neurotoxina botulínica (BoNT) para transportar un anticuerpo que bloquea la función al citosol neuronal, donde puede inhibir la toxicidad molecular del serotipo A de la BoNT (BoNT /A1). El tratamiento post-sintomático alivió los signos tóxicos del botulismo y rescató de la muerte a ratones, conejillos de indias y primates no humanos después de la exposición letal a BoNT / A1. Esta plataforma podría permitir la administración de anticuerpos y otros terapéuticos basados en proteínas a blancos intraneuronales que previamente eran inaccesibles.

Abstract: The present work studies the engagement of prosocial behavior as an antecedent of affective commitment within for-profit organizations. In order to accomplish this, the work focuses on the role of positive feelings. It tests a partial least square-structural equation model using a cross-sectional survey of 144 professional employees from several Colombian industries. Results obtained show that prosocial behavior is associated with affective commitment, but only with the intervention of meaningfulness at work. These associations provide insight into professional employees’ attitudes towards the search for intrinsic motivation and engagement in for-profit organizational environments. Further implications revolve around the justification for working on practices that not only found and foster prosocial behavior in the workplace but also promote skill variety, task identity, and task meaningfulness to obtain adequate levels of engagement and commitment. Finally, since most studies have been conducted in developed countries, this study also contributes to a better understanding of the topic in previously unexplored contexts. In this case, a Latin American emerging economy, like Colombia. Resumen: El presente trabajo estudia el comportamiento prosocial como un antecedente, tanto del trabajo significativo como del compromiso afectivo en el contexto de las organizaciones con fines de lucro. Para ello, el trabajo se enfoca en el papel de los sentimientos positivos y prueba un modelo de ecuaciones estructurales basado en mínimos cuadrados parciales, a partir de la aplicación transversal de un instrumento a 144 empleados profesionales de varias industrias en Colombia. Los resultados obtenidos muestran que el comportamiento prosocial está asociado con el compromiso afectivo, pero solo gracias la intervención de la experiencia de tener un trabajo significativo. Estas asociaciones proporcionan conocimiento sobre las actitudes de los empleados profesionales hacia la búsqueda de la motivación intrínseca y la participación en entornos organizacionales con fines de lucro. Las implicaciones giran en torno a la justificación para trabajar en prácticas gerenciales que no solo encuentran y fomentan el comportamiento prosocial en el lugar de trabajo, sino que también promuevan la variedad de habilidades, la identidad de la tarea y la significancia de la tarea para obtener niveles adecuados de responsabilidad y compromiso. Finalmente, dado que la mayoría de los estudios se han realizado en países desarrollados, este estudio también contribuye a una mejor comprensión del tema en contextos previamente inexplorados; en este caso, una economía en vías de desarrollo, como la colombiana.

Abstract: Using the theoretical-methodological perspective based on experience frameworks, this paper aims at analyzing and understanding the way in which organizations communicate aspects that are related to occupational safety and health. In this sense, we carry out an analysis of the narratives related to this topic and propose a diagnosis mechanism to subjectively measure the burden of the regulatory, strategic, and moral frameworks of these narratives. A panel of Latin American experts applied a three-round Delphi analysis on five case studies in Colombia to illustrate how this mechanism works. In addition to the use of a robust research paradigm, this work contributes by proposing a scheme capable of presenting the motivations and interests of occupational safety and health professionals in perspective, finding imbalances in the way relevant information is transmitted through official messages and channels. Therefore, its use is susceptible to study in this and other areas of knowledge of the organizational discipline, and its adoption could be worthwhile in order to generate more and better knowledge in this regard. Resumen: Haciendo uso de la perspectiva teórico-metodológica basada en los marcos de la experiencia, el presente trabajo tiene como propósito analizar y entender la forma en la que, usualmente, se comunican los aspectos relacionados con la seguridad y la salud en el trabajo en el contexto organizacional. En este sentido, se despliega un análisis sobre las narrativas propias de esta temática y se propone un mecanismo de diagnóstico para medir subjetivamente la carga de los marcos reglamentario, estratégico y moral de dichas narrativas. Un análisis Delphi de tres rondas aplicado por un panel de expertos latinoamericanos sobre cinco casos de estudio en Colombia ilustra la manera en la que el mecanismo en mención puede funcionar. Adicional al uso de un paradigma investigativo robusto, el trabajo contribuye, toda vez que propone un esquema capaz de exponer en perspectiva, las motivaciones y los intereses de los profesionales de la seguridad y salud en el trabajo, encontrando desequilibrios en cuanto a la forma de transmitir información relevante por medio de mensajes y canales oficiales. Por tanto, su uso es susceptible de estudio en esta y otras áreas del conocimiento de la disciplina organizacional, y su adopción podría valer la pena en aras de generar más y mejor conocimiento al respecto.

Abstract: This paper investigates the combined failure mode of the Extended Hollo-Bolt (EHB) and the effect of the column thickness on the tensile behaviour of the blind fastener. A three-dimensional Finite Element (FE) model was developed, validated against experimental data and used in a parametric study. The non-linear numerical model, which simulates a single row of two EHB in tension, presents reliable results of the column and bolt failure modes in agreement with experimental data. It is concluded that the failure mode is first controlled by the plastic resistance of the component limited by concrete the bolt. An analytical model which predicts the global force-displacement relationships when varying the column thickness is proposed. Therefore, the stiffness and the strength behaviours of this combined mode of failure for the studied blind fastener can be estimated. Resumen: Este artículo investiga el modo de falla combinado del Extended Hollo-Bolt (EHB) y el efecto del espesor de la columna en el comportamiento de tracción del tornillo ciego. Se desarrolló un modelo tridimensional de elementos finitos (FE), que se validó con datos experimentales y se utilizó en un estudio paramétrico. El modelo numérico no lineal, que simula una sola fila de dos EHBs en tensión, presenta resultados confiables de los modos de falla de la columna y el tornillo de acuerdo con los datos experimentales. Se concluye que el modo de falla se controla primero por la resistencia plástica del componente limitada por la falla del concreto junto con la deformación de la sección tubular de acero; luego es controlado por las propiedades del tornillo. Se propone un modelo analítico que predice la relación fuerza-desplazamiento global cuando se varía el espesor de la columna. Por lo tanto, se pueden estimar los comportamientos de rigidez y resistencia de este modo combinado de falla para el tornillo ciego estudiado.

Abstract: The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.

Abstract: Mobility is a multifaceted concept with social, economic and political implications. This article reflects on the role of mobility and its relation to precarity in the emergence of protests in both Quito (Ecuador) and Santiago (Chile) in 2019 by examining the interplay between mobility and inequality. It argues that the announced increases in transport and fuel costs in Chile and Ecuador exposed obstacles to spatial and social mobility and existing inequalities. Although the protests arose in response to the announced reduction in fuel subsidies and possible increases in transport costs, we propose that they reflect a deeper issue, relating to the vulnerability of the livelihoods of significant segments of the population, despite the fact that both Quito and Santiago have seen improvements in several poverty and inequality indicators in recent years. We discuss how mobility and geography relate to patterns of structural marginalisation that are not necessarily evident from aggregate economic indicators, and how understanding inequality in terms of the ‘right to the city’ and access to public services explain the protests in both countries as a response to existing segregation and deep-seated inequalities.

Abstract: One of the most valuable features of Capital and Ideology is its concern to take history seriously and consider how the emergence of different political and economic regimes relate to discourses about fairness and justice across time. This paper pushes this agenda further by acknowledging that the experience of a few developed nations should not be taken as the template for the generalized study of inequality dynamics across time and space. In this paper, we interrogate Piketty's analysis and policy proposals against specificities that are central to understanding the production and reproduction of inequalities within South Africa. We reflect on the South African case, the structure of inequality and its changes since 1994. We review a battery of policy interventions that have been implemented to address inequality in the last 25 years. We emphasize that the long shadow cast by centuries of colonialism and various forms of apartheid strongly affirm Piketty's emphasis on understanding history. But this is both affirmation and critique given the foundational, imbedded impact that this specific legacy has had on post-apartheid society and its policies. Piketty is aware that the levels of inequality in South Africa are so high that this is “unknown territory.” We map out some of this territory to reveal how these extreme initial wealth and racial inequities inform the reproduction of inequalities in all dimensions and undermine well intentioned policies. We claim that understanding extractive histories, imbedded wealth inequalities, and complex social and political institutions allows us to understand and confront some of the reasons why even in light of progressive policies, many of which are in line with the proposals from Piketty, government interventions have thus far failed to reduce inequality.

Abstract: Cornelia de Lange Syndrome (CdLS) is a congenital autosomal dominant (NIPBL, SMC3 and RAD21) or Xlinked (SMC1A and HDAC8) disorder characterized by facial dysmorphism, pre and postnatal growth retardation, developmental delay and/or intellectual disability, and multiorgan involvement. Musculoskeletal malformations are usually bilateral and affect mainly the upper limbs; the range goes from brachyclinodactyly to severe reduction defects. Instead lower extremities are usually less and mildly involved. Here, we report on a 3-year-old Senegalese boy with typical craniofacial CdLS features, pre and postnatal growth retardation, atrial septal defect, developmental delay and right ipsilateral limb malformations, consistent with oligodactyly of the 3rd and 4th fingers, tibial agenesis and fibula hypoplasia. Exome sequencing and Sanger sequencing showed a novel missense mutation in NIPBL gene (c.6647A>G; p.(Tyr2216Cys)), which affects a conserved residue located within NIPBL HEAT repeat elements. Pyrosequencing analysis of NIPBL gene, disclosed similar levels of wild-type and mutated alleles in DNA and RNA samples from all tissues analyzed (oral mucosa epithelial cells, peripheral blood leukocytes and fibroblasts). These findings indicated the absence of somatic mosaicism, despite of the segmental asymmetry of the limbs, and confirmed biallelic expression for NIPBL transcripts, respectively. Additionally, conditions like Split-hand/foot malformation with long-bone deficiency secondary to duplication of BHLHA9 gene have been ruled out by the array-CGH and MLPA analysis. To our knowledge, this is the first CdLS patient described with major ipsilateral malformations of both the upper and lower extremities, that even though this finding could be due to a random event, expands the spectrum of limb reduction defects in CdLS.

Abstract: Pigments synthesised by Chryseobacterium sp. kr6 growing on feather waste were extracted and characterised. The pigment extract was characterised by KOH test, UV–vis, CIELAB colour system, HPLCDAD- MS, FTIR and its antioxidant capacity was evaluated. A positive bathochromic shift was observed when kr6 colonies or pigment extracts were subjected to alkaline solution (20% KOH) and a λmax at 450 nm was detected for acetone extracts, although no typical fine structure of carotenoids was detected in the electomagnetic spectra. The HPLC profile of the extracted pigment showed that the compound has three different peaks with λmax near 450 nm. The FTIR analysis shows some principal functional groups from a flexirubinlike molecule. The pigmented compound also presents antioxidant activity evaluated by the scavenging of the ABTS radical.

Abstract: The world demands new solutions and products to be used as dyes for industrial applications. Microbial pigments represent an eco-friendly alternative as they can be produced in large amounts through biotechnological processes and do not present environmental risks, as they are easily decomposable. Moreover, some of these metabolites are recognized for their biological activities, which qualify them for potential uses as food colorants and nutraceuticals, protecting against degenerative diseases related with oxidative stress. Because of their genetic simplicity as compared with plants, microorganisms may be a better source to understand biosynthetic mechanisms and to be engineered for producing high pigment yields. Despite the origin of the pigmented microorganism,it seems very important to develop protocols using organic industrial residues and agricultural byproducts as substrates for pigment production and fi nd novel green strategies for rapid pigment extraction. This review looks for the most recent studies that describe microbial pigments from microalgae, fungi, and bacteria. In particular, the underexploited tools of omics science such as proteomics and metabolomics are addressed. The use of techniques involving mass spectrometry, allows to identify different protein and metabolite profi les that may be associated with a variety of biotechnologically-relevant pathways of pigment synthesis.