The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and in human cells.

Funder: Kanton of ZürichThe intracellular trafficking of growth factor receptors determines the activity of their downstream signaling pathways. Here, we show that the putative HSP-90 co-chaperone CHP-1 acts as a regulator of EGFR trafficking in C. elegans. Loss of chp-1 causes the retention of the EGFR in the ER and decreases MAPK signaling. CHP-1 is specifically required for EGFR trafficking, as the localization of other transmembrane receptors is unaltered in chp-1(lf) mutants, and the inhibition of hsp-90 or other co-chaperones does not affect EGFR localization. The role of the CHP-1 homolog CHORDC1 during EGFR trafficking is conserved in human cells. Analogous to C. elegans, the response of CHORDC1-deficient A431 cells to EGF stimulation is attenuated, the EGFR accumulates in the ER and ERK2 activity decreases. Although CHP-1 has been proposed to act as a co-chaperone for HSP90, our data indicate that CHP-1 plays an HSP90-independent function in controlling EGFR trafficking through the ER

Absence of protein A expression is associated with higher capsule production in staphylococcal isolates

Staphylococcus aureus is a major human pathogen, and a leading cause of soft tissue and blood stream infections. One of the causes of its success as a pathogen is the peculiar array of immune evasion factors through which the bacterium avoids host defenses, where the staphylococcal protein A (SpA) plays a major role thanks to its IgG binding activities. Moreover, SpA has recently been proposed as a promising vaccine antigen. In this study, we evaluated the expression of SpA in a collection of staphylococcal strains, about 7% of which did not express SpA (SpA- strains), despite the presence of the gene. By a comparative genomic analysis, we identified that a mutation in the spa 5′ UTR sequence affecting the RBS is responsible for the loss of SpA in a subset of SpA- strains. Using a high-throughput qRT-PCR approach on a selected panel of virulence-related genes, we identified that the SpA- phenotype is associated with lower spa transcript levels and increased expression and production of capsule as well as other changes in the transcription of several key virulence factors. Our data suggest that the SpA- phenotype has occurred in geographically distinct strains through different molecular mechanisms including both mutation, leading likely to translation alterations, and transcriptional deregulation. Furthermore, we provide evidence that SpA- strains are highly susceptible to phagocytic uptake mediated by anti-capsule antibodies. These data suggest that S. aureus may alter its virulence factor expression pattern as an adaptation to the host or environment. Vaccination strategies targeting both SpA and capsule could therefore result in broader coverage against staphylococcal isolates than SpA alone

Estudo Integrado de um Ambiente Lacustre: Laguna La Salada (Província de Buenos Aires, Argentina)

Los ambientes de lagos y lagunas contribuyen al sustento de las actividades humanas y cumplen un rol importante en la dinámica natural. Su estudio sectorizado dificulta la comprensión e interrelación de sus elementos y funciones. Por tal motivo, en el presente trabajo se propone un estudio integrado del espacio lacustre de La Salada (provincia de Buenos Aires, Argentina). Para ello, se realizó un análisis a partir de las cuatro dimensiones (Ecológica, Económica, Antropológica y de Gobernanza) que conforman este ambiente. Cada dimensión está integrada por una matriz y sus características correspondientes. Las matrices más destacadas fueron la Biofísica, Social y de Regulación que evidenciaron la predominancia de los aspectos naturales y su relación con el accionar de la población. Si bien la matriz Actividades obtuvo la menor valoración, en ella se identificó al Turismo como una de las principales actividades que cumple un importante rol en la organización del espacio lacustre de La Salada. Este análisis integrado permitió identificar las características relevantes del área de estudio, así como también aquellas que representan debilidades o problemas a evaluar y resolver. La aplicación de este tipo de estudios puede contribuir de manera positiva en la elaboración de planes de manejo ambientales y para el ordenamiento territorial de las actividades humanas.Lake environments contribute to human activities and have an important role in the natural dynamics. A sectorized study of them difficult the comprehenssion and interrelation of their elements and functions. In this sense, this researh suggests a integrated study of La Salada lake environment (Province of Buenos Aires, Argentina). An analysis of the diferent dimensions (Ecological, Economical, Antropological and Governance) that constitute this environment was made. Each dimension has an associated matrix with its corresponding characteristics. The most outstanding matrices were Biophysics, Social and Regulation, that evidenced a predominancy of natural aspects and their relation with human activities. Although the Activities matrix had a lower valuation, Tourism was identified as one of the main activities that play an essential role in the organization of the lake area of La Salada. This integrated analysis allowed to identify the relevant characteristics of the study area, as well as weaknesses to be assessed and solved. The implementation of this type of studies contributes positively to the development of environmental management plans and, also, for territorial planning of human activities.Os ambientes lacustres e lagunares contribuem para o sustento das atividades humanas e desempenham um papel importante na dinâmica natural. Seu estudo setorizado dificulta a compreensão e a inter-relação de seus elementos e funções. Por esse motivo, este artigo propõe um estudo integrado do espaço lacustre de La Salada (província de Buenos Aires, Argentina). Para isso, foi realizada uma análise baseada nas quatro dimensões (Ecológica, Econômica, Antropológica e Governança) que compõem esse ambiente. Cada dimensão é composta por uma matriz e suas características correspondentes. As matrizes mais destacadas foram Biofísica, Social e Regulatória, mostrando a predominância de aspectos naturais e sua relação com as ações da população. Embora a matriz de Atividades tenha obtido a classificação mais baixa, identificou o turismo como uma das principais atividades que desempenha um papel importante na organização do espaço lacustre de La Salada. Essa análise integrada permitiu identificar as características relevantes da área de estudo, bem como aquelas que representam fragilidades ou problemas a serem avaliados e resolvidos. A aplicação desse tipo de estudo pode contribuir positivamente na elaboração de planos de gestão ambiental e na ordenação territorial das atividades humanas.Fil: Huamantinco Cisneros, María Andrea. Universidad Nacional del Sur. Departamento de Geografía y Turismo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Haag, Maria Isabel. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Piccolo, Maria Cintia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Nacional del Sur. Departamento de Geografía y Turismo; Argentin

Estudo Integrado de um Ambiente Lacustre: Laguna La Salada (Província de Buenos Aires, Argentina)

Los ambientes de lagos y lagunas contribuyen al sustento de las actividades humanas y cumplen un rol importante en la dinámica natural. Su estudio sectorizado dificulta la comprensión e interrelación de sus elementos y funciones. Por tal motivo, en el presente trabajo se propone un estudio integrado del espacio lacustre de La Salada (provincia de Buenos Aires, Argentina). Para ello, se realizó un análisis a partir de las cuatro dimensiones (ecológica, económica, antropológica y de gobernanza) que conforman este ambiente. Cada dimensión está integrada por una matriz y sus características correspondientes. Las matrices más destacadas fueron la Biofísica, Social y de Regulación que evidenciaron la predominancia de los aspectos naturales y su relación con el accionar de la población. Si bien la matriz Actividades obtuvo la menor valoración, en ella se identificó al Turismo como una de las principales actividades que cumple un importante rol en la organización del espacio lacustre de La Salada. Este análisis integrado permitió identificar las características relevantes del área de estudio, así como también aquellas que representan debilidades o problemas a evaluar y resolver. La aplicación de este tipo de estudios puede contribuir de manera positiva en la elaboración de planes de manejo ambientales y para el ordenamiento territorial de las actividades humanas

Electronic Health Diary Campaigns to Complement Longitudinal Assessments in Persons With Multiple Sclerosis: Nested Observational Study

BACKGROUND Electronic health diaries hold promise in complementing standardized surveys in prospective health studies but are fraught with numerous methodological challenges. OBJECTIVE The study aimed to investigate participant characteristics and other factors associated with response to an electronic health diary campaign in persons with multiple sclerosis, identify recurrent topics in free-text diary entries, and assess the added value of structured diary entries with regard to current symptoms and medication intake when compared with survey-collected information. METHODS Data were collected by the Swiss Multiple Sclerosis Registry during a nested electronic health diary campaign and during a regular semiannual Swiss Multiple Sclerosis Registry follow-up survey serving as comparator. The characteristics of campaign participants were descriptively compared with those of nonparticipants. Diary content was analyzed using the Linguistic Inquiry and Word Count 2015 software (Pennebaker Conglomerates, Inc) and descriptive keyword analyses. The similarities between structured diary data and follow-up survey data on health-related quality of life, symptoms, and medication intake were examined using the Jaccard index. RESULTS Campaign participants (n=134; diary entries: n=815) were more often women, were not working full time, did not have a higher education degree, had a more advanced gait impairment, and were on average 5 years older (median age 52.5, IQR 43.25-59.75 years) than eligible nonparticipants (median age 47, IQR 38-55 years; n=524). Diary free-text entries (n=632; participants: n=100) most often contained references to the following standard Linguistic Inquiry and Word Count word categories: negative emotion (193/632, 30.5%), body parts or body functioning (191/632, 30.2%), health (94/632, 14.9%), or work (67/632, 10.6%). Analogously, the most frequently mentioned keywords (diary entries: n=526; participants: n=93) were "good," "day," and "work." Similarities between diary data and follow-up survey data, collected 14 months apart (median), were high for health-related quality of life and stable for slow-changing symptoms such as fatigue or gait disorder. Similarities were also comparatively high for drugs requiring a regular application, including interferon beta-1a (Avonex) and glatiramer acetate (Copaxone), and for modern oral therapies such as fingolimod (Gilenya) and teriflunomide (Aubagio). CONCLUSIONS Diary campaign participation seemed dependent on time availability and symptom burden and was enhanced by reminder emails. Electronic health diaries are a meaningful complement to regular structured surveys and can provide more detailed information regarding medication use and symptoms. However, they should ideally be embedded into promotional activities or tied to concrete research study tasks to enhance regular and long-term participation

Electronic Health Diary Campaigns to Complement Longitudinal Assessments in Persons With Multiple Sclerosis: Nested Observational Study.

BACKGROUND Electronic health diaries hold promise in complementing standardized surveys in prospective health studies but are fraught with numerous methodological challenges. OBJECTIVE The study aimed to investigate participant characteristics and other factors associated with response to an electronic health diary campaign in persons with multiple sclerosis, identify recurrent topics in free-text diary entries, and assess the added value of structured diary entries with regard to current symptoms and medication intake when compared with survey-collected information. METHODS Data were collected by the Swiss Multiple Sclerosis Registry during a nested electronic health diary campaign and during a regular semiannual Swiss Multiple Sclerosis Registry follow-up survey serving as comparator. The characteristics of campaign participants were descriptively compared with those of nonparticipants. Diary content was analyzed using the Linguistic Inquiry and Word Count 2015 software (Pennebaker Conglomerates, Inc) and descriptive keyword analyses. The similarities between structured diary data and follow-up survey data on health-related quality of life, symptoms, and medication intake were examined using the Jaccard index. RESULTS Campaign participants (n=134; diary entries: n=815) were more often women, were not working full time, did not have a higher education degree, had a more advanced gait impairment, and were on average 5 years older (median age 52.5, IQR 43.25-59.75 years) than eligible nonparticipants (median age 47, IQR 38-55 years; n=524). Diary free-text entries (n=632; participants: n=100) most often contained references to the following standard Linguistic Inquiry and Word Count word categories: negative emotion (193/632, 30.5%), body parts or body functioning (191/632, 30.2%), health (94/632, 14.9%), or work (67/632, 10.6%). Analogously, the most frequently mentioned keywords (diary entries: n=526; participants: n=93) were "good," "day," and "work." Similarities between diary data and follow-up survey data, collected 14 months apart (median), were high for health-related quality of life and stable for slow-changing symptoms such as fatigue or gait disorder. Similarities were also comparatively high for drugs requiring a regular application, including interferon beta-1a (Avonex) and glatiramer acetate (Copaxone), and for modern oral therapies such as fingolimod (Gilenya) and teriflunomide (Aubagio). CONCLUSIONS Diary campaign participation seemed dependent on time availability and symptom burden and was enhanced by reminder emails. Electronic health diaries are a meaningful complement to regular structured surveys and can provide more detailed information regarding medication use and symptoms. However, they should ideally be embedded into promotional activities or tied to concrete research study tasks to enhance regular and long-term participation

Challenges and best practices for digital unstructured data enrichment in health research: A systematic narrative review

Digital data play an increasingly important role in advancing health research and care. However, most digital data in healthcare are in an unstructured and often not readily accessible format for research. Unstructured data are often found in a format that lacks standardization and needs significant preprocessing and feature extraction efforts. This poses challenges when combining such data with other data sources to enhance the existing knowledge base, which we refer to as digital unstructured data enrichment. Overcoming these methodological challenges requires significant resources and may limit the ability to fully leverage their potential for advancing health research and, ultimately, prevention, and patient care delivery. While prevalent challenges associated with unstructured data use in health research are widely reported across literature, a comprehensive interdisciplinary summary of such challenges and possible solutions to facilitate their use in combination with structured data sources is missing. In this study, we report findings from a systematic narrative review on the seven most prevalent challenge areas connected with the digital unstructured data enrichment in the fields of cardiology, neurology and mental health, along with possible solutions to address these challenges. Based on these findings, we developed a checklist that follows the standard data flow in health research studies. This checklist aims to provide initial systematic guidance to inform early planning and feasibility assessments for health research studies aiming combining unstructured data with existing data sources. Overall, the generality of reported unstructured data enrichment methods in the studies included in this review call for more systematic reporting of such methods to achieve greater reproducibility in future studies

Calidad Territorial y Desarrollo Sustentable: Modelo de gestión para PyMes de agroturismo

El presente trabajo procura diseñar las bases de un Sistema de Gestión de Calidad con enfoque territorial, que en el marco del Desarrollo Rural Sustentable genere ventajas competitivas para la actividad agroturística de Pymes integrantes del Grupo Cambio Rural, Instituto Nacional de Tecnología Agropecuaria (INTA), “Cortaderas II” en el SO bonaerense. Se trata de un estudio de caso, para el cual se relevó información a través de entrevistas, encuestas y observación directa. El modelo se formula adaptando los elementos, principios y valores del sello “Marca de Calidad Territorial” europeo e incorpora un proceso de certificación participativa considerando la experiencia de Brasil, más cercana a la realidad argentina. Se concluye que los emprendimientos bajo estudio se encuentran en condiciones de aplicar dicha propuesta por los logros obtenidos en la dinámica de trabajo grupal, pudiendo así superar las dificultades de un proceso individual de certificación de normas de calidad, para avanzar en esta etapa cuando estén preparados.This paper attempts to design the basis for a Quality Management System with a territorial approach, which within the framework of Sustainable Rural Development generates competitive advantages for Agritourism SME’s belonging to the Rural Change Group, National Institute of Agricultural Technology, "Cortaderas II" in the south west of the Buenos Aires province. In this case study, information was gathered through interviews, surveys and direct observation. The model is formulated adapting the elements, principles and values of the European "Territorial Quality Mark" and it incorporates a participatory certification process considering the Brazilian experience, which is similar to what happens in Argentina. We conclude that, due to their successful group work dynamics, the enterprises under study are in a condition to implement this proposal and can thus overcome the difficulties of undergoing an individual certification process of quality standards in order to move on when they are prepared.Fil: Duran, Regina del Carmen. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Scoponi, Liliana. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Bustos Cara, Roberto Nicolas. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: de Batista, Marianela. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Piñeiro, Verónica Ana. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Casarsa, Fabiana Andrea. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Cordisco, Marina. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Haag, Maria Isabel. Universidad Nacional del Sur. Departamento de Geografía y Turismo; ArgentinaFil: Brandauer, Guillermo. Universidad Nacional del Sur. Departamento de Ciencias de la Administración; ArgentinaFil: Presa, Cecilia. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Bordenave; ArgentinaFil: Colonnella, Julieta. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Bordenave; ArgentinaFil: Chaz Sardi, María Celeste. Universidad Nacional del Sur. Departamento de Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; Argentin

Single domain antibodies: promising experimental and therapeutic tools in infection and immunity

Antibodies are important tools for experimental research and medical applications. Most antibodies are composed of two heavy and two light chains. Both chains contribute to the antigen-binding site which is usually flat or concave. In addition to these conventional antibodies, llamas, other camelids, and sharks also produce antibodies composed only of heavy chains. The antigen-binding site of these unusual heavy chain antibodies (hcAbs) is formed only by a single domain, designated VHH in camelid hcAbs and VNAR in shark hcAbs. VHH and VNAR are easily produced as recombinant proteins, designated single domain antibodies (sdAbs) or nanobodies. The CDR3 region of these sdAbs possesses the extraordinary capacity to form long fingerlike extensions that can extend into cavities on antigens, e.g., the active site crevice of enzymes. Other advantageous features of nanobodies include their small size, high solubility, thermal stability, refolding capacity, and good tissue penetration in vivo. Here we review the results of several recent proof-of-principle studies that open the exciting perspective of using sdAbs for modulating immune functions and for targeting toxins and microbes.Centro de Investigación y Desarrollo en Fermentaciones Industriale

A contour for the entanglement entropies in harmonic lattices

We construct a contour function for the entanglement entropies in generic harmonic lattices. In one spatial dimension, numerical analysis are performed by considering harmonic chains with either periodic or Dirichlet boundary conditions. In the massless regime and for some configurations where the subsystem is a single interval, the numerical results for the contour function are compared to the inverse of the local weight function which multiplies the energy-momentum tensor in the corresponding entanglement hamiltonian, found through conformal field theory methods, and a good agreement is observed. A numerical analysis of the contour function for the entanglement entropy is performed also in a massless harmonic chain for a subsystem made by two disjoint intervals