Inhaled multiwalled carbon nanotubes induce systemic inflammation and endothelial dysfunction via MMP-9 induction

Assessing the mechanisms underlying adverse cardiovascular effects induced by inhaled toxins presents a substantial research challenge. We propose that blood carries an as yet unknown inflammatory potential consisting of modified proteins or other biomolecules and reaction byproducts that affects a pathological bioactivity which can be assessed using naïve endothelial cells and blood vessels. The approach involves applying serum from exposed animals to cultured primary endothelial cells or ex vivo isolated arteries. Mice were exposed to multi-walled carbon nanotubes (MWCNT; 0, 10 or 40 μg) or other pollutants via pharyngeal aspiration and serum was collected at 4 and 24 h post-exposure. Serum from exposed mice increased endothelial cell surface vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression and proinflammatory transcripts, and decreased ATP-stimulated nitric oxide (NO) production. The functional impact of this loss of NO bioavailability was confirmed via myography, in which serum from pollutant-exposed mice significantly impaired vasodilation to acetylcholine. In addition, serum from pollutant-exposed mice reduced cell migration in a traditional scratch assay experiment. In vivo MWCNT exposure was able to both increase the permeability of the Blood Brain Barrier (BBB), as well as induce transcription of pro- inflammatory cytokines in the hippocampus and frontal cortex regions of the brain. This affect was abolished with the treatment of fasudil, or the absence of CD36. There was also evidence of astrocyte activation in the short and microglia activation at 24 hours. CD 36 has also been identified as playing a key role in mediating loss of vasodilatory properties ex vivo. In conclusion, pulmonary exposure to MWCNT dynamically alters circulating factors, which promotes endothelial cell activation, decreased NO bioavailability, and altered functionality all directionally predicting adverse cardiovascular outcomes

The cytoskeletal motor proteins Dynein and MyoV direct apical transport of Crumbs

Crumbs (Crb in Drosophila; CRB1-3 in mammals) is a transmembrane determinant of epithelial cell polarity and a regulator of Hippo signalling. Crb is normally localized to apical cell-cell contacts, just above adherens junctions, but how apical trafficking of Crb is regulated in epithelial cells remains unclear. We use the Drosophila follicular epithelium to demonstrate that polarized trafficking of Crb is mediated by transport along microtubules by the motor protein Dynein and along actin filaments by the motor protein Myosin-V (MyoV). Blocking transport of Crb-containing vesicles by Dynein or MyoV leads to accumulation of Crb within Rab11 endosomes, rather than apical delivery. The final steps of Crb delivery and stabilisation at the plasma membrane requires the exocyst complex and three apical FERM domain proteins – Merlin, Moesin and Expanded – whose simultaneous loss disrupts apical localization of Crb. Accordingly, a knock-in deletion of the Crb FERMbinding motif (FBM) also impairs apical localization. Finally, overexpression of Crb challenges this system, creating a sensitized background to identify components involved in cytoskeletal polarization, apical membrane trafficking and stabilisation of Crb at the apical domain.Funded by the Francis Crick Institute and the Australian National University

Los valores del Diseñador Industrial para la construcción de la sustentabilidad

El presente trabajo tiene la finalidad de examinar y reflexionar sobre los valores que debe tener un diseñador industrial en el desempeño de su actividad profesional. Derivado del protagonismo y el papel que juega en la producción de la cultura material de nuestros tiempos. Puede estar compuesta de objetos que promueven un consumismo desmedido como el que actualmente tenemos, o de objetos que ayuden a transitar de hábitos de consumo desmedido a uno regulado, ético y basado sólo en lo necesario. Siendo fundamental el cuidado de los recursos

Single dose of diclofenac or meloxicam for control of pain, facial swelling, and trismus in oral surgery

Background: Postoperative pain associated with removal of mandibular third molars has been documented from moderate to severe during the first 24 hours after surgery, with pain peaking between 6 and 8 hours when a conventional local anesthetic is used. Dental pain is largely inflammatory, and evidence-based medicine has shown that nonsteroidal anti-inflammatory drugs are the best analgesics for dental pain. The aim of this study was to compare the analgesic, anti-inflammatory and anti-trismus effect of a single dose of diclofenac and meloxicam after mandibular third molar extraction. Material and Methods: A total of 36 patients were randomized into two treatment groups, each with 18 patients, using a series of random numbers: Group A, was administered 100 mg of diclofenac; and Group B, 15 mg of meloxicam. Drugs were administered orally 1 hour prior to surgery. We evaluated pain intensity, analgesic consumption, swelling, as well as trismus. Results: The results of this study showed that patients receiving 15 mg of meloxicam had less postoperative pain ( P =0.04) and better aperture than those receiving 100 mg of diclofenac ( P =0.03). The meloxicam group presented less swelling than diclofenac group; however, significant statistical differences were not observed. Conclusions: Data of this double-blind, randomized, parallel-group clinical trial demonstrated that patients receiving 15 mg of preoperative meloxicam had a better postoperative analgesia and anti-trismus effect compared with who were given 100 mg of diclofenac after third molar extractions

Limitantes para la mecanización de cosecha en caña de azúcar del estrato de pequeños productores de Tucumán

En el sector sucroalcoholero de Tucumán existen 3500 productores con menos de 50 hectáreas. Aproximadamente el 80% de ellos adopta el sistema de cosecha semimecanizada, el cual utiliza la quema para limpieza a pesar que existen alternativas de cosecha en verde. Las emisiones y cenizas de la quema afectan al medio ambiente y a la salud de la población. Este trabajo analiza los costos y los beneficios económicos en predios de pequeños productores de caña a azúcar. Para ello se plantean escenarios según distintos rendimientos culturales para comparar los sistemas de cosecha semimecanizada y mecanizada integral, productores de 1 y 50 hectáreas respectivamente, concluyendo que adaptar pequeños lotes para el ingreso y maniobrabilidad de maquinarias de cosecha implica una reducción del área de cultivo, y por ende de los beneficios.Centro de Investigación en Economía y ProspectivaFil: Ortiz, Joaquín Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Jaldo Alvaro, Delia Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro de Investigación en Economía y Prospectiva (CIEP); ArgentinaFil: Ibern, Danila Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro. Agencia de Extensión Rural San Pedro; ArgentinaFil: Aragón, Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Aragón, Carlos. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentin

Análisis económico de la incorporación de la cosecha mecanizada en el sistema del pequeño productor cañero de Tucumán

Ponencia y presentación en diapositivasEn el sector sucroalcoholero de Tucumán existen 3500 productores con menos de 50 hectáreas. Aproximadamente el 80% de ellos adopta el sistema de cosecha semimecanizada, el cual utiliza la quema de los tallos cosechados como una etapa de la cosecha a pesar que existen alternativas de cosecha en verde. Las emisiones y cenizas generadas por la quema afectan al medio ambiente y a la salud de la población. Este trabajo aborda los costos y beneficios económicos en predios de pequeños productores de caña a azúcar con el fin de diagnosticar los resultados económicos de su campaña agrícola. Para ello se utilizan distintos escenarios según rendimientos culturales de entre 800- 1100 kilos por surcos, se comparan los sistemas de cosecha semimecanizada y mecanizada integral para 1 y 50 hectáreas. Adaptar pequeños lotes para el ingreso y maniobrabilidad de maquinarias de cosecha integral implica una reducción del área de cultivo, y por ende de los beneficios. Cuanto menor es la superficie plantada mayor es el impacto porcentual del área destinada, lo que explica que productores caracterizados continúen aplicando el sistema de cosecha semimecanizada en estrato en cuestión, quedando irresuelta problemática ambiental.In Tucumán, sugar and alcohol industry has 3,500 small sugar cane farmers with less than 50 hectares. Approximately 80% of them embrace semi-mechanized harvest with fire as a usual practice, besides the fact there are alternatives for a green harvesting. Ashes and GHGs seriously affect local population and environment. The objective of this work is to evaluate economic results from small sugar cane farmers crop year by comparing cost and benefits. To achieve these aims, different scenarios in which farmers with 1 or 50 hectares, cultural yields between 800-1100 kilograms per 100 meters row and both: semi-mechanized and mechanized harvest. In other to admit mechanized harvesters entering the farm the number of rows per hectare must be reduce from 60 to 53 to increase the machinery maneuvering area, this results in less income per hectare. The lower the plantation is, the higher the percentage of soil destine for machinery maneuvering, which evidence why small farmers embrace semi-mechanized harvesting despite burning environmental problem is not solved.Centro de Investigación en Economía y ProspectivaFil: Jaldo Alvaro, Delia Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro de Investigación en Economía y Prospectiva (CIEP); ArgentinaFil: Ortiz, Joaquín Mario. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Ibern, Danila Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Pedro. Agencia de Extensión Rural San Pedro; ArgentinaFil: Aragón, Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Aragón, Carlos. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; Argentin

The Hippo pathway integrates PI3K-Akt signals with mechanical and polarity cues to control tissue growth

The Hippo signalling pathway restricts cell proliferation in animal tissues by inhibiting Yesassociated protein (YAP or YAP1) and Transcriptional Activator with a PDZ domain (TAZ or WW-domain–containing transcriptional activator [WWTR1]), coactivators of the Scalloped (Sd or TEAD) DNA-binding transcription factor. Drosophila has a single YAP/TAZ homolog named Yorkie (Yki) that is regulated by Hippo pathway signalling in response to epithelial polarity and tissue mechanics during development. Here, we show that Yki translocates to the nucleus to drive Sd-mediated cell proliferation in the ovarian follicle cell epithelium in response to mechanical stretching caused by the growth of the germline. Importantly, mechanically induced Yki nuclear localisation also requires nutritionally induced insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) via phosphatidyl inositol-3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1 or PDPK1), and protein kinase B (Akt or PKB) in the follicular epithelium. We find similar results in the developing Drosophila wing, where Yki becomes nuclear in the mechanically stretched cells of the wing pouch during larval feeding, which induces IIS, but translocates to the cytoplasm upon cessation of feeding in the third instar stage. Inactivating Akt prevents nuclear Yki localisation in the wing disc, while ectopic activation of the insulin receptor, PI3K, or Akt/PKB is sufficient to maintain nuclear Yki in mechanically stimulated cells of the wing pouch even after feeding ceases. Finally, IIS also promotes YAP nuclear localisation in response to mechanical cues in mammalian skin epithelia. Thus, the Hippo pathway has a physiological function as an integrator of epithelial cell polarity, tissue mechanics, and nutritional cues to control cell proliferation and tissue growth in both Drosophila and mammals.This work was funded by the Francis Crick Institute core funding to BT (FC0011080). It was also funded by EMBL Australia & The John Curtin School of Medical Research at The Australian National University

Haemophilus parasuis (Glaesserella parasuis) as a Potential Driver of Molecular Mimicry and Inflammation in Rheumatoid Arthritis

Background: Haemophilus parasuis (Hps; now Glaesserella parasuis) is an infectious agent that causes severe arthritis in swines and shares sequence similarity with residues 261–273 of collagen type 2 (Coll261−273), a possible autoantigen in rheumatoid arthritis (RA). Objectives/methods: We tested the presence of Hps sequencing 16S ribosomal RNA in crevicular fluid, synovial fluids, and tissues in patients with arthritis (RA and other peripheral arthritides) and in healthy controls. Moreover, we examined the cross-recognition of Hps by Coll261−273-specific T cells in HLA-DRB1*04pos RA patients, by T-cell receptor (TCR) beta chain spectratyping and T-cell phenotyping. Results: Hps DNA was present in 57.4% of the tooth crevicular fluids of RA patients and in 31.6% of controls. Anti-Hps IgM and IgG titers were detectable and correlated with disease duration and the age of the patients. Peripheral blood mononuclear cells (PBMCs) were stimulated with Hps virulence-associated trimeric autotransporter peptide (VtaA10755−766), homologous to human Coll261−273 or co-cultured with live Hps. In both conditions, the expanded TCR repertoire overlapped with Coll261−273 and led to the production of IL-17. Discussion: We show that the DNA of an infectious agent (Hps), not previously described as pathogen in humans, is present in most patients with RA and that an Hps peptide is able to activate T cells specific for Coll261−273, likely inducing or maintaining a molecular mimicry mechanism. Conclusion: The cross-reactivity between VtaA10755−766 of a non-human infectious agent and human Coll261−273 suggests an involvement in the pathogenesis of RA. This mechanism appears emphasized in predisposed individuals, such as patients with shared epitope