806 research outputs found

    ZipA Uses a Two-Pronged FtsZ-Binding Mechanism Necessary for Cell Division

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    In most bacteria, cell division is centrally organized by the FtsZ protein, which assembles into dynamic filaments at the division site along the cell membrane that interact with other key cell division proteins. In gammaproteobacteria such as Escherichia coli, FtsZ filaments are anchored to the cell membrane by two essential proteins, FtsA and ZipA. Canonically, this interaction was believed to be mediated solely by the FtsZ C-terminal peptide (CTP) domain that interacts with these and several other regulatory proteins. However, we now provide evidence of a second interaction between FtsZ and ZipA. Using site-specific photoactivated cross-linking, we identified a noncanonical FtsZ-binding site on ZipA on the opposite side from the FtsZ CTP-binding pocket. Cross-linking at this site was unaffected by the truncation of the FtsZ linker and CTP domains, indicating that this noncanonical site must interact directly with the globular core domain of FtsZ. Mutations introduced into either the canonical or noncanonical binding sites on ZipA disrupted photo-cross-linking with FtsZ and normal ZipA function in cell division, suggesting that both binding modes are important for normal cell growth and division. One mutation at the noncanonical face was also found to suppress defects of several other canonical and noncanonical site mutations in ZipA, suggesting there is some interdependence between the two sites. Taken together, these results suggest that ZipA employs a two-pronged FtsZ-binding mechanism

    Dysregulation of Connexin expression plays a pivotal role in psoriasis

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    Background: Psoriasis, a chronic inflammatory disease affecting 2–3% of the population, is characterised by epidermal hyperplasia, a sustained pro-inflammatory immune response and is primarily a T-cell driven disease. Previous work determined that Connexin26 is upregulated in psoriatic tissue. This study extends these findings. Methods: Biopsies spanning psoriatic plaque (PP) and non-involved tissue (PN) were compared to normal controls (NN). RNA was isolated and subject to real-time PCR to determine gene expression profiles, including GJB2/CX26, GJB6/CX30 and GJA1/CX43. Protein expression was assessed by immunohistochemistry. Keratinocytes and fibroblasts were isolated and used in 3D organotypic models. The pro-inflammatory status of fibroblasts and 3D cultures was assessed via ELISA and RnD cytokine arrays in the presence or absence of the connexin channel blocker Gap27. Results: Connexin26 expression is dramatically enhanced at both transcriptional and translational level in PP and PN tissue compared to NN (>100x). In contrast, CX43 gene expression is not affected, but the protein is post-translationally modified and accumulates in psoriatic tissue. Fibroblasts isolated from psoriatic patients had a higher inflammatory index than normal fibroblasts and drove normal keratinocytes to adopt a “psoriatic phenotype” in a 3D-organotypic model. Exposure of normal fibroblasts to the pro-inflammatory mediator peptidoglycan, isolated from Staphylococcus aureus enhanced cytokine release, an event protected by Gap27. Conclusion: dysregulation of the connexin26:43 expression profile in psoriatic tissue contributes to an imbalance of cellular events. Inhibition of connexin signalling reduces pro-inflammatory events and may hold therapeutic benefit

    Analysis of Local and Global Aromaticity in Si3C5 and Si4C8 Clusters. Aromatic Species Containing Planar Tetracoordinate Carbon

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    The minimum energy structures of the Si3C5 and Si4C8 clusters are planar and contain planar tetracoordinate carbons (ptCs). These species have been classified, qualitatively, as global (π) and local (σ) aromatics according to the adaptive natural density partitioning (AdNDP) method, which is an orbital localization method. This work evaluates these species’ aromaticity, focusing on confirming and quantifying their global and local aromatic character. For this purpose, we use an orbital localization method based on the partitioning of the molecular space according to the topology of the electronic localization function (LOC-ELF). In addition, the magnetically induced current density is analyzed. The LOC-ELF-based analysis coincides with the AdNDP study (double aromaticity, global, and local). Moreover, the current density analysis detects global and local ring currents. The strength of the global and local current circuit is significant, involving 4n + 2 π- and σ-electrons, respectively. The latter implicates the Si-ptC-Si fragment, which would be related to the 3c-2e σ-bond detected by the orbital localization methods in this fragment.Fil: Torres Vega, Juan J.. Universidad Nacional Mayor de San Marcos; PerúFil: Alcoba, Diego Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Oña, Ofelia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Vasquez Espinal, A.. Universidad Andrés Bello; ChileFil: Baez Grez, R.. Universidad Andrés Bello; ChileFil: Lain, Luis. Universidad del País Vasco; EspañaFil: Torre, Alicia. Universidad del País Vasco; EspañaFil: García, Victor Raúl. Universidad Nacional Mayor de San Marcos; Perú. Universidad Andrés Bello; ChileFil: Tiznado, William. Universidad Andrés Bello; Chil

    Near Real-Time Automated Early Mapping of the Perimeter of Large Forest Fires from the Aggregation of VIIRS and MODIS Active Fires in Mexico

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    In contrast with current operational products of burned area, which are generally available one month after the fire, active fires are readily available, with potential application for early evaluation of approximate fire perimeters to support fire management decision making in near real time. While previous coarse-scale studies have focused on relating the number of active fires to a burned area, some local-scale studies have proposed the spatial aggregation of active fires to directly obtain early estimate perimeters from active fires. Nevertheless, further analysis of this latter technique, including the definition of aggregation distance and large-scale testing, is still required. There is a need for studies that evaluate the potential of active fire aggregation for rapid initial fire perimeter delineation, particularly taking advantage of the improved spatial resolution of the Visible Infrared Imaging Radiometer (VIIRS) 375 m, over large areas and long periods of study. The current study tested the use of convex hull algorithms for deriving coarse-scale perimeters from Moderate Resolution Imaging Spectroradiometer (MODIS) and Visible Infrared Imaging Radiometer Suite (VIIRS) active fire detections, compared against the mapped perimeter of the MODIS collection 6 (MCD64A1) burned area. We analyzed the effect of aggregation distance (750, 1000, 1125 and 1500 m) on the relationships of active fire perimeters with MCD64A1, for both individual fire perimeter prediction and total burned area estimation, for the period 2012–2108 in Mexico. The aggregation of active fire detections from MODIS and VIIRS demonstrated a potential to offer coarse-scale early estimates of the perimeters of large fires, which can be available to support fire monitoring and management in near real time. Total burned area predicted from aggregated active fires followed the same temporal behavior as the standard MCD64A1 burned area, with potential to also account for the role of smaller fires detected by the thermal anomalies. The proposed methodology, based on easily available algorithms of point aggregation, is susceptible to be utilized both for near real-time and historical fire perimeter evaluation elsewhere. Future studies might test active fires aggregation between regions or biomes with contrasting fuel characteristics and human activity patterns against medium resolution (e.g., Landsat and Sentinel) fire perimeters. Furthermore, coarse-scale active fire perimeters might be utilized to locate areas where such higher-resolution imagery can be downloaded to improve the evaluation of fire extent and impactFunding for this study was provided by CONAFOR/CONACYT Projects “CO2-2014-3-252620” and “CO-2018-2-A3-S-131553” for the development and enhancement of a Forest Fire Danger Prediction System for Mexico, funded by the Sectorial Fund for forest research, development and technological innovation “Fondo Sectorial para la investigación, el desarrollo y la innovación tecnológica forestal”S

    The Lyth Bound and the End of Inflation

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    We derive an extended version of the well-known Lyth Bound on the total variation of the inflaton field, incorporating higher order corrections in slow roll. We connect the field variation Δϕ\Delta\phi to both the spectral index of scalar perturbations and the amplitude of tensor modes. We then investigate the implications of this bound for ``small field'' potentials, where the field rolls off a local maximum of the potential. The total field variation during inflation is {\em generically} of order mPlm_{\rm Pl}, even for potentials with a suppressed tensor/scalar ratio. Much of the total field excursion arises in the last e-fold of inflation and in single field models this problem can only be avoided via fine-tuning or the imposition of a symmetry. Finally, we discuss the implications of this result for inflationary model building in string theory and supergravity.Comment: 10 pages, RevTeX, 2 figures (V3: version accepted for publication by JCAP

    Fístula enterocutánea en abdomen abierto. Experiencia del Hospital Universitario San Jorge (ESE) Pereira 2000-2001

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    Se analizó una serie clínica de 23 pacientes condiagnóstico de abdomen abierto asociado a fístulaenterocutánea a los cuales se les aplicó un protocolo desoporte nutricional con el fin de evaluar la eficacia dedicho protocolo en términos de cierre de la fístula. Losresultados mostraron una preponderancia de la causapost-quirúrgica no traumática sobre la traumática (60.9%y 39.1% respectivamente). El promedio de procedimientosquirúrgicos fue de 4.7 cirugias/paciente y el 74% de lospacientes recibió soporte nutricional mixto (enteral yparenteral). El número de pacientes con cierre exitoso fuede 15 (65%), 8 con tratamiento conservador y 7 con cierrequirúrgico. Los datos obtenidos permiten concluir que elabdomen abierto complicado con fístula enterocutáneaes una entidad de difícil manejo con una alta morbilidady mortalidad, que requiere un gran compromisointerdisciplinario e institucional. El protocolo aplicadose tradujo en tasas de cierre espontáneo del 35% y cierresantes del mes de tratamiento en más del 50% de lospacientes

    Fístula enterocutánea en abdomen abierto. Experiencia del Hospital Universitario San Jorge (ESE) Pereira 2000-2001

    Get PDF
    Se analizó una serie clínica de 23 pacientes condiagnóstico de abdomen abierto asociado a fístulaenterocutánea a los cuales se les aplicó un protocolo desoporte nutricional con el fin de evaluar la eficacia dedicho protocolo en términos de cierre de la fístula. Losresultados mostraron una preponderancia de la causapost-quirúrgica no traumática sobre la traumática (60.9%y 39.1% respectivamente). El promedio de procedimientosquirúrgicos fue de 4.7 cirugias/paciente y el 74% de lospacientes recibió soporte nutricional mixto (enteral yparenteral). El número de pacientes con cierre exitoso fuede 15 (65%), 8 con tratamiento conservador y 7 con cierrequirúrgico. Los datos obtenidos permiten concluir que elabdomen abierto complicado con fístula enterocutáneaes una entidad de difícil manejo con una alta morbilidady mortalidad, que requiere un gran compromisointerdisciplinario e institucional. El protocolo aplicadose tradujo en tasas de cierre espontáneo del 35% y cierresantes del mes de tratamiento en más del 50% de lospacientes
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