All-Atom Simulations Uncover Structural and Dynamical Properties of STING Proteins in the Membrane System

Recent studies have shown that the stimulator of interferon gene (STING) protein plays a central role in the immune system by facilitating the production of Type I interferons in cells. The STING signaling pathway is also a prominent activator of cancer-killing T cells that initiates a powerful adaptive immune response. Since biomolecular signaling pathways are complicated and not easily identified through traditional experiments, molecular dynamics (MD) has often been used to study these biological pathways’ structural and dynamical responses. Here, we carried out MD simulations for full-length chicken and human STING (chSTING and hSTING) proteins. Specifically, we investigated ligand-bound closed and ligand-unbound open forms of each STING in the membrane system by comparing conformational and dynamical differences among them. Our research provides clues for understanding the mechanism of the STING signaling pathway by uncovering some detailed insights for the examined systems: the residues from each chain in the binding pocket are strongly correlated to one another in the open STING structure compared with those in the closed STING structure. Ligand-bound closed STING displays approximately 170° rotation of the ligand-binding domain (LBD) relative to the open-STING structure. The detailed dynamical analysis of residue Cys148 in the linker region of hSTING does not support the earlier hypothesis that Cys148 can form disulfide bonds between adjacent STING dimers. We also reveal that using the full-length proteins is critical as the MD simulations of the LBD portion only cannot properly describe the global conformational properties of multiple domain proteins, such as STING

Servicos de atendimento ao consumidor : uma abordagem qualitativa na industria de alimentos

Uma prática que se tomou muito comum a partir da promulgação do Código de Defesa do Consumidor no Brasil, foi a implantação de Serviços de Atendimento ao Consumidor. O presente trabalho exarruna esta questão, em princípio, de forma ampla e generalizada, buscando uma compreensão do tema a partir das suas origens na evolução do comportamento do consumidor no mundo e em nosso país, situando o assunto dentro do panorama econômico mundial. Feito isso, o texto trata de definir o papel dos Serviços de Atendimento ao Consumidor, bem como suas funções e importância dentro de um mercado cada vez mais competitivo. Descreve ainda, o processo de implantação e operacionalização destes serviços, fornecendo diretrizes para um trabalho eficiente, mostrando as dificuldades envolvidas e apresentando exemplos de empresas que deles se utilizam para a obtenção de resultados positivos. Só então, a questão central é apresentada, isto é, como estes serviços são percebidos por aqueles a quem se destinam, os consumidores? O estudo não tem a pretensão de apresentar resultados definitivos, visto que esses só seriam obtidos através de uma avaliação quantitativa. Contudo, seus resultados servem como subsídio a orientar um aprofundamento do tema.A practice that became usual since the Consumer' s Defense C ode promulgation in Brazil, was the opening o f Consumer' s Affairs Departments. This work examines this question, at the begining, in a wide and generalized way, looking for an understanding of the subject starting from its origins in the consumption evolution, in the world and in our country, placing the theme inside the world's economical vtew. When it is dane, the text try to define the Consumer' s Affairs Departments rules, as well as its functions and importance inside a market each time more competitive and, still, to describe the process o f planning and operacionalization o f these services, providing !ines to an efficient work, showing the difficulties involved and presenting examples of enterprises that use them for getting positive results. Only at this moment, the main question is presented: How are these services seen for whom they were made for, the consumers? In the qualitative approach of discussion groups method, the research was oriented by the Consumer' s Affairs Departments o f food industries, whose products as caracterized by low unit prices and a relative importance to consumer' s health. The main proposal to the participants was to outline a perfect Consumer' s Service, to know their perception and what are the agents that inhibit them of contacting the manufacturer, even when a toll free is offered. This study does not have intention of presenting final results, since they would only be got by a quantitative avaliation. However, it presents results that serve as means to a deeper investigation ofthe subject

Atividade antimicrobiana de flavonóides e esteróides isolados de duas espécies de Chromolaena

Os extratos diclorometânicos e etanólicos de folhas e caule de Chromolaena squalida e de folhas e flores de Chromolaena hirsuta foram avaliados quanto à atividade antimicrobiana. Oito flavonóides e cinco esteróides foram desafiados frente a 22 cepas indicadoras, incluindo bactérias (Gram-positivas e Gram-negativas) e leveduras. Todos os extratos brutos, flavonóides e esteróides ensaiados mostraram atividade antimicrobiana, principalmente frente a bactérias Gram-positivas.The crude extracts (dichloromethanic and ethanolic) and some compounds (8 flavonoids and 5 steroids) isolated from Chromolaena squalida (leaves and stems) and Chromolaena hirsuta (leaves and flowers) have been evaluated against 22 strains of microorganisms including bacteria (Gram-positive and Gram-negative) and yeasts. All crude extracts, flavonoids and steroids evaluated have been shown actives, mainly against Gram-positive bacteria

Living Benthic Foraminifera from the Surface and Subsurface Sediment Layers Applied to the Environmental Characterization of the Brazilian Continental Slope (SW Atlantic)

Living benthic foraminifera (>63 µm) were studied to characterize the continental slope of the Potiguar Basin (SW Atlantic). Foraminifers from the surface (0–2 cm), subsurface (2–5 cm), and integrated (0–5 cm) sediment layers were analyzed to verify their contribution to environmental characterization. It was also estimated if and which changes occur when the subsurface is added. Sampling stations were distributed in five transects in four isobaths (150, 400, 1000, and 2000 m). Sediment samples were fixed with 4% buffered formaldehyde and stained with Bengal rose. Were recorded 396 species in the surface layer, 228 in the subsurface, and 449 in integrating both layers. This study did not include tubular agglutinated species. The assemblages from 150 m isobath indicated the upper slope, from 400 m indicated the middle slope and the ones from the 2000 m indicated the lower slope. The surface layer’s assemblage at 1000 m isobath was more similar to the middle slope; in contrast, its subsurface layer’s assemblage had more similarity with the lower slope. Rarefaction curves, Permanova, and NMDS routines indicated a high resemblance between surface and integrated layers. Therefore, the first two centimeters were sufficient to characterize this region based on living benthic foraminifera.Fil: de Carvalho Santa Rosa, Luciana Cristina. Universidade Federal do Paraná; BrasilFil: Trevisan Disaró, Sibelle. Universidade Federal do Paraná; BrasilFil: Totah, Violeta Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Watanabe, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Bittencourt Guimaraes, Ana Tereza. Universidade Estadual Do Oeste Do Pará; Brasi

Environmental constraints on benthic foraminifera communities during Middle Pleistocene from the Southwest South Atlantic Ocean

El océano Atlántico Sur es clave en la distribución de masas de agua profunda hacia otros océanos. Dado el papel que juega la circulación termohalina en el clima, el reconocimiento de variaciones en su distribución durante los ciclos glaciales/interglaciales reviste gran interés. Los foraminíferos bentónicos son utilizados como herramientas de reconstrucción paleoceanográ- fica, y la existencia de especies asociadas a masas de agua fue utilizada para definir cambios en la circulación oceánica profunda. Sin embargo, la relación entre foraminíferos bentónicos y masas de agua es controversial. Con el objetivo de determinar si las asociaciones de foraminíferos bentónicos reflejan la distribución de las masas de agua profunda durante un evento glacial del Pleistoceno Medio, se analizó un testigo ubicado en el límite entre dos masas de agua profunda: la North Atlantic Deep Water y la Circumpolar Deep Water. En las asociaciones se hallaron especies consideradas indicadoras de ambas masas de agua, aunque algunas especies asociadas a la Circumpolar Deep Water presentan abundancias relativas mayores, siendo Uvigerina peregrina dominante en ciertos niveles. Sin embargo, la escasa abundancia de Globocassidulina subglobosa, asociada a la Circumpolar Deep Water, y la constancia en el porcentaje de especies consideradas indicadoras de la North Atlantic Deep Water impiden atribuir la dominancia de Uvigerina peregrina a una mayor influencia de la Circumpolar Deep Water. El hecho de que esta especie está asociada a flujos elevados de materia orgánica y que su mayor dominancia coincida con aumentos en la abundancia de Globigerina bulloides indica que la productividad superficial fue el factor determinante en la estructuración de las asociaciones de foraminíferos bentónicos en el talud norbonaerense durante el Pleistoceno Medio.The Southern South Atlantic is crucial in the distribution of deep water masses towards other ocean basins. Given the role of the thermohaline circulation in the climatic system, insights into its variations during glacial/interglacial cycles is of great interest. Benthic foraminifera are used in paleoceanographic reconstructions, tracking changes in deep oceanic circulation by means of the distribution of indicator species associated with certain water masses. However, the relationship between benthic foraminifera and water masses is controversial. A sediment core drilled at the North Atlantic Deep Water-Circumpolar Deep Water limit was surveyed for benthic foraminifera in order to determine whether assemblages reflect patterns of deep watermasses distribution during a Middle Pleistocene glaciation event. The assemblages recovered comprised species indicative of both water types, with Circumpolar Deep Water-indicator species being slightly more abundant due to Uvigerina peregrina dominance. In spite of this, the low abundance of other Circumpolar Deep Water-indicator species such as Globocassidulina subglobosa coupled with the evenness in the relative abundance of North Atlantic Deep Water indicator-species preclude the interpretation of Uvigerina peregrina’s dominance in terms of a greater influence of Circumpolar Deep Water at the expense of North Atlantic Deep Water. The latter species, also an indicator of high organic matter fluxes, increases its relative abundance jointly with those of Globigerina bulloides, which suggests that surface productivity influenced deep benthic foraminifera assemblages in the Buenos Aires talus during Middle Pleistocene glaciations.Fil: Laprida, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos ; ArgentinaFil: García Chapori, Natalia Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos ; ArgentinaFil: Ramón Mercau, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos ; ArgentinaFil: Watanabe, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Totah, Violeta Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Marcolini, Susana. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; ArgentinaFil: Violante, Roberto Antonio. Ministerio de Defensa. Armada Argentina. Servicio de Hidrografía Naval; Argentin

Biologia e genetica del podocita

Progresses in podocyte biology have been strictly connected with genetic advances; the identification of genes mutated in familial and sporadic forms of nephrotic syndrome has been followed by functional studies of the encoded proteins, revealing numerous properties of the cell. The molecules uncovered so far belong to three main categories: a) proteins located at the slit diaphragm, the intercellular junction which laterally connects podocyte processes and is responsible for selectivity of the glomerular filter, b) molecules involved in regulation of actin dynamics, which are essential for the maintenance of podocyte structure and function, and c) molecules belonging to intracellular organelles, such as mitochondria and lysosomes, which are central players in podocyte metabolism. Considering the key role of the podocyte in health and disease of the glomerular filter, better knowledge of this cell is a pre-requisite for developing targeted therapies of glomerular diseases

Women with type 1 diabetes gain more weight during pregnancy compared to age-matched healthy women despite a healthier diet. a prospective case-control observational study

Purpose: Women with type 1 diabetes mellitus (T1D), especially those with suboptimal glucose control, have 3-4 greater chances of having babies with birth defects compared to healthy women. We aimed to evaluate glucose control and insulin regimen modifications during the pregnancy of women with T1D, comparing the offspring's weight and the mother's weight change and diet with those of non-diabetic, normal-weight pregnant women. Methods: Women with T1D and age-matched healthy women controls (CTR) were consecutively enrolled among pregnant women with normal weight visiting our center. All patients underwent physical examination and diabetes and nutritional counseling, and completed lifestyle and food intake questionnaires. Results: A total of 44 women with T1D and 34 healthy controls were enrolled. Women with T1D increased their insulin regimen during pregnancy, going from baseline 0.9 ± 0.3 IU/kg to 1.1 ± 0.4 IU/kg (p = 0.009), with a concomitant significant reduction in HbA1c (p = 0.009). Over 50% of T1D women were on a diet compared to < 20% of healthy women (p < 0.001). Women with T1D reported higher consumption of complex carbohydrates, milk, dairy foods, eggs, fruits, and vegetables, while 20% of healthy women never or rarely consumed them. Despite a better diet, women with T1D gained more weight (p = 0.044) and gave birth to babies with higher mean birth weight (p = 0.043), likely due to the daily increase in insulin regimen. Conclusion: A balance between achieving metabolic control and avoiding weight gain is crucial in the management of pregnant women with T1D, who should be encouraged to further improve lifestyle and eating habits with the aim of limiting upward insulin titration adjustments to a minimum

Experimental realization of a single-layer multiferroic

Multiferroic materials have garnered wide interest for their exceptional static and dynamical magnetoelectric properties. Intrinsic type-II multiferroics exhibit an inversion-symmetry-breaking magnetic order which directly induces a ferroelectric lattice distortion through mechanisms such as the inverse Dzyaloshinskii-Moriya interaction. This direct coupling between the magnetic and structural order parameters results in record-strength magnetoelectric effects. Two-dimensional materials possessing such intrinsic multiferroic properties have been long sought for harnessing magnetoelectric coupling in nanoelectronic devices. Here, we report the discovery of type-II multiferroic order in a single atomic layer of transition metal-based van der Waals material NiI2. Using a combination of optical birefringence, second harmonic generation, and Raman spectroscopy in bulk NiI2, we first identified multiple independent and robust signatures of the multiferroic state. Subsequently, we studied the evolution of the optical signatures as a function of temperature and layer number, to find that the multiferroic state is robust down to monolayer NiI2. These observations establish NiI2 as a new platform for studying emergent multiferroic phenomena, chiral magnetic textures and ferroelectricity in the two-dimensional limit

The role of ultrasound in systemic sclerosis: On the cutting edge to foster clinical and research advancement

Abstract Ultrasound has been widely explored in systemic sclerosis in the clinical and research settings. Ultrasound allows a non-invasive and ionising radiation-free ‘window’ into this complex disease and is well-suited to repeated examinations. Ultrasound provides novel insights into the pathogenesis and measurement of disease in systemic sclerosis, including early (preclinical) internal organ involvement. The purpose of this review is to describe the role of ultrasound to foster clinical and research advancements in systemic sclerosis relating to (1) musculoskeletal, (2) digital ulcer, (3) lung disease and (4) skin disease. We also highlight unmet needs which much be addressed for ultrasound to assume a central role in systemic sclerosis clinical care and research