Progress Report on pH-Influenced Photocatalysis for Active Motion

Living systems use catalysis to achieve chemical transformations to comply with their needs in terms of energy and building blocks. The pH is a powerful means to regulate such processes, which also influences synthetic systems. In fact, the pH sensitivity of artificial photocatalysts, such as bismuth vanadate, bears the strong potential of flexibly influencing both the motion pattern and the speed of catalytic microswimmers, but it has rarely been investigated to date. In this work, we first present a comprehensive view of the motion behavior of differently shaped bismuth vanadate microswimmers, discuss influences, such as shape, pH, and conductivity of the solutions, and find that the motion pattern of the swimmers switches between upright and horizontal at their point of zero charge. We then apply an immobilizable hydroxypyrene derivative to our substrates to locally influence the pH of the solution by excited-state proton transfer. We find that the motion pattern of our swimmers is strongly influenced by this functionalization and a third motion mode, called tumbling, is introduced. Taking other effects, such as an increased surface roughness of the modified substrates, into account, we critically discuss possible future developments

Estudio de prefactibilidad para la implementación de un darkstore por aplicación en Lima

El presente estudio de prefactibilidad es la implementación de un darkstore por aplicación en Lima Metropolitana. El servicio es un supermercado virtual que comercializará productos de consumo masivo a través de un aplicativo móvil. La ventaja competitiva diferenciadora del proyecto se basa en la implementación del “one click”, el cual permite al cliente hacer sus pedidos preestablecidos dando un click en la aplicación. De igual forma, se opera asegurando la cadena de frío en toda la distribución del producto, además de ofrecer un alto nivel de servicio y entregas rápidas. A lo largo del capítulo I se determinaron los objetivos generales y específicos, así como la hipótesis. En el capítulo II, se especificó las estrategias de marketing. Se analizó los factores externos y cuál es el nivel de respuesta hacia ellos. Asimismo, mediante una encuesta aplicada a personas, ubicadas en las zonas 6 y 7 de Lima Metropolitana, del NSE A/B, y que hayan realizado compras por supermercados virtuales previamente. En base a los resultados se determinó la demanda del proyecto hasta el 2026. En el capítulo III se realizó la elección de la ubicación del darkstore a nivel de macro localización, el cual se situará en el distrito de San Luis. En el capítulo IV se determinó la dimensión del servicio, limitada por la demanda del proyecto. En el capítulo V se detalló el flujo del servicio, la capacidad instalada (46 478 canasta). Por otro lado, se especifican los requerimientos de material, servicios y personal. Por último, se elabora la disposición de la instalación del servicio. En el capítulo VI, se detallan la formación organizativa prevista, así como el organigrama. En el capítulo VII se especifican los presupuestos necesarios y los indicadores financieros. Finalmente, en el capítulo VIII, se explican los indicadores sociales y los valores según el modelo de negocio.This prefeasibility study is the implementation of a darkstore per application in Metropolitan Lima. The service is a virtual supermarket that will market mass consumption products through a mobile application. The differentiating competitive advantage of the project is based on the implementation of the "one click", which allows the client to make their pre-established orders by clicking on the application. In the same way, it operates by ensuring the cold chain throughout the distribution of the product, in addition to offering a high level of service and fast deliveries. Throughout Chapter I, the general and specific objectives were determined, as well as the hypothesis. In Chapter II, marketing strategies were specified. External factors were analyzed and what is the level of response to them. Likewise, through a survey applied to people, located in zones 6 and 7 of Metropolitan Lima, of the NSE A / B, and who have made purchases through virtual supermarkets previously. Based on the results, the demand for the project until 2026 was determined. In chapter III, the choice of the location of the darkstore was made at the macro location level, which will be located in the district of San Luis. Chapter IV identified the size of the service, as limited by the demand for the project. The chapter detailed the flow of service, installed capacity (46 478 basket). On the other hand, the requirements of material, services and personnel are specified. Finally, the layout of the installation of the service is drawn up. Chapter VI details the planned organizational training as well as the organizational chart. Chapter VII specifies the necessary budgets and financial indicators. Finally, Chapter VIII explains the social indicators and values according to the business model

Lipoproteins Are Critical TLR2 Activating Toxins in Group B Streptococcal Sepsis

Abstract Group B streptococcus (GBS) is the most important cause of neonatal sepsis, which is mediated in part by TLR2. However, GBS components that potently induce cytokines via TLR2 are largely unknown. We found that GBS strains of the same serotype differ in released factors that activate TLR2. Several lines of genetic and biochemical evidence indicated that lipoteichoic acid (LTA), the most widely studied TLR2 agonist in Gram-positive bacteria, was not essential for TLR2 activation. We thus examined the role of GBS lipoproteins in this process by inactivating two genes essential for bacterial lipoprotein (BLP) maturation: the prolipoprotein diacylglyceryl transferase gene (lgt) and the lipoprotein signal peptidase gene (lsp). We found that Lgt modification of the N-terminal sequence called lipobox was not critical for Lsp cleavage of BLPs. In the absence of lgt and lsp, lipoprotein signal peptides were processed by the type I signal peptidase. Importantly, both the Δlgt and the Δlsp mutant were impaired in TLR2 activation. In contrast to released factors, fixed Δlgt and Δlsp GBS cells exhibited normal inflammatory activity indicating that extracellular toxins and cell wall components activate phagocytes through independent pathways. In addition, the Δlgt mutant exhibited increased lethality in a model of neonatal GBS sepsis. Notably, LTA comprised little, if any, inflammatory potency when extracted from Δlgt GBS. In conclusion, mature BLPs, and not LTA, are the major TLR2 activating factors from GBS and significantly contribute to GBS sepsis

CADASIL Affects Multiple Aspects of Cerebral Small Vessel Function on 7T-MRI

International audienceObjective: Cerebral small vessel diseases (cSVDs) are a major cause of stroke and dementia. We used cutting-edge 7T-MRI techniques in patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), to establish which aspects of cerebral small vessel function are affected by this monogenic form of cSVD. Methods: We recruited 23 CADASIL patients (age 51.1 AE 10.1 years, 52% women) and 13 age-and sex-matched controls (46.1 AE 12.6, 46% women). Small vessel function measures included: basal ganglia and centrum semiovale perforating artery blood flow velocity and pulsatility, vascular reactivity to a visual stimulus in the occipital cortex and reactivity to hypercapnia in the cortex, subcortical gray matter, white matter, and white matter hyperintensities. Results: Compared with controls, CADASIL patients showed lower blood flow velocity and higher pulsatility index within perforating arteries of the centrum semiovale (mean difference À 0.09 cm/s, p = 0.03 and 0.20, p = 0.009) and basal ganglia (mean difference À 0.98 cm/s, p = 0.003 and 0.17, p = 0.06). Small vessel reactivity to a short visual stimulus was decreased (blood-oxygen-level dependent [BOLD] mean difference À0.21%, p = 0.04) in patients, while reactivity to hypercapnia was preserved in the cortex, subcortical gray matter, and normal appearing white matter. Among patients, reactivity to hypercapnia was decreased in white matter hyperintensities compared to normal appearing white matter (BOLD mean difference À0.29%, p = 0.02). Interpretation: Multiple aspects of cerebral small vessel function on 7T-MRI were abnormal in CADASIL patients, indicative of increased arteriolar stiffness and regional abnormalities in reactivity, locally also in relation to white matter injury. These observations provide novel markers of cSVD for mechanistic and intervention studies

Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection

Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into firstline defense mechanisms against bacterial infections of the lung

The P-Loop Domain of Yeast Clp1 Mediates Interactions Between CF IA and CPF Factors in Pre-mRNA 3′ End Formation

Cleavage factor IA (CF IA), cleavage and polyadenylation factor (CPF), constitute major protein complexes required for pre-mRNA 3′ end formation in yeast. The Clp1 protein associates with Pcf11, Rna15 and Rna14 in CF IA but its functional role remained unclear. Clp1 carries an evolutionarily conserved P-loop motif that was previously shown to bind ATP. Interestingly, human and archaean Clp1 homologues, but not the yeast protein, carry 5′ RNA kinase activity. We show that depletion of Clp1 in yeast promoted defective 3′ end formation and RNA polymerase II termination; however, cells expressing Clp1 with mutant P-loops displayed only minor defects in gene expression. Similarly, purified and reconstituted mutant CF IA factors that interfered with ATP binding complemented CF IA depleted extracts in coupled in vitro transcription/3′ end processing reactions. We found that Clp1 was required to assemble recombinant CF IA and that certain P-loop mutants failed to interact with the CF IA subunit Pcf11. In contrast, mutations in Clp1 enhanced binding to the 3′ endonuclease Ysh1 that is a component of CPF. Our results support a structural role for the Clp1 P-loop motif. ATP binding by Clp1 likely contributes to CF IA formation and cross-factor interactions during the dynamic process of 3′ end formation