Notes

Book trojans linked to crops from the family Amaryllidaceae throughout Africa.
Cyanobacteriochromes (CBCRs) are bilin-binding photosensors of the phytochrome superfamily that show remarkable spectral diversity. The green/red CBCR subfamily is important for regulating chromatic acclimation of photosynthetic antenna in cyanobacteria and is applied for optogenetic control of gene expression in synthetic biology. It is suggested that the absorption change of this subfamily is caused by the bilin C15-Z/C15-E photoisomerization and a subsequent change in the bilin protonation state. However, structural information and direct evidence of the bilin protonation state are lacking. Here, we report a high-resolution (1.63Å) crystal structure of the bilin-binding domain of the chromatic acclimation sensor RcaE in the red-absorbing photoproduct state. The bilin is buried within a "bucket" consisting of hydrophobic residues, in which the bilin configuration/conformation is C5-Z,syn/C10-Z,syn/C15-E,syn with the A- through C-rings coplanar and the D-ring tilted. Three pyrrole nitrogens of the A- through C-rings are covered in the α-face with a hydrophobic lid of Leu249 influencing the bilin pK a, whereas they are directly hydrogen bonded in the β-face with the carboxyl group of Glu217. Glu217 is further connected to a cluster of waters forming a hole in the bucket, which are in exchange with solvent waters in molecular dynamics simulation. We propose that the "leaky bucket" structure functions as a proton exit/influx pathway upon photoconversion. NMR analysis demonstrated that the four pyrrole nitrogen atoms are indeed fully protonated in the red-absorbing state, but one of them, most likely the B-ring nitrogen, is deprotonated in the green-absorbing state. These findings deepen our understanding of the diverse spectral tuning mechanisms present in CBCRs.Groundwater pollution threatens human and ecosystem health in many regions around the globe. Raptinal concentration Fast flow to the groundwater through focused recharge is known to transmit short-lived pollutants into carbonate aquifers, endangering the quality of groundwaters where one quarter of the world's population lives. However, the large-scale impact of such focused recharge on groundwater quality remains poorly understood. Here, we apply a continental-scale model to quantify the risk of groundwater contamination by degradable pollutants through focused recharge in the carbonate rock regions of Europe, North Africa, and the Middle East. We show that focused recharge is the primary reason for widespread rapid transport of contaminants to the groundwater. Where it occurs, the concentration of pollutants in groundwater recharge that have not yet degraded increases from less then 1% to around 20 to 50% of their concentrations during infiltration. Assuming realistic application rates, our simulations show that degradable pollutants like glyphosate can exceed their permissible concentrations by 3 to 19 times when reaching the groundwater. Our results are supported by independent estimates of young water fractions at 78 carbonate rock springs over Europe and a dataset of observed glyphosate concentrations in the groundwater. They imply that in times of continuing and increasing industrial and agricultural productivity, focused recharge may result in an underestimated and widespread risk to usable groundwater volumes.This paper presents a modular software design for the construction of computational modeling technology that will help implement precision medicine. In analogy to a common industrial strategy used for preventive maintenance of engineered products, medical digital twins are computational models of disease processes calibrated to individual patients using multiple heterogeneous data streams. They have the potential to help improve diagnosis, prognosis, and personalized treatment for a wide range of medical conditions. Their large-scale development relies on both mechanistic and data-driven techniques and requires the integration and ongoing update of multiple component models developed across many different laboratories. Distributed model building and integration requires an open-source modular software platform for the integration and simulation of models that is scalable and supports a decentralized, community-based model building process. This paper presents such a platform, including a case study in an animal model of a respiratory fungal infection.Metabolic changes associated with tissue inflammation result in significant extracellular acidosis (EA). Within mucosal tissues, intestinal epithelial cells (IEC) have evolved adaptive strategies to cope with EA through the up-regulation of SLC26A3 to promote pH homeostasis. We hypothesized that EA significantly alters IEC gene expression as an adaptive mechanism to counteract inflammation. Using an unbiased RNA sequencing approach, we defined the impact of EA on IEC gene expression to define molecular mechanisms by which IEC respond to EA. This approach identified a unique gene signature enriched in cyclic AMP response element-binding protein (CREB)-regulated gene targets. Utilizing loss- and gain-of-function approaches in cultured epithelia and murine colonoids, we demonstrate that EA elicits prominent CREB phosphorylation through cyclic AMP-independent mechanisms that requires elements of the mitogen-activated protein kinase signaling pathway. Further analysis revealed that EA signals through the G protein-coupled receptor GPR31 to promote induction of FosB, NR4A1, and DUSP1. These studies were extended to an in vivo murine model in conjunction with colonization of a pH reporter Escherichia coli strain that demonstrated significant mucosal acidification in the TNFΔARE model of murine ileitis. Herein, we observed a strong correlation between the expression of acidosis-associated genes with bacterial reporter sfGFP intensity in the distal ileum. Finally, the expression of this unique EA-associated gene signature was increased during active inflammation in patients with Crohn's disease but not in the patient control samples. These findings establish a mechanism for EA-induced signals during inflammation-associated acidosis in both murine and human ileitis.
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