Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal ...barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2−/−Tlr4−/− mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
•Pregnane X receptor (PXR) is a physiologic regulator of intestinal permeability•Microbial-derived indoles can regulate intestinal barrier function through PXR•PXR regulates intestinal barrier function through TLR4•Specific indole-producing bacteria can reduce intestinal inflammation
How commensal microbial metabolites affect mucosal integrity and barrier function is unclear. Mani and colleagues show that indole 3 propionic acid regulates intestinal barrier permeability through the PXR-TLR4 pathway.
Global climate change linked to the accumulation of greenhouse gases has caused concerns regarding the use of fossil fuels as the major energy source. To mitigate climate change while keeping energy ...supply sustainable, one solution is to rely on the ability of microorganisms to use renewable resources for biofuel synthesis. In this Review, we discuss how microorganisms can be explored for the production of next-generation biofuels, based on the ability of bacteria and fungi to use lignocellulose; through direct CO2 conversion by microalgae; using lithoautotrophs driven by solar electricity; or through the capacity of microorganisms to use methane generated from landfill. Furthermore, we discuss how to direct these substrates to the biosynthetic pathways of various fuel compounds and how to optimize biofuel production by engineering fuel pathways and central metabolism.
Recent research has emphasized the promise of Immersive Virtual Reality (IVR) to bolster empathy. The underlying mechanisms of such an intriguing outcome are, however, underexplored. The present ...study examines the effect of distinct but interrelated user experiences (UX) dimensions underlying the bolstering effect of IVR on empathy. Sixty-five young adults participated in five 1-h weekly programs encompassing a total of 25 IVR experiences of different nature. Following each session, participants rated their UX of immersion-presence, illusion of body ownership, illusion of agency, engagement, and IVR-triggered mind-wandering for each IVR experience. Baseline empathy, operationalized in a multifaceted fashion, was measured both before and after the IVR program, spanning a total of seven weeks. Empathy significantly increased after the program with a moderate effect size (d = .52). Further, 27.6% of the variance in empathy change was explained by the combined effect of the UX variables. The largest predictors were illusion of body ownership and agency. The pattern of results was the same across types of IVR experience, suggesting that media content (whether empathy-evoking or not), did not moderate the relationship between UX and empathy. Together, this study highlights that IVR is more an effective “perspective taking-machine” than “empathy machine” per se.
•Empathy is a fundamental dimension of human development.•Immersive Virtual Reality (IVR) Experiences are related to increase in empathy.•The contribution of IVR user experience dimensions on empathy change is examined.•Illusion of Virtual Body Ownership and Agency best predict empathy change.•User experience is more predictive of empathy change than media content.
Ecological community assembly is governed by a combination of (i) selection resulting from among-taxa differences in performance; (ii) dispersal resulting from organismal movement; and (iii) ...ecological drift resulting from stochastic changes in population sizes. The relative importance and nature of these processes can vary across environments. Selection can be homogeneous or variable, and while dispersal is a rate, we conceptualize extreme dispersal rates as two categories; dispersal limitation results from limited exchange of organisms among communities, and homogenizing dispersal results from high levels of organism exchange. To estimate the influence and spatial variation of each process we extend a recently developed statistical framework, use a simulation model to evaluate the accuracy of the extended framework, and use the framework to examine subsurface microbial communities over two geologic formations. For each subsurface community we estimate the degree to which it is influenced by homogeneous selection, variable selection, dispersal limitation, and homogenizing dispersal. Our analyses revealed that the relative influences of these ecological processes vary substantially across communities even within a geologic formation. We further identify environmental and spatial features associated with each ecological process, which allowed mapping of spatial variation in ecological-process-influences. The resulting maps provide a new lens through which ecological systems can be understood; in the subsurface system investigated here they revealed that the influence of variable selection was associated with the rate at which redox conditions change with subsurface depth.
As the population of cancer survivors has grown into the millions, there has been increasing emphasis on understanding how the late effects of treatment affect survivors' ability to return to work ...school, their capacity to function and live independently, and their overall quality of life. This review focuses on cognitive change associated with cancer and cancer treatments. Research in this area has progressed from a pharmacotoxicology perspective to a view of the cognitive change as a complex interaction of aspects of the treatment, vulnerability factors that increase risk for posttreatment cognitive decline, cancer biology, and the biology of aging. Methodological advances include the development of (
a
) measurement approaches that assess more fine-grained subcomponents of cognition based on cognitive neuroscience and (
b
) advanced statistical approaches. Conceptual issues that arise from this multidimensional perspective are described in relation to future directions, understanding of mechanisms, and development of innovative interventions.
Vitamin D is a critical regulator of calcium and bone homeostasis. While vitamin D has multiple effects on bone and calcium metabolism, the regulation of intestinal calcium (Ca) absorption efficiency ...is a critical function for vitamin D. This is necessary for optimal bone mineralization during growth, the protection of bone in adults, and the prevention of osteoporosis. Intestinal Ca absorption is regulated by 1,25 dihydroxyvitamin D (1,25(OH)2 D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).
Over the past decade, peptide drug discovery has experienced a revival of interest and scientific momentum, as the pharmaceutical industry has come to appreciate the role that peptide therapeutics ...can play in addressing unmet medical needs and how this class of compounds can be an excellent complement or even preferable alternative to small molecule and biological therapeutics. In this Perspective, we give a concise description of the recent progress in peptide drug discovery in a holistic manner, highlighting enabling technological advances affecting nearly every aspect of this field: from lead discovery, to synthesis and optimization, to peptide drug delivery. An emphasis is placed on describing research efforts to overcome the inherent weaknesses of peptide drugs, in particular their poor pharmacokinetic properties, and how these efforts have been critical to the discovery, design, and subsequent development of novel therapeutics.
All mammalian cells display a diverse array of glycan structures that differ from those that are found on microbial pathogens. Siglecs are a family of sialic acid-binding immunoglobulin-like ...receptors that participate in the discrimination between self and non-self, and that regulate the function of cells in the innate and adaptive immune systems through the recognition of their glycan ligands. In this Review, we describe the recent advances in our understanding of the roles of Siglecs in the regulation of immune cell function in infectious diseases, inflammation, neurodegeneration, autoimmune diseases and cancer.
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