2-OMe-lysophosphatidylcholine analogues are GPR119 ligands and activate insulin secretion from βTC-3 pancreatic cells: Evaluation of structure-dependent biological activity

GPR119 receptor has been proposed as a metabolic regulator playing a pivotal role in the modulation of glucose homeostasis in type 2 diabetes. GPR119 was identified on pancreatic β cells and its ligands have the ability to enhance glucose-stimulated insulin secretion (GSIS). Lysophosphatidylcholine (LPC) was shown to potentiate GSIS and our present studies indicate that 2-methoxy-lysophosphatidylcholine (2-OMe-LPC) analogues, unable to undergo 1 → 2 acyl migration, stimulate GSIS from murine βTC-3 pancreatic cells even more efficiently. Moreover, biological assays in engineered Tango? GPR119-bla U2OS cells were carried out to ascertain the agonist activity of 2-OMe-LPC at GPR119. 2-OMe-LPC possessing in sn-1 position the residues of myristic, palmitic, stearic and oleic acid were also evaluated as factors regulating [Ca^2 +]_i mobilization and cAMP levels. Extension of these studies to R- and S-enantiomers of 14:0 2-OMe-LPC revealed that the overall impact on GSIS does not depend on chirality, however, the intracellular calcium mobilization data show that the R enantiomer is significantly more active than S one. Taking into account differences in chemical structure between various native LPCs and their 2-methoxy counterparts the possible binding mode of 2-OMe-LPC to the GPR119 receptor was determined using molecular modeling approach.     

Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14

Background

In humans, bitterness perception is mediated by ~25 bitter taste receptors present in the oral cavity. Among these receptors three, TAS2R10, TAS2R14 and TAS2R46, exhibit extraordinary wide agonist profiles and hence contribute disproportionally high to the perception of bitterness. Perhaps the most broadly tuned receptor is the TAS2R14, which may represent, because of its prominent expression in extraoral tissues, a receptor of particular importance for the physiological actions of bitter compounds beyond taste.

Next generation organoids for biomedical research and applications

Organoids are in vitro cultures of miniature fetal or adult organ-like structures. Their potentials for use in tissue and organ replacement, disease modeling, toxicology studies, and drug discovery are tremendous. Currently, major challenges facing human organoid technology include (i) improving the range of cellular heterogeneity for a particular organoid system, (ii) mimicking the native micro- and matrix-environment encountered by cells within organoids, and (iii) developing robust protocols for the in vitro maturation of organoids that remain mostly fetal-like in cultures. To tackle these challenges, we advocate the principle of reverse engineering that replicates the inner workings of in vivo systems with the goal of achieving functionality and maturation of the resulting organoid structures with the input of minimal intrinsic (cellular) and environmental (matrix and niche) constituents. Here, we present an overview of organoid technology development in several systems that employ cell materials derived from fetal and adult tissues and pluripotent stem cell cultures. We focus on key studies that exploit the self-organizing property of embryonic progenitors and the role of designer matrices and cell-free scaffolds in assisting organoid formation. We further explore the relationship between adult stem cells, niche factors, and other current developments that aim to enhance robust organoid maturation. From these works, we propose a standardized pipeline for the development of future protocols that would help generate more physiologically relevant human organoids for various biomedical applications.     

A Plausible Microtubule-Based Mechanism for Cell Division Orientation in Plant Embryogenesis

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Disruption of the E. coli LptC dimerization interface and characterization of lipopolysaccharide and LptA binding to monomeric LptC

Lipopolysaccharide (LPS) is an essential element of nearly all Gram‐negative bacterial outer membranes and serves to protect the cell from adverse environmental stresses. Seven members of the lipopolysaccharide transport (Lpt) protein family function together to transport LPS from the inner membrane (IM) to the outer leaflet of the outer membrane of bacteria such as Escherichia coli. Each of these proteins has a solved crystal structure, including LptC, which is a largely periplasmic protein that is associated with the IM LptB₂FG complex and anchored to the membrane by an N‐terminal helix. LptC directly binds LPS and is hypothesized to be involved in the transfer of LPS to another periplasmic protein, LptA. Purified and in solution, LptC forms a dimer. Here, point mutations designed to disrupt formation of the dimer are characterized using site‐directed spin labeling double electron electron resonance (DEER) spectroscopy, light scattering, circular dichroism, and computational modeling. The computational studies reveal the molecular interactions that drive dimerization of LptC and elucidate how the disruptive mutations change this interaction, while the DEER and light scattering studies identify which mutants disrupt the dimer. And, using electron paramagnetic resonance spectroscopy and comparing the results to the previous quantitative characterization of the interactions between dimeric LptC and LPS and LptA, the functional consequences of monomeric LptC were also determined. These results indicate that disruption of the dimer does not affect LPS or LptA binding and that monomeric LptC binds LPS and LptA at levels similar to dimeric LptC.     

Invited review: Helping dairy farmers to improve economic performance utilizing data-driving decision support tools

The objective of this review paper is to describe the development and application of a suite of more than 40 computerized dairy farm decision support tools contained at the University of Wisconsin-Madison (UW) Dairy Management website http://DairyMGT.info. These data-driven decision support tools are aimed to help dairy farmers improve their decision-making, environmental stewardship and economic performance. Dairy farm systems are highly dynamic in which changing market conditions and prices, evolving policies and environmental restrictions together with every time more variable climate conditions determine performance. Dairy farm systems are also highly integrated with heavily interrelated components such as the dairy herd, soils, crops, weather and management. Under these premises, it is critical to evaluate a dairy farm following a dynamic integrated system approach. For this approach, it is crucial to use meaningful data records, which are every time more available. These data records should be used within decision support tools for optimal decision-making and economic performance. Decision support tools in the UW-Dairy Management website (http://DairyMGT.info) had been developed using combination and adaptation of multiple methods together with empirical techniques always with the primary goal for these tools to be: (1) highly user-friendly, (2) using the latest software and computer technologies, (3) farm and user specific, (4) grounded on the best scientific information available, (5) remaining relevant throughout time and (6) providing fast, concrete and simple answers to complex farmers’ questions. DairyMGT.info is a translational innovative research website in various areas of dairy farm management that include nutrition, reproduction, calf and heifer management, replacement, price risk and environment. This paper discusses the development and application of 20 selected (http://DairyMGT.info) decision support tools.     

Modelling the responses of Australian subtropical rainforest birds to changes in environmental conditions along elevational gradients

Montane birds face significant threats from a warming climate, so determining the environmental factors that most strongly influence the composition of such assemblages is of critical conservation importance. Changes in temperature and other environmental conditions along elevational gradients are known to influence the species richness and abundance of bird assemblages occupying mountains. However, the role of species‐specific traits in mediating the responses of bird species to changing conditions remains poorly understood. We aimed to determine whether different bird species responded differently to changing environmental conditions in a relatively understudied biodiversity hotspot in subtropical rainforest on the east coast of Australia. We examined patterns in avian species richness and abundance along two rainforest elevational gradients using monthly point counts between September 2015 and October 2016. Environmental data on temperature, wetness, canopy cover and canopy height were collected simultaneously, and trait information on body size and feeding guild membership for each bird species was obtained from the Handbook of Australian, New Zealand and Antarctic Birds. We used a generalized linear mixed modelling (GLMM) framework to determine the drivers of species richness and abundance and to quantify species’ trait–environment interactions. GLMMs indicated that temperature alone was significantly positively correlated with species richness and abundance. Species richness declined with increasing elevation. When modelling abundance, we found that feeding guild membership did not significantly affect species’ responses to environmental conditions. In contrast, the predicted abundance of a species was found to depend on its body size, due to significant positive interactions between this trait, temperature and canopy cover. Our findings indicate that large‐bodied birds are likely to increase in abundance more rapidly than small‐bodied birds with continued climatic warming. These results underline the importance of temperature as a driving factor of avian community assembly along environmental gradients.     

Which species,how many,and from where: Integrating habitat suitability,population genomics,and abundance estimates into species reintroduction planning

Extirpated organisms are reintroduced into their former ranges worldwide to combat species declines and biodiversity losses. The growing field of reintroduction biology provides guiding principles for reestablishing populations, though criticisms remain regarding limited integration of initial planning, modeling frameworks, interdisciplinary collaborations, and multispecies approaches. We used an interdisciplinary, multispecies, quantitative framework to plan reintroductions of three fish species into Abrams Creek, Great Smoky Mountains National Park, USA. We first assessed the appropriateness of habitat at reintroduction sites for banded sculpin (Cottus carolinae), greenside darter (Etheostoma blennioides), and mottled sculpin (Cottus bairdii) using species distribution modeling. Next, we evaluated the relative suitability of nine potential source stock sites using population genomics, abundance estimates, and multiple‐criteria decision analysis (MCDA) based on known correlates of reintroduction success. Species distribution modeling identified mottled sculpin as a poor candidate, but banded sculpin and greenside darter as suitable candidates for reintroduction based on species‐habitat relationships and habitats available in Abrams Creek. Genotyping by sequencing revealed acceptable levels of genetic diversity at all candidate source stock sites, identified population clusters, and allowed for estimating the number of fish that should be included in translocations. Finally, MCDA highlighted priorities among candidate source stock sites that were most likely to yield successful reintroductions based on differential weightings of habitat assessment, population genomics, and the number of fish available for translocation. Our integrative approach represents a unification of multiple recent advancements in the field of reintroduction biology and highlights the benefit of shifting away from simply choosing nearby populations for translocation to an information‐based science with strong a priori planning coupled with several suggested posteriori monitoring objectives. Our framework can be applied to optimize reintroduction successes for a multitude of organisms and advances in the science of reintroduction biology by simultaneously addressing a variety of past criticisms of the field.