The atmospheric Hadley cells, which meet at the Intertropical Convergence Zone (ITCZ), play critical roles in transporting heat, driving ocean circulation and supplying precipitation to the most ...heavily populated regions of the globe. Paleo-reconstructions can provide concrete evidence of how these major features of the atmospheric circulation can change in response to climate perturbations. While most such reconstructions have focused on ITCZ-related rainfall, here we show that trade wind proxies can document dynamical aspects of meridional ITCZ shifts. Theoretical expectations based on angular momentum constraints and results from freshwater hosing simulations with two different climate models predict that ITCZ shifts due to anomalous cooling of one hemisphere would be accompanied by a strengthening of the Hadley cell and trade winds in the colder hemisphere, with an opposite response in the warmer hemisphere. This expectation of hemispherically asymmetric trade wind changes is confirmed by proxy data of coastal upwelling and windblown dust from the Atlantic basin during Heinrich stadials, showing trade wind strengthening in the Northern Hemisphere and weakening in the Southern Hemisphere subtropics in concert with southward ITCZ shifts. Data from other basins show broadly similar patterns, though improved constraints on past trade wind changes are needed outside the Atlantic Basin. The asymmetric trade wind changes identified here suggest that ITCZ shifts are also marked by intensification of the ocean's wind-driven subtropical cells in the cooler hemisphere and a weakening in the warmer hemisphere, which induces cross-equatorial oceanic heat transport into the colder hemisphere. This response would be expected to prevent extreme meridional ITCZ shifts in response to asymmetric heating or cooling. Understanding trade wind changes and their coupling to cross-equatorial ocean cells is key to better constraining ITCZ shifts and ocean and atmosphere dynamical changes in the past, especially for regions and time periods for which few paleodata exist, and also improves our understanding of what changes may occur in the future.
•In ITCZ shifts, trade winds strengthen in cooler hemisphere, weaken in warmer.•Asymmetric trade wind responses during ITCZ shifts predicted by theory and models.•Proxy data show stronger NH trades, weaker SH trades during Heinrich stadials.•Trade wind changes drive heat transport into the NH by ocean subtropical cells.•Trade wind proxies trace dynamics of Hadley cell and ocean response during stadials.
•First investigation of the effects of the 3 major whey proteins on EE cells.•BLG stimulates proliferation of intestinal EE cells and also secretion of GLP-1.•BLG’s activity appears to be lost ...following hydrolysis with trypsin or chymotrypsin.•ALA is a highly potent GLP-1 secretagogue & increases intracellular GLP-1 levels.
Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated.
Numerous studies have demonstrated that SARS-CoV-2 can be inactivated by ultraviolet (UV) radiation. However, there are few data available on the relative efficacy of different wavelengths of UV ...radiation and visible light, which complicates assessments of UV decontamination interventions. The present study evaluated the effects of monochromatic radiation at 16 wavelengths from 222 nm through 488 nm on SARS-CoV-2 in liquid aliquots and dried droplets of water and simulated saliva. The data were used to generate a set of action spectra which quantify the susceptibility of SARS-CoV-2 to genome damage and inactivation across the tested wavelengths. UVC wavelengths (≤280 nm) were most effective for inactivating SARS-CoV-2, although inactivation rates were dependent on sample type. Results from this study suggest that UV radiation can effectively inactivate SARS-CoV-2 in liquids and dried droplets, and provide a foundation for understanding the factors which affect the efficacy of different wavelengths in real-world settings.
Abstract The pathogenesis of Alzheimer's disease (AD) is complex involving multiple contributing factors. The extent to which AD pathology affects the metabolome is still not understood nor is it ...known how disturbances change as the disease progresses. For the first time, we have profiled longitudinally (6, 8, 10, 12, and 18 months) both the brain and plasma metabolome of APPswe/PS1deltaE9 double transgenic and wild-type mice. A total of 187 metabolites were quantified using a targeted metabolomic methodology. Multivariate statistical analysis produced models that distinguished APPswe/PS1deltaE9 from wild-type mice at 8, 10, and 12 months. Metabolic pathway analysis found perturbed polyamine metabolism in both brain and blood plasma. There were other disturbances in essential amino acids, branched-chain amino acids, and also in the neurotransmitter serotonin. Pronounced imbalances in phospholipid and acylcarnitine homeostasis were evident in 2 age groups. AD-like pathology, therefore, affects greatly on both the brain and blood metabolomes, although there appears to be a clear temporal sequence whereby changes to brain metabolites precede those in blood.
PURPOSE: Inhibitors of intestinal alpha-glucosidases are used therapeutically to treat type 2 diabetes mellitus. Bacteria such as Actinoplanes sp. naturally produce potent alpha-glucosidase inhibitor ...compounds, including the most widely available drug acarbose. It is not known whether lactic acid bacteria (LAB) colonising the human gut possess inhibitory potential against glucosidases. Hence, the study was undertaken to screen LABs having inherent alpha- and beta-glucosidase inhibitory potential. METHODS: This study isolated, screened, identified and extracted Lactobacillus strains (Lb1–15) from human infant faecal samples determining their inhibitory activity against intestinal maltase, sucrase, lactase and amylase. Lactobacillus reference strains (Ref1–7), a Gram positive control (Ctrl1) and two Gram negative controls (Ctrl2–3), were also analysed to compare activity. RESULTS: Faecal isolates were identified by DNA sequencing, with the majority identified as unique strains of Lactobacillus plantarum. Some strains (L. plantarum, L. fermentum, L. casei and L. rhamnosus) had potent and broad spectrum inhibitory activities (up to 89 %; p < 0.001; 500 mg/ml wet weight) comparable to acarbose (up to 88 %; p < 0.001; 30 mg/ml). Inhibitory activity was concentration-dependent and was freely available in the supernatant, and was not present in other bacterial genera (Bifidobacterium bifidum and Escherichia coli or Salmonella typhimurium). Interestingly, the potency and spectrum of inhibitory activity across strains of a single species (L. plantarum) differed substantially. Some Lactobacillus extracts had broader spectrum activities than acarbose, effectively inhibiting beta-glucosidase activity (lactase) as well as alpha-glucosidase activities (maltase, sucrase and amylase). Anti-diabetic potential was indicated by the fact that oral gavage with a L. rhamnosus extract (1 g/kg) was able to reduce glucose excursions (Area under curve; 22 %; p < 0.05) in rats during a carbohydrate challenge (starch; 2 g/kg). CONCLUSION: These results definitively demonstrate that Lactobacillus strains present in the human gut have alpha- and beta-glucosidase inhibitory activities and can reduce blood glucose responses in vivo. Although the potential use of LAB such as Lactobacillus as a dietary supplement, medicinal food or biotherapeutic for diabetes is uncertain, such an approach might offer advantages over drug therapies in terms of broader spectrum activities and fewer unpleasant side effects. Further characterisation of this bioactivity is warranted, and chronic studies should be undertaken in appropriate animal models or diabetic subjects.
Abstract
Every type of nucleic acid in cells undergoes programmed chemical post-transcriptional modification. Generally, modification enzymes use substrates derived from intracellular metabolism, one ...exception is queuine (q)/queuosine (Q), which eukaryotes obtain from their environment; made by bacteria and ultimately taken into eukaryotic cells via currently unknown transport systems. Here, we use a combination of molecular, cell biology and biophysical approaches to show that in Trypanosoma brucei tRNA Q levels change dynamically in response to concentration variations of a sub-set of amino acids in the growth media. Most significant were variations in tyrosine, which at low levels lead to increased Q content for all the natural tRNAs substrates of tRNA-guanine transglycosylase (TGT). Such increase results from longer nuclear dwell time aided by retrograde transport following cytoplasmic splicing. In turn high tyrosine levels lead to rapid decrease in Q content. Importantly, the dynamic changes in Q content of tRNAs have negligible effects on global translation or growth rate but, at least, in the case of tRNATyr it affected codon choice. These observations have implications for the occurrence of other tunable modifications important for ‘normal’ growth, while connecting the intracellular localization of modification enzymes, metabolites and tRNAs to codon selection and implicitly translational output.
Eukaryotic cells use numerous mechanisms to ensure that no segment of their DNA is inappropriately re-replicated, but the importance of this stringent control on genome stability has not been tested. ...Here we show that re-replication in Saccharomyces cerevisiae can strongly induce the initial step of gene amplification, increasing gene copy number from one to two or more. The resulting amplicons consist of large internal chromosomal segments that are bounded by Ty repetitive elements and are intrachromosomally arrayed at their endogenous locus in direct head-to-tail orientation. These re-replication-induced gene amplifications are mediated by nonallelic homologous recombination between the repetitive elements. We suggest that re-replication may be a contributor to gene copy number changes, which are important in fields such as cancer biology, evolution, and human genetics.
Stereolithography (SL) is an additive manufacturing technique that uses light to cure liquid resins into thin layers and fabricate 3-dimensional objects layer by layer. SL is of high interest for ...small-volume manufacturing and rapid prototyping because of its ability to relatively quickly create objects with intricate 100 μm or smaller features. However, widespread adoption of SL faces a number of obstacles including unsuitable thermomechanical properties, anisotropic properties, and limited resolution and fidelity. In this work, we incorporate a reversible addition-fragmentation chain transfer (RAFT) agent into a glassy acrylate formulation to modify mechanical properties and improve resolution of objects printed using digital light processing (DLP) SL. Incorporating a small amount of a trithiocarbonate RAFT agent into the formulation leads to increased elongation and toughness accompanied by a small decrease in tensile modulus. To determine anisotropic properties of DLP SL, samples were printed in “horizontal” or “vertical” directions, where the long axis of the sample was printed in the x-axis or z-axis, respectively. RAFT samples printed in a vertical orientation exhibit a higher modulus than non-RAFT controls prior to post-cure in addition to a similar modulus with increased toughness upon UV post-cure due to the living/controlled nature of RAFT polymerization. Furthermore, incorporating a RAFT agent into the formulation allows significantly higher fidelity printing of a broad range of positive and negative features as small as 100 μm. The RAFT formulation allows objects to be printed with significantly better fidelity than non-RAFT formulations, even when a radical scavenger is incorporated to mimic reaction rates observed from the RAFT formulation. Additionally, the RAFT agent significantly increases the critical energy parameter determined from the SL working curve, indicating an increase in gel point conversion. This work demonstrates the benefits of using controlled/living polymerization in a highly cross-linked acrylate system to improve toughness, modify anisotropic properties, and print high-fidelity features with enhanced properties in 3D printed materials.
In this paper we consider the problem of creating and controlling volume deformations used to articulate characters for use in high-end applications such as computer generated feature films. We ...introduce a method we call harmonic coordinates that significantly improves upon existing volume deformation techniques. Our deformations are controlled using a topologically flexible structure, called a cage, that consists of a closed three dimensional mesh. The cage can optionally be augmented with additional interior vertices, edges, and faces to more precisely control the interior behavior of the deformation. We show that harmonic coordinates are generalized barycentric coordinates that can be extended to any dimension. Moreover, they are the first system of generalized barycentric coordinates that are non-negative even in strongly concave situations, and their magnitude falls off with distance as measured within the cage.
Obestatin is a 23‐amino acid C‐terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an α helix. Although obestatin has a short biological half‐life and is rapidly ...degraded, it is proposed to exert wide‐ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain and gastrointestinal motility and also to mediate promotion of cell survival and prevention of apoptosis. Obestatin‐induced increases in beta cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with up‐regulation of genes associated with beta cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia–reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes.
PDF
