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Sorghum (Sorghum bicolor), a grass native to Africa, is a popular alternative to barley for brewing beer. The importance of sorghum to beer brewing is increasing because it is a naturally gluten-free cereal, and climate change is expected to cause a reduction in the production of barley over the coming decades. However, there are challenges associated with the use of sorghum instead of barley in beer brewing. Here, we used proteomics and metabolomics to gain insights into the sorghum brewing process to advise processes for efficient beer production from sorghum. We found that during malting, sorghum synthesizes the amylases and proteases necessary for brewing. Proteomics revealed that mashing with sorghum malt required higher temperatures than barley malt for efficient protein solubilization. Both α- and β-amylase were considerably less abundant in sorghum wort than in barley wort, correlating with lower maltose concentrations in sorghum wort. However, metabolomics revealed higher glucose concentrations in sorghum wort than in barley wort, consistent with the presence of an abundant α-glucosidase detected by proteomics in sorghum malt. Our results indicate that sorghum can be a viable grain for industrial fermented beverage production, but that its use requires careful process optimization for efficient production of fermentable wort and high-quality beer.

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics.

Rationale: Antral peristalsis is responsible for gastric emptying. Its failure is called gastroparesis and often caused by dysfunction of enteric neurons and interstitial cells of Cajal (ICC). Current treatment options, including gastric electrical stimulation, are non-satisfying and may improve symptoms but commonly fail to restore gastric emptying. Herein, we explore direct optogenetic stimulation of smooth muscle cells (SMC) via the light-gated non-selective cation channel Channelrhodopsin2 (ChR2) to control gastric motor function. Methods: We used a transgenic mouse model expressing ChR2 in fusion with eYFP under the control of the chicken-β-actin promoter. We performed patch clamp experiments to quantify light-induced currents in isolated SMC, Ca2+ imaging and isometric force measurements of antral smooth muscle strips as well as pressure recordings of intact stomachs to evaluate contractile responses. Light-induced propulsion of gastric contents from the isolated stomach preparation was quantified in video recordings. We furthermore tested optogenetic stimulation in a gastroparesis model induced by neuronal- and ICC-specific damage through methylene blue photo-toxicity. Results: In the stomachs, eYFP signals were restricted to SMC in which blue light (460 nm) induced inward currents typical for ChR2. These depolarizing currents led to contractions in antral smooth muscle strips that were stronger than those triggered by supramaximal electrical field stimulation and comparable to those evoked by global depolarization with high K+ concentration. In the intact stomach, panoramic illumination efficiently increased intragastric pressure achieving 239±46% (n=6) of the pressure induced by electrical field stimulation and triggered gastric transport. Within the gastroparesis model, electric field stimulation completely failed but light still efficiently generated pressure waves. Conclusions: We demonstrate direct optogenetic stimulation of SMC to control gastric contractility. This completely new approach could allow for the restoration of motility in gastroparesis in the future.

In this paper we show that the geodesic flow of a Finsler metric is Anosov if and only if there exists a C^2 open neighborhood of Finsler metrics all of whose closed geodesics are hyperbolic. For surfaces this result holds also for Riemannian metrics. This follows from a recent result of Contreras and Mazzucchelli [Duke Math. J. 173 (2024), pp. 347–390]. Furthermore, geodesic flows of Riemannian or Finsler metrics on surfaces are C^2 stably ergodic if and only if they are Anosov. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma continues to be one of the deadliest cancers worldwide. Preclinical studies involving animals rarely include sex as a major biological variable in testing the efficacy of new drugs. In an animal model of pancreatic cancer, we analyzed the impact of sex on the pathological features of the disease and on an experimental small molecule-based therapy tested in vivo for the first time. While the therapy shows potential, the obtained results are confounded by sex-specific effects. This study, therefore, highlights the importance of sex-inclusive research while simultaneously providing a basis for further studies of the therapy tested. Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds. [ABSTRACT FROM AUTHOR]

Two singularity theorems can be proven if one attempts to let a Lorentzian cobordism interpolate between two topologically distinct manifolds. On the other hand, Cartier and DeWitt-Morette have given a rigorous definition for quantum field theories (QFTs) by means of path integrals. This paper uses their results to study whether QFTs can be made compatible with topology changes. We show that path integrals over metrics need a finite norm for the latter and for degenerate metrics, this problem can sometimes be resolved with tetrads. We prove that already in the neighborhood of some cuspidal singularities, difficulties can arise to define certain QFTs. On the other hand, we show that simple QFTs can be defined around conical singularities that result from a topology change in a simple setup. We argue that the ground state of many theories of quantum gravity will imply a small cosmological constant and, during the expansion of the universe, will cause frequent topology changes. Unfortunately, it is difficult to describe the transition amplitudes consistently due to the aforementioned problems. We argue that one needs to describe QFTs by stochastic differential equations, and in the case of gravity, by Regge calculus in order to resolve this problem. [ABSTRACT FROM AUTHOR]

The Weight Efficacy Life-Style Questionnaire (WEL) and the International Physical Activity Questionnaire (IPAQ) assessed self-efficacy and physical activity for 124 volunteers aged 17-61. It was administered before and after participants attended a video modelling workshop. Half of the participants in the treatment and control groups were given copies of the videos to review at home. Predictions were that self-efficacy would increase most for participants who took home the videos after the group-based intervention that was built on models of successful weight loss behaviours. Self-efficacy was also expected to lead to increased physical activity. Results demonstrated that weight loss self-efficacy can be increased by watching successful models. Physical activity, however, did not increase. (Contains 3 tables and 1 figure.)

The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N -glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N -glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody COVA2-17 binding. Glycan site-occupancy analyses revealed that the mutation resulted in N -glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles. [ABSTRACT FROM AUTHOR]

Sustainable beer production requires a comprehensive assessment of potential hazards such as pesticides in both the finished product and waste streams, as these streams can be used to create high-value by-products. This study presents the tracking of 13 fungicides (azoxystrobin, boscalid, epoxiconazole, fenpropidin, fenpropimorph, fluquiconazole, flutriafol, fluxapyroxad, kresoxym-methyl, spiroxamine, propiconazole, prothioconazole-desthio, and tebuconazole), two insecticides (chlorpyrifos-methyl and deltamethrin), one herbicide (glyphosate), and one growth regulator (mepiquat) through the beer brewing process. Field-treated rye, wheat, and barley samples containing pesticide residues were used as adjunct during brewing. Samples of the beer as well as the by-products (spent grain, spent hops, trub and spent yeast) were collected and extracted with a modified QuEChERS method for pesticide residues analysis using GC-MS/MS and LC-MS/MS. Results show that an average of 58% of pesticide residues are retrieved in the by-products with the highest fraction (53%) recovered in the spent grain, 4% in trub, 1% in spent hops, no residues detected in spent yeast and 9% in the beer. This is consistent with these nonpolar pesticides tending to remain adsorbed to the spent grain during brewing. Glyphosate and mepiquat, the most polar pesticides included in this study, showed a different behavior, with the largest fraction (>80%) being retrieved in sweet wort and transferred to the beer. Processing factors were generated for each pesticide from the adjunct to the beer and to the four by-products. [ABSTRACT FROM AUTHOR]