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Managing the environmental impacts associated with livestock production is a challenge for farmers, public and regulatory agencies. Sustainable solutions that take into account technical and socioeconomic factors are needed. For example, the comprehensive control of odors, ammonia (NH3), hydrogen sulfide (H2S), and greenhouse gas (GHG) emissions from swine production is a critical need. Stored manure is a major source of gaseous emissions. Mitigation technologies based on bio-based products such as biochar are of interest due to the potential benefits of nutrient cycling. The objective of this study was to test non-activated (non-functionalized) biochar for the mitigation of gaseous emissions from stored manure. Specifically, this included testing the effects of: (1) time; and (2) dosage of biochar application to the swine manure surface on gaseous emissions from deep-pit storage. The biochar surface application was tested with three treatments (1.14, 2.28 and 4.57 kg·m−2 manure) over a month. Significant reductions in emissions were observed for NH3 (12.7–22.6% reduction as compared to the control). Concomitantly, significant increases in CH4 emissions (22.1–24.5%) were measured. Changes to emissions of other target gases (including CO2, N2O, H2S, dimethyl disulfide/methanethiol, dimethyl trisulfide, n-butyric-, valeric-, and isovaleric acids, p-cresol, indole, and skatole) were not statistically significant. Biochar treatment could be a promising and comparably-priced option for reducing NH3 emissions from stored swine manure.

Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs. O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.

Foam accumulation in swine manure deep-pits has been linked to explosions and flash fires that pose devastating threats to humans and livestock. It is clear that methane accumulation within these pits is the fuel for the fire; it is not understood what microbial drivers cause the accumulation and stabilization of methane. Here, we conducted a 13-month field study to survey the physical, chemical, and biological changes of pit-manure across 46 farms in Iowa. Our results showed that an increased methane production rate was associated with less digestible feed ingredients, suggesting that diet influences the storage pit’s microbiome. Targeted sequencing of the bacterial 16S rRNA and archaeal mcrA genes was used to identify microbial communities’ role and influence. We found that microbial communities in foaming and non-foaming manure were significantly different, and that the bacterial communities of foaming manure were more stable than those of non-foaming manure. Foaming manure methanogen communities were enriched with uncharacterized methanogens whose presence strongly correlated with high methane production rates. We also observed strong correlations between feed ration, manure characteristics, and the relative abundance of specific taxa, suggesting that manure foaming is linked to microbial community assemblage driven by efficient free long-chain fatty acid degradation by hydrogenotrophic methanogenesis.

Livestock in the state of Iowa, United States (US) produce over 50 × 106 Mg of wet-basis manure yearly. Biogas production from manure’s anaerobic digestion (AD) can reduce greenhouse gas emissions, control odors, and provide renewable energy. Despite these benefits, AD is rarely deployed at swine farms in Iowa. In this work, we explore the economics of AD systems in Iowa to evaluate reasons for low deployment and explore the production cost impacts of biogas cleaning and injection into the natural gas grid, amending manure with biomass, and centralizing digesters across multiple farms. This work presents a static, spreadsheet-based technoeconomic model that embodies literature-based estimates of key system technical parameters, costs, and transportation fuel incentives and permits the examination of various scenarios. Key findings include that under the model assumptions, distributed, farm-scale digesters are not competitive with average natural gas prices in Iowa. A centralized production scenario can be competitive, provided that programs such as the low-carbon fuel standard (LCFS) and the renewable fuel standard (RFS) have sufficiently high credit values.

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus , uses a selective somatostatin receptor 2 (SSTR 2 ) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin’s N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR 2 . Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture. Venomous animals typically disrupt nervous, locomotor, and cardiovascular systems to incapacitate prey, but certain fish-hunting cone snails evolved toxins that specifically target glucose homeostasis. Here, the authors show the combinatorial nature of weaponized insulin and somatostatin mimetics, exemplifying the use of combinatorial chemical mimicry for prey capture.

Aims/hypothesisSodium–glucose cotransporter (SGLT) 2 inhibitors constitute a new class of glucose-lowering drugs, but they increase glucagon secretion, which may counteract their glucose-lowering effect. Previous studies using static incubation of isolated human islets or the glucagon-secreting cell line α-TC1 suggested that this results from direct inhibition of alpha cell SGLT1/2-activity. The aim of this study was to test whether the effects of SGLT2 on glucagon secretion demonstrated in vitro could be reproduced in a more physiological setting.MethodsWe explored the effect of SGLT2 activity on glucagon secretion using isolated perfused rat pancreas, a physiological model for glucagon secretion. Furthermore, we investigated Slc5a2 (the gene encoding SGLT2) expression in rat islets as well as in mouse and human islets and in mouse and human alpha, beta and delta cells to test for potential inter-species variations. SGLT2 protein content was also investigated in mouse, rat and human islets.ResultsGlucagon output decreased three- to fivefold within minutes of shifting from low (3.5 mmol/l) to high (10 mmol/l) glucose (4.0 ± 0.5 pmol/15 min vs 1.3 ± 0.3 pmol/15 min, p < 0.05). The output was unaffected by inhibition of SGLT1/2 with dapagliflozin or phloridzin or by addition of the SGLT1/2 substrate α-methylglucopyranoside, whether at low or high glucose concentrations (p = 0.29–0.99). Insulin and somatostatin secretion (potential paracrine regulators) was also unaffected. Slc5a2 expression and SGLT2 protein were marginal or below detection limit in rat, mouse and human islets and in mouse and human alpha, beta and delta cells.Conclusions/interpretationOur combined data show that increased plasma glucagon during SGLT2 inhibitor treatment is unlikely to result from direct inhibition of SGLT2 in alpha cells, but instead may occur downstream of their blood glucose-lowering effects.

Background Cerebrospinal fluid (CSF) is produced and absorbed at a balanced rate to maintain a constant intracranial pressure (ICP). The CSF dynamics are, however, disturbed in several pathological conditions, leading to elevated ICP, which may have fatal outcomes if left untreated. Treatment options for these conditions are limited to invasive neurosurgery, and novel pharmacological approaches to manage ICP in pathology are sought. Here, we aimed to demonstrate the potential of the glucagon-like peptide-1 receptor (GLP-1R) as such a target. Methods We administered male rats with intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) GLP-1R agonist (exendin-4) or antagonist (exendin-9-39) followed by in vivo determination of CSF dynamics. GLP-1R expression in the CSF-secreting choroid plexus was demonstrated with RNAScope in situ hybridization and western blotting and transporter activity with radio-isotope flux assays. Results GLP-1R activation increased the CSF secretion rate with an associated elevation of the ICP, whereas inhibition of the receptor reduced the rate of CSF secretion. These effects were observed with central, but not peripheral, administration of the agonist and antagonist, suggesting receptor expression on the luminal, CSF-facing side of the choroid plexus, which aligned with GLP-1R-mediated modulation of luminally-expressed transporters in excised choroid plexus. Low level GLP-1R expression was demonstrated in the choroid plexus at mRNA and protein levels. Conclusion Modulation of GLP-1R affects CSF production, which suggests that GLP-1R-mediated signalling may have the potential to control ICP in pathological conditions with disturbed CSF homeostasis.

ObjectivesGastrointestinal hormones contribute to the beneficial effects of Roux-en-Y gastric bypass surgery (RYGB) on glycemic control. Secretin is secreted from duodenal S cells in response to low luminal pH, but it is unknown whether its secretion is altered after RYGB and if secretin contributes to the postoperative improvement in glycemic control. We hypothesized that secretin secretion increases after RYGB as a result of the diversion of nutrients to more distal parts of the small intestine, and thereby affects islet hormone release.MethodsA specific secretin radioimmunoassay was developed, evaluated biochemically, and used to quantify plasma concentrations of secretin in 13 obese individuals before, 1 week after, and 3 months after RYGB. Distribution of secretin and its receptor was assessed by RNA sequencing, mass-spectrometry and in situ hybridization in human and rat tissues. Isolated, perfused rat intestine and pancreas were used to explore the molecular mechanism underlying glucose-induced secretin secretion and to study direct effects of secretin on glucagon, insulin, and somatostatin secretion. Secretin was administered alone or in combination with GLP-1 to non-sedated rats to evaluate effects on glucose regulation.ResultsPlasma postprandial secretin was more than doubled in humans after RYGB (P < 0.001). The distal small intestine harbored secretin expressing cells in both rats and humans. Glucose increased the secretion of secretin in a sodium-glucose cotransporter dependent manner when administered to the distal part but not into the proximal part of the rat small intestine. Secretin stimulated somatostatin secretion (fold change: 1.59, P < 0.05) from the perfused rat pancreas but affected neither insulin (P = 0.2) nor glucagon (P = 0.97) secretion. When administered to rats in vivo, insulin secretion was attenuated and glucagon secretion increased (P = 0.04), while blood glucose peak time was delayed (from 15 to 45 min) and gastric emptying time prolonged (P = 0.004).ConclusionsGlucose-sensing secretin cells located in the distal part of the small intestine may contribute to increased plasma concentrations observed after RYGB. The metabolic role of the distal S cells warrants further studies.

Aim/hypothesisUrocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved.MethodsWe studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis.ResultsIn rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3’s cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion.Conclusions/interpretationOur combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.

Background: Healthcare infrastructure, personnel and persons seeking healthcare are protected under international humanitarian law. However, attacks on healthcare are increasingly a part of modern armed conflicts, including in the Occupied Palestinian Territory (oPt). Aim: To quantify and characterize reported attacks on healthcare in the West Bank and Gaza and correlate reported attacks involving explosives with publicly available data. Methods: This retrospective study analysed publicly available and geolocated health facility and weapons data from 7 October 2023 to 30 June 2024. Reports of attacks on healthcare were categorized by location, outcome and typology. Z-test and Chi-square analyses were conducted to compare attack types between Gaza and the West Bank using R software, and geospatial analyses were conducted using ArcGIS Pro software. Results: A total of 1280 attacks on healthcare were reported in the oPt during the study period, of which 1052 were included in the analysis. Most of the attacks occurred in Gaza (78.3%), followed by the West Bank (21.7%). The typology of these attacks varied. There was a significant difference between the types of attacks in Gaza and West Bank (P < 0.05), but no significant association between type of weapon used and type of attack in Gaza (|R| < 2). The hotspots of attacks in Gaza were around al-Shifa, Nasser and al-Awda hospitals. Conclusion: There was a high burden of attacks on healthcare in the oPt during the study period. The differences in types of attacks between Gaza and the West Bank highlight the need for context-specific interventions in the two territories. There is an urgent need for actions to end the use of 2000-lb MK-84 bombs in densely populated areas and near health facilities, in addition to calls for adherence to the international humanitarian law during armed conflicts.