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Harnessing the translational potential of the GLP-1/GLP-1R system in pancreatic beta cells has led to the development of established GLP-1R-based therapies for the long-term preservation of beta cell function. In this review, we discuss recent advances in the current research on the GLP-1/GLP-1R system in beta cells, including the regulation of signaling by endocytic trafficking as well as the application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic receptor variants, spatial compartmentalization of cAMP signaling and new downstream signaling targets involved in the control of beta cell function. Unlabelled Image • GLP-1R signaling can be regulated by a number of biological processes. • These include modulation of receptor trafficking and conformational dynamics. • Dual/triple GLP-1RAs activating additional GPCRs have recently been developed. • GLP-1R cAMP signaling is compartmentalized by ACs, PDEs and AKAPs. • GLP-1R-induced cAMP activates multiple pathways to regulate beta cell function. [ABSTRACT FROM AUTHOR]

Highlight: [•] Exercise decreases function of lung-homing chemokine receptors on Th cells. [Copyright &y& Elsevier]

Abstract: European foulbrood (EFB) persists in England and Wales despite current treatment methods, all of which include feeding honey bee colonies with the antibiotic oxytetracycline (OTC). A large-scale field experiment was conducted to monitor a husbandry-based method, using comb replacement (known as Shook swarm), as a drug free EFB control option. The understanding of EFB epidemiology is limited, with little information on the presence of Melissococcus plutonius in disease free colonies. Additional samples were collected from diseased and disease free apiaries to identify symptomless infection. EFB reoccurrence was not significantly different between OTC and husbandry methods and real-time PCR data demonstrated that fewer Shook swarm treated colonies contained M. plutonius carryover to the Spring following treatment. Asymptomatic colonies from diseased apiaries showed an increased risk of testing positive for M. plutonius compared to asymptomatic colonies from disease free apiaries. The probability of a sample being symptomatic increased when a greater quantity of M. plutonius was detected in adult bees and larvae. The possibility of treating EFB as an apiary disease rather than a colony disease and the implications of a control strategy without antibiotics are discussed. [Copyright &y& Elsevier]

Intestinal helminths are extremely widespread and highly prevalent infections of humans, particularly in rural and poor urban areas of low and middle-income countries. These parasites have chronic and often insidious effects on human health and child development including abdominal problems, anaemia, stunting and wasting. Certain animals play a fundamental role in the transmission of many intestinal helminths to humans. However, the contribution of zoonotic transmission to the overall burden of human intestinal helminth infection and the relative importance of different animal reservoirs remains incomplete. Moreover, control programmes and transmission models for intestinal helminths often do not consider the role of zoonotic reservoirs of infection. Such reservoirs will become increasingly important as control is scaled up and there is a move towards interruption and even elimination of parasite transmission. With a focus on southeast Asia, and the Philippines in particular, this review summarises the major zoonotic intestinal helminths, risk factors for infection and highlights knowledge gaps related to their epidemiology and transmission. Various methodologies are discussed, including parasite genomics, mathematical modelling and socio-economic analysis, that could be employed to improve understanding of intestinal helminth spread, reservoir attribution and the burden associated with infection, as well as assess effectiveness of interventions. For sustainable control and ultimately elimination of intestinal helminths, there is a need to move beyond scheduled mass deworming and to consider animal and environmental reservoirs. A One Health approach to control of intestinal helminths is proposed, integrating interventions targeting humans, animals and the environment, including improved access to water, hygiene and sanitation. This will require coordination and collaboration across different sectors to achieve best health outcomes for all. [ABSTRACT FROM AUTHOR]

Feeding treatments were imposed in two feeding trials involving Cobb broiler and Bond Brown layer birds. Three feed additives (biochar, bentonite and zeolite) were supplied at four rates (0, 1, 2 and 4% w/w) in feed, as previously considered in the context of animal production, was considered in the context of Excreta chemical and water retention properties and granulation characteristics of decomposed excreta (manure) were characterised. At field capacity (– 0.01 MPa), manure produced from control and 4% bentonite diets contained significantly (p = 0.001) more water (at 1.93 and 2.44% v/v water, respectively) than zeolite and biochar treatments. Manure mesoporosity was significantly (p = 0.015) higher in 2 and 4% bentonite treatments than other feed additives. Fresh excreta from layer birds on the control diet contained 6% w/dw N and 35% C, which was decreased to 2.6% N and 28% C after decomposition, with C:N ratio changing from 5.9 to 12.1. Ammonia loss was higher from biochar and zeolite manures than control or bentonite, associated with higher pH in the biochar and zeolite manures. More N was unaccounted from bentonite manure than other treatments, presumably lost as N 2 O or N 2 , a result linked to its higher moisture content and its enhanced rate of denitrification. The highest proportion of granules in the size class desired for fertilizer spreading was achieved using decomposed manure from the 1 and 2% w/w biochar treatments of the broiler trial, and 1 and 2% zeolite and 4% biochar treatments of the layer trial. Thus the feed amendments improved poultry manure in specific ways. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the study was the characterization of ABCA1 gene mutations in 10 patients with extremely low HDL-cholesterol. Five patients (aged 6months to 76years) presented with splenomegaly and thrombocytopenia suggesting the diagnosis of Tangier disease (TD). Three of them were homozygous for novel mutations either in intron (c.4465-34A>G) or in exons (c.4376delT and c.5449C>T), predicted to encode truncated proteins. One patient was compound heterozygous for a nucleotide insertion (c.1758_1759insG), resulting in a truncated protein and for a nucleotide substitution c.4799A>G, resulting in a missense mutation (p.H1600R). The last TD patient, found to be heterozygous for a known mutation (p.D1009Y), had a complete defect in ABCA1-mediated cholesterol efflux in fibroblasts, suggesting the presence of a second undetected mutant allele. Among the other patients, four were asymptomatic, but one, with multiple risk factors, had severe peripheral artery disease. Three of these patients were heterozygous for known mutations (p.R130K+p.N1800H, p.R1068C, p.N1800H), while two were carriers of novel mutations (c.1195-27G>A and c.396_397insA), predicted to encode truncated proteins. The pathogenic effect of the two intronic mutations (c. 1195-27G>A and c.4465-34A>G) was demonstrated by the analysis of the transcripts of splicing reporter mutant minigenes expressed in COS-1 cells. Both mutations activated an intronic acceptor splice site which resulted in a partial intron retention in mature mRNA with the production of truncated proteins. This study confirms the allelic heterogeneity of TD and suggests that the diagnosis of TD must be considered in patients with an unexplained splenomegaly, associated with thrombocytopenia and hypocholesterolemia. [Copyright &y& Elsevier]

Abstract: Ugandan honey bees (Apis mellifera L.) produce honey, and are key pollinators within commercial crops and natural ecosystems. Real-time RT-PCR was used to screen immature and adult bees collected from 63 beekeeping sites across Uganda for seven viral pathogens. No samples tested positive for Chronic bee paralysis virus, Sacbrood virus, Deformed wing virus, Acute bee paralysis virus, Apis iridescent virus or Israeli acute paralysis virus. However, Black queen cell virus (BQCV) was found in 35.6% of samples. It occurred in adults and larvae, and was most prevalent in the Western highlands, accounting for over 40% of positive results nationally. [Copyright &y& Elsevier]

Abstract: Mesenchymal stromal cells (MSC) are multipotent cells that can be derived from many different organs and tissues. They have been demonstrated to play a role in tissue repair and regeneration in both preclinical and clinical studies. They also have remarkable immunosuppressive properties. We describe their application in settings that include the cardiovascular, central nervous, gastrointestinal, renal, orthopaedic and haematopoietic systems. Manufacturing of MSC for clinical trials is also discussed. Since tissue matching between MSC donor and recipient does not appear to be required, MSC may be the first cell type able to be used as an “off-the-shelf” therapeutic product. [Copyright &y& Elsevier]