The Effects of Offering Hay, Pit-Stored Grass Silage or Big-Bale Silage to Pregnant Ewes on Ewe and Lamb Performance

Hay and pit silage have been used extensively for feeding sheep over the winter period, but in recent years, especially on smaller farms, big-bale silage has become increasingly popular. However, there is limited comparative information on the use of big-bale silage for sheep, especially in relation to the effects of chopping and growth stage at harvest. This study compared the performance of ewes offered hay, pit silage, or big-bale grass silage made from either chopped or unchopped grass and cut from the same field at the same time

Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1

Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI-tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr83 and Glu73, respectively. When Glu73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu73 residue

Genetically Determined Uric Acid and the Risk of Cardiovascular and Neurovascular Diseases: A Mendelian Randomization Study of Outcomes Investigated in Randomized Trials.

Background Higher serum uric acid levels are associated with cardiovascular and neurovascular disease, but whether these relationships are causal is not known. We applied Mendelian randomization approaches to assess the association between genetically determined uric acid levels and outcomes under study in large clinical trials. Methods and Results We used 28 genetic variants related to serum uric acid as instruments to perform a range of 2-sample Mendelian randomization methods. Our analysis had statistical power to detect clinically relevant effects of genetically determined serum uric acid levels on the considered clinical outcomes; cognitive function, Alzheimer disease, coronary heart disease, myocardial infarction, systolic blood pressure, and stroke. There was some suggestive evidence for an association between higher genetically determined serum uric acid and cognitive function. There was also some suggestive evidence of a relationship between coronary heart disease, systolic blood pressure, and the serum uric acid genetic instruments, but likely related to genetic pleiotropy. Overall, there was no consistent evidence of a clinically relevant effect of genetically determined serum uric acid on any of the considered outcomes. Conclusions This Mendelian randomization study does not support a clinically relevant causal effect of genetically determined serum urate on a range of cardiovascular and neurovascular outcomes. The weak association of genetically determined serum urate with coronary heart disease and systolic blood pressure may be because of pleiotropic effects. If urate lowering drugs such as allopurinol are found to affect these outcomes in clinical trials, then the effects may be mediated through urate independent mechanisms

Teaching-Communication Methodologies in the Medical Profession

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66477/2/10.1177_108056997603900103.pd

Scaling the nexus: towards integrated frameworks for analysing water, energy and food

The emergence of the water-energy-food (WEF) nexus concept following the 2011 Bonn Nexus Conference has resulted in a change to the way we perceive our natural resources. Global pressures such as climate change, and population growth have highlighted the fragility of our WEF systems, necessitating integrated solutions across multiple scales and levels. Whilst a number of frameworks and analytical tools have been developed since 2011, a comprehensive WEF nexus tool remains elusive, hindered in part by our limited data and understanding of the interdependencies and connections across the WEF systems. To achieve this, the community of academics, practitioners and policy-makers invested in WEF nexus research are addressing several critical areas that currently remain as barriers. Firstly, the plurality of scales (e.g., spatial, temporal, institutional, jurisdictional) necessitates a more comprehensive effort to assess interdependencies between water, energy and food, from household to institutional and national levels. Secondly, and closely related to scale, a lack of available data often hinders our ability to quantify physical stocks and flows of resources. In this paper, we elucidate many of the challenges that have arisen across nexus research, including the impact of multiple scales in operation across the nexus, and concomitantly, what impact these scales have on data accessibility. We review some of the critical frameworks and tools that are applied by nexus researchers and discuss some of the steps required to develop from nexus thinking to an operationalizable concept, with a consistent focus on scale and data availability

Loss of tolerance to gut immunity protein; glycoprotein 2 (GP2) is associated with progressive disease course in primary sclerosing cholangitis

Abstract Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn’s disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2 antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4% (13/19) of anti-GP2 IgA antibodies were bound with secretory component, suggesting an active retro-transportation of anti-GP2 from the gut lumen to the mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9–99] months) and remained an independent predictor after adjusting for Mayo risk score(HR: 4.69 [1.05–21.04], P = 0.043). These results highlight the significance of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk stratification in PSC and considered as a potential therapeutic target

Scaling the nexus: Towards integrated frameworks for analyzing water, energy and food

The emergence of the water-energy-food (WEF) nexus has resulted in changes to the way we perceive our natural resources. Stressors such as climate change and population growth have highlighted the fragility of our WEF systems, necessitating integrated solutions across multiple scales. Whilst a number of frameworks and analytical tools have been developed since 2011, a comprehensive WEF nexus tool remains elusive, hindered in part by our limited data and understanding of the interdependencies and connections across the WEF systems. To achieve this, the community of academics, practitioners and policy-makers invested in WEF nexus research are addressing several critical areas that currently remain as barriers. Firstly, the plurality of scales (e.g., spatial, temporal, institutional, jurisdictional) necessitates a more comprehensive effort to assess interdependencies between water, energy and food, from household to institutional and national levels. Secondly, and closely related to scale, a lack of available data often hinders our ability to quantify physical stocks and flows of resources. Overcoming these barriers necessitates engaging multiple stakeholders, and using experiences and local insights to better understand nexus dynamics in particular locations or scenarios, and we exemplify this with the inclusion of a UK-based case-study on exploring the nexus in a particular geographical area. We elucidate many challenges that have arisen across nexus research, including the impact of multiple scales in operation, and concomitantly, what impact these scales have on data accessibility. We assess some of the critical frameworks and tools that are applied by nexus researchers and articulate some of the steps required to develop from nexus thinking to an operationalizable concept, with a consistent focus on scale and data availability