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Recent industry roadmaps such as Crops 2030 and the Irish Whiskey Association's Sustainability Roadmap 2022 emphasize the importance of increasing the use of Irish-grown grain in brewing and distilling. With the growth of the Irish distilling sector, there is a corresponding demand for raw materials and locally sourced grains. In Ireland, approximately 500 hectares of rye are harvested annually, with rye containing a similar range of starch as wheat. However, because rye contains more hemicelluloses and pentosans than other cereals, and because water-soluble pentosans tend to form viscous solutions in concentrated flour-water slurries, it is not widely utilised as a fermentation substrate. The purpose of this study is to examine pre-treatment with β-glucanase to enhance the alcohol output from rye flour. The research determined a baseline alcohol production of 187.1 LA/tonne dwb without the addition of β-glucanase. Using four predictor variables, response surface techniques were used to investigate the influence of β-glucanase on alcohol yield. A Box-Bekhan design was used to investigate time, temperature, calcium ions, and β-glucanase. When β-glucanase was administered at a dose rate of 3 U/g with the addition of 200 mg/L calcium ions and run at 50 °C for 30 min, the response surface approach yielded the highest alcohol output of 406 LA/tonne dwb. While, this yield is consistent with previous authors' findings; it is lower than average yields for malted barley, wheat, and maize. [ABSTRACT FROM AUTHOR]

Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that α-ketoglutarate (α-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit β is identified as a novel binding protein of α-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that α-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α-KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α-KG levels are increased on starvation and α-KG does not extend the lifespan of dietary-restricted animals, indicating that α-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.

Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms. Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits. Recently, several metabolites have been identified that modulate ageing; however, the molecular mechanisms underlying this are largely undefined. Here we show that α-ketoglutarate (α-KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans. ATP synthase subunit β is identified as a novel binding protein of α-KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS). The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution. Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan. We show that α-KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α-KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α-KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α-KG levels are increased on starvation and α-KG does not extend the lifespan of dietary-restricted animals, indicating that α-KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases.

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress [beta]-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated [beta]-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute-specific mouse models showed diminished [beta]-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma's AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/[beta]-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models., Introduction Peripheral artery disease (PAD) is a global health problem affecting 200 million adults worldwide (1, 2). Chronic PAD is characterized by limb hypoperfusion caused by arterial occlusive disease. It [...]

It is widely believed that discovery of specific, sensitive, and reliable tumor biomarkers can improve the treatment of cancer. Currently, there are no obvious targets that can be used in treating triple-negative breast cancer (TNBC).To better understand TNBC and find potential biomarkers for targeted treatment, we combined a novel hydrophobic fractionation protocol with mass spectrometry LTQ-orbitrap to explore and compare the hydrophobic sub-proteome of TNBC with another subtype of breast cancer, hormone-receptor-positive-Her2-negative breast cancer (non-TNBC).Hydrophobic sub-proteome of breast cancer is rich in membrane proteins. Hundreds of proteins with various defined key cellular functions were identified from TNBC and non-TNBC tumors. In this study, protein profiles of TNBC and non-TNBC were systematically examined, compared, and validated. We have found that nine keratins are down-regulated and several heat shock proteins are up-regulated in TNBC tissues. Our study may provide insights of molecules that are responsible for the aggressiveness of TNBC.The initial results obtained using a combination of hydrophobic fractionation and nano-LC mass spectrometry analysis of these proteins appear promising in the discovery of potential cancer biomarkers and bio-signatures. When sufficiently refined, this approach may prove useful in improving breast cancer treatment.

The article informs about a report titled "Financing first home ownership: opportunities and challenges," authored by Stephen Whelan, Hal Pawson, Laurence Troy, Rachel Ong ViforJ, and Julie Lawson. Topics include the challenges and opportunities related to first-time home ownership, mortgage financing, and demand-side subsidies in Australia, providing insights and recommendations for policymakers and stakeholders in the housing sector.

The Irish distilling industry is rapidly expanding, diversifying its growth with an increased interest in using different grains in whiskey production. To effectively use Irish-grown wheat in distillation, the identification of cultivars that are suited to the Irish climate and provide high alcohol yields, via a quick screening test for grain alcohol yield that is consistent with Irish industry standards, is required. The current study used response surface methodology (RSM) to optimize mashing parameters, enzyme dosage rate (α-amylase and amyloglucosidase), time, temperature, and malt inclusion rate, using a hard wheat (Triticum aestivum cv. Costello). By optimizing all factors, a maximum alcohol yield (AY) of 471 LA/tonne dry weight basis was achieved, equating to previous research. The enzyme, α-amylase plays a critical part in the process, of converting starch to sugars, and 48 U/g α-amylase was used to reach maximum alcohol yield. Furthermore, an optimal protocol was evaluated on soft wheat cultivars, producing alcohol yields in the range of 483–496 LA/tonne, suggesting the applicability of this product for use across multiple varieties and grain endosperm types. In summary, an optimal alcohol yield methodology was created, with increased AY across four distinct varieties, demonstrating the possibility for Irish cultivated wheat to be used in Irish distilleries. [ABSTRACT FROM AUTHOR]

The article focuses on the effectiveness and implications of policy settings influencing the availability of finance for Australians purchasing their first home. Topics include the decline in interest rates contributing to the rise in house prices, the difficulties faced by young households in meeting borrowing constraints, and the evaluation of first home buyer assistance schemes such as mortgage guarantee and shared equity schemes.