Willpower Satisficing

Satisficing Consequentialism is often rejected as hopeless. Perhaps its greatest problem is that it risks condoning the gratuitous prevention of goodness above the baseline of what qualifies as “good enough”. I propose a radical new willpower-based version of the view that avoids this problem, and that better fits with the motivation of avoiding an excessively demanding conception of morality. I further demonstrate how, by drawing on the resources of an independent theory of blameworthiness, we may obtain a principled specification of what counts as “good enough”

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

Roadmap on data-centric materials science

Science is and always has been based on data, but the terms ‘data-centric’ and the ‘4th paradigm’ of materials research indicate a radical change in how information is retrieved, handled and research is performed. It signifies a transformative shift towards managing vast data collections, digital repositories, and innovative data analytics methods. The integration of artificial intelligence and its subset machine learning, has become pivotal in addressing all these challenges. This Roadmap on Data-Centric Materials Science explores fundamental concepts and methodologies, illustrating diverse applications in electronic-structure theory, soft matter theory, microstructure research, and experimental techniques like photoemission, atom probe tomography, and electron microscopy. While the roadmap delves into specific areas within the broad interdisciplinary field of materials science, the provided examples elucidate key concepts applicable to a wider range of topics. The discussed instances offer insights into addressing the multifaceted challenges encountered in contemporary materials research

Does Insulin and Leucine Stimulate Muscle Protein Synthesis?

Improvement of protein synthesis in muscle will greatly enhance the production of lean pork. This improvement can be traced to changes at the cellular level. The object of this study was to identify the effects of insulin and the branched chain amino acid, leucine on the extent and rate that messenger RNA (mRNA) is translated into protein. Porcine satellite cells were isolated from a 30 lb pig and cultured. The cultured cells were treated with varying levels of insulin and leucine. Increasing levels of insulin and leucine caused an increase in ribosomes, the organelles responsible for synthesis, only after leucine was present in the media in adequate concentrations. With increasing levels of insulin there was an increase in the recruitment of ribosomes into polyribosomes for mRNA translation. However, increasing leucine levels had no effect on polyribosome percentage. In conclusion, insulin stimulates translation of mRNA by increasing both ability and rate. However, adequate levels of amino acid must be available for the stimulation to occur. Increased levels of branched chain amino acid do not create a synergistic effect with insulin to increase polyribosomes for protein synthesis

Lysophosphatidic acid, but neither clenbuterol nor salbutamol, stimulates increases in ERK-1/2 phosphorylation which is not associated with an appreciable increase in proliferation

Extracellular signal-related kinases (ERK-1/2) are important signaling components for the regulation of cell proliferation. Both β-adrenergic receptor agonists (β-AA) and lysophosphatidic acid (LPA) have been shown to stimulate phosphorylation of ERK-1/2 in several cell lines. The β-AA have been used to stimulate skeletal muscle growth in livestock, yet there are still questions about the signaling mechanisms involved. The effects of LPA on skeletal muscle have not been investigated. The objective of these studies was to evaluate the effects of β-AA and LPA on ERK-1/2 phosphorylation and proliferation in muscle cell lines. In both studies, proliferation was assessed by [3H]thymidine incorporation and ERK-1/2 activation was determined by western blot analysis and a cell cycle analysis was conducted by flow cytometry. In study one, muscle-derived cells were treated with 2×10 -11 M clenbuterol. Clenbuterol treatment did not increase [ 3H]thymidine incorporation and had no effect on ERK-1/2 activation (P\u3c0.05). Clenbuterol treatment also did not increase the percentage of cells in the S or G2/M phases of the cell cycle. In study two, the effect of LPA on proliferation and ERK-1/2 activation in C2C 12 myoblasts was assessed. LPA treatment induced increases in [ 3H]thymidine incorporation were similar to that observed with 10% fetal bovine serum (FBS; P\u3e0.05) with the exception of the lowest concentration of LPA (12.5 μM; P\u3c0.05). Lysophosphatidic acid stimulated a rapid increase in ERK-1/2 phosphorylation which was attenuated by 2h. Likewise, 10% FBS stimulated phosphorylation of ERK-1/2, but the increase in phosphorylation was sustained past 4h. Analysis of cell cycle showed LPA induced a transient increase in the percentage of cells in S phase at 12h, but this increase was abated by 24h. These data demonstrate that although LPA treatment does induce an increase in ERK-1/2 phosphorylation, neither β-AA or LPA treatment resulted in an appreciable change in proliferation of muscle cell lines, suggesting that LPA treatment and ERK-1/2 activation are not sufficient to induce persistent cell growth in vitro

Quantifying Attitudes and Knowledge Change About the Meat-Animal Industry via a Massive Open Online Course

Massive open online courses (MOOCs) offer a unique platform through which Extension can provide valuable education. We explored The Meat We Eat, a MOOC designed to create a more informed meat consumer and increase perceptions of transparency surrounding meat production. Compared to pretest respondents (n = 490), students who completed the posttest (n = 226) had an improved attitude toward meat and slaughter, an improved perception of the meat industry’s transparency, and increased knowledge. These findings suggest the relevance and value of MOOCs as Extension activities for improving knowledge and attitudes toward animal agriculture and other topics

Association of μ-Calpain and Calpastatin Polymorphisms with Meat Tenderness in a Brahman–Angus Population

Autogenous proteolytic enzymes of the calpain family are implicated in myofibrillar protein degradation. As a result, the μ-calpain gene and its specific inhibitor, calpastatin, have been repeatedly investigated for their association with meat quality traits in cattle; however, no functional mutation has been identified for these two genes. The objectives of this study were: (1) to assess breed composition effect on tenderness; (2) to perform a linkage disequilibrium (LD) analysis in μ-calpain and calpastatin genes as well as an association analyses with tenderness; and (3) to analyze putative functional SNPs inside the significant LD block for an effect on tenderness. Tenderness measurements and genotypes for 16 SNPs in μ-calpain gene and 28 SNPs in calpastatin gene from 673 steers were analyzed. A bioinformatic analysis identified “putative functional SNPs” inside the associated LD block – polymorphisms able to produce a physical and/or chemical change in the DNA, mRNA, or translated protein in silico. Breed composition had a significant (P < 0.0001) effect on tenderness where animals with more than 80% Angus composition had the most tender meat. One 11-kb LD-block and three LD-blocks of 37, 17, and 14 kb in length were identified in the μ-calpain and calpastatin genes, respectively. Out of these, the LD-block 3 in calpastatin, tagged by SNPs located at 7-98566391 and 7-98581038, had a significant effect on tenderness with the TG-CG diplotype being approximately 1 kg more tender than the toughest diplotype, TG-CG. A total of 768 SNPs in the LD-block 3 of calpastatin were included in the bioinformatic analysis, and 28 markers were selected as putative functional SNPs inside the LD-block 3 of calpastatin; however, none of them were polymorphic in this population. Out of 15 initial polymorphisms segregating inside the LD-block 3 of calpastatin in this population, markers ARSUSMARC116, Cast5, rs730723459, and rs210861835 were found to be significantly associated with tenderness

Energy dense, protein restricted diet increases adiposity and perturbs metabolism in young, genetically lean pigs.

Animal models of obesity and metabolic dysregulation during growth (or childhood) are lacking. Our objective was to increase adiposity and induce metabolic syndrome in young, genetically lean pigs. Pre-pubertal female pigs, age 35 d, were fed a high-energy diet (HED; n = 12), containing 15% tallow, 35% refined sugars and 9.1-12.9% crude protein, or a control corn-based diet (n = 11) with 12.2-19.2% crude protein for 16 wk. Initially, HED pigs self-regulated energy intake similar to controls, but by wk 5, consumed more (P<0.001) energy per kg body weight. At wk 15, pigs were subjected to an oral glucose tolerance test (OGTT); blood glucose increased (P<0.05) in control pigs and returned to baseline levels within 60 min. HED pigs were hyperglycemic at time 0, and blood glucose did not return to baseline (P = 0.01), even 4 h post-challenge. During OGTT, glucose area under the curve (AUC) was higher and insulin AUC was lower in HED pigs compared to controls (P = 0.001). Chronic HED intake increased (P<0.05) subcutaneous, intramuscular, and perirenal fat deposition, and induced hyperglycemia, hypoinsulinemia, and low-density lipoprotein hypercholesterolemia. A subset of HED pigs (n = 7) was transitioned back to a control diet for an additional six weeks. These pigs were subjected to an additional OGTT at 22 wk. Glucose AUC and insulin AUC did not improve, supporting that dietary intervention was not sufficient to recover glucose tolerance or insulin production. These data suggest a HED may be used to increase adiposity and disrupt glucose homeostasis in young, growing pigs

Table_1.XLSX

<p>Autogenous proteolytic enzymes of the calpain family are implicated in myofibrillar protein degradation. As a result, the μ-calpain gene and its specific inhibitor, calpastatin, have been repeatedly investigated for their association with meat quality traits in cattle; however, no functional mutation has been identified for these two genes. The objectives of this study were: (1) to assess breed composition effect on tenderness; (2) to perform a linkage disequilibrium (LD) analysis in μ-calpain and calpastatin genes as well as an association analyses with tenderness; and (3) to analyze putative functional SNPs inside the significant LD block for an effect on tenderness. Tenderness measurements and genotypes for 16 SNPs in μ-calpain gene and 28 SNPs in calpastatin gene from 673 steers were analyzed. A bioinformatic analysis identified “putative functional SNPs” inside the associated LD block – polymorphisms able to produce a physical and/or chemical change in the DNA, mRNA, or translated protein in silico. Breed composition had a significant (P < 0.0001) effect on tenderness where animals with more than 80% Angus composition had the most tender meat. One 11-kb LD-block and three LD-blocks of 37, 17, and 14 kb in length were identified in the μ-calpain and calpastatin genes, respectively. Out of these, the LD-block 3 in calpastatin, tagged by SNPs located at 7-98566391 and 7-98581038, had a significant effect on tenderness with the TG-CG diplotype being approximately 1 kg more tender than the toughest diplotype, TG-CG. A total of 768 SNPs in the LD-block 3 of calpastatin were included in the bioinformatic analysis, and 28 markers were selected as putative functional SNPs inside the LD-block 3 of calpastatin; however, none of them were polymorphic in this population. Out of 15 initial polymorphisms segregating inside the LD-block 3 of calpastatin in this population, markers ARSUSMARC116, Cast5, rs730723459, and rs210861835 were found to be significantly associated with tenderness.</p