Ractopamine-induced changes in sarcoplasmic proteome profile of post-rigor pork semimembranosus muscle

Ractopamine is a beta-adrenergic agonist that increases leanness and carcass weight in finishing pigs. Our previous study observed that dietary ractopamine increased the abundance of several glycolytic enzymes in the sarcoplasmic proteome of post-rigor pork longissimus thoracis muscle. Pork semimembranosus is an economically important muscle and demonstrates differences in biochemistry compared with longissimus thoracis. Nonetheless, the effects of ractopamine on sarcoplasmic proteome of semimembranosus have not been evaluated yet. Therefore, this study examined the influence of ractopamine on sarcoplasmic proteome of post-rigor pork semimembranosus. Analyses of sarcoplasmic proteome of semimembranosus muscles from control (CON; diet without ractopamine) and ractopamine-fed (RAC; 7.4 mg/kg for 14 days followed by 10.0 mg/kg for 14 days) barrows revealed that haemoglobin subunit beta, alpha-crystallin B, and titin fragments were over-abundant in CON. In contrast, myosin light chain 1/3 and tripartite motif-containing protein 72 were over-abundant in RAC. The low abundance of haemoglobin subunit beta and alpha crystallin B in RAC could be attributed to fibre type shift (from oxidative to glycolytic) in response to ractopamine. The over-abundance of MLC 1/3 and tripartite motif-containing protein 72 in RAC could be due to the increased myofibrillar protein synthesis and muscle mass in ractopamine-fed pigs. Dietary ractopamine decreased the abundance of sarcoplasmic proteins involved in oxygen transport and chaperone activity, but increased the abundance of proteins involved in muscle contraction and plasma membrane repair in pork semimembranosus muscle.Keywords: Pork, ractopamine, sarcoplasmic proteome, semimembranosu

Supranutritional supplementation of vitamin E influences mitochondrial proteome profile of post-mortem longissimus lumborum from feedlot heifers

Supplementation of vitamin E improves beef colour stability by minimizing lipid oxidation-induced myoglobin oxidation. Mitochondria affect myoglobin redox stability, and dietary vitamin E influences mitochondrial functionality in skeletal muscles. Nonetheless, the influence of vitamin E on the mitochondrial proteome of beef skeletal muscles has yet to be  investigated. Therefore, the objective of this study was to examine the effect of dietary vitamin E on mitochondrial proteome of post-mortem beef longissimus lumborum (LL) muscle. Beef LL muscle samples (24 hours post-mortem) were obtained from the carcasses of nine (n = 9) vitamin E-fed (VITE) (1000 IU vitamin E for 89 days) and nine (n = 9) control (CONT) (diet without supplemental vitamin E) heifers. The mitochondrial proteome was analysed using two-dimensional gel electrophoresis and mass spectrometry, and nine differentially abundant spots were identified. All the differentially abundant spots were over-abundant in CONT, and the proteins were electron transport chain enzymes (NADH dehydrogenase iron-sulphur protein 8, NADH dehydrogenase flavoprotein 2, and cytochrome c oxidase subunit 5B), metabolic enzymes (succinate-CoA ligase (ADP-forming) subunit beta; dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex; pyruvate dehydrogenase protein X component), and enzymes involved in ATP regeneration (creatine kinase S-type). The low abundance of these proteins in VITE may decrease mitochondrial activity, resulting in low oxidative activity. These findings suggest that the strong antioxidant activity of vitamin E leads to less expression of mitochondrial oxidative enzymes in beef skeletal muscles.Keywords: Beef colour, lipid oxidation, mitochondrial enzyme

Ractopamine-induced changes in the proteome of post-mortem beef longissimus lumborum muscle

Ractopamine is a beta-adrenergic agonist that is approved for use in beef cattle, pigs and turkeys as a repartitioning agent to increase lean muscle deposition and decrease lipogenesis. Although the effects of dietary ractopamine on the proteome profile of post-mortem pork muscles have been examined, its influence on beef muscle proteome has not been studied. Therefore, the objective of this study was to examine the effect of ractopamine on the proteome profile of post-mortem beef longissimus lumborum (LL) muscle. LL muscle samples were obtained from the carcasses of six (n = 6) steers fed ractopamine (RAC; 400 mg ractopamine hydrochloride for 28 days) and six (n = 6) steers fed no ractopamine (CON). The muscle proteome was analysed using two-dimensional gel electrophoresis and tandem mass spectrometry. Five differentially abundant spots were identified, and all the spots were over-abundant in RAC. The identified proteins were involved in muscle structure development (F-actin-capping protein subunit beta-2; PDZ and LIM domain protein-3), chaperone activity (heat shock protein beta-1), oxygen transport (myoglobin), and glycolysis (L-lactate dehydrogenase A chain). These results suggested that dietary ractopamine could influence the abundance of enzymes associated with muscle development and muscle fibre type shift in beef LL muscle.Keywords: growth promotants, meat quality, proteomic

Application concepts for ultrafast laser induced skyrmion creation and annihilation

Magnetic skyrmions can be created and annihilated in ferromagnetic multilayers using single femtosecond infrared laser pulses above a material dependent fluence threshold. From the perspective of applications, optical control of skyrmions offers a route to a faster and, potentially, more energy efficient new class of information technology devices. Here, we investigate laser induced skyrmion generation in two different materials, mapping out the dependence of the process on the applied field and the laser fluence. We observe that sample properties like strength of the Dzyaloshinskii Moriya interaction and pinning do not considerably influence the initial step of optical creation. In contrast, the number of skyrmions created can be directly and robustly controlled via the applied field and the laser fluence. Based on our findings, we propose concepts for applications, such as all optical writing and deletion, an ultrafast skyrmion reshuffling device for probabilistic computing, and a combined optical and spin orbit torque controlled racetrac

Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein Sampling Study (S4)

Immunohistochemical (IHC) α-synuclein (Asyn) pathology in peripheral biopsies may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology is being evaluated by a blinded panel of specially trained neuropathologists. Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD and control autopsy-derived sections from formalin-fixed, paraffin-embedded blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the 5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen for further use in S4. Four trainee neuropathologists were trained to perform S4 histopathology readings; in subsequent testing, their scoring was compared to that of the trainer neuropathologist on both glass slides and digital images. Specificity and sensitivity were both close to 100% with all readers in all tissue types on both glass slides and digital images except for skin, where sensitivity averaged 75% with digital images and 83.5% with glass slides. Semiquantitative (0-3) density score agreement between trainees and trainer averaged 67% for glass slides and 62% for digital images

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder