Tag SNP selection for prediction of adaptation traits in Braford and Hereford cattle using Bayesian methods.

This study utilized Bayesian inference in a genome-wide association study (GWAS) to identify genetic markers associated with traits relevant to the adaptation of Hereford and Braford cattle breeds. We focused on eye pigmentation (EP), weaning hair coat (WHC), yearling hair coat (YHC), and breeding standard (BS). Our dataset comprised 126,290 animals in the pedigree. Out of these, 233 sires were genotyped using high-density (HD) chips, and 3750 animals with medium-density (50 K) single-nucleotide polymorphism (SNP) chips. Employing the Bayes B method with a prior probability of π = 0.99, we identified and tagged single nucleotide polymorphisms (Tag SNPs), ranging from 18 to 117 SNPs depending on the trait. These Tag SNPs facilitated the construction of reduced SNP panels. We then evaluated the predictive accuracy of these panels in comparison to traditional medium-density SNP chips. The accuracy of genomic predictions using these reduced panels varied significantly depending on the clustering method, ranging from 0.13 to 0.65. Additionally, we conducted functional enrichment analysis that found genes associated with the most informative SNP markers in the current study, thereby providing biological insights into the genomic basis of these traits.

Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy.

Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P =  0.038) and SFI with anti-PD-1 therapy ( P =  0.006). Both NLR and dNLR were associated with OS ( P =  0.038 and P =  0.046, respectively) and SFI ( P =  0.001 and P =  0.019, respectively). NLR was also associated with immunotherapy response ( P =  0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.

Synthesis of 6,8-diaminopurines via acid-induced cascade cyclization of 5-aminoimidazole precursors and preliminary anticancer evaluation.

Inspired by the pharmacological interest generated by 6-substituted purine roscovitine for cancer treatment, 5-aminoimidazole-4-carboxamidine precursors containing a cyanamide unit were prepared by condensation of 5-amino-N-cyanoimidazole-4-carbimidoyl cyanides with a wide range of primary amines. When these amidine precursors were combined with acids, a fast cascade cyclization occurred at room temperature, affording new 6,8-diaminopurines with the N-3 and N-6 substituents changed relatively to the original positions they occupied in the amidine and imidazole moieties of precursors. The efficacy and wide scope of this method was well demonstrated by an easy and affordable synthesis of 22 6,8-diaminopurines decorated with a wide diversity of substituents at the N-3 and N-6 positions of the purine ring. Preliminary in silico and in vitro assessments of these 22 compounds were carried out and the results showed that 13 of these tested compounds not only exhibited IC50 values between 1.4 and 7.5 µM against the colorectal cancer cell line HCT116 but also showed better binding energies than known inhibitors in docking studies with different cancer-related target proteins. In addition, good harmonization observed between in silico and in vitro results strengthens and validates this preliminary evaluation, suggesting that these novel entities are good candidates for further studies as new anticancer agents.

Multisensory Stimulation Reverses Memory Impairment in Adrß3KO Male Mice.

Norepinephrine plays an important role in modulating memory through its beta-adrenergic receptors (Adrß: ß1, ß2 and ß3). Here, we hypothesized that multisensory stimulation would reverse memory impairment caused by the inactivation of Adrß3 (Adrß3KO) with consequent inhibition of sustained glial-mediated inflammation. To test this, 21- and 86-day-old Adrß3KO mice were exposed to an 8-week multisensory stimulation (MS) protocol that comprised gustatory and olfactory stimuli of positive and negative valence; intellectual challenges to reach food; the use of hidden objects; and the presentation of food in ways that prompted foraging, which was followed by analysis of GFAP, Iba-1 and EAAT2 protein expression in the hippocampus (HC) and amygdala (AMY). The MS protocol reduced GFAP and Iba-1 expression in the HC of young mice but not in older mice. While this protocol restored memory impairment when applied to Adrß3KO animals immediately after weaning, it had no effect when applied to adult animals. In fact, we observed that aging worsened the memory of Adrß3KO mice. In the AMY of Adrß3KO older mice, we observed an increase in GFAP and EAAT2 expression when compared to wild-type (WT) mice that MS was unable to reduce. These results suggest that a richer and more diverse environment helps to correct memory impairment when applied immediately after weaning in Adrß3KO animals and indicates that the control of neuroinflammation mediates this response.

Juçara Fruit (Euterpe Edulis Martius) Valorization Combining Emergent Extraction Technologies and Aqueous Solutions of Alkanediols.

Anthocyanins from juçara fruits were extracted by pressurized liquid extraction (PLE) or ultrasound-assisted extraction (UAE), using aqueous solutions of 1,2-alkanediols and glycerol ethers as biobased solvents. The PLE (100 bar, 13 min, 1 mL/min flow rate) in the optimal extraction conditions originated 23.1 mganthocyanins·gdry biomass-1. On the other hand, the UAE was 10 min long, and the optimal conditions using 1,2-propanediol were 42.6 wt%, 160 W, and pH 7.0, leading to 50 mganthocyanins·gdry biomass-1. Extractions at the UAE optimized conditions, with aqueous solutions of five different 1,2-alkanediols and three glycerol ethers were performed, and compared to water and ethanolic extracts. The biobased solvent solutions presented anthocyanin yields up to 33% higher than water, and were shown to be as efficient as ethanol/water, but generated extracts with higher antioxidant capacity. The anthocyanin-rich extract of juçara, obtained with 1,2-propanediol, was used in the production of a natural soap and incorporated into a cream, showing that the addition of the juçara extract resulted in an antioxidant capacity in both products.

Histopathological analysis of chronic paronychia.

BACKGROUND: Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of the cuticle. Treatment involves clinical measures and, when there is no response or the hypertrophy of the folds is very pronounced, surgical treatment is indicated. Post-surgical histopathology is little studied in the literature. In this sense, we believe that the histopathological study is important not only for the individualized understanding of the patient's chronic disease, avoiding relapses, but also for the understanding of its pathophysiology and treatment possibilities. OBJECTIVE: To describe the histopathological changes found in biopsies of the proximal nail fold of patients with chronic paronychia undergoing surgical treatment. MATERIALS AND METHODS: A histopathological study of 16 nail folds from 6 patients after surgery was performed at 2 study centers. RESULTS: The most prevalent epidermal findings were orthokeratosis, hypergranulosis, acanthosis and spongiosis and the dermal findings were fibrosis and mononuclear inflammatory infiltrate. CONCLUSION: The histopathological study allowed us to conclude that chronic paronychia is primarily an inflammatory process, but it is not possible to conclude whether microorganisms such as Candida and bacterial cocci are part of the etiology or just secondary and opportunistic agents.

The effect of caffeine on exercise performance is not influenced by ADORA2A genotypes, alone or pooled with CYP1A2 genotypes, in adolescent athletes.

PURPOSE: This study investigated the influence of the different genotypes of ADORA2A (1976 C > T, rs 5751876), alone or pooled with CYP1A2 (163 C > A rs 762551) genotypes, on the ergogenic effects of caffeine (CAF) on various aspects of physical performance in male adolescent athletes. METHODS: Ninety male adolescent athletes (age = 15.5 ± 2 years) were classified according to their genotypes for 1976 C > T ADORA2A (TT homozygous or CADORA2A allele carriers) and 163 C > A CYP1A2 (AA homozygous or CCYP1A2 allele carriers). Participants were further divided in four groups (1-TTADORA2A + AACYP1A2; 2-TTADORA2A + AC/CCCYP1A2; 3-AACYP1A2 + CT/CCADORA2A;4-AC/CCCYP1A2 + CT/CCADORA2A). Using a randomized, crossover, counterbalanced, and double-blind design, participants ingested CAF (6 mg kg-1) or a placebo (PLA, 300 mg of cellulose) one hour before performing a sequence of physical tests: handgrip strength, agility test, countermovement jump (CMJ), Spike Jump (SJ), sit-ups, push-ups, and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). RESULTS: CAF enhanced handgrip strength (CAF: 35.0 ± 9.2 kg force; PLA: 33.5 ± 8.9 kg force; p = 0.050), CMJ height (CAF: 49.6 ± 12.3 cm; PLA: 48.3 ± 13.6 cm; p = 0.013), SJ height (CAF: 54.7 ± 13.3 cm; PLA: 53.1 ± 14.8 cm; p = 0.013), number of sit-ups (CAF: 37 ± 8; PLA: 35 ± 8; p = 0.001), and distance covered on the Yoyo IR1 test (CAF: 991.6 ± 371.0 m; PLA: 896.0 ± 311.0 m; p = 0.001), This CAF-induced improvement on exercise performance was, however, independent of genotypes groups (all p > 0.05). CAF had no effect on agility (CAF: 15.8 ± 1.2 s; PLA: 15.9 ± 1.3 s; p = 0.070) and push-up (CAF: 26.6 ± 12.0; PLA: 25.0 ± 11.0; p = 0.280) tests. CONCLUSION: The acute caffeine intake of 6.0 mg.kg-1 improves several aspects of physical performance, which seems to be independent of ADORA2A genotypes, alone or in combination with CYP1A2 genotypes.

Advancing drug repurposing research: Trends, collaborative networks, innovation and knowledge leaders.

The advancement of drug repurposing (DR) relies on scientific leadership and innovative institutions with access to knowledge. We performed a bibliometric and social network analysis (covering the period 2011-2020) to map the DR research trends and to identify innovation and knowledge leaders (IKLs). The indexing rate of DR publications has steadily increased. Major research areas included emerging viruses, cancer, methodological approaches, preclinical research, and infectious diseases. Government and academia accounted for nearly 65% of funding. Using a combination of network centrality metrics, 41 IKLs affiliated to central and pericentral institutions in the global research network were identified. These IKLs can facilitate the flow of knowledge and are best positioned to promote interactions within the network, with the potential to contribute significantly to advancing the DR field.

Artificial intelligence for oral cancer diagnosis: What are the possibilities?

Oral cancer could be prevented. The primary strategy is based on prevention. Most patients with oral cancer present to the hospital network with advanced staging and a low chance of cure. This condition may be related to physicians' difficulty of making an early diagnosis. With the advancement of information technology, artificial intelligence (AI) holds great promise in terms of assisting in diagnosis. Few machine learning algorithms have been developed for this purpose to date. In this paper, we will discuss the possibilities for diagnosing oral cancer using AI as a tool, as well as the implications for the population. A set of photographic images of oral lesions has been segmented, indicating not only the area of the lesion but also the class of lesion associated with it. Different neural network architectures were trained with the goal of fine segmentation (pixel by pixel), classification of image crops, and classification of whole images based on the presence or absence of a lesion. The accuracy results are acceptable, opening up possibilities not only for identifying lesions but also for classifying the pathology associated with them.

Multisensory Stimulation Improves Cognition and Behavior in Adult Male Rats Born to LT4-treated Thyroidectomized Dams.

Gestational hypothyroidism can impair development, cognition, and mood. Here, we tested whether multisensory stimulation (MS) improves the phenotype of rats born to surgically thyroidectomized (Tx) dams suboptimally treated with LT4. 8-week-old female Tx Wistar rats were kept on daily LT4 (0.7 µg/100 g body weight) dosed by gavage (serum TSH and T4 levels indicated moderate hypothyroidism) and 3 weeks later placed for breeding. MS of the litter started at age 60 days and lasted for 8 weeks. It consisted of twice per week of physical, cognitive, sensorial, and food stimuli. The offspring were assessed before and after MS for standardized tests of locomotor activity, cognition, and mood. Gestational hypothyroidism resulted in reduced litter size and increased offspring mortality. The pups exhibited delayed physical development, impairment of short- and long-term memory, and anxiety- and depressive-like behaviors. Nonetheless, ambulatory activity, social memory, and social preference were not affected by gestational hypothyroidism. MS restored short-term memory and anxiety while improving depressive like-behaviors. MS did not improve long-term memory. MS also did not modify the performance of control litter born to intact dams. We conclude that cognition and mood impairments caused by moderate gestational hypothyroidism were reversed or minimized in rats through MS. Further studies should define the molecular mechanisms involved.

MeHg exposure impairs both the catecholaminergic and cholinergic systems resulting in motor and non-motor behavioral changes in Drosophila melanogaster.

Human exposure to the natural environmental contaminant methylmercury (MeHg) has been associated to adverse health effects. Importantly, the mechanisms by which this organomercurial exerts its neurotoxicity have yet to be fully clarified. Therefore, the aim of this study was to evaluate whether exposure to MeHg alters dopamine (DA) and octopamine (OA) levels, acetylcholinesterase (AChE) activity and impacts both motor and non-motor behaviours. We studied the effect of MeHg by feeding 1-2 d old flies (male and females) with 25 and 50 µM MeHg for 4 d and determined effects on survival, motor and non-motor behaviours, oxidative stress, AChE and tyrosine hydroxylase (TH) activities, as well as DA and OA levels. We found that Drosophila melanogaster (D. melanogaster) exposed to MeHg showed a reduction in survival rate, associated with the inhibition of AChE and TH activities in head of flies and decreased DA and OA levels. These changes were accompanied by behavioural alterations, such as locomotor deficit and increased grooming behaviour, in addition to an increase in oxidative stress markers both in head and in body of flies, and an increase in glutathione-S-transferase (GST) activity in head of flies. Collectively, our data support the hypothesis that MeHg neurotoxicity is associated with altered OA and DA levels, AChE inhibition, which may serve, at least in part, as the underpinnings of both motor and non-motor behavioural changes.

Triiodothyronine Treatment reverses Depression-Like Behavior in a triple-transgenic animal model of Alzheimer's Disease.

Alzheimer disease's (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. The central nervous system is an important target of thyroid hormones (TH). An inverse association between serum triiodothyronine (T3) levels and the risk of AD symptoms and progression has been reported. We investigated the effects of T3 treatment on the depression-like behavior in male transgenic 3xTg-AD mice. Animals were divided into 2 groups treated with daily intraperitoneal injections of 20 ng/g of body weight (b.w.) L-T3 (T3 group) or saline (vehicle, control group). The experimental protocol lasted 21 days, and behavioral tests were conducted on days 18-20. At the end of the experiment, the TH profile and hippocampal gene expression were evaluated. The T3-treated group significantly increased serum T3 and decreased thyroxine (T4) levels. When compared to control hippocampal samples, the T3 group exhibited attenuated glycogen synthase kinase-3 (GSK3), metalloproteinase 10 (ADAM10), amyloid-beta precursor-protein (APP), serotonin transporter (SERT), 5HT1A receptor, monocarboxylate transporter 8 (MCT8) and bone morphogenetic protein 7 (BMP-7) gene expression, whereas augmented superoxide dismutase 2 (SOD2) and Hairless gene expression. T3-treated animals also displayed reduced immobility time in both the tail suspension and forced swim tests, and in the latter presented a higher latency time compared to the control group. Therefore, our findings suggest that in an AD mouse model, T3 supplementation promotes improvements in depression-like behavior, through the modulation of the serotonergic related genes involved in the transmission mediated by 5HT1A receptors and serotonin reuptake, and attenuated disease progression.

Age Worsens the Cognitive Phenotype in Mice Carrying the Thr92Ala-DIO2 Polymorphism.

The Thr92Ala-Dio2 polymorphism has been associated with reduced cognition in 2-month-old male mice and increased risk for cognitive impairment and Alzheimer's disease in African Americans. This has been attributed to reduced thyroid hormone (TH) signaling and endoplasmic reticulum (ER) stress in the brain. Here we studied the Thr92Ala-Dio2 mouse model and saw that older male mice (7-8-month-old) exhibited a more severe cognition impairment, which extended to different aspects of declarative and working memories. A similar phenotype was observed in 4-5-month-old female mice. There were no structural alterations in the prefrontal cortex (PFC) and hippocampus of the Thr92Ala-Dio2 mouse. Nonetheless, in both male and female PFC, there was an enrichment in genes associated with TH-dependent processes, ER stress, and Golgi apparatus, while in the hippocampus there was additional enrichment in genes associated with inflammation and apoptosis. Reduced TH signaling remains a key mechanism of disease given that short-term treatment with L-T3 rescued the cognitive phenotype observed in males and females. We conclude that in mice, age is an additional risk factor for cognitive impairment associated with the Thr92Ala-Dio2 polymorphism. In addition to reduced TH signaling, ER-stress, and involvement of the Golgi apparatus, hippocampal inflammation and apoptosis were identified as potentially important mechanisms of a disease.

Balance Exercise Circuit for fall prevention in older adults: a randomized controlled crossover trial.

Objectives: This study aimed to assess the immediate and short-term effects of the Balance Exercise Circuit (BEC) on muscle strength, postural balance, and quality of life, with the aim of preventing falls in older adults. Methods: Twenty-two volunteers participated in this randomized controlled crossover study. Group A performed BEC training in the initial 3 months and received no intervention in the following 3 months. Group B received no intervention during the first 3 months and then participated in BEC training for the next 3 months. In addition, participants were followed for an additional 3 months. Muscle strength, postural balance, functional mobility, and quality of life were assessed, respectively, using an isokinetic dynamometer, force platform, TUG test, and the WHOQOL. Results: After 3 months of training, Group A presented improved balance and rate of force development (RFD), while Group B presented improvements in RFD, TUG performance, and WHOQOL physical and psychological domains. Regarding the short-term effects, the participants maintained the training effects in WHOQOL balance, RFD, and the social domain. In addition, the number of falls decreased during follow-up. Conclusion: The BEC intervention improved muscle strength, postural balance, and quality of life in older adults, in addition to reducing the risk of falls. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) - RBR-5nvrwm.

The impact of size and shape in the performance of hydrotropes: a case-study of alkanediols.

Inspired by the recently proposed cooperative mechanism of hydrotropy, where water molecules mediate the aggregation of hydrotrope around the solute, this work studies the impact of apolar volume and polar group position on the performance of hydrotropes. To do so, the ability of two different families of alkanediols (1,2-alkanediols and 1,n-alkanediols) to increase the aqueous solubility of syringic acid is initially investigated. Interestingly, it is observed that in the dilute region (low hydrotrope concentration), the relative position of the hydroxyl groups of the alkanediols does not impact their performance. Instead, their ability to increase the solubility of syringic acid correlates remarkably well with the size of their alkyl chains. However, this is not the case for larger hydrotrope concentrations, where 1,2-alkanediols are found to perform, in general, better than 1,n-alkanediols. These seemingly contradictory findings are reconciled using theoretical and experimental techniques, namely the cooperative model of hydrotropy and chemical environment probes (Kamlet-Taft and pyrene polarity scales). It is found that the number of hydrotropes aggregated around a solute molecule does not increase linearly with the apolar volume of the former, reaching a maximum instead. This maximum is discussed in terms of competing solute-hydrotrope and hydrotrope-hydrotrope interactions. The results suggest that hydrotrope self-aggregation is more prevalent in 1,n-alkanediols, which negatively impacts their performance as hydrotropes. The results reported in this work support the cooperative model of hydrotropy and, from an application perspective, show that hydrotropes should be designed taking into consideration not only their apolar volume but also their ability to stabilize their self-aggregation in water, which negatively impacts their performance as solubility enhancers.

The model of litter size reduction induces long-term disruption of the gut-brain axis: An explanation for the hyperphagia of Wistar rats of both sexes.

The gut microbiota affects the host's metabolic phenotype, impacting health and disease. The gut-brain axis unites the intestine with the centers of hunger and satiety, affecting the eating behavior. Deregulation of this axis can lead to obesity onset. Litter size reduction is a well-studied model for infant obesity because it causes overnutrition and programs for obesity. We hypothesize that animals raised in small litters (SL) have altered circuitry between the intestine and brain, causing hyperphagia. We investigated vagus nerve activity, the expression of c-Fos, brain-derived neurotrophic factor (BDNF), gastrointestinal (GI) hormone receptors, and content of bacterial phyla and short-chain fatty acids (SCFAs) in the feces of adult male and female Wistar rats overfed during lactation. On the 3rd day after birth, litter size was reduced to 3 pups/litter (SL males or SL females) until weaning. Controls had normal litter size (10 pups/litter: 5 males and 5 females). The rats were killed at 5 months of age. The male and female offspring were analyzed separately. The SL group of both sexes showed higher food consumption and body adiposity than the respective controls. SL animals presented dysbiosis (increased Firmicutes, decreased Bacteroidetes) and had increased vagus nerve activity. Only the SL males had decreased hypothalamic GLP-1 receptor expression, while only the SL females had lower acetate and propionate in the feces and higher CCK receptor expression in the hypothalamus. Thus, overfeeding during lactation differentially changes the gut-brain axis, contributing to hyperphagia of the offspring of both sexes.

Suplementação de Vitamina D Induz Remodelação Cardíaca em Ratos: Associação com a Proteína de Interação com a Tiorredoxina e a Tiorredoxina / Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin

Resumo Fundamento: A vitamina D (VD) tem um importante papel na função cardíaca. No entanto, a vitamina exerce uma curva "dose-resposta" bifásica na fisiopatologia cardiovascular e pode causar efeitos deletérios, mesmo em doses não tóxicas. A VD exerce suas funções celulares ligando-se ao seu receptor. Ainda, a expressão da proteína de interação com a tiorredoxina (TXNIP) é positivamente regulada pela VD. A TXNIP modula diferentes visa de sinalização celular que podem ser importantes para a remodelação cardíaca. Objetivos: Avaliar se a suplementação com VD leva à remodelação cardíaca, e se a TXNIP e a tiorredoxina (Trx) estão associadas com esse processo. Métodos: Duzentos e cinquenta ratos Wistar machos foram alocados em três grupos: controle (C, n=21), sem suplementação com VD; VD3 (n = 22) e VD10 (n=21), suplementados com 3,000 e 10,000 UI de VD/ kg de ração, respectivamente, por dois meses. Os grupos foram comparados por análise de variância (ANOVA) com um fator e teste post hoc de Holm-Sidak (variáveis com distribuição normal), ou pelo teste de Kruskal-Wallis e análise post-hoc de Dunn. O nível de significância para todos os testes foi de 5%. Resultados: A expressão de TXNIP foi mais alta e a atividade do Trx foi mais baixa no grupo VD10. Os animais que receberam suplementação com VD apresentaram aumento de hidroperóxido lipídico e diminuição de superóxido dismutase e glutationa peroxidase. A proteína Bcl-2 foi mais baixa no grupo VD10. Observou-se uma diminuição na β-oxidação de ácidos graxos, no ciclo do ácido tricarboxílico, na cadeia transportadora de elétrons, e um aumento na via glicolítica. Conclusão: A suplementação com VD levou à remodelação cardíaca e esse processo pode ser modulado por TXNIP e Trx, e consequentemente por estresse oxidativo.

Abstract Background: Vitamin D (VD) has been shown to play an important role in cardiac function. However, this vitamin exerts a biphasic "dose response" curve in cardiovascular pathophysiology and may cause deleterious effects, even in non-toxic doses. VD exerts its cellular functions by binding to VD receptor. Additionally, it was identified that the thioredoxin-interacting protein (TXNIP) expression is positively regulated by VD. TXNIP modulate different cell signaling pathways that may be important for cardiac remodeling. Objective: To evaluate whether VD supplementation lead to cardiac remodeling and if TXNIP and thioredoxin (Trx) proteins are associated with the process. Methods: A total of 250 Male Wistar rats were allocated into three groups: control (C, n=21), with no VD supplementation; VD3 (n = 22) and VD10 (n=21), supplemented with 3,000 and 10,000 IU of VD/ kg of chow respectively, for two months. The groups were compared by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc analysis, (variables with normal distribution), or by Kruskal-Wallis test and Dunn's test post hoc analysis. The significance level for all tests was 5%. Results: TXNIP protein expression was higher and Trx activity was lower in VD10. The animals supplemented with VD showed increased lipid hydroperoxide and decreased superoxide dismutase and glutathione peroxidase. The protein Bcl-2 was lower in VD10. There was a decrease in fatty acid β-oxidation, tricarboxylic acid cycle and electron transport chain with shift to increase in glycolytic pathway. Conclusion: VD supplementation led to cardiac remodeling and this process may be modulated by TXNIP and Trx proteins and consequently oxidative stress.

Long-term obesity is associated with depression and neuroinflammation.

OBJECTIVE: Obesity is characterized by a state of chronic, low-intensity systemic inflammation frequently associated with insulin resistance and dyslipidemia. METHODS: Given that chronic inflammation has been implicated in the pathogenesis of mood disorders, we investigated if chronic obesity that was initiated early in life - lasting through adulthood - could be more harmful to memory impairment and mood fluctuations such as depression. RESULTS: Here we show that pre-pubertal male rats (30 days old) treated with a high-fat diet (40%) for 8-months gained ~50% more weight when compared to controls, exhibited depression and anxiety-like behaviors but no memory impairment. The prefrontal cortex of the obese rats exhibited an increase in the expression of genes related to inflammatory response, such as NFKb, MMP9, CCl2, PPARb, and PPARg. There were no alterations in genes known to be related to depression. CONCLUSION: Long-lasting obesity with onset in prepuberal age led to depression and neuroinflammation but not to memory impairment.

Genome-wide association and genomic prediction for scrotal circumference in Hereford and Braford bulls.

Scrotal circumference (SC) is widely used as a selection criterion for bulls in breeding programs, since it is easily assessed and correlated with several desirable reproductive traits. The objectives of this study were: to perform a genome-wide association study (GWAS) to identify genomic regions associated with SC adjusted for age (SCa) and for both age and weight (SCaw); to select Tag SNPs from GWAS to construct low-density panel for genomic prediction; and to compare the prediction accuracy of the SC through different methods for Braford and Hereford bulls from the same genetic breeding program. Data of SC from 18,172 bulls (30.4 ± 3.7 cm) and of genotypes from 131 sires and 3,545 animals were used. From GWAS, the top 1% of 1-Mb windows were observed on chromosome (BTA) 2, 20, 7, 8, 15, 3, 16, 27, 6 and 8 for SCa and on BTA 8, 15, 16, 21, 19, 2, 6, 5 and 10 for SCaw, representing 17.4% and 18.8% of the additive genetic variance of SCa and SCaw, respectively. The MeSH analysis was able to translate genomic information providing biological meanings of more specific gene functions related to the SCa and SCaw. The genomic enhancement methods, especially single step GBLUP, that combined phenotype and pedigree data with direct genomic values generated gains in accuracy in relation to pedigree BLUP, suggesting that genomic predictions should be applied to improve genetic gain and to narrow the generation interval compared to traditional methods. The proposed Tag-SNP panels may be useful for lower-cost commercial genomic prediction applications in the future, when the number of bulls in the reference population increases for SC in Hereford and Braford breeds.