Quantitative Trait Loci (QTLs) mapping for growth traits in the mouse: A review

The attainment of a specific mature body size is one of the most fundamental differences among species of mammals. Moreover, body size seems to be the central factor underlying differences in traits such as growth rate, energy metabolism and body composition. An important proportion of this variability is of genetic origin. The goal of the genetic analysis of animal growth is to understand its "genetic architecture", that is the number and position of loci affecting the trait, the magnitude of their effects, allele frequencies and types of gene action. In this review, the different strategies developed to identify and characterize genes involved in the regulation of growth in the mouse are described, with emphasis on the methods developed to map loci contributing to the regulation of quantitative traits (QTLs)

Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains

BACKGROUND: High growth (hg) modifier and background independent quantitative trait loci (QTL) affecting growth, adiposity and carcass composition were previously identified on mouse chromosomes (MMU) 1, 2, 5, 8, 9, 11 and 17. To confirm and further characterize each QTL, two panels of speed congenic strains were developed by introgressing CAST/EiJ (CAST) QTL alleles onto either mutant C57Bl/6J-hg/hg (HG) or wild type C57Bl/6J (B6) genetic backgrounds. RESULTS: The first speed congenic panel was developed by introgressing four overlapping donor regions spanning MMU2 in its entirety onto both HG and B6 backgrounds, for a total of eight strains. Phenotypic characterization of the MMU2 panel confirmed the segregation of multiple growth and obesity QTL and strongly suggested that a subset of these loci modify the effects of the hg deletion. The second panel consisted of individual donor regions on an HG background for each QTL on MMU1, 5, 8, 9, 11 and 17. Of the six developed strains, five were successfully characterized and displayed significant differences in growth and/or obesity as compared to controls. All five displayed phenotypes similar to those originally attributed to each QTL, however, novel phenotypes were unmasked in several of the strains including sex-specific effects. CONCLUSION: The speed congenic strains developed herein constitute an invaluable genomic resource and provide the foundation to identify the specific nature of genetic variation influencing growth and obesity

The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation.

Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is in part created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high-quality draft genome assemblies for cattle and goat; re-annotated sheep, pig, and horse genome assemblies; and the published human, rat, and mouse lemur NKC. The major NKC genes are largely in the equivalent positions in all eight species, with significant independent expansions and deletions between species, allowing us to propose a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ, and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between the NKC genes concentrated in the predicted extracellular ligand-binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting that this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination

Deducing signaling pathways from parallel actions of arsenite and antimonite in human epidermal keratinocytes.

Inorganic arsenic oxides have been identified as carcinogens in several human tissues, including epidermis. Due to the chemical similarity between trivalent inorganic arsenic (arsenite) and antimony (antimonite), we hypothesized that common intracellular targets lead to similarities in cellular responses. Indeed, transcriptional and proteomic profiling revealed remarkable similarities in differentially expressed genes and proteins resulting from exposure of cultured human epidermal keratinocytes to arsenite and antimonite in contrast to comparisons of arsenite with other metal compounds. These data were analyzed to predict upstream regulators and affected signaling pathways following arsenite and antimonite treatments. A majority of the top findings in each category were identical after treatment with either compound. Inspection of the predicted upstream regulators led to previously unsuspected roles for oncostatin M, corticosteroids and ephrins in mediating cellular response. The influence of these predicted mediators was then experimentally verified. Together with predictions of transcription factor effects more generally, the analysis has led to model signaling networks largely accounting for arsenite and antimonite action. The striking parallels between responses to arsenite and antimonite indicate the skin carcinogenic risk of exposure to antimonite merits close scrutiny

Is Acute Lower Back Pain Associated with Heart Rate Variability Changes? A Protocol for Systematic Reviews

Acute lower back pain (ALBP) is an extremely common musculoskeletal problem. ALBP consists of a sudden onset of short-duration pain in the lower back. However, repeated attacks can make the pain chronic. It can be measured through a self-report scale as well as through physical and physiological evaluations. Heart Rate Variability (HRV) has been used to evaluate the body’s response to pain. However, to the best of our knowledge, no clear consensus has been reached regarding the relationship between both variables and on an optimal protocol for ALBP evaluation based on HRV. The objective of this review is to analyze the relationship and effectiveness of HRV as an instrument for measuring ALBP. Furthermore, we consider the influence of different types of interventions in this relationship. The protocol of this review was previously recorded in the International Prospective Register of Systematic Reviews (number CRD42023437160). The PRISMA guidelines for systematic reviews and PubMed, WOS and Scopus databases are employed. Studies with samples of adults with ALBP are included. This study sets out a systematic review protocol to help identify the relationship between HRV and ALBP. Understanding this relationship could help in designing early detection or action protocols that alleviate ALBP.This research was funded by the Valencian Innovation Agency of Spain (grant number INNVA1/2020/81)

Acute effects of different external compression with blood flow restriction on force-velocity profile during squat and bench press exercises

The aim was to compare the acute effects of bench press (BP) and squat (SQ) exercises with blood flow restriction (BFR) (40%, 60%, 80% and 100% of the complete arterial occlusion pressure (AOP)) and without BFR (CON) on the mean propulsive (VelMED) and maximum (VelMAX) bar velocity. Fourteen healthy, physically active males (age, 23.6±4.1 years; height, 1.85±0.11 m; body weight 85.4±4.1 kg) took part in the study. There was one set for each testing condition (CON, 40%, 60%, 80% and 100%) with 6 repetitions for BP and 6 repetitions for SQ, at 60% of 1RM, and 3 minutes of recovery between sets. The results showed statistically significant differences of the sets with 80% BFR vs. CON (mean difference [MD] = 0.035 m·s-1, p < 0.05, ES = 0.52 [1.02–0.03]) and 100% BFR sets vs. CON (MD = 0.074, p < 0.001, ES = 1.08 [1.79–0.38]) for BP. In the SQ exercise, statistically significant differences were found between 100% BFR vs. CON (DM = 0.031 m·s-1, p < 0.05), vs. 100% BFR 40% (MD = 0.04 m·s-1, p < 0.05). Trend analysis showed a statistically significant linear trend (F[1,9] = 34.9, p < 0.001, F[1,13] = 27.32, p < 0.001) for the VelMED in relation to the different levels of BFR. In conclusion, our results showed that BFR levels above ~80% AOP (BP) and ~100% AOP (SQ) produce a VelMED improvement at 60% 1RM

Non-Coding RNA Sequencing of Equine Endometrium During Maternal Recognition of Pregnancy.

Maternal recognition of pregnancy (MRP) in the mare is not well defined. In a non-pregnant mare, prostaglandin F2α (PGF) is released on day 14 post-ovulation (PO) to cause luteal regression, resulting in loss of progesterone production. Equine MRP occurs prior to day 14 to halt PGF production. Studies have failed to identify a gene candidate for MRP, so attention has turned to small, non-coding RNAs. The objective of this study was to evaluate small RNA (&lt;200 nucleotides) content in endometrium during MRP. Mares were used in a cross-over design with each having a pregnant and non-mated cycle. Each mare was randomly assigned to collection day 11 or 13 PO (n = 3/day) and endometrial biopsies were obtained. Total RNA was isolated and sequencing libraries were prepared using a small RNA library preparation kit and sequenced on a HiSeq 2000. EquCab3 was used as the reference genome and DESeq2 was used for statistical analysis. On day 11, 419 ncRNAs, representing miRNA, snRNA, snoRNA, scaRNA, and vaultRNA, were different between pregnancy statuses, but none on day 13. Equine endometrial ncRNAs with unknown structure and function were also identified. This study is the first to describe ncRNA transcriptome in equine endometrium. Identifying targets of these ncRNAs could lead to determining MRP

Exercise, the diurnal cycle of cortisol and cognitive impairment in older adults

Exercise has been shown to reduce the risk of developing Mild Cognitive Impairment and Alzheimer's disease as well as to improve cognition in healthy and cognitively impaired individuals. However, the mechanisms of these benefits are not well understood. The stress hypothesis suggests that the cognitive benefits attributed to exercise may partially be mediated by changes in the cortisol secretion pattern. Chronic stress may increase the risk of AD and exacerbate the cognitive deficits and brain pathology characteristic of the condition while physical activity has been shown to attenuate most of stress consequences and risk factors for AD. Initially, research on the effects of cortisol on cognition and physical activity focused on cortisol levels at one time point but the circadian pattern of cortisol secretion is complex and it is still unclear which aspects are most closely associated with cognitive function. Thus, the aim of this review was to analyze the exercise/stress/cognition hypothesis focusing on the effects of the diurnal cycle of cortisol on cognitive function and physical activity in older adults with and without cognitive impairment

Acute Effects of Resistance Training with Blood Flow Restriction on Achilles Tendon Thickness

The Achilles tendon is one of the strongest and thickest tendons of the human body. Several studies have reported an immediate decrease in Achilles tendon thickness after a single bout of resistance training. However, the effects of blood flow restriction training on Achilles tendon thickness have not been investigated. The purpose of this study was to investigate the acute effects of different regimens of resistance training on Achilles tendon thickness. Fiftytwo participants (27.3 ± 7 years; 177.6 ± 11 cm; 72.2 ± 13.7 kg) were randomly allocated into one of the three groups: low-intensity exercise without (LI, n = 13) and with blood flow restriction (LI-BFR, n = 24), and high-intensity exercise (HI, n = 15). Participants from LI and LI-BFR groups performed four sets (1 x 30 + 3 x 15 reps) at 30% 1RM, while the HI group performed four sets (1 x 30 with 30% 1RM + 3 x 10 reps with 75% 1RM). All groups performed a plantar flexion exercise. For the LI-BFR group, a blood pressure cuff was placed on the dominant calf and inflated at 30% of the individual´s occlusion pressure (47.6 ± 19.8 mmHg). Sonographic images of Achilles tendon thickness were taken at pre, immediately after, 60 min and 24 h following acute bouts of exercise. Achilles tendon thickness was significantly reduced immediately after, 60 min and 24 h post-LI-BFR exercise (pre: 4.4 ± 0.4 mm vs. IA: 3.8 ± 0.4 mm vs. 60 min: 3.7 ± 0.3 mm vs. 24 h: 4.1 ± 0.3 mm; p 0.05). These results suggest that blood flow restriction training may be an effective strategy to stimulate a positive response in Achilles tendon thickness