Longitudinal genomic analyses of automatically-recorded vaginal temperature in lactating sows under heat stress conditions based on random regression models.

BACKGROUND: Automatic and continuous recording of vaginal temperature (TV) using wearable sensors causes minimal disruptions to animal behavior and can generate data that enable the evaluation of temporal body temperature variation under heat stress (HS) conditions. However, the genetic basis of TV in lactating sows from a longitudinal perspective is still unknown. The objectives of this study were to define statistical models and estimate genetic parameters for TV in lactating sows using random regression models, and identify genomic regions and candidate genes associated with HS indicators derived from automatically-recorded TV. RESULTS: Heritability estimates for TV ranged from 0.14 to 0.20 over time (throughout the day and measurement period) and from 0.09 to 0.18 along environmental gradients (EG, - 3.5 to 2.2, which correspond to dew point values from 14.87 to 28.19 ËšC). Repeatability estimates of TV over time and along EG ranged from 0.57 to 0.66 and from 0.54 to 0.77, respectively. TV measured from 12h00 to 16h00 had moderately high estimates of heritability (0.20) and repeatability (0.64), indicating that this period might be the most suitable for recording TV for genetic selection purposes. Significant genotype-by-environment interactions (GxE) were observed and the moderately high estimates of genetic correlations between pairs of extreme EG indicate potential re-ranking of selection candidates across EG. Two important genomic regions on chromosomes 10 (59.370-59.998 Mb) and16 (21.548-21.966 Mb) were identified. These regions harbor the genes CDC123, CAMK1d, SEC61A2, and NUDT5 that are associated with immunity, protein transport, and energy metabolism. Across the four time-periods, respectively 12, 13, 16, and 10 associated genomic regions across 14 chromosomes were identified for TV. For the three EG classes, respectively 18, 15, and 14 associated genomic windows were identified for TV, respectively. Each time-period and EG class had uniquely enriched genes with identified specific biological functions, including regulation of the nervous system, metabolism and hormone production. CONCLUSIONS: TV is a heritable trait with substantial additive genetic variation and represents a promising indicator trait to select pigs for improved heat tolerance. Moderate GxE for TV exist, indicating potential re-ranking of selection candidates across EG. TV is a highly polygenic trait regulated by a complex interplay of physiological, cellular and behavioral mechanisms.

Genetic parameters for automatically-measured vaginal temperature, respiration efficiency, and other thermotolerance indicators measured on lactating sows under heat stress conditions.

BACKGROUND: Genetic selection based on direct indicators of heat stress could capture additional mechanisms that are involved in heat stress response and enable more accurate selection for more heat-tolerant individuals. Therefore, the main objectives of this study were to estimate genetic parameters for various heat stress indicators in a commercial population of Landrace × Large White lactating sows measured under heat stress conditions. The main indicators evaluated were: skin surface temperatures (SST), automatically-recorded vaginal temperature (TV), respiration rate (RR), panting score (PS), body condition score (BCS), hair density (HD), body size (BS), ear size, and respiration efficiency (Reff). RESULTS: Traits based on TV presented moderate heritability estimates, ranging from 0.15 ± 0.02 to 0.29 ± 0.05. Low heritability estimates were found for SST traits (from 0.04 ± 0.01 to 0.06 ± 0.01), RR (0.06 ± 0.01), PS (0.05 0.01), and Reff (0.03 ± 0.01). Moderate to high heritability values were estimated for BCS (0.29 ± 0.04 for caliper measurements and 0.25 ± 0.04 for visual assessments), HD (0.25 ± 0.05), BS (0.33 ± 0.05), ear area (EA; 0.40 ± 0.09), and ear length (EL; 0.32 ± 0.07). High genetic correlations were estimated among SST traits (> 0.78) and among TV traits (> 0.75). Similarly, high genetic correlations were also estimated for RR with PS (0.87 ± 0.02), with BCS measures (0.92 ± 0.04), and with ear measures (0.95 ± 0.03). Low to moderate positive genetic correlations were estimated between SST and TV (from 0.25 ± 0.04 to 0.76 ± 0.07). Low genetic correlations were estimated between TV and BCS (from - 0.01 ± 0.08 to 0.06 ± 0.07). Respiration efficiency was estimated to be positively and moderately correlated with RR (0.36 ± 0.04), PS (0.56 ± 0.03), and BCS (0.56 ± 0.05 for caliper measurements and 0.50 ± 0.05 for the visual assessments). All other trait combinations were lowly genetically correlated. CONCLUSIONS: A comprehensive landscape of heritabilities and genetic correlations for various thermotolerance indicators in lactating sows were estimated. All traits evaluated are under genetic control and heritable, with different magnitudes, indicating that genetic progress is possible for all of them. The genetic correlation estimates provide evidence for the complex relationships between these traits and confirm the importance of a sub-index of thermotolerance traits to improve heat tolerance in pigs.

Evaluating phenotypes associated with heat tolerance and identifying moderate and severe heat stress thresholds in lactating sows housed in mechanically or naturally ventilated barns during the summer under commercial conditions.

An accurate understanding of heat stress (HS) temperatures and phenotypes that indicate HS tolerance is necessary to improve swine HS resilience. Therefore, the study objectives were 1) to identify phenotypes indicative of HS tolerance, and 2) to determine moderate and severe HS threshold temperatures in lactating sows. Multiparous (4.10 ± 1.48) lactating sows and their litters (11.10 ± 2.33 piglets/litter) were housed in naturally ventilated (n = 1,015) or mechanically ventilated (n = 630) barns at a commercial sow farm in Maple Hill, NC, USA between June 9 and July 24, 2021. In-barn dry bulb temperatures (TDB) and relative humidity were continuously recorded for naturally ventilated (26.38 ± 1.21 °C and 83.38 ± 5.40%, respectively) and mechanically ventilated (26.91 ± 1.80 °C and 77.13 ± 7.06%, respectively) barns using data recorders. Sows were phenotyped between lactation days 11.28 ± 3.08 and 14.25 ± 3.26. Thermoregulatory measures were obtained daily at 0800, 1200, 1600, and 2000 h and included respiration rate, and ear, shoulder, rump, and tail skin temperatures. Vaginal temperatures (TV) were recorded in 10 min intervals using data recorders. Anatomical characteristics were recorded, including ear area and length, visual and caliper-assessed body condition scores, and a visually assessed and subjective hair density score. Data were analyzed using PROC MIXED to evaluate the temporal pattern of thermoregulatory responses, phenotype correlations were based on mixed model analyses, and moderate and severe HS inflection points were established by fitting TV as the dependent variable in a cubic function against TDB. Statistical analyses were conducted separately for sows housed in mechanically or naturally ventilated barns because the sow groups were not housed in each facility type simultaneously. The temporal pattern of thermoregulatory responses was similar for naturally and mechanically ventilated barns and several thermoregulatory and anatomical measures were significantly correlated with one another (P < 0.05), including all anatomical measures as well as skin temperatures, respiration rates, and TV. For sows housed in naturally and mechanically ventilated facilities, moderate HS threshold TDB were 27.36 and 26.69 °C, respectively, and severe HS threshold TDB were 29.45 and 30.60 °C, respectively. In summary, this study provides new information on the variability of HS tolerance phenotypes and environmental conditions that constitute HS in commercially housed lactating sows.

Climate change and the associated increase in global temperatures have a well-described negative impact on swine production. Therefore, improving swine heat stress resilience is of utmost importance to reduce the deleterious effects of heat stress on swine health, performance, and welfare. Genomic selection for heat stress resilience may be a viable strategy to improve swine productivity in a changing climate. However, identifying environmental conditions that constitute heat stress and deriving novel traits that can be easily collected on farm and provide accurate and precise predictions of heat stress tolerance is a necessary step. The present study demonstrated that housing conditions had a limited influence on heat stress tolerance phenotypes, several anatomical and thermoregulatory measures were correlated, and housing conditions impacted heat stress threshold temperatures. Results from this study may be applied to large-scale phenotyping initiatives to develop or refine genomic selection indexes for heat stress resilience in pigs.

E.L., a modern-day Phineas Gage: Revisiting frontal lobe injury.

Background: How the prefrontal cortex (PFC) recovers its functionality following lesions remains a conundrum. Recent work has uncovered the importance of transient low-frequency oscillatory activity (LFO; < 4 Hz) for the recovery of an injured brain. We aimed to determine whether persistent cortical oscillatory dynamics contribute to brain capability to support 'normal life' following injury. Methods: In this 9-year prospective longitudinal study (08/2012-2021), we collected data from the patient E.L., a modern-day Phineas Gage, who suffered from lesions, impacting 11% of his total brain mass, to his right PFC and supplementary motor area after his skull was transfixed by an iron rod. A systematic evaluation of clinical, electrophysiologic, brain imaging, neuropsychological and behavioural testing were used to clarify the clinical significance of relationship between LFO discharge and executive dysfunctions and compare E.L.´s disorders to that attributed to Gage (1848), a landmark in the history of neurology and neuroscience. Findings: Selective recruitment of the non-injured left hemisphere during execution of unimanual right-hand movements resulted in the emergence of robust LFO, an EEG-detected marker for disconnection of brain areas, in the damaged right hemisphere. In contrast, recruitment of the damaged right hemisphere during contralateral hand movement, resulted in the co-activation of the left hemisphere and decreased right hemisphere LFO to levels of controls enabling performance, suggesting a target for neuromodulation. Similarly, transcranial magnetic stimulation (TMS), used to create a temporary virtual-lesion over E.L.'s healthy hemisphere, disrupted the modulation of contralateral LFO, disturbing behaviour and impairing executive function tasks. In contrast to Gage, reasoning, planning, working memory, social, sexual and family behaviours eluded clinical inspection by decreasing LFO in the delta frequency range during motor and executive functioning. Interpretation: Our study suggests that modulation of LFO dynamics is an important mechanism by which PFC accommodates neurological injuries, supporting the reports of Gage´s recovery, and represents an attractive target for therapeutic interventions. Funding: Fundação de Amparo Pesquisa Rio de Janeiro (FAPERJ), Universidade Federal do Rio de Janeiro (intramural), and Fiocruz/Ministery of Health (INOVA Fiocruz).

Genotype-by-environment interactions for reproduction, body composition, and growth traits in maternal-line pigs based on single-step genomic reaction norms.

BACKGROUND: There is an increasing need to account for genotype-by-environment (G × E) interactions in livestock breeding programs to improve productivity and animal welfare across environmental and management conditions. This is even more relevant for pigs because selection occurs in high-health nucleus farms, while commercial pigs are raised in more challenging environments. In this study, we used single-step homoscedastic and heteroscedastic genomic reaction norm models (RNM) to evaluate G × E interactions in Large White pigs, including 8686 genotyped animals, for reproduction (total number of piglets born, TNB; total number of piglets born alive, NBA; total number of piglets weaned, NW), growth (weaning weight, WW; off-test weight, OW), and body composition (ultrasound muscle depth, MD; ultrasound backfat thickness, BF) traits. Genetic parameter estimation and single-step genome-wide association studies (ssGWAS) were performed for each trait. RESULTS: The average performance of contemporary groups (CG) was estimated and used as environmental gradient in the reaction norm analyses. We found that the need to consider heterogeneous residual variance in RNM models was trait dependent. Based on estimates of variance components of the RNM slope and of genetic correlations across environmental gradients, G × E interactions clearly existed for TNB and NBA, existed for WW but were of smaller magnitude, and were not detected for NW, OW, MD, and BF. Based on estimates of the genetic variance explained by the markers in sliding genomic windows in ssGWAS, several genomic regions were associated with the RNM slope for TNB, NBA, and WW, indicating specific biological mechanisms underlying environmental sensitivity, and dozens of novel candidate genes were identified. Our results also provided strong evidence that the X chromosome contributed to the intercept and slope of RNM for litter size traits in pigs. CONCLUSIONS: We provide a comprehensive description of G × E interactions in Large White pigs for economically-relevant traits and identified important genomic regions and candidate genes associated with GxE interactions on several autosomes and the X chromosome. Implementation of these findings will contribute to more accurate genomic estimates of breeding values by considering G × E interactions, in order to genetically improve the environmental robustness of maternal-line pigs.

Genetic Diversity and Signatures of Selection for Thermal Stress in Cattle and Other Two Bos Species Adapted to Divergent Climatic Conditions.

Understanding the biological mechanisms of climatic adaptation is of paramount importance for the optimization of breeding programs and conservation of genetic resources. The aim of this study was to investigate genetic diversity and unravel genomic regions potentially under selection for heat and/or cold tolerance in thirty-two worldwide cattle breeds, with a focus on Chinese local cattle breeds adapted to divergent climatic conditions, Datong yak (Bos grunniens; YAK), and Bali (Bos javanicus) based on dense SNP data. In general, moderate genetic diversity levels were observed in most cattle populations. The proportion of polymorphic SNP ranged from 0.197 (YAK) to 0.992 (Mongolian cattle). Observed and expected heterozygosity ranged from 0.023 (YAK) to 0.366 (Sanhe cattle; SH), and from 0.021 (YAK) to 0.358 (SH), respectively. The overall average inbreeding (±SD) was: 0.118 ± 0.028, 0.228 ± 0.059, 0.194 ± 0.041, and 0.021 ± 0.004 based on the observed versus expected number of homozygous genotypes, excess of homozygosity, correlation between uniting gametes, and runs of homozygosity (ROH), respectively. Signatures of selection based on multiple scenarios and methods (F ST, HapFLK, and ROH) revealed important genomic regions and candidate genes. The candidate genes identified are related to various biological processes and pathways such as heat-shock proteins, oxygen transport, anatomical traits, mitochondrial DNA maintenance, metabolic activity, feed intake, carcass conformation, fertility, and reproduction. This highlights the large number of biological processes involved in thermal tolerance and thus, the polygenic nature of climatic resilience. A comprehensive description of genetic diversity measures in Chinese cattle and YAK was carried out and compared to 24 worldwide cattle breeds to avoid potential biases. Numerous genomic regions under positive selection were detected using three signature of selection methods and candidate genes potentially under positive selection were identified. Enriched function analyses pinpointed important biological pathways, molecular function and cellular components, which contribute to a better understanding of the biological mechanisms underlying thermal tolerance in cattle. Based on the large number of genomic regions identified, thermal tolerance has a complex polygenic inheritance nature, which was expected considering the various mechanisms involved in thermal stress response.

Use of polyphenols as a strategy to prevent bond degradation in the dentin-resin interface.

This study evaluated the effect of dentin pretreatment with the polyphenols quercetin and resveratrol on the resin-dentin microtensile bonding strength (µTBS) and collagen fibrils stability of the adhesive interface. Different concentrations (100, 250, 500, or 1,000 µg ml-1 ) of quercetin or resveratrol, or a mixture of quercetin and resveratrol (3:1, 1:1, 1:3; vol:vol), as well as distilled water or 2% chlorhexidine digluconate, were applied to etched dentin. Then, a two-step etch-and-rinse adhesive was applied followed by composite restoration. Measurements of resin-dentin µTBS were made after 1 and 120 d. The stability of collagen fibrils in the hybrid layer was evaluated using transmission electron microscopy. The Student's t-test and two-way factorial anova with Tukey's test were used to analyze the effects of dentin pretreatment and storage time on µTBS values. Comparisons between µTBS measurements made on 1 and 120 d showed that resveratrol had the best performance, with significantly higher µTBS values after 120 d for all concentrations of resveratrol tested. Quercetin pretreatment resulted in a significant rise of µTBS when used at concentrations of 100 and 500 µg ml-1 . Quercetin + resveratrol at the ratio of 1:1 performed better than when used at ratios of either 3:1 or 1:3. Resveratrol might represent a potential approach to achieve desirable bonding stability and reduce the frequent replacement of composite restorations.

Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus.

AIMS: Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation. Abnormal miRNA expressions have been described in autoimmune diseases and T1DM. Polymorphisms in genes codifying miRNAs may alter the expression of the corresponding miRNA and, thus, confer susceptibility for a given disease. Therefore, the aim of this study was to investigate whether polymorphisms in genes encoding miR-155, miR-146a, and miR-375 are associated with T1DM. METHODS: Frequencies of the miRNA-146a rs2910164, miRNA-155 rs767649 and miRNA-375 rs6715345 polymorphisms were analyzed in 490 T1DM patients and in 469 nondiabetic subjects. RESULTS: The miR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM, and the strongest association was observed for the dominant model [odds ratio (OR) = 0.557 95% CI 0.355-0.874 and OR = 0.508, 95% CI 0.265-0.973, respectively, after adjustment for age, ethnicity, and risk HLA loci]. However, miR-375 rs6715345 frequencies did not differ between cases and controls. CONCLUSION: MiR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM.