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Topic:Physiology

The physiology of horses encompasses the study of the biological functions and processes that occur within the equine body. This includes the examination of various systems such as the cardiovascular, respiratory, musculoskeletal, digestive, and nervous systems. Understanding equine physiology is essential for comprehending how horses adapt to different environmental conditions, perform physical activities, and respond to health challenges. Research in this field often focuses on the mechanisms of energy metabolism, thermoregulation, and muscle function during exercise, as well as the physiological responses to stress and disease. This page compiles peer-reviewed research studies and scholarly articles that explore the diverse aspects of equine physiology, providing insights into the biological processes that support the health and performance of horses.
Intracellular calcium chelating agent (BAPTA-AM) aids stallion semen cooling and freezing-thawing.
Reproduction in domestic animals = Zuchthygiene    July 9, 2018   Volume 53, Issue 5 1235-1242 doi: 10.1111/rda.13245
Wu S, Canisso IF, Yang W, Ul Haq I, Liu Q, Han Y, Zeng S.This study aimed to investigate the effects of different concentrations of 1,2-bis-(o-aminophenoxy)-ethane-N,N,N0 N0-tetraacetic acid, tetra-acetoxymethyl ester (BAPTA-AM), an intracellular calcium chelating agent, on stallion semen cooling and freezing-thawing. After collection, semen was extended (1:1 v/v) on a skim milk-based extender, centrifuged and resuspended at 400 million/ml into cooling or freezing extenders containing 0, 5, 25, 50, 100 and 200 μΜ BAPTA-AM. Motility parameters were assessed after cooling in Equitainer at 5°C for 12, 24, 48, 72 and 120 hr and after freezing-tha...
Physiological costs of infection: herpesvirus replication is linked to blood oxidative stress in equids.
Scientific reports    July 9, 2018   Volume 8, Issue 1 10347 doi: 10.1038/s41598-018-28688-0
Costantini D, Seeber PA, Soilemetzidou SE, Azab W, Bohner J, Buuveibaatar B, Czirják GÁ, East ML, Greunz EM, Kaczensky P, Lamglait B, Melzheimer J....Viruses may have a dramatic impact on the health of their animal hosts. The patho-physiological mechanisms underlying viral infections in animals are, however, not well understood. It is increasingly recognized that oxidative stress may be a major physiological cost of viral infections. Here we compare three blood-based markers of oxidative status in herpes positive and negative individuals of the domestic horse (Equus ferus caballus) and of both captive and free-ranging Mongolian khulan (Equus hemionus hemionus) and plains zebra (Equus quagga). Herpes positive free-ranging animals had signifi...
Comparison of Enterprise Point-of-Care and Nova Biomedical Critical Care Xpress analyzers for determination of arterial pH, blood gas, and electrolyte values in canine and equine blood.
Veterinary clinical pathology    July 9, 2018   Volume 47, Issue 3 415-424 doi: 10.1111/vcp.12635
Elmeshreghi TN, Grubb TL, Greene SA, Ragle CA, Wardrop JA.Point-of-care analyzers can provide a rapid turnaround time for critical blood test results. Agreement between the Enterprise Point-of-Care (EPOC) and bench-top laboratory analyzers is important to determine the clinical reliability of the EPOC. Objective: The aim of the study was (1) to evaluate the precision (repeatability) of blood gas values measured by the EPOC and (2) to determine the level of agreement between the EPOC and Nova Critical Care Express (Nova CCX) for the assessment of arterial pH, blood gases, and electrolyte variables in canine and equine blood. Methods: Arterial blood sa...
Rifaximin anti-inflammatory activity on bovine endometrium primary cell cultures: a preliminary study.
Veterinary medicine and science    July 9, 2018   Volume 4, Issue 4 326-332 doi: 10.1002/vms3.115
Flammini L, Mantelli L, Volpe A, Domenichini G, Di Lecce R, Dondi M, Cantoni AM, Barocelli E, Quintavalla F.Rifaximin is an unabsorbed oral antibiotic showing anti-inflammatory properties in human pathologies like irritable bowel syndrome and inflammatory bowel disease. In veterinary medicine, rifaximin is primarily used in the treatment of dermatological diseases in all animal species, in therapy and prophylaxis of mastitis in cows and in the treatment of endometritis in cattle and horses. The aim of this preliminary study was to evaluate the anti-inflammatory properties of rifaximin on primary cell cultures from bovine endometrium in which inflammatory response was induced by Lipopolysaccaride (LP...
Expression of activin receptors in the equine uteroplacental tissue: an immunohistochemical analysis.
Journal of equine science    July 6, 2018   Volume 29, Issue 2 33-37 doi: 10.1294/jes.29.33
Kimura Y, Sasaki M, Watanabe K, Dhakal P, Sato F, Taya K, Nambo Y.Activin is secreted from equine uterine glands and plays important roles in establishment and maintenance of pregnancy in mares. This study aimed to localize activin receptors (ActRs) IA/B and IIA/B using immunohistochemistry in the uteroplacental tissues of seven pregnant Thoroughbred mares. At the time of tissue collection, the mares were at the following days of pregnancy: 88, 120, 161, 269, 290, 313, and 335 days. We fixed the uteroplacental tissues in 4% paraformaldehyde and obtained serial sections that were subsequently stained for analysis. All four isoforms of ActR were expressed in t...
Treating insect bite hypersensitivity in horses by using active vaccination against IL-5.
The Journal of allergy and clinical immunology    July 5, 2018   Volume 142, Issue 4 1060-1061 doi: 10.1016/j.jaci.2018.06.031
Wu AY, Sur S, Grant JA.No abstract available
Attentional state and brain processes: state-dependent lateralization of EEG profiles in horses.
Scientific reports    July 5, 2018   Volume 8, Issue 1 10153 doi: 10.1038/s41598-018-28334-9
Rochais C, Sébilleau M, Menoret M, Oger M, Henry S, Hausberger M, Cousillas H.Lateralization of brain functions has been suggested to provide individuals with advantages, such as an increase of neural efficiency. The right hemisphere is likely to be specialized for processing attention for details and the left hemisphere for categorization of stimuli. Thus attentional processes actually may underlie lateralization. In the present study, we hypothesized that the attentional state of horses could be reflected in the lateralization of brain responses. We used i) a recently developed attention test to measure horses' visual attentional responses towards a standardized stimu...
Concentrations of non-permeable cryoprotectants and equilibration temperatures are key factors for stallion sperm vitrification success.
Animal reproduction science    June 30, 2018   Volume 196 91-98 doi: 10.1016/j.anireprosci.2018.06.022
Hidalgo M, Consuegra C, Dorado J, Diaz-Jimenez M, Ortiz I, Pereira B, Sanchez R, Crespo F.Vitrification is based on rapid freezing by direct exposure of sperm to liquid nitrogen (LN). This study evaluated the effect of non-permeable CPAs and equilibration temperature on stallion sperm quality after vitrification. In Experiment 1, different concentrations of sucrose (20, 50, 100 mM; mmol/L) and bovine serum albumin (BSA 1%, 5%, 10%) were compared including different temperatures for the equilibration (≈22 °C or 5 °C). Vitrification was performed dropping 30 μl sperm suspension directly into LN In Experiment 2, conventional sperm freezing using 2.2% of glycerol in 0.5 ...
Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.
PloS one    June 29, 2018   Volume 13, Issue 6 e0200070 doi: 10.1371/journal.pone.0200070
de Laat MA, Kheder MH, Pollitt CC, Sillence MN.Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated. It would be useful to be able to attenuate the large post-prandial insulin response that typically occurs when a carbohydrate-rich meal is fed to insulin-dysregulated horses. Here we have determined the efficacy of two T1R2/3 inhibitors, lactisole and Gymnema sylvestre, for reducing glucose upta...
Echocardiographic identification of atrial-related structures and vessels in horses validated by computed tomography of casted hearts.
Equine veterinary journal    June 29, 2018   Volume 51, Issue 1 90-96 doi: 10.1111/evj.12969
Vandecasteele T, Cornillie P, van Steenkiste G, Vandevelde K, Gielen I, Vanderperren K, van Loon G.Echocardiography is the imaging technique of choice for the equine heart. Nevertheless, knowledge about ultrasonographic identification of dorsally located structures and vessels, related to the atria, in horses is scarce. Objective: To describe the echocardiographic approach and the identification of structures and vessels in relation to the atria in healthy horses. Methods: CT images from two equine hearts, casted with self-expanding foam, were segmented and used to identify atrial-related structures and vessels. These images were compared with standard and nonstandard ultrasound images from...
The Fate of Autologous Endometrial Mesenchymal Stromal Cells After Application in the Healthy Equine Uterus.
Stem cells and development    June 29, 2018   Volume 27, Issue 15 1046-1052 doi: 10.1089/scd.2018.0056
Rink BE, Beyer T, French HM, Watson E, Aurich C, Donadeu FX.Because of their distinct differentiation, immunomodulatory, and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded, and fluorescence labeled in culture. Phosphate-buffered saline (PBS) or MSCs (15 × 10) were autologously infused into ea...
Causal and functional interpretation of mu- and delta-opioid receptor profiles in mesoaccumbens and nigrostriatal pathways of an oral stereotypy phenotype.
Behavioural brain research    June 28, 2018   Volume 353 108-113 doi: 10.1016/j.bbr.2018.06.031
Hemmings A, Parker MO, Hale C, McBride SD.Spontaneous stereotypic behaviours are repetitive, compulsive, topographically invariant response patterns commonly observed in captive or domestic animals, which have been linked to dysfunction of basal ganglia input/output pathways. There is evidence that endogenous opioids play a key regulatory role in basal ganglia direct and indirect pathways, but their precise role, both causally and functionally, in spontaneous stereotypic behaviour is unclear. Here we examined the profile of mu- and delta-opioid receptors (density [Bmax] and affinity [Kd]) of basal ganglia structures in stereotypy (n...
Synovial nerve fiber density decreases with naturally-occurring osteoarthritis in horses.
Osteoarthritis and cartilage    June 26, 2018   Volume 26, Issue 10 1379-1388 doi: 10.1016/j.joca.2018.06.006
Pujol R, Girard CA, Richard H, Hassanpour I, Binette MP, Beauchamp G, McDougall JJ, Laverty S.To measure the nerve fiber density in synovial membranes from healthy and OA equine joints and to investigate the relationship between synovial innervation and OA severity, synovial vascularity and synovitis. Twenty-five equine metacarpophalangeal joints were collected post-mortem. The joints were dissected and the macroscopic lesions of the articular cartilage were scored. Synovial membrane specimens (n = 50) were harvested, fixed, sectioned and scored histologically. Immunohistochemical staining and immunofluorescence with S-100 protein, that identifies nerve fibers, and ⍺-actin, that st...
Expression of glucose transporters in the endometrium and early conceptus membranes of the horse.
Placenta    June 25, 2018   Volume 68 23-32 doi: 10.1016/j.placenta.2018.06.308
Gibson C, de Ruijter-Villani M, Rietveld J, Stout TAE.Glucose is the primary energy substrate for early conceptus development and, for the first 40 days of gestation, the equine conceptus depends solely on glucose available in the histotroph; thereafter, histotrophic glucose provision continues to support transport across the definitive placenta. To investigate glucose provision routes during early equine pregnancy we examined expression of glucose transporters in conceptus membranes and endometrium recovered on days 7, 14, 21 and 28 after ovulation. To further differentiate the contributions of maternal progesterone priming and conceptus-endomet...
Genome data uncover four synergistic key regulators for extremely small body size in horses.
BMC genomics    June 25, 2018   Volume 19, Issue 1 492 doi: 10.1186/s12864-018-4877-5
Metzger J, Rau J, Naccache F, Bas Conn L, Lindgren G, Distl O.Miniature size in horses represents an extreme reduction of withers height that originated after domestication. In some breeds, it is a highly desired trait representing a breed- or subtype-specific feature. The genomic changes that emerged due to strong-targeted selection towards this distinct type remain unclear. Results: Comparisons of whole-genome sequencing data from two Miniature Shetland ponies and one standard-sized Shetland pony, performed to elucidate genetic determinants for miniature size, revealed four synergistic variants, limiting withers height to 34.25 in. (87 cm). Runs of h...
Alterations in Metabolic Status and Headshaking Behavior Following Intravenous Administration of Hypertonic Solutions in Horses with Trigeminal-Mediated Headshaking.
Animals : an open access journal from MDPI    June 25, 2018   Volume 8, Issue 7 doi: 10.3390/ani8070102
Sheldon S, Aleman M, Costa L, Santoyo AC, Howey Q, Madigan J.Trigeminal-nerve-mediated headshaking represents a major welfare challenge for owners and veterinarians and is caused by a low threshold firing of the trigeminal nerve resulting in pain manifested as violent head jerking that often terminates the horse’s career and life due to poor quality of life and suffering. As metabolic changes such as acid⁻base status and electrolytes play a role in nerve firing, this study sought to assess the effects following administration of hypertonic solutions on headshaking behavior in affected horses. This prospective randomized controlled crossover desi...
Addition of seminal plasma to thawed stallion spermatozoa did not repair cryoinjuries.
Animal reproduction science    June 25, 2018   Volume 196 48-58 doi: 10.1016/j.anireprosci.2018.06.018
Al-Essawe EM, Johannisson A, Wulf M, Aurich C, Morrell JM.Freezing and thawing processes induce structural and functional damage to sperm plasma membranes and internal organelles. Adding seminal plasma (SP) has been found to minimize or repair the cryoinjuries in some species. The objective of this study was to investigate whether adding SP from stallions of known freezability after thawing could repair cryoinjuries. Semen was collected from warmblood stallions (n = 8, three ejaculates/stallion) and processed by Single Layer Centrifugation (SLC) to remove SP prior to freezing. Pooled SP (5%) from bad freezer (BF) or good freezer (GF) stallions wa...
Carnosine as malondialdehyde scavenger in stallion seminal plasma and its role in sperm function and oxidative status.
Theriogenology    June 23, 2018   Volume 119 10-17 doi: 10.1016/j.theriogenology.2018.06.016
Rocha CC, Kawai GKV, de Agostini Losano JD, Angrimani DSR, Rui BR, de Cássia Bicudo L, da Silva BDCS, Alonso MA, Mendes CM....Semen biotechniques may impair sperm quality due to excessive production of reactive oxygen species (ROS). Additionally, products of the oxidative reaction, especially involving lipids (e.g., malondialdehyde - MDA), may be even more harmful to sperm. Carnosine, previously reported to be present in seminal plasma of several species, may be a key factor on sperm tolerance to biotechniques by counterattacking the deleterious influence of MDA. Therefore, the aim of this study was to measure the levels of carnosine present in equine seminal plasma and relate these findings with sperm function and o...
Cell specific microvesicles vary with season and disease predisposition in healthy and previously laminitic ponies.
Veterinary immunology and immunopathology    June 23, 2018   Volume 202 85-92 doi: 10.1016/j.vetimm.2018.06.001
Finding EJT, Lawson C, Elliott J, Harris PA, Menzies-Gow NJ.Microvesicles are small (up to 1 μm) vesicles found in plasma and other bodily fluids. They are recognised as part of the normal system of inter-cellular communication but altered numbers are also used as biomarkers of disease. Microvesicles have not been studied in detail in the horse but may be relevant to diseases such as laminitis. Identification of equine cell specific microvesicles was performed by developing a panel of cross reactive antibodies to use in flow cytometry to detect microvesicles of platelet, leucocyte and endothelial origin in plasma from healthy ponies and those predis...
Impact of Equine and Bovine Oocyte Maturation in Follicular Fluid From Young and Old Mares on Embryo Production in Vitro.
Journal of equine veterinary science    June 22, 2018   Volume 68 94-100 doi: 10.1016/j.jevs.2018.04.009
Spacek SG, Carnevale EM.Equine follicular fluid (FF) provides autocrine and paracrine factors from theca, granulosa, and cumulus cells, both reflecting and impacting oocyte and follicle maturation. We hypothesized that maturation of oocytes in FF from old versus young mares has a deleterious effect on oocyte maturation and their subsequent developmental potential. Follicular fluid was collected from the large, dominant follicle from young mares (4-13 years) or old mares (21-26 years) and classified as: (1) Noninduced follicular fluid (NFF), FF from noninduced follicle 33 ± 3 mm, or (2) Induced follicular fluid (I...
Male Flat Jockeys Do Not Display Deteriorations in Bone Density or Resting Metabolic Rate in Accordance With Race Riding Experience: Implications for RED-S.
International journal of sport nutrition and exercise metabolism    June 22, 2018   Volume 28, Issue 4 434-439 doi: 10.1123/ijsnem.2017-0371
Wilson G, Martin D, Morton JP, Close GL.Despite consistent reports of poor bone health in male jockeys, it is not yet known if this is a consequence of low energy availability or lack of an osteogenic stimulus. Given the rationale that low energy availability is a contributing factor in low bone health, we tested the hypothesis that both hip and lumbar bone mineral density (BMD) should progressively worsen in accordance with the years of riding. In a cross-sectional design, male apprentice (n = 17) and senior (n = 14) jockeys (matched for body mass and fat-free mass) were assessed for hip and lumbar spine BMD, as well as bot...
Glycosphingolipids of porcine, bovine, and equine pericardia as potential immune targets in bioprosthetic heart valve grafts.
Xenotransplantation    June 22, 2018   Volume 25, Issue 5 e12406 doi: 10.1111/xen.12406
Barone A, Benktander J, Whiddon C, Jin C, Galli C, Teneberg S, Breimer ME.Pericardial tissue from various animal species is utilized for the production of the bioprosthetic heart valves (BHV) used clinically. Experimental data show that the eventual breakdown of BHV is partly due to immunological interactions with carbohydrate tissue antigens. To understand these processes, we have examined the glycolipid-based carbohydrate antigens in naïve porcine, bovine, and equine pericardia. Total non-acid and acid glycosphingolipid fractions were isolated from porcine, bovine, and equine pericardia, and individual glycolipid compounds were characterized by thin-layer chromat...
Determination of body proportion factor in draft horses for the use of bioimpedance spectroscopy.
The Canadian veterinary journal = La revue veterinaire canadienne    June 19, 2018   Volume 59, Issue 6 650-653 
Greco-Otto PR, Léguillette R.Bioelectrical impedance spectroscopy (BIS) instantly assesses body composition to monitor the effects of diet, competition, and illness, though it requires a body proportion factor (Kb). This study aimed to validate a draft horse-specific Kb. The calculated Kb was 1.42, resulting in significantly lower body composition values, with the exception of fat mass. Une spectroscopie de bio-impédance bioélectrique (SBB) évalue instantanément la composition corporelle pour surveiller les effets de la diète, de la compétition et de la maladie, même si elle exige un facteur de proportion corporel...
Amino acid transporter expression in the endometrium and conceptus membranes during early equine pregnancy.
Reproduction, fertility, and development    June 16, 2018   Volume 30, Issue 12 1675-1688 doi: 10.1071/RD17352
Gibson C, de Ruijter-Villani M, Rietveld J, Stout TAE.Maternally derived amino acids (AA) are essential for early conceptus development, and specific transporters enhance histotrophic AA content during early ruminant pregnancy. In the present study we investigated AA transporter expression in early equine conceptuses and endometrium, during normal pregnancy and after induction of embryo-uterus asynchrony. 'Normal' conceptuses and endometrium were recovered on Days 7, 14, 21 and 28 after ovulation. To investigate asynchrony, Day 8 embryos were transferred to recipient mares on Day 8 or Day 3, and conceptuses were recovered 6 or 11 days later. Endo...
[Clinical signs in late pregnant mares].
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    June 14, 2018   Volume 46, Issue 3 164-171 doi: 10.15653/TPG-180125
Neuhauser S, Gösele P, Handler J.During the peripartal period, interpretation of basic clinical signs may be challenging. In the present study, heart rate (HR), respiratory rate (RR) and body temperature (BT) were evaluated in healthy mares of different breed types and compared to reference values for adult horses from the literature. Methods: During daily physical exams of periparturient mares, the HR, RR and BT were evaluated. Differences according to the horse's size were investigated and in large breeds, the influence of dystocia or retained placenta was analysed. Results: During the last weeks before parturition (a. p.),...
Effects of mares’ age and day of gestation on efficacy of transvaginal ultrasound-guided twin reduction.
Tierarztliche Praxis. Ausgabe G, Grosstiere/Nutztiere    June 14, 2018   Volume 46, Issue 3 172-177 doi: 10.15653/TPG-170741
Rau J, Tiedemann D, Sielhorst J, Tönissen A, Burger D, Martinsson G, Rohn K, Oldenhof H, Sieme H.Transvaginal ultrasound-guided aspiration (TUA) is a procedure which can be used for the reduction of twins post-fixation in the mare. The aim of this study was to evaluate the effect of the age of mares and the day of gestation on the outcome of TUA treatment. Methods: In 88 mares, diagnosed pregnant with twins, TUA of the yolk sac or allantoic fluid was performed between day 30 and 62 of gestation. Mares were aged 3-22 years. Ultrasonographic examination for a viable singleton pregnancy was performed by referring veterinarians 5-7 days and 4 weeks after TUA. Based on reported findings, effec...
Using the indicator amino acid oxidation technique to study threonine requirements in horses receiving a predominantly forage diet.
Journal of animal physiology and animal nutrition    June 14, 2018   Volume 102, Issue 5 1366-1381 doi: 10.1111/jpn.12927
Mok CH, Levesque CL, Urschel KL.Threonine has been reported to be the second limiting amino acid in typical equine diets, but its actual requirement has not been determined in horses. To evaluate amino acid metabolism and requirements, the indicator amino acid oxidation (IAAO) method has been successfully used in other species. The objective of this research was to estimate threonine requirements in mature horses fed timothy hay and concentrate in 4:1 ratio using the IAAO method. Six Thoroughbred mares (579.9 ± 46.7 kg) received each of 6 levels of threonine intake, 41, 51, 61, 70, 80 and 89 mg/kg BW/day, in a randomly ...
Spatial distribution of preantral follicles in the equine ovary.
PloS one    June 13, 2018   Volume 13, Issue 6 e0198108 doi: 10.1371/journal.pone.0198108
Alves BG, Alves KA, Gastal GDA, Gastal MO, Figueiredo JR, Gastal EL.Comprehensive studies on spatial distribution of preantral follicles in the ovary are scarce. Considering that preantral follicles represent the main ovarian reserve, harvesting of these follicles is crucial for the development/use of assisted reproductive techniques. Therefore, knowledge on follicle spatial distribution can be helpful for targeting areas with richer number of preantral follicles through biopsy procedures. The aim of this study was to assess the distribution and localization of equine preantral follicles according to: (i) age, (ii) ovarian portion (lateral and intermediary) an...
Equine mesenchymal stromal cells from different tissue sources display comparable immune-related gene expression profiles in response to interferon gamma (IFN)-γ.
Veterinary immunology and immunopathology    June 11, 2018   Volume 202 25-30 doi: 10.1016/j.vetimm.2018.06.008
Cassano JM, Fortier LA, Hicks RB, Harman RM, Van de Walle GR.Mesenchymal stromal cells (MSC) have the therapeutic potential to decrease inflammation due to their immunomodulatory properties. They can be isolated from various tissue sources such as bone marrow, adipose tissue, and blood, but it is unknown how the tissue source of origin affects the responses of MSC to inflammatory stimuli. Here, we conceptually addressed this question by evaluating the immune-related gene expression profiles of equine MSC from different tissue sources in response to interferon gamma (IFN-γ) stimulation, with the goal to determine if there is a preferable MSC source for ...
Sensory laterality in affiliative interactions in domestic horses and ponies (Equus caballus).
Animal cognition    June 9, 2018   Volume 21, Issue 5 631-637 doi: 10.1007/s10071-018-1196-9
Farmer K, Krüger K, Byrne RW, Marr I.Many studies have been carried out into both motor and sensory laterality of horses in agonistic and stressful situations. Here we examine sensory laterality in affiliative interactions within four groups of domestic horses and ponies (N = 31), living in stable social groups, housed at a single complex close to Vienna, Austria, and demonstrate for the first time a significant population preference for the left side in affiliative approaches and interactions. No effects were observed for gender, rank, sociability, phenotype, group, or age. Our results suggest that right hemisphere specializ...
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