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Topic:Genetics

Genetics in horses encompasses the study of hereditary traits and the genetic makeup that influences various characteristics and health conditions in equine populations. This field involves the analysis of genes and their functions, inheritance patterns, and the impact of genetic variations on traits such as coat color, performance ability, and susceptibility to diseases. Research in equine genetics employs techniques such as genome mapping, sequencing, and genetic testing to identify specific genes and mutations associated with these traits. This page gathers peer-reviewed research studies and scholarly articles that explore the genetic basis of equine traits, the methodologies used in genetic research, and the implications for breeding, health management, and conservation of horse breeds.
New methods for isolation of keratolytic bacteria inducing intractable hoof wall cavity (Gidoh) in a horse; double screening procedures of the horn powder agar-translucency test and horn zymography.
Journal of equine science    March 28, 2017   Volume 28, Issue 1 19-25 doi: 10.1294/jes.28.19
Kuwano A, Niwa H, Arai K.To establish a new system to isolate keratolytic bacteria from the hoof wall cavity () of a racehorse, we invented the horn powder agar-translucency (HoPAT) test and horn zymography (HZ). Using routine bacteriological techniques and these methods, we isolated five strains of keratolytic soil bacteria, which were then identified by means of 16S ribosomal RNA (rRNA) gene sequencing analysis. The findings from the study on the horse suggested that Brevibacterium luteolum played the main role in the local fragility of the hoof, eventually forming a in coordination with four other strains of kerat...
Covalent conjugation of the equine infectious anemia virus Gag with SUMO.
Biochemical and biophysical research communications    March 22, 2017   Volume 486, Issue 3 712-719 doi: 10.1016/j.bbrc.2017.03.103
Wang J, Wen S, Zhao R, Qi J, Liu Z, Li W, An J, Wood C, Wang Y.The conjugation of small ubiquitin-like modifier (SUMO) to the target protein, namely, SUMOylation, is involved in the regulation of many important biological events including host-pathogen interaction. Some viruses have evolved to exploit the host SUMOylation machinery to modify their own protein. Retroviral Gag protein plays critical roles in the viral life cycle. The HIV-1 p6 and the Moloney murine leukemia virus CA have been reported to be conjugated with SUMO. In this study, we report for the first time, to our knowledge, the covalent conjugation of equine infectious anemia virus (EIAV) G...
Genome-Wide Identification and Evolutionary Analysis of Sarcocystis neurona Protein Kinases.
Pathogens (Basel, Switzerland)    March 21, 2017   Volume 6, Issue 1 12 doi: 10.3390/pathogens6010012
Murungi EK, Kariithi HM.The apicomplexan parasite Sarcocystis neurona causes equine protozoal myeloencephalitis (EPM), a degenerative neurological disease of horses. Due to its host range expansion, S. neurona is an emerging threat that requires close monitoring. In apicomplexans, protein kinases (PKs) have been implicated in a myriad of critical functions, such as host cell invasion, cell cycle progression and host immune response evasion. Here, we used various bioinformatics methods to define the kinome of S. neurona and phylogenetic relatedness of its PKs to other apicomplexans. We identified 97 putative PKs clust...
Identification and Expression of Equine MER-Derived miRNAs.
Molecules and cells    March 21, 2017   Volume 40, Issue 4 262-270 doi: 10.14348/molcells.2017.2295
Gim JA, Kim HS.MicroRNAs (miRNAs) are single-stranded, small RNAs (21-23 nucleotides) that function in gene silencing and translational inhibition via the RNA interference mechanism. Most miRNAs originate from host genomic regions, such as intergenic regions, introns, exons, and transposable elements (TEs). Here, we focused on the palindromic structure of medium reiteration frequencies (MERs), which are similar to precursor miRNAs. Five MER consensus sequences (MER5A1, MER53, MER81, MER91C, and MER117) were matched with paralogous transcripts predicted to be precursor miRNAs in the horse genome (equCab2) and...
Parelaphostrongylus tenuis Cerebrospinal Nematodiasis in a Horse with Cervical Scoliosis and Meningomyelitis.
Journal of veterinary internal medicine    March 20, 2017   Volume 31, Issue 3 890-893 doi: 10.1111/jvim.14691
Mittelman NS, Divers TJ, Engiles JB, Gerhold R, Ness S, Scrivani PV, Southard T, Johnson AL.There are reports of horses with acute onset acquired cervical scoliosis and cutaneous analgesia. The underlying dorsal gray column myelitis that produces these neurologic signs has been only presumptively attributed to migration of Parelaphostrongylus tenuis within the spinal cord. Despite previous confirmation brain by polymerase chain reaction testing, of P. tenuis within the brain of horses by polymerase chain reaction testing, genetic testing has failed to definitively identify the presence of this parasite in cases of equine myelitis. This case report provides molecular confirmation via ...
Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses.
Immunogenetics    March 18, 2017   Volume 69, Issue 5 351-358 doi: 10.1007/s00251-017-0978-6
Bergmann T, Lindvall M, Moore E, Moore E, Sidney J, Miller D, Tallmadge RL, Myers PT, Malaker SA, Shabanowitz J, Osterrieder N, Peters B, Hunt DF....Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Uti...
Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during pronuclear development in equine zygotes produced by ICSI.
Epigenetics & chromatin    March 15, 2017   Volume 10 13 doi: 10.1186/s13072-017-0120-x
Heras S, Smits K, De Schauwer C, Van Soom A.Global epigenetic reprogramming is considered to be essential during embryo development to establish totipotency. In the classic model first described in the mouse, the genome-wide DNA demethylation is asymmetric between the paternal and the maternal genome. The paternal genome undergoes ten-eleven translocation (TET)-mediated active DNA demethylation, which is completed before the end of the first cell cycle. Since TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine, the latter is postulated to be an intermediate stage toward DNA demethylation. The maternal genome, on the other ha...
Deep sequencing and variant analysis of an Italian pathogenic field strain of equine infectious anaemia virus.
Transboundary and emerging diseases    March 15, 2017   Volume 64, Issue 6 2104-2112 doi: 10.1111/tbed.12631
Cappelli K, Cook RF, Stefanetti V, Passamonti F, Autorino GL, Scicluna MT, Coletti M, Verini Supplizi A, Capomaccio S.Equine infectious anaemia virus (EIAV) is a lentivirus with an almost worldwide distribution that causes persistent infections in equids. Technical limitations have restricted genetic analysis of EIAV field isolates predominantly to gag sequences resulting in very little published information concerning the extent of inter-strain variation in pol, env and the three ancillary open reading frames (ORFs). Here, we describe the use of long-range PCR in conjunction with next-generation sequencing (NGS) for rapid molecular characterization of all viral ORFs and known transcription factor binding mot...
Repetitive mammalian dwarfing during ancient greenhouse warming events.
Science advances    March 15, 2017   Volume 3, Issue 3 e1601430 doi: 10.1126/sciadv.1601430
D'Ambrosia AR, Clyde WC, Fricke HC, Gingerich PD, Abels HA.Abrupt perturbations of the global carbon cycle during the early Eocene are associated with rapid global warming events, which are analogous in many ways to present greenhouse warming. Mammal dwarfing has been observed, along with other changes in community structure, during the largest of these ancient global warming events, known as the Paleocene-Eocene Thermal Maximum [PETM; ~56 million years ago (Ma)]. We show that mammalian dwarfing accompanied the subsequent, smaller-magnitude warming event known as Eocene Thermal Maximum 2 [ETM2 (~53 Ma)]. Statistically significant decrease in body size...
Quality of seminal fluids varies with type of stimulus at ejaculation.
Scientific reports    March 13, 2017   Volume 7 44339 doi: 10.1038/srep44339
Jeannerat E, Janett F, Sieme H, Wedekind C, Burger D.The theory of ejaculate economics was mainly built around different sperm competition scenarios but also predicts that investments into ejaculates depend on female fecundity. Previous tests of this prediction focused on invertebrates and lower vertebrate, and on species with high female reproductive potential. It remains unclear whether the prediction also holds for polygynous mammals with low female reproductive potential (due to low litter size and long inter-birth intervals). We used horses (Equus caballus) to experimentally test whether semen characteristics are adjusted to the oestrous cy...
Evaluation of equine oocyte developmental competence using polarized light microscopy.
Reproduction (Cambridge, England)    March 10, 2017   Volume 153, Issue 6 775-784 doi: 10.1530/REP-17-0125
Bertero A, Ritrovato F, Evangelista F, Stabile V, Fortina R, Ricci A, Revelli A, Vincenti L, Nervo T.The purpose of this study was to observe -matured equine oocytes with an objective computerized technique that involves the use of a polarized light microscope (PLM) in addition to the subjective morphological evaluation obtained using a classic light microscope (LM). Equine cumulus-oocyte complexes (COCs,  = 922) were subjected to different maturation times (24, 36 or 45 h), however, only 36-h matured oocytes were analyzed using CLM. The 36-h matured oocytes that reached maturity were parthenogenetically activated to evaluate the quality and meiotic competence. Average maturation perce...
Occurrence and Genetic Characteristics of Cryptosporidium hominis and Cryptosporidium andersoni in Horses from Southwestern China.
The Journal of eukaryotic microbiology    March 8, 2017   Volume 64, Issue 5 716-720 doi: 10.1111/jeu.12399
Deng L, Li W, Zhong Z, Gong C, Cao X, Song Y, Wang W, Huang X, Liu X, Hu Y, Fu H, He M, Wang Y, Zhang Y, Wu K, Peng G.A total of 333 fecal specimens from horses in southwestern China were genotyped based on analysis of the small subunit rRNA (SSU rRNA) gene. Cryptosporidium hominis and Cryptosporidium andersoni were identified in 2 and 4 stool specimens, respectively. The identification of C. hominis was confirmed by sequence analysis of the 70-kDa heat shock protein (HSP70) and oocyst wall protein (COWP) genes. Subtyping analysis of the 60-kDa glycoprotein (GP60) gene sequence of C. hominis revealed a new rare subtype Id, named IdA15; only three Id isolates have been reported in humans to date. Multilocus ...
Characterization of Theileria equi genotypes in horses in Israel, the Palestinian Authority and Jordan.
Ticks and tick-borne diseases    March 4, 2017   Volume 8, Issue 4 499-505 doi: 10.1016/j.ttbdis.2017.02.010
Ketter-Ratzon D, Tirosh-Levy S, Nachum-Biala Y, Saar T, Qura'n L, Zivotofsky D, Abdeen Z, Baneth G, Steinman A.Equine theileriosis caused by Theileria equi is endemic in the Middle East, where it causes a severe disease as well as widespread subclinical infection. The aim of this study was to evaluate the diversity of T. equi genotypes in Israel and the neighboring Palestinian Authority and Jordan. Blood samples from 355 horses from Israel, the Palestinian Authority and Jordan were tested for the prevalence of T. equi DNA. Two hundred and fourteen (60%) were found positive for T. equi infection by PCR. Of those, the 18S rRNA (1458bp) and the EMA-1 (745bp) genes of T. equi were sequenced from 15 horse s...
Localization of the 5-hydroxytryptamine 4 receptor in equine enteric neurons and extrinsic sensory fibers.
Neurogastroenterology and motility    March 3, 2017   Volume 29, Issue 7 doi: 10.1111/nmo.13045
Giancola F, Rambaldi AM, Bianco F, Iusco S, Romagnoli N, Tagliavia C, Bombardi C, Clavenzani P, De Giorgio R, Chiocchetti R.Serotonin plays a pivotal role in regulating gut motility, visceral sensitivity, and fluid secretion via specific receptors. Among these receptors, 5-HT exerts a prominent control on gut motor function. Although the prokinetic effect exerted by 5-HT agonists is well known, the cellular sites of 5-HT expression remain poorly understood in large mammals, e.g., horses. In this study, we evaluated the distribution of 5-HT in the horse intestine and in foals with enteric aganglionosis, reminiscent of human Hirschsprung's disease. Methods: The intestine and spinal ganglia were obtained from three he...
Purified horse milk exosomes contain an unpredictable small number of major proteins.
Biochimie open    March 1, 2017   Volume 4 61-72 doi: 10.1016/j.biopen.2017.02.004
Sedykh SE, Purvinish LV, Monogarov AS, Burkova EE, Grigor'eva AE, Bulgakov DV, Dmitrenok PS, Vlassov VV, Ryabchikova EI, Nevinsky GA.Exosomes are 40-100 nm nanovesicles containing RNA and different proteins. Exosomes containing proteins, lipids, mRNAs, and microRNAs are important in intracellular communication and immune function. Exosomes from different sources are usually obtained by combination of centrifugation and ultracentrifugation and according to published data can contain from a few dozens to thousands of different proteins. Crude exosome preparations from milk of eighteen horses were obtained for the first time using several standard centrifugations. Exosome preparations were additionally purified by FPLC gel fi...
Testosterone metabolism of equine single CYPs of the 3A subfamily compared to the human CYP3A4.
Toxicology in vitro : an international journal published in association with BIBRA    February 24, 2017   Volume 41 83-91 doi: 10.1016/j.tiv.2017.02.017
Vimercati S, Büchi M, Zielinski J, Peduto N, Mevissen M.Cytochrome P450 enzymes (CYPs) are responsible for the phase I metabolism of drugs, xenobiotics and endogenous substances. Knowledge of single CYPs and their substrates is important for drug metabolism, helps to predict adverse effects and may prevent reduced drug efficacy in polypharmacy. In this study, three equine isoenzymes of the 3A subfamily, the equine flavoprotein NADPH-P450 oxidoreductase (POR), and the cytochrome b5 (CYB5) were cloned, sequenced and heterologously expressed in a baculovirus expression system. Testosterone, the standard compound for characterization of the human CYP3A...
Proteomic, toxicological and immunogenic characterization of Mexican west-coast rattlesnake (Crotalus basiliscus) venom and its immunological relatedness with the venom of Central American rattlesnake (Crotalus simus).
Journal of proteomics    February 24, 2017   Volume 158 62-72 doi: 10.1016/j.jprot.2017.02.015
Segura Á, Herrera M, Reta Mares F, Jaime C, Sánchez A, Vargas M, Villalta M, Gómez A, Gutiérrez JM, León G.The venom of the Mexican west-coast rattlesnake (Crotalus basiliscus) was characterized for its protein composition, toxicological profile and immunogenic properties. This venom is composed of 68% Zn2+-dependent metalloproteinases (SVMPs), 14% phospholipases A2 (PLA2s), 11% serine proteinases, 4% SVMPs-inhibitor tripeptides (SVMP-ITs), 2% bradykinin-potentiating peptides (BPPs), 0.6% cysteine-rich secretory proteins (CRISPs), and 0.2% l-amino acid oxidases (LAAOs). SVMPs present in the venom are responsible for azocasein hydrolysis and hemorrhagic activity, but their contribution to the lethal...
Characterisation and intracellular labelling of mesenchymal stromal cells derived from synovial fluid of horses and sheep.
Veterinary journal (London, England : 1997)    February 24, 2017   Volume 222 1-8 doi: 10.1016/j.tvjl.2017.02.006
Burk J, Glauche SM, Brehm W, Crovace A, Francioso E, Hillmann A, Schubert S, Lacitignola L.Multipotent mesenchymal stromal cells (MSCs) derived from synovial fluid (SF) are considered to be a promising cell type for therapeutic applications in joint disease. However, despite their potential relevance for clinical and experimental studies, there is insufficient knowledge about SF-derived MSCs isolated from horses and sheep. In this study, cells were recovered from healthy SF and bone marrow (BM) of sheep, and from healthy and osteoarthritic SF of horses. Ovine SF-MSCs were used to assess the efficiency of intracellular labelling with quantum dots (QDs). Colony forming units, generati...
Genomics and genetics: A daily double for the horse industry.
Equine veterinary journal    February 22, 2017   Volume 49, Issue 3 260-262 doi: 10.1111/evj.12668
Rothschild MF.No abstract available
Sex chromosomal abnormalities associated with equine infertility: validation of a simple molecular screening tool in the Purebred Spanish Horse.
Animal genetics    February 22, 2017   Volume 48, Issue 4 412-419 doi: 10.1111/age.12543
Chromosomal abnormalities in the sex chromosome pair (ECAX and ECAY) are widely associated with reproductive problems in horses. However, a large proportion of these abnormalities remains undiagnosed due to the lack of an affordable diagnostic tool that allows for avoiding karyotyping tests. Hereby, we developed an STR (single-tandem-repeat)-based molecular method to determine the presence of the main sex chromosomal abnormalities in horses in a fast, cheap and reliable way. The frequency of five ECAX-linked (LEX026, LEX003, TKY38, TKY270 and UCDEQ502) and two ECAY-linked (EcaYH12 and SRY) mar...
Gingival Fibrosarcoma in a Horse.
Journal of veterinary dentistry    February 22, 2017   Volume 33, Issue 4 243-248 doi: 10.1177/0898756417690845
Horbal A, Dixon PM.A 4-year-old thoroughbred cross mare was referred to the University of Edinburgh Veterinary School Equine Hospital for treatment of a soft tissue tumor on the buccal gingival margin of the rostral right maxillary cheek teeth. The lesion was initially surgically excised and diagnosed as a fibrosarcoma via histopathology. Adjunctive treatment with intralesional cisplatin chemotherapy was begun. The tumor recurred and was repeatedly treated with intralesional cisplatin injections and additional surgical resection over the course of 14 weeks. Despite the initial poor response to treatment, no furt...
Stemness Signature of Equine Marrow-derived Mesenchymal Stem Cells.
International journal of stem cells    February 22, 2017   Volume 10, Issue 1 93-102 doi: 10.15283/ijsc16036
Zahedi M, Parham A, Dehghani H, Mehrjerdi HK.Application of competent cells such as mesenchymal stem cells (MSCs) for treatment of musculoskeletal disorders in equine athletes is increasingly needed. Moreover, similarities of horse and human in size, load and types of joint injuries, make horse as a good model for MSCs therapy studies. This study was designed to isolate and characterize stemness signature of equine bone marrow-derived mesenchymal stem cells (BM-MSCs). Methods: BM of three mares was aspirated and the mononuclear cells (MNCs) were isolated using density gradient. The primary MNCs were cultured and analyzed after tree passa...
Cardiac findings in Quarter Horses with heritable equine regional dermal asthenia.
Journal of the American Veterinary Medical Association    February 17, 2017   Volume 250, Issue 5 538-547 doi: 10.2460/javma.250.5.538
Brinkman EL, Weed BC, Patnaik SS, Brazile BL, Centini RM, Wills RW, Olivier B, Sledge DG, Cooley J, Liao J, Rashmir-Raven AM.OBJECTIVE To compare biomechanical and histologic features of heart valves and echocardiographic findings between Quarter Horses with and without heritable equine regional dermal asthenia (HERDA). DESIGN Prospective case-control study. ANIMALS 41 Quarter Horses. PROCEDURES Ultimate tensile strength (UTS) of aortic and mitral valve leaflets was assessed by biomechanical testing in 5 horses with HERDA and 5 horses without HERDA (controls). Histologic evaluation of aortic and mitral valves was performed for 6 HERDA-affected and 3 control horses. Echocardiography was performed in 14 HERDA-affected...
Multilocus sequence typing identifies an avian-like Chlamydia psittaci strain involved in equine placentitis and associated with subsequent human psittacosis.
Emerging microbes & infections    February 15, 2017   Volume 6, Issue 2 e7 doi: 10.1038/emi.2016.135
Jelocnik M, Branley J, Heller J, Raidal S, Alderson S, Galea F, Gabor M, Polkinghorne A.No abstract available
Androgen Insensitivity Syndrome in a Family of Warmblood Horses Caused by a 25-bp Deletion of the DNA-Binding Domain of the Androgen Receptor Gene. Welsford GE, Munk R, Villagómez DA, Hyttel P, King WA, Revay T.Testicular feminization, an earlier term coined for describing a syndrome resulting from failure of masculinization of target organs by androgen secretions during embryo development, has been well documented not only in humans but also in the domestic horse. The pathology, actually referred to as androgen insensitivity syndrome (AIS), has been proposed to follow an X-linked recessive pattern of inheritance in some horse breeds already investigated. Affected individuals are characterized by a female phenotype but with a stallion genotype of 64,XY SRY+ constitution. We identified a Warmblood hor...
The legacy of Columbus in American horse populations assessed by microsatellite markers.
Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie    February 14, 2017   Volume 134, Issue 4 340-350 doi: 10.1111/jbg.12255
Cortés O, Dunner S, Gama LT, Martínez AM, Delgado JV, Ginja C, Jiménez LM, Jordana J, Luis C, Oom MM, Sponenberg DP, Zaragoza P, Vega-Pla JL.Criollo horse populations descend from horses brought from the Iberian Peninsula over the period of colonization (15th to 17th century). They are spread throughout the Americas and have potentially undergone genetic hybridization with other breeds in the recent past. In this study, 25 autosomal microsatellites were genotyped in 50 horse breeds representing Criollo populations from 12 American countries (27 breeds), breeds from the Iberian Peninsula (19), one breed each from France and Morocco and two cosmopolitan horse breeds (Thoroughbred and Arabian). The genetic relationships among breeds i...
A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse.
Veterinary journal (London, England : 1997)    February 14, 2017   Volume 221 62-67 doi: 10.1016/j.tvjl.2017.02.005
Gardner AK, van Eps AW, Watts MR, Burns TA, Belknap JK.Supporting limb laminitis (SLL) is a devastating sequela to severe unilateral lameness in equine patients. The manifestation of SLL, which usually only affects one limb, is unpredictable and the etiology is unknown. A novel, non-painful preferential weight bearing model designed to mimic the effects of severe unilateral forelimb lameness was developed to assess lamellar signaling events in the supporting limb (SL). A custom v-shaped insert was attached to the shoe of one forelimb to prevent normal weight bearing and redistribute weight onto the SL. Testing of the insert using a custom scale pl...
Pedigree analysis of the Turkish Arab horse population: structure, inbreeding and genetic variability.
Animal : an international journal of animal bioscience    February 13, 2017   Volume 11, Issue 9 1449-1456 doi: 10.1017/S175173111700009X
Duru S.The aim of this study was to evaluate genetic variability in the Turkish Arab horse population using pedigree information. This study is the first detailed pedigree analysis of the breed in Turkey. Pedigree data were collected from the National Studbook. The pedigree data for 23 668 horses, born between 1904 and 2014, were used in the analysis. From this data set, a reference population (RP) of 14 838 animals symbolising the last generation was defined. Demographic parameters, the inbreeding level (F), the average relatedness (AR), the effective population size (N e), the effective number of f...
Decoupled ecomorphological evolution and diversification in Neogene-Quaternary horses.
Science (New York, N.Y.)    February 12, 2017   Volume 355, Issue 6325 627-630 doi: 10.1126/science.aag1772
Cantalapiedra JL, Prado JL, Hernández Fernández M, Alberdi MT.Evolutionary theory has long proposed a connection between trait evolution and diversification rates. In this work, we used phylogenetic methods to evaluate the relationship of lineage-specific speciation rates and the mode of evolution of body size and tooth morphology in the Neogene and Quaternary radiation of horses (7 living and 131 extinct species). We show that diversification pulses are a recurrent feature of equid evolution but that these pulses are not correlated with rapid bursts in phenotypic evolution. Instead, rapid cladogenesis seems repeatedly associated with extrinsic factors t...
Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs.
Veterinary sciences    February 12, 2017   Volume 4, Issue 1 9 doi: 10.3390/vetsci4010009
Shave R, Howatson G, Dickson D, Young L.Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the "athlete's heart" in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling i...
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