Peptides are short chains of amino acids that are involved in various biological processes in horses. They function as signaling molecules, influencing physiological activities such as metabolism, immune response, and tissue repair. Peptides can be naturally occurring or synthetically derived, and they may serve as therapeutic agents in veterinary medicine. In equine health, peptides are studied for their potential applications in enhancing performance, supporting recovery, and managing conditions like osteoarthritis. This page compiles peer-reviewed research studies and scholarly articles that explore the structure, function, and potential applications of peptides in the context of equine health and disease management.
Andrews KE, Sibthorpe PEM, Fitzgerald DM, de Laat MA.Equine insulin dysregulation (ID) is a common condition that predisposes to hyperinsulinaemia-associated laminitis. Improved pathophysiological understanding would enable better management of ID and reduce the risk of laminitis. The incretin peptides, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), augment the insulin response to dietary glucose and GLP-1 has been implicated in the pathophysiology of ID. However, their temporal variation in response to a low-energy diet has not been reported. This study determined the variation in GLP-1, GIP and insulin ...
Durham AE.This study aimed to further define and quantify possible cross-reactive peptides when measuring plasma adrenocorticotropic hormone (ACTH) concentration in equids. Equine plasma samples were spiked with known concentrations of exogenous manufactured peptides comprising human ACTH, ACTH (corticotropin-like intermediate lobe peptide, CLIP) and ACTH (corticotropin inhibiting peptide, CIP). All samples were assayed in duplicate using Siemens Immulite 2000xpi chemiluminescent assay (CLA) and Tosoh AIA-900 immunoflurorescent assay (IFA). As expected, ACTH was measured by both assays although higher v...
Ajeeb B, Kiyotake EA, Keefe PA, Phillips JN, Hatzel JN, Goodrich LR, Detamore MS.Cartilage injuries pose significant challenges in horses and often lead to post-traumatic osteoarthritis (PTOA). Despite the advances in surgical and regenerative techniques, the result in most cases is the formation of a fibrocartilage repair tissue. Cell-based cartilage therapies are mainly focused on equine bone marrow-derived mesenchymal stem cells (eBMSCs) as they are easily accessible, and multipotent. Nonetheless, alternative allogeneic sources, for example equine umbilical cord matrix mesenchymal stromal cells (eUCMSCs), hold promise given their non-invasive and readily accessible natu...
Ma Z, Li Y, Zhao Z, Song Q, Wang Q, Lu S, Wang J.In this study, we purified and identified antioxidant peptides from equine plasma protein hydrolysates and assessed their protective effects against HO-induced oxidative stress in Caco-2 cells. Four antioxidant peptides were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in equine plasma protein hydrolysate, namely: GTMVGC (567.69 Da), FGMTST (662.88 Da), VGYHSHF (847.01 Da) and ALSPFFKE (939.18 Da). Among them, ALSPFFKE showed the strongest antidigestive properties after modelled digestion studies. Moreover, ALSPFFKE enhanced intracellular superoxide dismutase (SO...
Stafford LS, Plummer CE, Smith WC, Gibson DJ, Sharma J, Vicuna V, Diakite S, Larkin J.Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases. Topical administration of SOCS1-KIR, a peptide mimic of SOCS1, was previously correlated to reduced ocular pathologies within ERU patients. Unassigned: To further assess the translational potential of a SOCS1 mimetic to treat RU, we assessed peptide-mediated modulatio...
Terlinden A, Jacquet S, Manivong S, Cullier A, Cassé F, Legendre F, Garcia AA, Roullin G, Moldovan F, Sirois P, Banquy X, Galéra P, Audigié F....Osteoarthritis is a leading cause of pain and retirement in athletic horses. Hydro-expansive functionalized nanogels, acting as Drug Delivery Systems, constitute one of the current therapeutic prospects. These nanogels have the potential to combine mechanical benefits through polymers with the biological effect of prolonged release of bioactive molecules. The purpose of this double-blinded randomized tolerance study versus negative control was to evaluate the response of healthy joints to a single injection of the expected efficient dose (further referred to as the trial dose) and overdose of ...
Kemp KL, Skinner JE, Bertin FR.Phenylbutazone is prescribed for laminitis-associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID). Objective: Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses. Methods: Sixteen horses, including 7 with ID. Methods: Randomized cross-over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10-day washout period, administration of the alternative trea...
Lou X, Shao W, Wu Y, Ma H, Chen H, Zheng N, Zhao Y.Active peptides in mare milk have unique biological activities, but how the bioactive protein in mare's milk changes under the influence of temperature has not been fully studied. Therefore, in this study, the differential expression of bioactive peptides potentially present in horse milk under different heat treatment conditions was investigated for the first time using peptidomic and bioinformatic techniques. We collected a total of 15 samples. In this study, we divided the samples into five groups, specifically, 65 °C, 30 min; 72 °C, 15 min; 83 °C; 10 min; 95 °C, 5 min; and an untreated...
Shimizu Y, Sugai-Bannai M, Saito K, Hirano-Kodaira M, Leung GN.Somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone (rhGH) are protein-based drugs generally used to treat growth disorders and GH deficiency in humans. Due to their potential to enhance the horse performance, the use of these drugs is prohibited at-all-times by the International Federation of Horseracing Authorities for horseracing and the Fédération Equestre Internationale for equestrian sports. In this study, we developed a test method for the identification and differentiation of somapacitan and rhGH in equine plasma by using liquid chromatography h...
Ohnuma K, Hirano-Kodaira M, Bannai M, Shimizu Y, Yamada M, Kinoshita K, Ngai-Wa Leung G, Ishii H.The abuse of prohibited peptide-based drugs with a broad spectrum of chemical characteristics poses a significant concern for the horseracing industry. Recently, there has been a notable increase in positive cases of small-peptide drugs reported in equine and canine sports. In addition to small peptides, large peptides (over 2 kDa) with structural diversity have also entered the market in increasing numbers as drugs for humans and livestock. However, the simultaneous analysis of both small- and large-peptide-based drugs is still challenging. In this study, a screening method was developed to c...
Wu J, Na H, Bai F, Li S, Gao H, Sha R.Horse bone is rich in collagen, with a composition similar to that of human collagen. Collagen peptides supply nutrients needed for human growth that act as antioxidants, lower blood pressure. This study explored the extraction of collagen and the preparation of collagen short peptides from Mongolian horse bones. Bones were collected from horses of varying ages, and the collagen content along with calcium salt distribution were observed through staining and imaging analyses. Next, the bones were processed into a powder and then subjected to ultra-high-pressure processing for degreasing. The de...
Delcourt V, Garcia P, Chabot B, Aber N, Pescher M, Cacault M, Scholtes P, Loup B, Barnabé A, Popot MA, Bailly-Chouriberry L.Thymosin 4 (TB4) is a ubiquitous, highly conserved and abundant peptide among mammals with a critical role in cytoskeleton organization. In spite of its yet non-authorized use as a medicine and being forbidden by the IFHA, the FEI, and the WADA, intelligence and doping control laboratories reported numerous products available online claiming to contain a synthetic acetylated fragment of TB4 or TB4 itself, promoted as a growth factor with regenerative properties. In this article, the first estimation of the endogenous TB4 concentration in racing horses' blood samples was performed through a po...
Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA.Equine insulin dysregulation (ID) is a significant metabolic problem because the hyperinsulinaemia that develops increases the animal's risk of developing laminitis, a debilitating foot condition. The role of gastrointestinal factors, such as incretin hormones, in the pathogenesis of ID and hyperinsulinaemia in horses is poorly understood, particularly in comparison to other species. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic peptide released from L cells in the gastrointestinal tract and is implicated in metabolic dysfunction in other species. The aim of this study in vitro was to...
Pihl TH, Engelhart KE, Houen G.Polyclonal antibodies are relatively easy to produce and may supplement monoclonal antibodies for some applications or even have some advantages.The choice of species for production of (peptide) antisera is based on practical considerations, including availability of immunogen (vaccine) and animals. Two major factors govern the production of antisera: the nature of adaptive immune responses, which take place over days/weeks and ethical guidelines for animal welfare.Here, simple procedures for immunization of mice, rabbits, sheep, goats, pigs, horses, and chickens are presented.
Steel R, Timms M, Bamford N, Spence R, Sillence M.Previous liquid chromatography/mass spectrometry (LC/MS) methods for the detection of insulin and other similar peptide hormones in equine plasma relied on the use of antibody affinity extraction. As a result, these methods were not suitable for routine high-throughput analysis. A solid-phase extraction (SPE) method incorporating size exclusion as well as reversed-phase interactions allows the selective extraction of peptide hormones such as adrenocorticotropic hormone (ACTH), insulin and their synthetic analogues from equine plasma with approximately 80% extraction efficiencies. This extracti...
Moroni R, Fanelli D, Camillo F, Rota A, Cantile C, Marmorini P, Salamone G, Ori M, Panzani D.Endometritis is a major cause of subfertility in mares. Multiparous old mares are more susceptible to developing endometritis given that ageing is associated with an altered immune response and with inadequate physiological uterine clearance after breeding, which can lead to degenerative changes in the endometrium. Molecules such as antimicrobial peptides (AMPs) have been proposed as endometritis markers in the equine species. Methods: Cross-sectional. Objective: To investigate the endometrial expression of defensin-beta 4B (DEFB4B), lysozyme (LYZ) and secretory leukocyte peptidase inhibitor (...
McGrath BM, Norman ST, Gaspardis CA, Rose JL, Scott CJ.To understand better the role that kisspeptin plays in regulating seasonal and estrous cycle changes in the mare, this study investigated the number, location and interactions between GnRH, kisspeptin and RFRP-3 neurons in the equine hypothalamus. Hypothalami were collected from mares during the non-breeding season, vernal transition and various stages of the breeding season. Fluorescent immunohistochemistry was used to label the neuropeptides of interest. GnRH cells were observed primarily in the arcuate nucleus (ARC), while very few labeled cells were identified in the pre-optic area (POA). ...
Faber E, van Schalkwyk A, Ivy Tshilwane S, Van Kleef M, Pretorius A.The viral proteins VP1-1, VP2, VP4, VP7 and NS3, of African horse sickness virus serotype 4 (AHSV4), have previously been identified to contain CD8+ T cell epitopes. In this study, overlapping peptides spanning the entire sequences of these AHSV4 proteins were synthesized and used to map epitopes. Peripheral blood mononuclear cells (PBMC) isolated from five horses immunized with an attenuated AHSV4 were stimulated in vitro with the synthesized peptides. Various memory immune assays were used to identify the individual peptides that contain CD8+ T cell epitopes, CD4+ T cell epitopes and linear ...
Xiao T, Zeng J, Zhao C, Hou Y, Wu T, Deng Z, Zheng L.An infant in vitro digestion model was utilized to investigate protein digestion characteristics in human and diverse mammalian milk (i.e., cow, goat, sheep, mare, and camel milk) using electrophoresis and chromatography. Digestive differences among milks were mainly manifested in the infant gastric phase, as evidenced by varying degrees of protein digestion. Notably, proteins (i.e., lactoferrin, serum albumin, and immunoglobulin G-heavy chain) remained partially intact in human milk, whereas these proteins in animal milk were exclusively degraded after gastrointestinal digestion. The peptide ...
Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA.Gastrointestinal peptides, such as glucagon-like peptide-2 (GLP-2), could play a direct role in the development of equine hyperinsulinaemia. Objective: To describe the secretory pattern of endogenous GLP-2 over 24 h in healthy ponies and determine whether oral administration of a synthetic GLP-2 peptide increases blood glucose or insulin responses to feeding. Methods: A cohort study followed by a randomised, controlled, cross-over study. Methods: In the cohort study, blood samples were collected every 2 h for 24 h in seven healthy ponies and plasma [GLP-2] was measured. In the cross-over...
Borovikov S, Ryskeldina A, Tursunov K, Syzdykova A, Akibekov O. abortion in mares is caused by subspecies serovar infection and is characterized by premature (abortion) or non-viable fetus birth. Although all horses are susceptible to infection, the condition is more often clinically manifested in pregnant mares, with most abortions recorded in young females. In addition, nonspecific clinical disease signs and poorly sensitive and effective bacteriological diagnostic methods hinder rapid and reliable infection diagnoses. Immunochemical methods such as enzyme-linked immunosorbent assay (ELISA) and immunochromatography assays can facilitate effective and...
Cui C, Li L, Wu L, Wang X, Zheng Y, Wang F, Wei H, Peng J.A healthy intestine plays an important role in the growth and development of farm animals. In small intestine, Paneth cells are well known for their regulation of intestinal microbiota and intestinal stem cells (ISCs). Although there has been a lot of studies and reviews on human and murine Paneth cells under intestinal homeostasis or disorders, little is known about Paneth cells in farm animals. Most farm animals possess Paneth cells in their small intestine, as identified by various staining methods, and Paneth cells of various livestock species exhibit noticeable differences in cell shape, ...
Flores L, Hargrave S, Clifford A, Alarcio G, Moeller BC.The abuse of prohibited agents including peptides and basic small-molecule drugs is an area of great concern in horseracing due to their high potential to act as doping agents. These compound classes include agents such as growth hormone-releasing peptides, peptide analgesics, beta-2-adrenergic receptor agonists, and quaternary ammonium drugs that can be challenging to detect and regulate because of their chemical properties and potential rapid elimination following administration. The use of highly sensitive and selective analytical techniques such as liquid chromatography-mass spectrometry (...
Liu L, Yu W, Cai K, Ma S, Wang Y, Ma Y, Zhao H. () is a zoonotic opportunistic pathogen that can cause life-threatening infections. The rapid evolution of multidrug-resistant and the fact that there is no currently licensed effective vaccine against warrant the need for vaccine development. Reverse vaccinology (RV), which involves screening a pathogen's entire genome and proteome using various web-based prediction tools, is considered one of the most effective approaches for identifying vaccine candidates. Here, we performed a pangenome analysis to determine the core proteins of . We then used the RV approach to examine the subcellular l...
Pinetre J, Delcourt V, Becher F, Garcia P, Barnabé A, Loup B, Popot MA, Fenaille F, Bailly-Chouriberry L.Many innovative biotherapeutics have been marketed in the last decade. Monoclonal antibodies (mAbs) and Fc-fusion proteins (Fc-proteins) have been developed for the treatment of diverse diseases (cancer, autoimmune diseases, and inflammatory disorders) and now represent an important part of targeted therapies. However, the ready availability of such biomolecules, sometimes characterized by their anabolic, anti-inflammatory, or erythropoiesis-stimulating properties, raises concerns about their potential misuse as performance enhancers for human and animal athletes. In equine doping control labo...
Jaeser M, Wunderlich C, Henle T.To study the protein-bound glycans of equine κ-casein, equine sodium caseinate was first obtained from raw mare's milk by acid precipitation and then fractionated by cation-exchange chromatography. The oligosaccharides of the obtained equine κ-casein were analyzed by RP-HPLC-UV-HRMS after β-elimination with simultaneous derivatization with 1-phenyl-3-methyl-5-pyrazolone (PMP). In addition to the acidic tetrasaccharide derivative Neu5Ac-Gal-[Neu5Ac]-GalNAc-2PMP known from bovine κ-casein, the acidic pentasaccharide derivative Neu5Ac-Gal-[Gal-GlcNAc]-GalNAc-2PMP was identified as the most ab...
So YM, Wong JKY, Wong ASY, Tse ATL, Wan TSM, Ho ENM.The erythropoietin mimetic peptide 1 linear form (EMP1-linear), GGTYSCHFGPLTWVCKPQGG-NH , was identified in an unknown preparation consisting of white crystalline powder contained in sealed glass vials using ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). The white crystalline powder, allegedly used for doping racehorses, was found to contain around 2% (w/w) of EMP1-linear. EMP1-linear can be cyclised in equine plasma at physiological temperature of 37°C by forming an intramolecular disulfide bond to give EMP1, which is a well-known erythropoiesis st...
Timms M, Botteon A, Manos C, Griffin J, Levina V, Steel R.Gonadotropin-releasing hormone (GnRH) and its synthetic analogues are considered banned substances by the racing industry. GnRH is used as a pharmaceutical to regulate the female oestrous cycle, but the hormone is also thought to increase the production of testosterone in male animals. Using liquid chromatography in conjunction with high-resolution mass spectrometry (LC-HRMS) and data-independent acquisition (DIA), a method is presented for the detection of intact and truncated peptides of GnRH and its analogues down to the low picogram level in equine urine. The study of the catabolism of GnR...
Kuckova S, Smirnova TA, Straka D, Meledina A, Santrucek J, Humpolakova K, Hoskova M, Cejnar P, Hynek R.The aim of this work is to offer an alternative or complementary analytical tool to the time-consuming and expensive methods commonly used for the recognition of animal species according to their hair. The paper introduces a simple and fast way for species differentiation of animal hairs called in-sample digestion. A total of 10 European animal species, including cat, cow, common degu, dog, fallow deer, goat, horse, sika deer, rabbit, roe deer, and 17 different breeds of dogs were examined using specific tryptic cleavage directly in hair followed by matrix-assisted laser desorption/ionization-...
Puffer BA, Parent LJ, Wills JW, Montelaro RC.We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences con...
Snijder EJ, Wassenaar AL, Spaan WJ.To study the proteolytic processing of the equine arteritis virus (EAV) replicase open reading frame 1a (ORF1a) protein, specific antisera were raised in rabbits, with six synthetic peptides and a bacterial fusion protein as antigens. The processing of the EAV ORF1a product in infected cells was analyzed with Western blot (immunoblot) and immunoprecipitation techniques. Additional information was obtained from transient expression of ORF1a cDNA constructs. The 187-kDa ORF1a protein was found to be subject to at least five proteolytic cleavages. The processing scheme, which covers the entire OR...
Garmashova N, Atasheva S, Kang W, Weaver SC, Frolova E, Frolov I.The encephalitogenic New World alphaviruses, including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses, constitute a continuing public health threat in the United States. They circulate in Central, South, and North America and have the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that these viruses have developed the ability to interfere with cellular transcription and use it as a means of downregulating a cellular antiviral response. The results of the present study suggest that the N-terminal, approxima...
Hu S, Vincenz C, Buller M, Dixit VM.Molluscum contagiosum virus proteins MC159 and MC160 and the equine herpesvirus 2 protein E8 share substantial homology to the death effector domain present in the adaptor molecule Fas-associated death domain protein (FADD) and the initiating death protease FADD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8). FADD and FLICE participate in generating the death signal from both tumor necrosis factor receptor-1 (TNFR-1) and the CD-95 receptor. The flow of death signals from TNFR-1 occurs through the adaptor molecule tumor necrosis factor receptor-associated death domain protein (TRA...
Schneider J, Kaaden O, Copeland TD, Oroszlan S, Hunsmann G.Two glycopolypeptides with molecular weights 160,000 and 120,000 (gp120) are regularly recognized by human immunodeficiency virus (HIV)-specific antisera in lysates of cells persistently infected with HIV. In the present study, gp120 was characterized as the major envelope glycopolypeptide of HIV. Gp120 was identified as the external viral glycoprotein by radiosequencing and by its presence in purified virus. However gp120 was predominantly shed as a soluble protein into the culture fluid. Furthermore gp120 was precipitated by sera from horses infected with equine infectious anaemia virus (EIA...
Russo AT, White MA, Watowich SJ.Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two dist...
Harman RM, Yang S, He MK, Van de Walle GR.The prevalence of chronic skin wounds in humans is high, and treatment is often complicated by the presence of pathogenic bacteria. Therefore, safe and innovative treatments to reduce the bacterial load in cutaneous wounds are needed. Mesenchymal stromal cells (MSC) are known to provide paracrine signals that act on resident skin cells to promote wound healing, but their potential antibacterial activities are not well described. The present study was designed to examine the antibacterial properties of MSC from horses, as this animal model offers a readily translatable model for MSC therapies i...
Telford EA, Watson MS, Aird HC, Perry J, Davison AJ.The complete DNA sequence of equine herpesvirus 2 (EHV-2) strain 86/67 was determined. The genome is 184,427 bp in size and has a base composition of 57.5% G + C. Unusually for a herpesvirus, about a third of the sequence distributed in several large blocks appears not to encode proteins. The 79 open reading frames that were identified as probably polypeptide-coding are predicted to encode 77 distinct proteins. Amino acid sequence comparisons confirmed that EHV-2 is a gamma-herpesvirus that is genetically collinear with herpesvirus saimiri (HVS; a gamma 2-herpesvirus) and Epstein-Barr virus (E...
Atasheva S, Garmashova N, Frolov I, Frolova E.Venezuelan equine encephalitis virus (VEEV) represents a continuous public health threat in the United States. It has the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that replicating VEEV interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. VEEV capsid protein was found to play a critical role in this process, and its approximately 35-amino-acid-long peptide, fused with green fluorescent protein, functioned as efficiently as did the entire capsid. We detected a...
van Aken D, Zevenhoven-Dobbe J, Gorbalenya AE, Snijder EJ.The positive-stranded RNA genome of the arterivirus Equine arteritis virus (order Nidovirales) encodes the partially overlapping replicase polyproteins pp1a (1727 aa) and pp1ab (3175 aa). Previously, three viral proteinases were reported to cleave these large polyproteins into 12 non-structural proteins (nsps). The chymotrypsin-like viral main proteinase residing in nsp4 is responsible for eight of these cleavages. Processing of the C-terminal half of pp1a (the nsp3-8 region) was postulated to occur following either of two alternative proteolytic pathways (the 'major' and 'minor' pathways). He...
Bossart KN, Wang LF, Eaton BT, Broder CC.Hendra virus (HeV) is an emerging paramyxovirus first isolated from cases of severe respiratory disease that fatally affected both horses and humans. Understanding the mechanisms of host cell infection and cross-species transmission is an important step in addressing the risk posed by such emerging pathogens. We have initiated studies to characterize the biological properties of the HeV envelope glycoproteins. Recombinant vaccinia viruses encoding the HeV F and G open reading frames were generated and glycoprotein expression was verified by metabolic labeling and detection using specific antis...
Peffers MJ, Thorpe CT, Collins JA, Eong R, Wei TK, Screen HR, Clegg PD.Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs ...
Shehu-Xhilaga M, Ablan S, Demirov DG, Chen C, Montelaro RC, Freed EO.The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion...
Marx C, Gardner S, Harman RM, Van de Walle GR.Mesenchymal stromal cells (MSCs) from various species, such as humans, mice, and horses, were recently found to effectively inhibit the growth of various bacteria associated with chronic infections, such as nonhealing cutaneous wounds, via secretion of antimicrobial peptides. These MSC antimicrobial properties have primarily been studied in the context of the planktonic phenotype, and thus, information on the effects on bacteria in biofilms is largely lacking. The objectives of this study were to evaluate the in vitro efficacy of the MSC secretome against various biofilm-forming wound pathogen...
Ahmed A, Siman-Tov G, Keck F, Kortchak S, Bakovic A, Risner K, Lu TK, Bhalla N, de la Fuente-Nunez C, Narayanan A.Venezuelan equine encephalitis virus (VEEV), a new world alphavirus belonging to the Togaviridae family, causes periodic disease outbreaks in humans and equines with high associated mortality and morbidity. VEEV is highly infectious via the aerosol route and so has been developed as a biological weapon (Hawley and Eitzen, 2001). Despite its current classification as a category B select agent, there are no FDA approved vaccines or therapeutics to counter VEEV infections. Here we utilize a naturally occurring host defense peptide, LL-37, as a therapeutic strategy to inhibit VEEV multiplication i...
Harris RC, Marlin DJ, Dunnett M, Snow DH, Hultman E.1. Muscle buffering capacity (beta m) and dipeptide content were measured in locomotory muscles of the Thoroughbred horse, Greyhound dog and Man. 2. Beta m and carnosine contents were highest in the horse. Anserine was only found in dog muscle. 3. The higher beta m in horse and dog muscle, compared with man, appears to be predominantly due to higher muscle contents of histidine containing dipeptides in these species.
Stephens RM, Derse D, Rice NR.We isolated and characterized six cDNA clones from an equine infectious anemia virus-infected cell line that displays a Rev-defective phenotype. With the exception of one splice site in one of the clones, all six cDNAs exhibited the same splicing pattern and consisted of four exons. Exon 1 contained the 5' end of the genome; exon 2 contained the tat gene from mid-genome; exon 3 consisted of a small section of env, near the 5' end of the env gene; and exon 4 contained the putative rev open reading frame from the 3' end of the genome. The structures of the cDNAs predict a bicistronic message in ...
Laverty G, McCloskey AP, Gilmore BF, Jones DS, Zhou J, Xu B.Self-assembling dipeptides conjugated to naphthalene show considerable promise as nanomaterial structures, biomaterials, and drug delivery devices. Biomaterial infections are responsible for high rates of patient mortality and morbidity. The presence of biofilm bacteria, which thrive on implant surfaces, are a huge burden on healthcare budgets, as they are highly resistant to current therapeutic strategies. Ultrashort cationic self-assembled peptides represent a highly innovative and cost-effective strategy to form antibacterial nanomaterials. Lysine conjugated variants display the greatest po...
de Grauw JC, van de Lest CH, van Weeren PR.Inflammation is an important feature of many joint diseases, and levels of cartilage biomarkers measured in synovial fluid may be influenced by local inflammatory status. Little is known about the magnitude and time course of inflammation-induced changes in cartilage tissue turnover as measured in vivo by synovial fluid markers. We aimed to study temporal changes in concentrations of inflammatory mediators, matrix metalloproteinase activity and cartilage biomarkers over 1 week in joints with experimentally induced inflammation. Methods: Localized inflammation was induced in the intercarpal joi...
Ball JM, Rushlow KE, Issel CJ, Montelaro RC.We describe here a detailed analysis of the antigenic determinants of the surface unit glycoprotein (gp90) of equine infectious anemia virus (EIAV), using a comprehensive panel of synthetic peptides in enzyme-linked immunosorbent assays with immune serum from naturally and experimentally infected horses and with a panel of gp90-specific neutralizing and nonneutralizing monoclonal antibodies. The results of these studies identify immunoreactive segments throughout the conserved and variable domains of gp90 but localize immunodominant (100% reactivity) determinants to the amino and carboxyl term...
Fornstedt B, Rosengren E, Carlsson A.The 5-S-cysteinyl derivatives of dopamine, dopa (3,4-dihydroxyphenylalanine) and dopac (3,4-dihydroxyphenylacetic acid) were synthesized and used as reference compounds in high performance liquid chromatography analyses of extracts from various brain regions of eight mammalian species. All three metabolites were detected in the brains of all the species studied. The regional distribution of the metabolites was similar to that of dopamine; the metabolite concentrations ranged from less than 0.1 percent to more than 1 percent of the dopamine level, the highest ratios generally being found in sub...
Mancuso VA, Hope TJ, Zhu L, Derse D, Phillips T, Parslow TG.By systematically dissecting the Rev proteins of feline immunodeficiency virus (FIV) and equine infectious anemia virus (EIAV), we have identified within each a short peptide that is functionally interchangeable with the effector domains found in Rev-like proteins from other retroviruses. The active sequences from FIV and EIAV differ in several respects from other known effectors and may represent a distinct class of effector domain.
Gibson SJ, Polak JM, Allen JM, Adrian TE, Kelly JS, Bloom SR.The distribution of neuropeptide Y [NPY]-immunoreactive material was examined in the spinal cord and dorsal root ganglia of rat, guinea-pig, cat, marmoset, and horse. Considerable concentrations of NPY and similar distribution patterns of immunoreactive nerve fibres were found in the spinal cord of all species investigated. The dorsal root ganglia of the cat and the horse contained numerous immunoreactive nerve fibres, but in these species, as in the other three studied [rat, guinea-pig, marmoset], no positively stained cell bodies were found. Neuropeptide Y-immunoreactive nerves were observed...
de la Rosa G, Olvera F, Archundia IG, Lomonte B, Alagón A, Corzo G.Antivenoms are fundamental in the therapy for snakebites. In elapid venoms, there are toxins, e.g. short-chain α-neurotoxins, which are quite abundant, highly toxic, and consequently play a major role in envenomation processes. The core problem is that such α-neurotoxins are weakly immunogenic, and many current elapid antivenoms show low reactivity towards them. We have previously developed a recombinant consensus short-chain α-neurotoxin (ScNtx) based on sequences from the most lethal elapid venoms from America, Africa, Asia, and Oceania. Here we report that an antivenom generated by immu...
Villalta M, Pla D, Yang SL, Sanz L, Segura A, Vargas M, Chen PY, Herrera M, Estrada R, Cheng YF, Lee CD, Cerdas M, Chiang JR, Angulo Y, León G....The proteomes of the venoms of the snakes Viridovipera stejnegeri and Protobothrops mucrosquamatus from Taiwan were characterized by N-terminal sequencing, MALDI-TOF mass fingerprinting, and collision-induced dissociation tandem mass spectrometry of in-gel generated tryptic peptides. Proteins belonging to the following toxin classes were identified: metalloproteinase, phospholipase A(2) (PLA(2)), serine proteinase, C-type lectin-like, CRISP, l-amino acid oxidase, disintegrin, and peptides (vasoactive and inhibitors of SVMPs). Nine horses were immunized with a mixture of these venoms. All horse...
Bruhn O, Grötzinger J, Cascorbi I, Jung S.Antimicrobial peptides play a pivotal role as key effectors of the innate immune system in plants and animals and act as endogenous antibiotics. The molecules exhibit an antimicrobial activity against bacteria, viruses, and eukaryotic pathogens with different specificities and potencies depending on the structure and amino-acid composition of the peptides. Several antimicrobial peptides were comprehensively investigated in the last three decades and some molecules with remarkable antimicrobial properties have reached the third phase of clinical studies. Next to the peptides themselves, numerou...
Payne SL, Salinovich O, Nauman SM, Issel CJ, Montelaro RC.Comparisons of peptide and oligonucleotide maps of glycoproteins and RNA from nine isolates of equine infectious anemia virus (EIAV) that were generated during parallel infections of two Shetland ponies revealed that each isolate was structurally unique. Each EIAV isolate contained a unique subset of variant peptides, oligonucleotides, or both, indicating that structural variation in EIAV is a random and noncumulative process and that a large spectrum of possible EIAV variants can be generated in infected animals.
McFarlane D, Dybdal N, Donaldson MT, Miller L, Cribb AE.Equine pituitary pars intermedia dysfunction (PPID) is a spontaneously occurring progressive disease affecting aged horses and ponies. The pathogenesis of PPID is poorly understood, but the available evidence supports a loss of dopaminergic inhibition of the melanotropes of the pars intermedia. Horses with PPID have increased plasma concentrations of pars intermedia pro-opiomelanocortin-derived peptides that decrease in response to dopamine or dopamine agonist administration. Dopamine and dopamine metabolite concentrations are decreased in the pars intermedia of affected horses compared to age...
Derse D, Carvalho M, Carroll R, Peterlin BM.Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of b...
Bonnefoy A, Romijn RA, Vandervoort PA, VAN Rompaey I, Vermylen J, Hoylaerts MF.Binding of von Willebrand factor (VWF) to platelet GPIbalpha and to collagen is attributed to VWF A1 and A3 domains, respectively. Objective: Using VWF, VWF lacking A1 (DeltaA1-VWF) or A3 (DeltaA3-VWF) and VWF with defective A3 (H1786A-VWF), in combination with recombinant A1 (residues 1262-1492) or A3 (residues 1671-1878), fused to glutathione-S-transferase (GST-A1 and GST-A3), we have re-investigated the role of A1 in platelet recruitment to surfaces of collagen. Results: In flow, measurable binding of DeltaA3-VWF occurred to horse tendon, but also to human type III collagen. GST-A1 and GST-...
