RESUMEN
Gene therapy approaches using adeno-associated viral vectors have been successfully tested in the equine post-traumatic osteoarthritis (PTOA) model. Owing to differences in the levels of transgene expression and adverse tissue reactions observed in published studies, we sought to identify a safe therapeutic dose of scAAVIL-1ra in an inflamed and injured joint that would result in improved functional outcomes without any adverse events. scAAVIL-1ra was delivered intra-articularly over a 100-fold range, and horses were evaluated throughout and at the end of the 10-week study. A dose-related increase in IL-1ra levels with a decrease in PGE2 levels was observed, with the peak IL-1ra concentration being observed 7 days post-treatment in all groups. Perivascular infiltration with mononuclear cells was observed within the synovial membrane of the joint treated with the highest viral dose of 5 × 1012 vg, but this was absent in the lower-dosed joints. The second-highest dose of scAAVeqIL-1ra 5 × 1011 vg demonstrated elevated IL-1ra levels without any cellular response in the synovium. Taken together, the data suggest that the 10-fold lower dose of 5 × 1011vg scAAVIL-1ra would be a safe therapeutic dose in an equine model of PTOA.
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Proteína Antagonista del Receptor de Interleucina 1 , Osteoartritis , Animales , Caballos/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Proyectos Piloto , Vectores Genéticos , Osteoartritis/terapia , Osteoartritis/metabolismo , Modelos AnimalesRESUMEN
Aims: To compare the outcome, in terms of lameness score or return to athletic function, of horses with acute vs. chronic digital lameness that underwent magnetic resonance imaging (MRI) of the distal limb and to compare the proportion of horses that received intra-articular therapy of the distal interphalangeal (DIP) joint and pattern of diagnostic analgesia in these groups. Methods: This is a retrospective study of horses (n = 95) with acute (≤12 weeks; n = 46) or chronic (>12 weeks; n = 49) digital lameness that underwent MRI of the distal limb from 2009-2016, at two equine referral centres in the USA. Criteria for inclusion in the study were that a majority of lameness localised distal to the fetlock, and that lameness assessments for ≥12 months following MRI could be obtained from the medical record or the owner could be interviewed regarding their horse's athletic function. Outcome was characterised by an improvement score where 2 = return to work at a previous or higher level or lameness improved by one grade or more, 1 = return to work at a lower level or lameness improved by less than one grade, and 0 = did not return to work or lameness grade worsened. Whether horses had received intra-articular therapy of the DIP joint and the pattern of diagnostic analgesia prior to MRI was also obtained from medical records or by interviewing the owner. Results: There was a difference (p = 0.004) in the proportion of horses assigned to improvement scores of 0, 1 and 2 between horses with acute or chronic lameness. There was no evidence of a difference in the likelihood of having received intra-articular therapy of the DIP joint prior to MRI between horses with chronic or acute lameness (p = 0.085). Similarly, there was no evidence of a difference in the pattern of diagnostic analgesia prior to MRI between the two groups (p = 0.94). Eighty-two percent of owners of horses with acute and 62% of those with horses with chronic lameness had a positive opinion of the utility of MRI as a diagnostic modality. Conclusion: In a population of horses with digital lameness undergoing MRI, a difference in the outcome, in terms of lameness score or return to athletic function was identified between horses with acute lameness compared to those with chronic lameness. Clinical relevance: Horses with digital lameness that undergo MRI when the lameness is acute may have an improved prognosis due to accurate diagnosis and earlier application of appropriate therapy.
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Enfermedad Aguda , Enfermedad Crónica/veterinaria , Enfermedades de los Caballos/diagnóstico por imagen , Cojera Animal/diagnóstico por imagen , Recuperación de la Función , Enfermedad Aguda/terapia , Analgesia/métodos , Analgesia/veterinaria , Animales , California , Enfermedad Crónica/terapia , Colorado , Femenino , Miembro Anterior/diagnóstico por imagen , Enfermedades de los Caballos/tratamiento farmacológico , Caballos , Cojera Animal/tratamiento farmacológico , Imagen por Resonancia Magnética/veterinaria , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model. DESIGN: Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.). RESULTS: Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (Eeq) (r = 0.79, P < 0.0001) and safranin-O histological score (r = -0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = -0.44, P < 0.0001) of bone. Mean [95% CI] cationic CECT attenuation at the impact site (2215 [1987, 2443] Hounsfield Units [HUs]) was lower than site-matched controls (2836 [2490, 3182] HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), Eeq (r = 0.26, P = 0.025) and safranin-O histology score (r = -0.32, P = 0.0046). CONCLUSIONS: Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners.
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Cartílago Articular/diagnóstico por imagen , Cartílago Articular/lesiones , Microtomografía por Rayos X , Animales , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/patología , Cartílago Articular/metabolismo , Cartílago Articular/patología , Condrocitos/patología , Colorantes , Fuerza Compresiva , Medios de Contraste , Glicosaminoglicanos/metabolismo , Caballos , Imagen por Resonancia Magnética , Modelos Animales , Osteoartritis de la Rodilla , Fenazinas , Rodilla de Cuadrúpedos/lesiones , Membrana Sinovial/patologíaRESUMEN
OBJECTIVE: IGF-I is one of several anabolic factors being investigated for the treatment of osteoarthritis (OA). Due to the short biological half-life, extended administration is required for more robust cartilage healing. Here we create a self-complimentary adeno-associated virus (AAV) gene therapy vector utilizing the transgene for IGF-I. DESIGN: Various biochemical assays were performed to investigate the cellular response to scAAVIGF-I treatment vs an scAAVGFP positive transduction control and a negative for transduction control culture. RNA-sequencing analysis was also performed to establish a differential regulation profile of scAAVIGF-I transduced chondrocytes. RESULTS: Biochemical analyses indicated an average media IGF-I concentration of 608 ng/ml in the scAAVIGF-I transduced chondrocytes. This increase in IGF-I led to increased expression of collagen type II and aggrecan and increased protein concentrations of cellular collagen type II and media glycosaminoglycan vs both controls. RNA-seq revealed a global regulatory pattern consisting of 113 differentially regulated GO categories including those for chondrocyte and cartilage development and regulation of apoptosis. CONCLUSIONS: This research substantiates that scAAVIGF-I gene therapy vector increased production of IGF-I to clinically relevant levels with a biological response by chondrocytes conducive to increased cartilage healing. The RNA-seq further established a set of differentially expressed genes and gene ontologies induced by the scAAVIGF-I vector while controlling for AAV infection. This dataset provides a static representation of the cellular transcriptome that, while only consisting of one time point, will allow for further gene expression analyses to compare additional cartilage healing therapeutics or a transient cellular response.
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Cartílago Articular/metabolismo , Condrocitos/metabolismo , Terapia Genética/métodos , Caballos/metabolismo , Factor I del Crecimiento Similar a la Insulina/genética , Animales , Cartílago Articular/citología , Dependovirus/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Ontología de Genes , Vectores Genéticos/genética , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Análisis de Secuencia de ARN/métodos , Transducción Genética , TransgenesRESUMEN
A gene therapeutic approach to treat osteoarthritis (OA) appears to be on the horizon for millions of people who suffer from this disease. Previously we described optimization of a scAAVIL-1ra gene therapeutic vector and initially tested this in an equine model verifying long-term intrasynovial IL-1ra protein at therapeutic levels. Using this vector, we carried out a dosing trial in six horses to verify protein levels and establish a dose that would express relevant levels of therapeutic protein for extended periods of time (8 months). A novel arthroscopic procedure used to detect green fluorescence protein (GFP) fluorescence intrasynovially confirmed successful transduction of the scAAVGFP vector in both the synovial and cartilage tissues. No evidence of intra-articular toxicity was detected. Immune responses to vector revealed development of neutralizing antibodies (Nabs) within 2 weeks of administration, which persisted for the duration of the study but did not lower protein expression intra-articularly. Re-dosing with a different serotype to attain therapeutic levels of protein confirmed establishment of successful transduction. This is the first study in an equine model to establish a dosing/redosing protocol, as well as examine the Nab response to capsid and supports further clinical investigation to determine the clinical efficacy of scAAVIL-1ra to treat OA.
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Expresión Génica/inmunología , Vectores Genéticos/administración & dosificación , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Osteoartritis/inmunología , Osteoartritis/terapia , Animales , Anticuerpos Neutralizantes/metabolismo , Articulaciones del Carpo/inmunología , Articulaciones del Carpo/metabolismo , Articulaciones del Carpo/patología , Cartílago Articular/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta Inmunológica , Terapia Genética , Vectores Genéticos/inmunología , Vectores Genéticos/uso terapéutico , Caballos , Proteína Antagonista del Receptor de Interleucina 1/inmunología , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Membrana Sinovial/metabolismoRESUMEN
We review variable-temperature, transport critical-current (I c) measurements made on commercial superconductors over a range of critical currents from less than 0.1 A to about 1 kA. We have developed and used a number of systems to make these measurements over the last 15 years. Two exemplary variable-temperature systems with coil sample geometries will be described: a probe that is only variable-temperature and a probe that is variable-temperature and variable-strain. The most significant challenge for these measurements is temperature stability, since large amounts of heat can be generated by the flow of high current through the resistive sample fixture. Therefore, a significant portion of this review is focused on the reduction of temperature errors to less than ±0.05 K in such measurements. A key feature of our system is a pre-regulator that converts a flow of liquid helium to gas and heats the gas to a temperature close to the target sample temperature. The pre-regulator is not in close proximity to the sample and it is controlled independently of the sample temperature. This allows us to independently control the total cooling power, and thereby fine tune the sample cooling power at any sample temperature. The same general temperature-control philosophy is used in all of our variable-temperature systems, but the addition of another variable, such as strain, forces compromises in design and results in some differences in operation and protocol. These aspects are analyzed to assess the extent to which the protocols for our systems might be generalized to other systems at other laboratories. Our approach to variable-temperature measurements is also placed in the general context of measurement-system design, and the perceived advantages and disadvantages of design choices are presented. To verify the accuracy of the variable-temperature measurements, we compared critical-current values obtained on a specimen immersed in liquid helium ("liquid" or I c liq) at 5 K to those measured on the same specimen in flowing helium gas ("gas" or I c gas) at the same temperature. These comparisons indicate the temperature control is effective over the superconducting wire length between the voltage taps, and this condition is valid for all types of sample investigated, including Nb-Ti, Nb3Sn, and MgB2 wires. The liquid/gas comparisons are used to study the variable-temperature measurement protocol that was necessary to obtain the "correct" critical current, which was assumed to be the I c liq. We also calibrated the magnetoresistance effect of resistive thermometers for temperatures from 4 K to 35 K and magnetic fields from 0 T to 16 T. This calibration reduces systematic errors in the variable-temperature data, but it does not affect the liquid/gas comparison since the same thermometers are used in both cases.
RESUMEN
Chromosome 3q alterations occur frequently in many types of tumours. In a genetic screen for loci present in rhabdomyosarcomas, we identified an isochromosome 3q [i(3q)], which inhibits muscle differentiation when transferred into myoblasts. The i(3q) inhibits MyoD function, resulting in a non-differentiating phenotype. Furthermore, the i(3q) induces a 'cut' phenotype, abnormal centrosome amplification, aneuploidy and loss of G1 arrest following gamma-irradiation. Testing candidate genes within this region reveals that forced expression of ataxia-telangiectasia and rad3-related (ATR) results in a phenocopy of the i(3q). Thus, genetic alteration of ATR leads to loss of differentiation as well as cell-cycle abnormalities.
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Aneuploidia , Proteínas de Ciclo Celular/genética , Fase G1/efectos de la radiación , Familia de Multigenes , Proteína MioD/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas , Proteínas de la Ataxia Telangiectasia Mutada , División Celular , Cromosomas Humanos Par 3 , Humanos , Isocromosomas , Músculos/citología , Proteína MioD/fisiología , Rabdomiosarcoma/genética , Rabdomiosarcoma/patología , Células Tumorales CultivadasRESUMEN
We describe the successful application of a modified gene-trap approach, the secretory trap, to systematically analyze the functions in vivo of large numbers of genes encoding secreted and membrane proteins. Secretory-trap insertions in embryonic stem cells can be transmitted to the germ line of mice with high efficiency and effectively mutate the target gene. Of 60 insertions analyzed in mice, one-third cause recessive lethal phenotypes affecting various stages of embryonic and postnatal development. Thus, secretory-trap mutagenesis can be used for a genome-wide functional analysis of cell signaling pathways that are critical for normal mammalian development and physiology.
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Proteínas de la Membrana/genética , Ratones/genética , Biología Molecular/métodos , Proteínas/metabolismo , Animales , Blastocisto/citología , Cruzamiento , Genes Letales , Vectores Genéticos , Genotipo , Mutagénesis Insercional , Fenotipo , Reacción en Cadena de la Polimerasa , Selección Genética , Lugares Marcados de Secuencia , Células Madre/citologíaRESUMEN
We compare methods for estimating the residual resistivity ratio (RRR) of high-purity niobium and investigate the effects of using different functional models. RRR is typically defined as the ratio of the electrical resistances measured at 273 K (the ice point) and 4.2 K (the boiling point of helium at standard atmospheric pressure). However, pure niobium is superconducting below about 9.3 K, so the low-temperature resistance is defined as the normal-state (i.e., non-superconducting state) resistance extrapolated to 4.2 K and zero magnetic field. Thus, the estimated value of RRR depends significantly on the model used for extrapolation. We examine three models for extrapolation based on temperature versus resistance, two models for extrapolation based on magnetic field versus resistance, and a new model based on the Kohler relationship that can be applied to combined temperature and field data. We also investigate the possibility of re-defining RRR so that the quantity is not dependent on extrapolation.
RESUMEN
The ability to perceive and interact with the world depends on a diverse array of neural circuits specialized for carrying out specific computations. Each circuit is assembled using a relatively limited number of molecules and common developmental steps, from cell fate specification to activity-dependent synaptic refinement. Given this shared toolkit, how do individual circuits acquire their characteristic properties? We explore this question by comparing development of the circuitry for seeing and hearing, highlighting a few examples where differences in each system's sensory demands necessitate different developmental strategies.
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Vías Auditivas/embriología , Núcleo Coclear/embriología , Neurogénesis , Retina/embriología , Vías Visuales/embriología , Animales , Audición/fisiología , Ratones , Células Receptoras Sensoriales/ultraestructura , Sinapsis/ultraestructura , Visión Ocular/fisiologíaRESUMEN
UNLABELLED: Summary Reasons for performing study: Medial meniscal injuries and subchondral cystic lesions (SCL) are known to occur independently within the medial femorotibial (MFT) joint in horses. However, there are no reports of a potential clinical relationship between these 2 types of lesions. OBJECTIVES: To: 1) document the concurrent presence or sequential development of medial meniscal and SCL of the medial femoral condyle within the MFT joint; and 2) determine the prognosis with both types of lesions. METHODS: Retrospective case series of horses with both a medial meniscal and SCL of the medial femoral condyle identified concurrently or sequentially by radiography, arthroscopy or post mortem examination. Case records and radiographs were reviewed, and a telephone survey of referring veterinarians, owners and trainers was conducted. RESULTS: Twenty-one horses (9.1% of all horses undergoing MFT joint arthroscopy) were identified to have both a medial meniscal injury and SCL of the medial femoral condyle. Thirteen horses had both abnormalities identified concurrently, 6 developed a meniscal lesion subsequent to SCL debridement, and 2 developed a SCL subsequent to a medial meniscal injury. Only 4/19 horses were classified as successful and returned to their intended use. The severity of the meniscal injury was significantly associated with the severity of lameness but not with outcome. CONCLUSIONS: A low percentage of horses may develop both a meniscal injury and SCL of the medial femoral condyle within the MFT joint and have a poor prognosis. POTENTIAL RELEVANCE: Trauma to the MFT joint may lead to both meniscal and subchondral bone damage of the medial femoral condyle that may be recognised concurrently or sequentially.
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Cartílago Articular/patología , Quistes/veterinaria , Enfermedades de los Caballos/patología , Rodilla de Cuadrúpedos/patología , Animales , Artroscopía/veterinaria , Quistes/patología , Femenino , Caballos , Masculino , Estudios RetrospectivosRESUMEN
In the developing nervous system, axons navigate through complex terrains that change depending on when and where outgrowth begins. For instance, in the developing cochlea, spiral ganglion neurons extend their peripheral processes through a growing and heterogeneous environment en route to their final targets, the hair cells. Although the basic principles of axon guidance are well established, it remains unclear how axons adjust strategies over time and space. Here, we show that neurons with different positions in the spiral ganglion employ different guidance mechanisms, with evidence for both glia-guided growth and fasciculation along a neuronal scaffold. Processes from neurons in the rear of the ganglion are more directed and grow faster than those from neurons at the border of the ganglion. Further, processes at the wavefront grow more efficiently when in contact with glial precursors growing ahead of them. These findings suggest a tiered mechanism for reliable axon guidance.
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Cóclea/citología , Cóclea/embriología , Neuroglía/citología , Ganglio Espiral de la Cóclea/citología , Animales , Orientación del Axón/fisiología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Movimiento Celular , Femenino , Ratones Transgénicos , Proteínas del Tejido Nervioso/genética , Neuritas/fisiología , Neuroglía/fisiología , Neuronas/citología , Neuronas/fisiología , Técnicas de Cultivo de Órganos , Embarazo , Ganglio Espiral de la Cóclea/fisiología , Imagen de Lapso de TiempoRESUMEN
BACKGROUND: Allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) could provide multiple advantages over autologous BMDMSCs, including creating an 'off-the-shelf' treatment together with the ability to control for donor variation. OBJECTIVES: The objective of the study was to compare the clinical and synovial fluid response of the normal equine joint to autologous and pooled-allogeneic BMDMSCs while controlling for individual variation and joint variations in response to intra-articular injections. We hypothesised that, by controlling for individual animal and joint variation, we could identify differences between allogeneic vs. autologous BMDMSCs in noninflamed joints. STUDY DESIGN: Randomised-controlled experiment. METHODS: Bone marrow was harvested from eight horses. Autologous BMDMSCs were culture expanded, cryopreserved and thawed immediately prior to administration. For allogeneic BMDMSC treatments, four horses' BMDMSCs were culture expanded, pooled, cryopreserved and thawed immediately prior to use. Ten million (autologous or pooled-allogeneic) BMDMSCs were administered into contralateral forelimb metacarpophalangeal joints so that every autologous and allogeneic injection could be compared within the same animal. Clinical parameters included subjective lameness, objective lameness (Lameness Locator™), response to flexion, joint circumference and joint effusion. Arthrocentesis was performed for assessment of the nucleated cell count, differential cell count, total protein, and synovial concentrations of prostaglandin E2 (PGE2) and c-reactive protein (CRP). All parameters were measured at baseline, 6, 12, 24, 72, 168 and 336 h post-injection. RESULTS: No difference was detected in any parameters between forelimb metacarpophalangeal joints administered autologous or pooled-allogeneic BMDMSCs. MAIN LIMITATIONS: This study did not attempt to measure efficacy of BMDMSCs for musculoskeletal disease and should be followed by properly controlled efficacy trials. CONCLUSIONS: The study did not identify any clinical or cytological differences in the normal joint response to allogeneic or autologous BMDMSCs. A larger study to prove equivalence is warranted as allogeneic BMDMSCs may be a feasible alternative to autologous BMDMSCs.
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Células de la Médula Ósea , Caballos , Trasplante de Células Madre Mesenquimatosas/veterinaria , Células Madre Mesenquimatosas/fisiología , Animales , Biomarcadores/química , Inyecciones Intraarticulares , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Líquido Sinovial , Trasplante Autólogo , Trasplante HomólogoRESUMEN
The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS). Functions of PTC were investigated by inactivating the mouse gene. Mice homozygous for the ptc mutation died during embryogenesis and were found to have open and overgrown neural tubes. Two Shh target genes, ptc itself and Gli, were derepressed in the ectoderm and mesoderm but not in the endoderm. Shh targets that are, under normal conditions, transcribed ventrally were aberrantly expressed in dorsal and lateral neural tube cells. Thus Ptc appears to be essential for repression of genes that are locally activated by Shh. Mice heterozygous for the ptc mutation were larger than normal, and a subset of them developed hindlimb defects or cerebellar medulloblastomas, abnormalities also seen in BCNS patients.
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Sistema Nervioso Central/embriología , Neoplasias Cerebelosas/genética , Regulación del Desarrollo de la Expresión Génica , Meduloblastoma/genética , Proteínas de la Membrana/genética , Anomalías Múltiples/genética , Animales , Tipificación del Cuerpo , Linaje de la Célula , Sistema Nervioso Central/citología , Neoplasias Cerebelosas/patología , Ectodermo/metabolismo , Endodermo/metabolismo , Genes Supresores de Tumor , Heterocigoto , Homocigoto , Péptidos y Proteínas de Señalización Intracelular , Meduloblastoma/patología , Proteínas de la Membrana/fisiología , Mesodermo/metabolismo , Ratones , Ratones Endogámicos C57BL , Mutación , Proteínas Oncogénicas/genética , Receptores Patched , Receptor Patched-1 , Receptores de Superficie Celular , Transactivadores , Factores de Transcripción/genética , Proteína con Dedos de Zinc GLI1RESUMEN
The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.
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Síndrome del Nevo Basocelular/genética , Proteínas de Drosophila , Genes Supresores de Tumor , Proteínas de la Membrana/genética , Adulto , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN de Neoplasias , Drosophila , Femenino , Mutación del Sistema de Lectura , Humanos , Hormonas de Insectos/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Receptores Patched , Receptor Patched-1 , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , Conformación Proteica , Receptores de Superficie CelularRESUMEN
The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signaling protein, its receptor Patched, the transcription factor Cubitus interruptus, and the engrailed target gene that break the conserved compartmental restrictions on this regulatory circuit in insect wings. Redeployment of preexisting regulatory circuits may be a general mechanism underlying the evolution of novelties.
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Mariposas Diurnas/genética , Proteínas de Drosophila , Regulación de la Expresión Génica , Proteínas de Insectos/genética , Alas de Animales/crecimiento & desarrollo , Animales , Evolución Biológica , Tipificación del Cuerpo , Mariposas Diurnas/anatomía & histología , Mariposas Diurnas/crecimiento & desarrollo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/fisiología , Genes de Insecto , Proteínas Hedgehog , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/fisiología , Proteínas de Insectos/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Pigmentación , Receptores de Superficie Celular , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Transcripción Genética , Alas de Animales/anatomía & histología , Alas de Animales/metabolismoRESUMEN
Almond harvest accounts for substantial particulate matter less than 10 microm in aerodynamic diameter (PM10) emissions in California each harvest season. This paper addresses the reduction of harvester ground speed from a standard 8 km/hr (5 mph) to 4 km/hr (2.5 mph) as a possible mitigation measure for reducing PM10 emissions. Ambient total suspended particulate (TSP) and PM10 sampling was conducted during harvest with alternating control (8 km/hr [5 mph]) and experimental (4 km/hr [2.5 mph]) treatments. On-site meteorological data were used in conjunction with both Industrial Source Complex-Short Term version 3 (ISCST3) and the American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model (AERMOD) dispersion models to back-calculate emission rates from the measured concentrations. Baseline annual emission factors for nut pickup of 381 +/- 122 and 361 +/- 123 kg PM10/km2 x yr were determined using ISCST3 and AERMOD, respectively. Both of these values are substantially lower than the current PMIo emission factor for almond pickup of 4120 kg PM10/ km2 x yr. The particulate matter less than 2.5 microm in aerodynamic diameter (PM2.5) emission factors for nut pickup developed from this study were 25 +/- 8 kg PM2.5/km2 x yr and 24 +/- 8 kg PM10/km2 x yr were determined using ISCST3 and AERMOD, respectively. Reducing harvester speed resulted in an emissions reduction of 42% for TSP, but no differences were detected in emissions of PM10 and PM2.5. Differences detected in the emission factors developed using ISCST3 and AERMOD were not statistically significant, indicating that almond harvest emission factors previously developed using ISCST3 may be applied appropriately in AERMOD.
Asunto(s)
Contaminación del Aire/análisis , Material Particulado/análisis , Prunus , Agricultura , Contaminación del Aire/prevención & control , California , Monitoreo del Ambiente , Modelos Teóricos , Tamaño de la Partícula , Material Particulado/químicaRESUMEN
BACKGROUND: Lameness can be multifactorial and may result from the accumulation of multiple seemingly unrelated causes. The identification of factors associated with lameness could be one method to decrease incidence of lameness and prolong the equine athlete's competitive life. OBJECTIVES: To determine if there is an association between hoof balance in the sagittal plane and hindlimb lameness. STUDY DESIGN: Case-control study. METHODS: Eighty client-owned horses with hindlimb lameness (cases) and 80 horses with no detectable hindlimb lameness (controls) were prospectively enroled following lameness evaluation as either cases (lameness localised with regional anaesthesia) or controls (no hindlimb lameness). Lameness cases were divided based on location (stifle, tarsus, proximal metatarsus and other sites). Lateromedial radiographs were performed on hind hooves and plantar angle of the distal phalanx (PADP) was determined. The prevalence of negative/neutral PADP and median PADPs were calculated. Conditional logistic regression and Wilcoxon signed rank tests were used to analyse PADPs, and odds ratios were calculated. Significance was set at P<0.05. RESULTS: The mean PADP was significantly smaller in cases compared to controls. The mean PADP was significantly smaller in horses with lameness localised to tarsus and proximal suspensory, but not the stifle. Lameness in horses was associated with a negative/neutral PADP (Odds ratio [OR] 3.87, 95% confidence interval [95% CI] 1.97-7.61, P<0.01), with lameness localised to the tarsus (OR 4.98, 95% CI 1.34-18.54, P = 0.01) and proximal suspensory (OR 5.16, 95% CI 1.11-23.89, P = 0.03) being associated with a negative/neutral PADP. MAIN LIMITATIONS: It is unknown whether the negative/neutral PADP contributed to lameness or lameness resulted in lower PADP. CONCLUSIONS: Horses with hindlimb lameness localised to the distal tarsus and proximal metatarsus, but not the stifle, were more likely to have negative/neutral PADPs. Corrective farriery to improve PADP may be investigated further as one component in the treatment of hindlimb lameness localised to regions proximal to the foot. The Summary is available in Portuguese - see Supporting Information.
Asunto(s)
Miembro Posterior/patología , Pezuñas y Garras/anatomía & histología , Enfermedades de los Caballos/diagnóstico , Cojera Animal/diagnóstico , Animales , Estudios de Casos y Controles , Pezuñas y Garras/patología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/terapia , Caballos , Cojera Animal/terapia , Trastornos del MovimientoRESUMEN
REASONS FOR PERFORMING STUDY: There are no published results of subchondral cystic lesions (SCLs) in the medial femoral condyle (MFC) treated with arthroscopic injection of corticosteroids into the lining of the cyst. OBJECTIVES: 1) To determine the success rate for treatment of SCLs in the MFC with arthroscopic injection of the fibrous tissue of the cyst with corticosteroids. 2) To identify any factors that may predict outcome. HYPOTHESES: Injection of the fibrous tissue of SCLs of the MFC with corticosteroids utilising arthroscopic guidance yields a similar or higher chance for intended performance than does arthroscopic debridement as previously reported; this technique will be effective for treating SCLs in older horses. METHODS: Horses with clinical and radiographic evidence of a SCL in the MFC were injected with corticosteroids under arthroscopic guidance, and case records and radiographs were reviewed retrospectively. A telephone survey of referring veterinarians, owners and trainers was conducted. RESULTS: Thirty-five of 52 (67%) cases were classified as successful involving 73 SCLs of which 56 (77%) were classified as successful. There was no significant association between age group (age
Asunto(s)
Corticoesteroides/uso terapéutico , Quistes Óseos/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Inyecciones Intraarticulares/veterinaria , Corticoesteroides/administración & dosificación , Animales , Artroscopía/veterinaria , Quistes Óseos/tratamiento farmacológico , Femenino , Fémur/efectos de los fármacos , Fémur/patología , Miembro Anterior , Miembro Posterior , Caballos , Cojera Animal/tratamiento farmacológico , Masculino , Recuperación de la Función , Estudios Retrospectivos , Rodilla de Cuadrúpedos/efectos de los fármacos , Rodilla de Cuadrúpedos/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Articular cartilage is a critical joint tissue and its evaluation remains a diagnostic challenge in horses. Coupled with a poor capacity for healing, early degenerative changes in articular cartilage are difficult to characterise using routine diagnostic imaging evaluations. Both computed tomography (CT) and magnetic resonance imaging (MRI) provide volumetric joint assessment and highlight morphological and quantitative properties of articular cartilage, improving assessment of this essential tissue. While the use of CT and MRI for joint evaluation is not new, there still remains a shortage of literature and scientific studies on the ability of these methods to evaluate articular cartilage in the horse. This review article summarises current CT and MRI techniques capable of characterising equine articular cartilage, highlights recent advances in these techniques and discusses the numerous methods studied in human subjects that have been minimally investigated in horses. Imaging techniques are presented in terms of their capabilities of offering morphological and quantitative evaluation along with a discussion of their benefits and limitations. Finally, it summarises the current state-of-the-art approaches and identifies unmet clinical imaging needs to propel the advancement of articular cartilage and joint imaging in the horse.