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1.
J Dairy Sci ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908711

RESUMEN

Milking speed is an important trait influencing udder health of dairy cows as well as labor efficiency. Yet, it has received little attention in genomic association studies. The main objective of this study was to determine regions and genes on the genome with a potential effect on milking speed in Fleckvieh (dual purpose Simmental) cattle. Genome-wide association studies were conducted using de-regressed breeding values of bulls as phenotypes. Six SNP on 4 autosomes were significantly associated with milking speed for additive effects. Significant regions on BTA4 and BTA19 correspond with findings for other dairy cattle breeds. Based on the observation of Fleckvieh breed managers, variation of milking speed in batches of daughters of some bulls is much higher than in daughter groups of other bulls. This difference in within family variation may be caused by transmission of alternative alleles of bulls being heterozygous for a gene affecting milking speed. To check on this, we considered standard deviation of yield deviations in milking speed of half-sib daughters as a new trait and performed GWAS for dominance effects. One signal on BTA5 passed the genome wide Bonferroni threshold that corresponded to the significant signal from standard GWAS on de-regressed breeding values. The key conclusion of this study is that several strong genomic signals were found for milking speed in Fleckvieh cattle and that the strongest of them are supported by similar findings in Brown Swiss and Holstein Friesian cattle. Milking speed is a complex trait whose sub-processes have not yet been elucidated in detail. Hence, it remains a challenge to link the associated regions on the genome with causal genes and their functions.

2.
Trop Anim Health Prod ; 52(4): 2179-2189, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32128662

RESUMEN

Cattle production is an essential livelihood strategy in south-western Burkina Faso. Although having a distinct cultural role and known to be resistant against African animal trypanosomosis, the Lobi taurine cattle breed is endangered due to its low market value. As the first step in preservation efforts, our study aimed to develop a typology of production systems at the farm level. We used a structured questionnaire and focus group discussions for collecting data on household characteristics, socioeconomic activities, livestock, and access to services. The sample comprised 169 households in three communities. The analytical strategy included factor analysis of mixed data and hierarchical clustering. We identified four distinct types of cattle production systems: (1) sedentary Lobi farms, (2) sedentary crossbreed farms, (3) semi-transhumant Fulani zebu farms, and (4) transhumant Fulani zebu farms. Significant factors in developing this typology were the farmers' ethnic group, crop diversity, cattle herd size, cattle herd composition, number of small ruminants, and livestock management strategies. Across all production systems, men were considered being primary decision-makers in cattle production, with women, herders, and children being responsible for specific tasks. All identified production systems are increasingly confronting disease pressure and scarcity of water and land. Future efforts in preservation and breeding will need to respond to these trends in the agroecosystem, integrate risk management measures, and resonate with the specific needs of the different household members involved in cattle rearing.


Asunto(s)
Crianza de Animales Domésticos , Cruzamiento , Agricultores , Ganado , Animales , Burkina Faso , Bovinos , Composición Familiar , Granjas , Femenino , Grupos Focales , Humanos , Masculino , Encuestas y Cuestionarios
3.
Anim Genet ; 50(5): 423-429, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31294880

RESUMEN

A specific white spotting phenotype, termed finching or line-backed spotting, is known for all Pinzgauer cattle and occurs occasionally in Tux-Zillertaler cattle, two Austrian breeds. The so-called Pinzgauer spotting is inherited as an autosomal incompletely dominant trait. A genome-wide association study using 27 white spotted and 16 solid-coloured Tux-Zillertaler cattle, based on 777k SNP data, revealed a strong signal on chromosome 6 at the KIT locus. Haplotype analyses defined a critical interval of 122 kb downstream of the KIT coding region. Whole-genome sequencing of a Pinzgauer cattle and comparison to 338 control genomes revealed a complex structural variant consisting of a 9.4-kb deletion and an inversely inserted duplication of 1.5 kb fused to a 310-kb duplicated segment from chromosome 4. A diagnostic PCR was developed for straightforward genotyping of carriers for this structural variant (KITPINZ ) and confirmed that the variant allele was present in all Pinzgauer and most of the white spotted Tux-Zillertaler cattle. In addition, we detected the variant in all Slovenian Cika, British Gloucester and Spanish Berrenda en negro cattle with similar spotting patterns. Interestingly, the KITPINZ variant occurs in some white spotted animals of the Swiss breeds Evolèner and Eringer. The introgression of the KITPINZ variant confirms admixture and the reported historical relationship of these short-headed breeds with Austrian Tux-Zillertaler and suggests a mutation event, occurring before breed formation.


Asunto(s)
Bovinos/genética , Cromosomas de los Mamíferos , Pigmentación , Proteínas Proto-Oncogénicas c-kit/genética , Animales , Bovinos/clasificación , Duplicación Cromosómica , Estudio de Asociación del Genoma Completo , Variación Estructural del Genoma , Polimorfismo de Nucleótido Simple
4.
J Dairy Sci ; 102(5): 4238-4248, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30827548

RESUMEN

The genetic correlations (ra) of milk lactose percentage (LP), lactose yield (LY), and ratios of LP to other milk solids with udder, metabolic, and fertility disorders have not been assessed in dairy cattle so far. To evaluate the potential role of milk lactose as indicator of cow health, 142,285 lactation records of 84,289 Austrian Fleckvieh cows were analyzed with univariate and bivariate animal models. Milk traits were on a 150-d basis and health traits were coded as binary (0/1). Other than LP and LY, 3 new phenotypes were defined and included in the present study, namely the lactose-to-fat, lactose-to-protein, and lactose-to-solids ratios. The most heritable trait was LP (0.566 ± 0.008) and heritability of LY was much lower (0.145 ± 0.005). Heritability estimates close to 0.50 were assessed for the ratios. The frequency of health disorders was higher in multiparous cows yielding milk with low LP (≤4.553%) compared with cows yielding milk with high LP (≥5.045%). Heritabilities of health traits were in the expected ranges, with the highest estimate for ovarian cysts (CYS; 0.037 ± 0.004) and the lowest for retained placenta (0.005 ± 0.001). Mastitis (MAS) genetically correlated with LY (0.518 ± 0.057); considering that the amount of synthesized lactose is the key regulator of milk volume, this result confirmed that high-producing cows are more genetically susceptible to MAS than low-producing animals. Similar to MAS, ketosis (KET) was also positively genetically associated with LY (0.420 ± 0.077) and a weak and unfavorable ra between KET and lactose-to-protein ratio was estimated (0.159 ± 0.077). The ra of LY with milk fever (MFV) and CYS were approximately 0.20. The ra of LP with MAS, KET, and MFV were negative (-0.142 on average), supporting the idea that LP is a potential health indicator. Genetic correlations between health traits ranged from zero (retained placenta with MAS and CYS) to 0.463 ± 0.090 (MAS and MFV). Results of the present study suggest that LP has potentiality to be used as indicator trait to improve udder health in Austrian Fleckvieh population.


Asunto(s)
Enfermedades de los Bovinos/genética , Bovinos/genética , Lactosa/genética , Leche/química , Animales , Austria , Femenino , Predisposición Genética a la Enfermedad , Cetosis/genética , Cetosis/veterinaria , Lactancia/genética , Masculino , Glándulas Mamarias Animales , Mastitis/genética , Mastitis/veterinaria , Fenotipo , Retención de la Placenta/veterinaria , Embarazo , Carácter Cuantitativo Heredable
5.
J Dairy Sci ; 102(12): 11217-11224, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31548062

RESUMEN

Heterosis is the beneficial deviation of crossbred progeny from the average of parental lines for a particular trait. Heterosis is due to nonadditive genetic effects with dominance and epistatic components. Recent advances in genotyping technology have encouraged researchers to estimate and scan heterosis components for a range of traits in crossbred populations, applying various definitions of such components. In this study, we defined the intralocus (dominance) component of heterosis using local genetic ancestry and performed genome-wide association analysis for admixed Swiss Fleckvieh bulls and their parental populations, Red Holstein Friesian and Swiss Simmental, for semen traits. A linear mixed model for 41,824 SNP, including SNP additive genetic, breed additive, and breed dominance effects on 1,178 bulls (148 Red Holstein Friesian, 213 Swiss Simmental, and 817 Swiss Fleckvieh) with a total of 43,782 measurements was performed. In total, 19 significant regions for breed dominance were identified for volume (2 regions on Bos taurus autosome 10 and 22) and percentage of live spermatozoa (17 regions on Bos taurus autosome 3, 4, 5, 7, 13, 14, and 17), and genes associated with spermatogenesis, sperm motility, and male fertility traits were located there. No significant region for breed dominance was detected for total number of spermatozoa. The signals for breed dominance were relatively wide, most likely due to limited numbers of recombination events in a small number of generations (10-15 generations) of crossbreeding in the recent Swiss Fleckvieh composite.


Asunto(s)
Bovinos/genética , Genes Dominantes , Semen , Animales , Cruzamiento , Estudio de Asociación del Genoma Completo/veterinaria , Vigor Híbrido , Masculino , Fenotipo , Polimorfismo de Nucleótido Simple , Motilidad Espermática/genética , Espermatozoides
6.
Phys Rev Lett ; 120(1): 016601, 2018 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-29350952

RESUMEN

A simple and fast analysis method to sort large data sets into groups with shared distinguishing characteristics is described and applied to single molecular break junction conductance versus electrode displacement data. The method, based on principal component analysis, successfully sorts data sets based on the projection of the data onto the first or second principal component of the correlation matrix without the need to assert any specific hypothesis about the expected features within the data. This is an improvement on the current correlation matrix analysis approach because it sorts data automatically, making it more objective and less time consuming, and our method is applicable to a wide range of multivariate data sets. Here the method is demonstrated on two systems. First, it is demonstrated on mixtures of two molecules with identical anchor groups and similar lengths, but either a π (high conductance) or a σ (low conductance) bridge. The mixed data are automatically sorted into two groups containing one molecule or the other. Second, it is demonstrated on break junction data measured with the π bridged molecule alone. Again, the method distinguishes between two groups. These groups are tentatively assigned to different geometries of the molecule in the junction.

7.
J Anim Breed Genet ; 135(1): 45-53, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29164741

RESUMEN

The aim of this study was to estimate the non-additive genetic effects of the dominance component of heterosis as well as epistatic loss on semen traits in admixed Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF) cattle. Heterosis is the additional gain in productivity or fitness of cross-bred progeny over the mid-purebred parental populations. Intralocus gene interaction usually has a positive effect, while epistatic loss generally reduces productivity or fitness due to lack of evolutionarily established interactions of genes from different breeds. Genotypic data on 38,205 SNP of 818 admixed, as well as 148 RHF and 213 SI bulls as the parental breeds were used to predict breed origin of alleles. The genomewide locus-specific breed ancestries of individuals were used to calculate effects of breed difference as well as the dominance component of heterosis, while proxies for two definitions of epistatic loss were derived from 100,000 random pairs of loci. The average Holstein Friesian ancestry in admixed bulls was estimated 0.82. Results of fitting different linear mixed models showed including the dominance component of heterosis considerably improved the model adequacy for three of the four traits. Inclusion of epistatic loss increased the accuracy of the models only for our new definition of the epistatic effect for two traits, while the other definition was so highly correlated with the dominance component that statistical separation was impossible.


Asunto(s)
Cruzamiento , Bovinos/genética , Vigor Híbrido , Semen , Animales , Epistasis Genética , Genotipo , Modelos Estadísticos , Polimorfismo de Nucleótido Simple
8.
J Dairy Sci ; 100(7): 5411-5421, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28527795

RESUMEN

The composition of cow milk is strongly affected by the feeding regimen. Because milk components are routinely determined using mid-infrared (MIR) spectrometry, MIR spectra could also be used to estimate an animal's ration composition. The objective of this study was to determine whether and how well amounts of dry matter intake and the proportions of concentrates, hay, grass silage, maize silage, and pasture in the total ration can be estimated using MIR spectra at an individual animal level. A total of 10,200 milk samples and sets of feed intake data were collected from 90 dairy cows at 2 experimental farms of the Agricultural Research and Education Centre in Raumberg-Gumpenstein, Austria. For each run of analysis, the data set was split into a calibration and a validation data set in a 40:60 ratio. Estimated ration compositions were calculated using a partial least squares regression and then compared with the respective observed ration compositions. In separate analyses, the factors milk yield and concentrate intake were included as additional predictors. To evaluate accuracy, the coefficient of determination (R2) and ratio to performance deviation were used. The highest R2 values (for kg of dry matter intake/for % of ration) for the individual feedstuffs were as follows: pasture, 0.63/0.66; grass silage, 0.32/0.43; concentrate intake, 0.39/0.34; maize silage, 0.32/0.33; and hay, 0.15/0.16. Estimation of groups of feedstuffs (forages, energy-dense feedstuffs) mostly resulted in R2 values >0.50. Including the parameters milk yield or concentrate intake improved R2 values by up to 0.21, with an average improvement of 0.04. The results of this study indicate that not all ration components may be estimated equally accurately. Even if some estimates are good on average, there may be strong deviations between estimated and observed values in individual data sets, and therefore individual estimates should not be overemphasized. Further research including pooled samples (e.g., bulk milk, farm samples) or variations in ration composition is called for.


Asunto(s)
Alimentación Animal/análisis , Dieta/veterinaria , Leche/química , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Austria , Bovinos , Industria Lechera , Femenino , Lactancia , Ensilaje , Espectroscopía Infrarroja Corta/veterinaria , Zea mays
9.
J Dairy Sci ; 100(7): 5479-5490, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28527809

RESUMEN

Genomic selection may accelerate genetic progress in breeding programs of indicine breeds when compared with traditional selection methods. We present results of genomic predictions in Gyr (Bos indicus) dairy cattle of Brazil for milk yield (MY), fat yield (FY), protein yield (PY), and age at first calving using information from bulls and cows. Four different single nucleotide polymorphism (SNP) chips were studied. Additionally, the effect of the use of imputed data on genomic prediction accuracy was studied. A total of 474 bulls and 1,688 cows were genotyped with the Illumina BovineHD (HD; San Diego, CA) and BovineSNP50 (50K) chip, respectively. Genotypes of cows were imputed to HD using FImpute v2.2. After quality check of data, 496,606 markers remained. The HD markers present on the GeneSeek SGGP-20Ki (15,727; Lincoln, NE), 50K (22,152), and GeneSeek GGP-75Ki (65,018) were subset and used to assess the effect of lower SNP density on accuracy of prediction. Deregressed breeding values were used as pseudophenotypes for model training. Data were split into reference and validation to mimic a forward prediction scheme. The reference population consisted of animals whose birth year was ≤2004 and consisted of either only bulls (TR1) or a combination of bulls and dams (TR2), whereas the validation set consisted of younger bulls (born after 2004). Genomic BLUP was used to estimate genomic breeding values (GEBV) and reliability of GEBV (R2PEV) was based on the prediction error variance approach. Reliability of GEBV ranged from ∼0.46 (FY and PY) to 0.56 (MY) with TR1 and from 0.51 (PY) to 0.65 (MY) with TR2. When averaged across all traits, R2PEV were substantially higher (R2PEV of TR1 = 0.50 and TR2 = 0.57) compared with reliabilities of parent averages (0.35) computed from pedigree data and based on diagonals of the coefficient matrix (prediction error variance approach). Reliability was similar for all the 4 marker panels using either TR1 or TR2, except that imputed HD cow data set led to an inflation of reliability. Reliability of GEBV could be increased by enlarging the limited bull reference population with cow information. A reduced panel of ∼15K markers resulted in reliabilities similar to using HD markers. Reliability of GEBV could be increased by enlarging the limited bull reference population with cow information.


Asunto(s)
Genómica/normas , Técnicas de Genotipaje/veterinaria , Glucolípidos/metabolismo , Glicoproteínas/metabolismo , Leche/metabolismo , Polimorfismo de Nucleótido Simple , Selección Artificial/genética , Factores de Edad , Animales , Brasil , Bovinos , Industria Lechera , Femenino , Marcadores Genéticos , Genotipo , Técnicas de Genotipaje/métodos , Lactancia , Gotas Lipídicas , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/veterinaria , Embarazo , Reproducibilidad de los Resultados
10.
Anim Genet ; 47(6): 637-646, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27435758

RESUMEN

Identification of selection signatures is one of the current endeavors of evolutionary genetics. Admixed populations may be used to infer post-admixture selection. We calculated local ancestry for Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF), to infer such signals. Illumina Bovine SNP50 BeadChip data for 300 admixed, 88 SI and 97 RHF bulls were used. The average RHF ancestry across the whole genome was 0.70. To identify regions with high deviation from average, we considered two significance thresholds, based on a permutation test and extreme deviation from normal distribution. Regions on chromosomes 13 (46.3-47.3 Mb) and 18 (18.7-25.9 Mb) passed both thresholds in the direction of increased SI. Extended haplotype homozygosity within (iHS) and between (Rsb) populations was calculated to explore additional patterns of pre- and post-admixture selection signals. The Rsb score of admixed and SI was significant in a wide region of chromosome 18 (6.6-24.6 Mb) overlapped with one area of strong local ancestry deviation. FTO, with pleiotropic effect on milk and fertility, NOD2 on dairy and NKD1 and SALL1 on fertility traits are located there. Genetic differentiation of RHF and SI (Fst ), an alternative indicator of pre-admixture selection in pure populations, was calculated. No considerable overlap of peaks of local ancestry deviations and Fst was observed. We found two regions with significant signatures of post-admixture selection in this very young composite, applying comparatively stringent significance thresholds. The signals cover relatively large genomic areas and did not allow pinpointing of the gene(s) responsible for the apparent shift in ancestry proportions.


Asunto(s)
Cruzamiento , Bovinos/genética , Genética de Población , Selección Genética , Animales , Fertilidad/genética , Genotipo , Haplotipos , Homocigoto , Masculino , Polimorfismo de Nucleótido Simple
11.
J Anim Breed Genet ; 133(5): 357-65, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26991632

RESUMEN

We have evaluated the use of genomic coancestry coefficients based on shared segments for the maintenance of genetic diversity through optimal contributions methodology for populations of three different Austrian cattle breeds. This coancestry measure has been compared with the genomic coancestry coefficient calculated on a SNP-by-SNP basis and with pedigree-based coancestry. The regressions of the shared segments coancestry on the other two coefficients suggest that the former mainly reflect Identity By Descent but with the advantage over pedigree-based coancestry of providing the realized Identity By Descent rather than an expectation. The effective population size estimated from the rate of coancestry based on shared segments was very similar to those obtained with the other coefficients and of small magnitude (from 26.24 to 111.90). This result highlights the importance of implementing active management strategies to control the increase of inbreeding and the loss of genetic diversity in livestock breeds, even when the population size is reasonably large. One problem for the implementation of coancestry based on shared segments is the need of estimating the gametic phases of the SNPs which, given the techniques used to obtain the genotypes, are a priori unknown. This study shows, through computer simulations, that using estimates of gametic phases for computing coancestry based on shared segments does not lead to a significant loss in the diversity maintained. This has been shown to be true even when the size of the population is very small as it is usually the case in populations subjected to conservation programmes.


Asunto(s)
Bovinos/genética , Variación Genética , Animales , Simulación por Computador , Femenino , Genética de Población , Masculino , Polimorfismo de Nucleótido Simple
12.
J Anim Breed Genet ; 132(2): 100-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25823836

RESUMEN

GRain is freely available software intended to enable and promote testing of hypotheses with respect to purging and heterogeneity of inbreeding depression. The program is based on a stochastic approach, the gene dropping method, and calculates various coefficients from large and complex pedigrees. GRain calculates, together with the 'classical' inbreeding coefficient, ancestral inbreeding coefficients proposed by Ballou, (1997) J. Hered., 88, 169 and Kalinowski et al., (2000) Conserv. Biol., 14, 1375 as well as an ancestral history coefficient (AHC ), defined here for the first time. AHC is defined as the number that tells how many times during pedigree segregation (gene dropping) a randomly taken allele has been in IBD status. Furthermore, GRain enables testing of heterogeneity and/or purging of inbreeding depression with respect to different founders/ancestors by calculating partial coefficients for all previously obtained coefficients.


Asunto(s)
Endogamia , Programas Informáticos , Animales , Genética de Población , Linaje
13.
Clin Exp Obstet Gynecol ; 42(2): 133-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26054104

RESUMEN

PURPOSE OF INVESTIGATION: To compare methods, epidemiological features, and legislations of first trimester termination of pregnancy in two European Union University Hospital: Szeged, Hungary, (UHS) and Rome, Italy (UHR). MATERIALS AND METHODS: The study included 195 women in UHS and 197 women in UHR undergoing a termination of pregnancy, The method used in UHR was electric vacuum aspiration, while in UHS it is chosen according to the patients' features. RESULTS: Mean gestational week at the time of interruption was 8.21 ± 0.12 SD for UHS and 9.00 ± 0.08 SD for UHR (p = 0.000 1). Previous artificial termination of pregnancy was 0.40 ± 0.05 SD for UHR, and 0.77 ± 0.07 SD for UHS (p = 0.0001). Foreign women were 32.5% in UHR and 0.5% in UHS. Incidence of side effects was 1% for UHS and 0.5% for UHR. Parity was 2.54 ± 0.12 SD for UHR and 3.00 ± 0.14 SD for UHS (p = 0.01). CONCLUSIONS: The methods for interruption resulted safe and effective. Antibiotic prophylaxis, routinely provided in UHR, turned out to be effective to pre- vent post-operative infections. Cervical priming with Laminaria is safe, but patient's hospitalization is required. Different legislations may account for some epidemiological differences between the two hospitals.


Asunto(s)
Aborto Inducido/métodos , Primer Trimestre del Embarazo , Aborto Inducido/efectos adversos , Aborto Inducido/legislación & jurisprudencia , Adulto , Femenino , Edad Gestacional , Hospitales Universitarios , Humanos , Hungría , Italia , Embarazo , Estudios Retrospectivos , Legrado por Aspiración
14.
J Anim Breed Genet ; 131(6): 529-35, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25073548

RESUMEN

The aim of this study was to analyse the duration of the competitive life of jumping horses in Hungary to assess the potential for genetic evaluation and to get information about the risk factors affecting jumping performance of sport horses. The data set included lifetime performance in jumping competitions for 8475 horses born from 1992 onwards with records between 1996 and 2011 (32.7% were right-censored). Longevity was measured as the number of years spent in the competition. Discrete time survival model included fixed effects of gender, age at first competition, and the time-dependent effect of competition level. All fixed effects were highly significant (p < 0.001). The highest risk of ending the race career was estimated for horses competing in the lowest level (category 1) events. The smallest risk was found in horses competing in the highest category. The culling risk for stallions was 15% higher, for geldings 20% lower when compared to mares. As the age at the first competition result increased, the risk ratio also increased. Risk ratios of horses starting as 8 years old or older were 56% higher than those of 5-year-old horses. The longest time in sport tracks belonged to horses starting their career as 4 years old. Their culling risk was 20% lower than those of 5-year-old horses. The heritability of the length of competitive life was 0.17. Breeding values were predicted for each animals, and 47 showed an accuracy greater than 0.60. The clear benefit of the analysis was shown by comparison of offspring to extreme stallion groups.


Asunto(s)
Caballos/fisiología , Deportes , Animales , Cruzamiento , Femenino , Caballos/genética , Hungría , Masculino , Factores de Riesgo , Factores Sexuales , Factores de Tiempo
15.
J Int Med Res ; 37(6): 1982-7, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20146898

RESUMEN

Doxazosin, an alpha(1)-adrenergic receptor inhibitor, is commonly administered to patients with type 2 diabetes, hypertension and nephropathy. The impact of 3 months' doxazosin therapy on the prevalence of activated and regulatory T lymphocytes was analysed in this pilot study of men with type 2 diabetes (n = 10) who received doxazosin 4 mg/day in addition to their ongoing therapy. The prevalence of CD4(+), CD8(+), CD25(+) and CD69(+) cells at baseline and after 3 months of add-on therapy was determined. The prevalence of regulatory T-cells was detected by two different approaches: forkhead box P3 (FoxP3) positivity; and the number of CD4(+)CD25(+high) cells. During 3 months of doxazosin therapy, patients' blood pressure, blood glucose control and lipid profiles all significantly improved. Simultaneously, the prevalence of activated T-cells (CD4(+)CD69(+) and CD8(+)CD69(+) cells) decreased, whereas that of regulatory T-cells increased. These results indicate an immunomodulatory action of doxazosin in type 2 diabetic patients.


Asunto(s)
Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos alfa/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inmunología , Doxazosina/farmacología , Doxazosina/uso terapéutico , Subgrupos de Linfocitos T/efectos de los fármacos , Albuminuria/complicaciones , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Subgrupos de Linfocitos T/inmunología , Factores de Tiempo
16.
Curr Med Chem ; 15(26): 2760-70, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18991635

RESUMEN

Tuberculosis causes nearly two million deaths per year world-wide. In addition multidrug-resistant mycobacterial strains rapidly emerge so novel therapeutic approaches are needed. Recently, several promising mycobacterial target molecules were identified, which are involved in bacterial or host cell signalling e.g. the serine/threonine protein kinases, PknB and PknG, NAD kinase and the NAD synthetase. Here we describe some early efforts in the development of novel signal transduction inhibitory anti-mycobacterial drugs using a multiple target approach, with special emphasis on the kinase inhibitory field. Initially, we are using the Nested Chemical Library (NCL) technology and pharmacophore modelling. A hit-finding library, consisting of approximately 19000 small molecules with a bias for prototypic kinase inhibitors from our NCL library and commercial sources was virtually screened against these validated target molecules. Protein structures for the virtual screening were taken from the published three dimensional crystal structures of the enzymes. The hits from the virtual screening were subsequently tested in enzymatic assay systems. Potent hits were then tested for biological activity in macrophages, infected with mycobacteria. The final goal of this exercise is not only to identify potent anti-mycobacterial substances, but also a common pharmacophore for the mycobacterial target PknG in combination with PknB, NAD kinase and/or NAD synthetase. This common pharmacophore still needs to be a unique pharmacophore for the mycobacterial target proteins over human off-targets. Such a pharmacophore might then drive the optimization of a completely new profile of an antibiotic agent with activity against latent mycobacteria and resistance mycobacterial strains.


Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/metabolismo , Transducción de Señal/efectos de los fármacos , Tuberculosis/tratamiento farmacológico , Tuberculosis/metabolismo , Antibacterianos/toxicidad , Evaluación Preclínica de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Inhibidores Enzimáticos/toxicidad , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/enzimología
17.
Amino Acids ; 34(2): 293-300, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17252310

RESUMEN

Numerous indolyl amino acids and their derivatives inhibited arginase activity. The inhibition was found to be non-competitive, - at least partly - allosteric, and independent on manganese ions in the active site, and it cannot be explained by the dissociation of arginase homotrimers. Indole alone is weakly inhibitory; however, the presence of three-carbon side chains and their net charges is favorable for the inhibition. The binding of the inhibitory compounds caused only minor changes in the steric structure of arginase: a slight increase in alpha-helix content was detected by circular dichroism together with a decrease in parallel pleated sheet and beta-turn sections. A slight alteration in the tertiary structure was also found using tryptophane fluorescence studies, but buried apolar side chains were not transposed to the protein surface. Computer studies that were performed did not provide additional structural information.


Asunto(s)
Aminoácidos/farmacología , Arginasa/antagonistas & inhibidores , Indoles/farmacología , Aminoácidos Aromáticos/farmacología , Animales , Bovinos , Dicroismo Circular , Cinética , Macrófagos Peritoneales/enzimología , Manganeso/farmacología , Ratones , Subunidades de Proteína/química , Espectrometría de Fluorescencia
18.
Equine Vet J ; 49(3): 288-293, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27566678

RESUMEN

BACKGROUND: Longevity/durability is a relevant trait in racehorses. Genetic analysis and knowledge of factors that influence number of harness race starts would be advantageous for both horse welfare and the equine industry. OBJECTIVES: To perform a genetic analysis on harness racing using number of races as a measure of longevity/durability and to identify factors associated with career length in Spanish Trotter Horses (STH). STUDY DESIGN: Longitudinal study. METHODS: Performance data (n = 331,970) on the STH population for harness racing at national level between 1990 and 2014 were used. A grouped data model was fitted to assess factors influencing the risk of ending harness racing career and to estimate the heritability and breeding values for total number of harness races starts as an indicator of horses' longevity and durability. The model included sex, age at first race and first start earnings as time-independent effects, and the calendar year, driver, trainer, racetrack category and season of competition as time-dependent effects. RESULTS: Across the whole dataset, the average number of harness races horses achieved in Spain was 54.7 races, and this was associated with the horses' sex, age at first race and first start earnings, calendar year, driver, racetrack category, and season. The heritability estimated (0.17 ± 0.01) for number of harness race starts indicates that a beneficial response to direct genetic selection can be expected. MAIN LIMITATIONS: Data on horses' health status were not available. CONCLUSIONS: Horses' total number of harness race starts is a promising tool for genetic analysis and the evaluation of racing longevity and durability. The estimated heritability provides evidence to support the application of genetic selection of total career number of races to improve longevity/durability of STH.


Asunto(s)
Caballos/fisiología , Deportes , Animales , Femenino , Marcha , Caballos/genética , Masculino
19.
J Anim Sci ; 94(7): 2761-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27482663

RESUMEN

Covariance components and genetic parameters were estimated for birth weight (BiW); adjusted weights at 4, 7, 12, and 18 mo; and ADG between 0 and 4 mo, between 4 and 7 mo, between 7 and 12 mo, and between 12 and 18 mo. Additionally, reproductive traits, calving interval, and age at first calving were analyzed, together with traits measured by ultrasound: loin eye area, deep fat mean, back fat, and rump fat. Analyses were performed using an animal model, considering the fixed effects of the farm ( = 37), year and month of birth, sex, calving number (1 to 7), season (dry and rainy seasons), region (North Coast, Andean Region, and Oriental Savannas), and conception (natural mating or AI), whereas the age of the cows at calving was considered a polynomial covariate with linear and quadratic effects. Three different models were used to find the one with the best fit for each trait: a single-trait model with an additive direct genetic effect, a single-trait model with additive direct and maternal genetic effects, and finally, a multitrait model with an additive direct genetic effect. For the growth traits, the heritability was between 0.24 and 0.47, with the lowest value for weight at 7 mo and the greatest value for BiW, and the maternal heritability was found to be between 0.15 and 0.21 but did not decrease later on. The correlation between direct and maternal effects was high and negative (-0.59 to -0.76). With ultrasound traits, a model with only direct effects was used. The heritability was between 0.13 and 0.28 for back fat and loin eye area, respectively. The heritabilities for deep fat mean and rump fat were similar, being 0.19 and 0.21, respectively. The reproductive traits showed high residual variance. In particular, the heritability of calving interval was low (0.06). The results showed that the growth traits have an important genetic component, which is a favorable indicator for obtaining improvement progress in the zebu Brahman breed for beef production in tropical regions of Colombia. The maternal effects influenced the weight performance from 4 to 18 mo and should be taken into account in genetic analyses. In general, the direct heritability of medium magnitude estimated for growth and traits measured by ultrasound suggests that individual selection for these traits will be effective.


Asunto(s)
Peso al Nacer/fisiología , Composición Corporal/fisiología , Bovinos/fisiología , Reproducción/fisiología , Ultrasonografía/veterinaria , Animales , Peso al Nacer/genética , Bovinos/genética , Colombia , Femenino , Masculino , Reproducción/genética
20.
Biochim Biophys Acta ; 632(4): 649-60, 1980 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-6254578

RESUMEN

A protein fraction of molecular weight 33,000-36,000 accounted for about 40% of the cyclic AMP binding capacity of the cytoplasmic extract of human tonsillar lymphocytes. This cyclic AMP binding fraction (designated as R' protein [10]) proved to be a proteolytic fragment of the regulatory subunit of the cyclic AMP-dependent protein kinase. The Scatchard plot of cyclic AMP binding by the isolated R' fraction indicated positive cooperativity. 50% saturation of the cyclic AMP binding sites was achieved at about 4 . 10(-9) M cyclic AMP. An upward concave curve was obtained in the Scatchard plot of cyclic GMP binding by the R' protein. These results strongly suggest that more than one molecule of cyclic nucleotide can be bound by one molecule of the R' protein. The R' protein could not be detected in the physiological salt extract of isolated nuclei in which type I cyclic AMP-dependent protein kinase was the dominating isoenzyme (according to the terminology used by Corbin, S.D., Keely, S.L. and Park, C.R. (1975) J. Biol. Chem. 250, 218-225). The cytoplasm of cells contained a higher amount of type II than type I regulatory subunit. In the cytoplasm the predominant part of RII was present in the dissociated state in all preparations, while when the RII was found in the nucleus it was mainly in the holoenzyme form. The R' protein presumably from the dissociated type II regulatory subunit.


Asunto(s)
Proteínas Portadoras/metabolismo , AMP Cíclico/aislamiento & purificación , Linfocitos/metabolismo , AMP Cíclico/metabolismo , Humanos , Cinética , Sustancias Macromoleculares , Peso Molecular , Tonsila Palatina/metabolismo , Proteínas Quinasas/metabolismo
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