Bayesian estimation of (co) variance components in Argentinian Brangus for carcass traits using the FCG algorithm

Se emplearon los datos de 2273 toritos y vaquillonas Brangus para estimar las heredabilidades (h2 ) y las correlaciones aditivas y ambientales de caracteres de calidad de carne medidos por ultrasonido. Los registros provenían del programa de evaluación genética de la Asociación Argentina de Brangus. Los caracteres medidos fueron el área del ojo del bife (AOB), el marmoreado (MB), la grasa dorsal (GD) y la grasa de cadera (GC). La edad media de los animales al momento de la medición fue 641 días en machos y 685 días en hembras. Los parámetros genéticos y ambientales fueron estimados mediante un algoritmo bayesiano conjugado. Los valores estimados de h2 fueron 0,22, 0,16, 0,12 y 0,21, para AOB, GD, CC y MB, respectivamente. En términos generales, las estimaciones de las correlaciones genéticas y ambientales se encontraron cercanas a la cifra media de la literatura. Si bien los valores estimados de h2 fueron inferiores al promedio de la investigación realizada en vacunos para carne, la variabilidad encontrada es suficiente como para que la respuesta a la selección por estos caracteres – empleando predicciones de los valores de cría calculadas con los parámetros estimados - sea moderadamente efectiva.Data on 2273 Brangus young bulls and heifers were used to estimate heritabilities (h2 ) and genetics and environmental correlations for ultrasound carcass measures. Records were from the genetic evaluation program of Asociación Argentina de Brangus. Traits measured were rib-eye area (AOB), marbling (MB), back-fat thickness (GD), and hip-fat thickness (GC). Average ages of measure were 641 days in males and 685 in females. The genetic and environmental dispersion parameters were estimated by a conjugate Bayesian algorithm (FCG). Estimates of h2 were 0,22, 0,16, 0,12, and 0,21, for AOB, GD, CC, and MB, respectively. In general, estimates of genetic and environmental correlations were close to the average published values. Even tough estimates of h2 were below the average of published estimates for beef cattle, the additive genetic variation found in the current study would lead to a moderate response to selection – using predictions of breeding value that are calculated with the estimate parameters.Fil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Birchmeier, A. N.. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentin

Estimación bayesiana de componentes de (co) varianza en Brangus argentino para caracteres de res mediante el algoritmo FCG

19-26Data on 2273 Brangus young bulls and heifers were used to estimate heritabilities (h2) and genetics and environmental correlations for ultrasound carcass measures. Records were from the genetic evaluation program of Asociación Argentina de Brangus. Traits measured were rib-eye area (AOB), marbling (MB), back-fat thickness (GD), and hip-fat thickness (GC). Average ages of measure were 641 days in males and 685 in females. The genetic and environmental dispersion parameters were estimated by a conjugate Bayesian algorithm (FCG). Estimates of h2 were 0,22, 0,16, 0,12, and 0,21, for AOB, GD, CC, and MB, respectively. In general, estimates of genetic and environmental correlations were close to the average published values. Even tough estimates of h2 were below the average of published estimates for beef cattle, the additive genetic variation found in the current study would lead to a moderate response to selection - using predictions of breeding value that are calculated with the estimate parameters

Estimación bayesiana de componentes de (co) varianza en Brangus argentino para caracteres de res mediante el algoritmo FCG

19-26Data on 2273 Brangus young bulls and heifers were used to estimate heritabilities (h2) and genetics and environmental correlations for ultrasound carcass measures. Records were from the genetic evaluation program of Asociación Argentina de Brangus. Traits measured were rib-eye area (AOB), marbling (MB), back-fat thickness (GD), and hip-fat thickness (GC). Average ages of measure were 641 days in males and 685 in females. The genetic and environmental dispersion parameters were estimated by a conjugate Bayesian algorithm (FCG). Estimates of h2 were 0,22, 0,16, 0,12, and 0,21, for AOB, GD, CC, and MB, respectively. In general, estimates of genetic and environmental correlations were close to the average published values. Even tough estimates of h2 were below the average of published estimates for beef cattle, the additive genetic variation found in the current study would lead to a moderate response to selection - using predictions of breeding value that are calculated with the estimate parameters

The BCL9-2 proto-oncogene governs estrogen receptor alpha expression in breast tumorigenesis

The majority of human breast cancers express estrogen receptor {Alpha} (ER), which is important for therapy with anti-estrogens. Here we describe the role of BCL9-2, a proto-oncogene previously characterized as co-activator of Wnt/{beta}-catenin signaling, for mammary tumorigenesis in mice and human. ER positive human breast cancers showed overexpression of BCL9-2 and tamoxifen treated patients with high BCL9-2 demonstrated a better survival. BCL9-2 was upregulated during puberty and pregnancy in normal mammary epithelia, but downregulated in the involuted gland. BCL9-2 overexpression in vivo delayed the mammary involution and induced alveolar hyperplasia. Moreover, aged BCL9-2 transgenic mice developed ductal-like mammary tumors with high nuclear ER expression. We found, that primary cell cultures of BCL9-2 breast tumors responded to tamoxifen treatment. Moreover, BCL9-2 regulated the expression of ER and the proliferation of human breast cancer cells independently of {beta}-catenin. Finally, we describe a novel mechanism, how BCL9-2 regulates ER transcription by interaction with Sp1 through the proximal ESR1 gene promoter. In summary, BCL9-2 induces ER positive breast cancers in vivo, regulates ER expression by a novel {beta}-catenin independent mechanism in breast cancer cells, and might predict the therapy response to tamoxifen treatment

Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse

Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm, respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons. We used conditional mutation of Tshz1 in the progenitor zone of motor neurons (Tshz1(MNΔ)) to show that Tshz1 is essential for survival and function of hypoglossal and phrenic motor neurons. Hypoglossal and phrenic motor neurons are born in correct numbers, but many die between embryonic day 13.5 and 14.5 in Tshz1(MNΔ) mutant mice. In addition, innervation and electrophysiological properties of phrenic and hypoglossal motor neurons are altered. Severe feeding and breathing problems accompany this developmental deficit. Although motor neuron survival can be rescued by elimination of the pro-apoptotic factor Bax, innervation, feeding and breathing defects persist in Bax(-/-); Tshz1(MNΔ) mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons

Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function

Key transcription factors control the gene expression program in mature pancreatic {beta}-cells, but their integration into regulatory networks is little understood. Here, we show that Insm1, Neurod1 and Foxa2 directly interact and together bind regulatory sequences in the genome of mature pancreatic {beta}-cells. We used Insm1 ablation in mature {beta}-cells in mice and found pronounced deficits in insulin secretion and gene expression. Insm1-dependent genes identified previously in developing {beta}-cells markedly differ from the ones identified in the adult. In particular, adult mutant {beta}-cells resemble immature {beta}-cells of newborn mice in gene expression and functional properties. We defined Insm1, Neurod1 and Foxa2 binding sites associated with genes deregulated in Insm1 mutant {beta}-cells. Remarkably, combinatorial binding of Insm1, Neurod1 and Foxa2 but not binding of Insm1 alone explained a significant fraction of gene expression changes. Human genomic sequences corresponding to the murine sites occupied by Insm1/Neurod1/Foxa2 were enriched in single nucleotide polymorphisms associated with glycolytic traits. Thus, our data explain part of the mechanisms by which {beta}-cells maintain maturity: Combinatorial Insm1/Neurod1/Foxa2 binding identifies regulatory sequences that maintain the mature gene expression program in {beta}-cells, and disruption of this network results in functional failure

Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration

RNA localization is a key determinant of neurite-enriched proteome

Protein subcellular localization is fundamental to the establishment of the body axis, cell migration, synaptic plasticity, and a vast range of other biological processes. Protein localization occurs through three mechanisms: protein transport, mRNA localization, and local translation. However, the relative contribution of each process to neuronal polarity remains unknown. Using neurons differentiated from mouse embryonic stem cells, we analyze protein and RNA expression and translation rates in isolated cell bodies and neurites genome-wide. We quantify 7323 proteins and the entire transcriptome, and identify hundreds of neurite-localized proteins and locally translated mRNAs. Our results demonstrate that mRNA localization is the primary mechanism for protein localization in neurites that may account for half of the neurite-localized proteome. Moreover, we identify multiple neurite-targeted non-coding RNAs and RNA-binding proteins with potential regulatory roles. These results provide further insight into the mechanisms underlying the establishment of neuronal polarity. Subcellular localization of RNAs and proteins is important for polarized cells such as neurons. Here the authors differentiate mouse embryonic stem cells into neurons, and analyze the local transcriptome, proteome, and translated transcriptome in their cell bodies and neurites, providing a unique resource for future studies on neuronal polarity