Recombinant R-spondin2 and Wnt3a Up- and Down-Regulate Novel Target Genes in C57MG Mouse Mammary Epithelial Cells

R-spondins (Rspos) comprise a family of four secreted proteins that have important roles in cell proliferation, cell fate determination and organogenesis. Rspos typically exert their effects by potentiating the Wnt/β-catenin signaling pathway. To systematically investigate the impact of Rspo/Wnt on gene expression, we performed a microarray analysis using C57MG mouse mammary epithelial cells treated with recombinant Rspo2 and/or Wnt3a. We observed the up- and down-regulation of several previously unidentified target genes, including ones that encode proteins involved in immune responses, effectors of other growth factor signaling pathways and transcription factors. Dozens of these changes were validated by quantitative real time RT-PCR. Time course experiments showed that Rspo2 typically had little or no effect on Wnt-dependent gene expression at 3 or 6 h, but enhanced expression at 24 h, consistent with biochemical data indicating that Rspo2 acts primarily to sustain rather than acutely increase Wnt pathway activation. Up-regulation of gene expression was inhibited by pre-treatment with Dickkopf1, a Wnt/β-catenin pathway antagonist, and by siRNA knockdown of β-catenin expression. While Dickkopf1 blocked Rspo2/Wnt3a-dependent down-regulation, a number of down-regulated genes were not affected by β-catenin knockdown, suggesting that in these instances down-regulation was mediated by a β-catenin-independent mechanism

Describing Ecological Potential and Ecological States of Rangeland to Support Livestock Management in Mongolia

Perception of rangeland degradation in Mongolia and its causes are well known but herders and policy makers lack clear messages on how much rangeland is degraded, whether is it reversible, and what management changes should be implemented. This paper illustrates a portion of our ongoing efforts to develop ESDs that can be used at the grass roots level as management tools. At the Undurshireet soum study site, which is split mainly into Gravelly, Loamy, Sandy, and Deep sandy ecological sites, rangeland community shifts in Gravelly and Loamy ecological sites are interpreted as reversible shifts in species composition or species proportion within the states, indicating that a change to grazing management may be effective for restoration of desired conditions. Sandy and Deep sandy ecological sites in this area are at high risk of erosion and may be more difficult to restore

The use of mid-infrared spectra to map genes affecting milk composition.

The aim of this study was to investigate the feasibility of using mid-infrared (MIR) spectroscopy analysis of milk samples to increase the power and precision of genome-wide association studies (GWAS) for milk composition and to better distinguish linked quantitative trait loci (QTL). To achieve this goal, we analyzed phenotypic data of milk composition traits, related MIR spectra, and genotypic data comprising 626,777 SNP on 5,202 Holstein, Jersey, and crossbred cows. We performed a conventional GWAS on protein, lactose, fat, and fatty acid concentrations in milk, a GWAS on individual MIR wavenumbers, and a partial least squares regression (PLS), which is equivalent to a multi-trait GWAS, exploiting MIR data simultaneously to predict SNP genotypes. The PLS detected most of the QTL identified using single-trait GWAS, usually with a higher significance value, as well as previously undetected QTL for milk composition. Each QTL tends to have a different pattern of effects across the MIR spectrum and this explains the increased power. Because SNP tracking different QTL tend to have different patterns of effect, it was possible to distinguish closely linked QTL. Overall, the results of this study suggest that using MIR data through either GWAS or PLS analysis applied to genomic data can provide a powerful tool to distinguish milk composition QTL

Current State of Ixodidae Research in Mongolia

Our research presents the Ixodidae-fauna in Mongolia. The current taxonomic state in Mongolia shows 19 Ixodidae taxa extracted in 308 locations from 115 bird and mammal species. In 1980, the species Ixodes persulcatus SCHULZE, 1930 and Ixodes berlesei Birula, 1895 were detected in Inget Tolgoi and Ixodes laguri OLENEV, 1929 on Meriones unguiculatus 10 km southeast of Ulaanbaatar for the first time. In 2000 the species Haemaphysalis concinna Koch, 1844 was detected in the Selenge-river area and Argas (Argas) vulgaris FILIPPOVA, 1961 was detected in the Gobi area. From the collection of M. and A. STUBBE 1 N (Nymphae) Ixodes persulcatus was detected on Microtus sp. at the Minž-gol (river in Khentey) on July 25, 2002

Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10 . In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type

Functional consequences of Wnt-induced dishevelled 2 phosphorylation in canonical and non-canonical Wnt signaling

This research was originally published in Journal of Biological Chemitry. González-Sancho. Functional Consequences of Wnt-Induced Dishevelled2 Phosphorylation in Canonical and Non-Canonical Signaling. Journal of Biological Chemistry . 2013. 288 9428-9437 © the American Society for Biochemistry and Molecular BiologyEl título del postprint: Functional Consequences of Wnt-Induced Dishevelled2 Phosphorylation in Canonical and Non-Canonical SignalingDishevelled (Dvl) proteins are intracellular effectors of Wnt signaling that have essential roles in both canonical and noncanonical Wnt pathways. It has long been known that Wnts stimulate Dvl phosphorylation, but relatively little is known about its functional significance. We have previously reported that both Wnt3a and Wnt5a induce Dvl2 phosphorylation that is associated with an electrophoretic mobility shift and loss of recognition by monoclonal antibody 10B5. In the present study, we mapped the 10B5 epitope to a 16-amino acid segment of human Dvl2 (residues 594–609) that contains four Ser/Thr residues. Alanine substitution of these residues (P4m) eliminated the mobility shift induced by either Wnt3a or Wnt5a. The Dvl2 P4m mutant showed a modest increase in canonical Wnt/β-catenin signaling activity relative to wild type. Consistent with this finding, Dvl2 4Pm preferentially localized to cytoplasmic puncta. In contrast to wild-type Dvl2, however, the P4m mutant was unable to rescue Wnt3a-dependent neurite outgrowth in TC-32 cells following suppression of endogenous Dvl2/3. Earlier work has implicated casein kinase 1δ/ϵ as responsible for the Dvl mobility shift, and a CK1δ in vitro kinase assay confirmed that Ser594, Thr595, and Ser597 of Dvl2 are CK1 targets. Alanine substitution of these three residues was sufficient to abrogate the Wnt-dependent mobility shift. Thus, we have identified a cluster of Ser/Thr residues in the C-terminal domain of Dvl2 that are Wnt-induced phosphorylation (WIP) sites. Our results indicate that phosphorylation at the WIP sites reduces Dvl accumulation in puncta and attenuates β-catenin signaling, whereas it enables noncanonical signaling that is required for neurite outgrowth.This work was supported, in whole or in part, by National Institutes of Health Grant R01 CA123238 (to A. M. C. B.) and Postdoctoral Fellowship F32 CA117662 (to C. L. A.). This work was also supported by a fellowship from the Ministerio de Educación, Cultura, y Deportes, of Spain (to J. M. G.-S.), by New York State Department of Health postdoctoral Fellowship NYS C021339 (to Y. T.), and by charitable donations to Strang Cancer Prevention Center. This research also was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institut

Evaluation of updated Feed Saved breeding values developed in Australian Holstein dairy cattle.

Although selection for increased milk production traits has led to a genetic increase in body weight (BW), the genetic gain in milk production has exceeded the gain in BW, so gross feed efficiency has improved. Nonetheless, greater gains may be possible by directly selecting for a measure of feed efficiency. Australia first introduced Feed Saved (FS) estimated breeding value (EBV) in 2015. Feed Saved combines residual feed intake (RFI) genomic EBV and maintenance requirements calculated from mature BW EBV. The FS EBV was designed to enable the selection of cows for reduced energy requirements with similar milk production. In this study, we used a reference population of 3,711 animals in a multivariate analysis including Australian heifers (AUSh), Australian cows (AUSc), and overseas cows (OVEc) to update the Australian EBV for lifetime RFI (i.e., a breeding value that incorporated RFI in growing and lactating cows) and to recalculate the FS EBV in Australian Holstein bulls (AUSb). The estimates of genomic heritabilities using univariate (only AUSc or AUSh) to trivariate (including the OVEc) analyses were similar. Genomic heritabilities for RFI were estimated as 0.18 for AUSc, 0.27 for OVEc, and 0.36 for AUSh. The genomic correlation for RFI between AUSc and AUSh was 0.47 and that between AUSc and OVEc was 0.94, but these estimates were associated with large standard errors (range: 0.18-0.28). The reliability of lifetime RFI (a component of FS) in the trivariate analysis (i.e., including OVEc) increased from 11% to 20% compared with the 2015 model and was greater, by 12%, than in a bivariate analysis in which the reference population included only AUSc and AUSh. By applying the prediction equation of the 2020 model, the average reliability of the FS EBV in 20,816 AUSb that were born between 2010 and 2020 improved from 33% to 43%. Previous selection strategies-that is, using the predecessor of the Balanced Performance Index (Australian Profit Ranking index) that did not include FS-have resulted in an unfavorable genetic trend in FS. However, this unfavorable trend has stabilized since 2015, when FS was included in the Balanced Performance Index, and is expected to move in a favorable direction with selection on Balanced Performance Index or the Health Weighted Index. Doubling the reference population, particularly by incorporating international data for feed efficiency, has improved the reliability of the FS EBV. This could lead to increased genetic gain for feed efficiency in the Australian industry

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle

SummaryFatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1bm−/−). Cpt1bm−/− mice have increased glucose utilization and are resistant to diet-induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b-deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity

Current State of Ixodidae Research in Mongolia

Our research presents the Ixodidae-fauna in Mongolia. The current taxonomic state in Mongolia shows 19 Ixodidae taxa extracted in 308 locations from 115 bird and mammal species. In 1980, the species Ixodes persulcatus SCHULZE, 1930 and Ixodes berlesei Birula, 1895 were detected in Inget Tolgoi and Ixodes laguri OLENEV, 1929 on Meriones unguiculatus 10 km southeast of Ulaanbaatar for the first time. In 2000 the species Haemaphysalis concinna Koch, 1844 was detected in the Selenge-river area and Argas (Argas) vulgaris FILIPPOVA, 1961 was detected in the Gobi area. From the collection of M. and A. STUBBE 1 N (Nymphae) Ixodes persulcatus was detected on Microtus sp. at the Minž-gol (river in Khentey) on July 25, 2002