Analysis of cattle olfactory subgenome: the first detail study on the characteristics of the complete olfactory receptor repertoire of a ruminant

BACKGROUND: Mammalian olfactory receptors (ORs) are encoded by the largest mammalian multigene family. Understanding the OR gene repertoire in the cattle genome could lead to link the effects of genetic differences in these genes to variations in olfaction in cattle. RESULTS: We report here a whole genome analysis of the olfactory receptor genes of Bos taurus using conserved OR gene-specific motifs and known OR protein sequences from diverse species. Our analysis, using the current cattle genome assembly UMD 3.1 covering 99.9% of the cattle genome, shows that the cattle genome contains 1,071 OR-related sequences including 881 functional, 190 pseudo, and 352 partial OR sequences. The OR genes are located in 49 clusters on 26 cattle chromosomes. We classified them into 18 families consisting of 4 Class I and 14 Class II families and these were further grouped into 272 subfamilies. Comparative analyses of the OR genes of cattle, pigs, humans, mice, and dogs showed that 6.0% (n = 53) of functional OR cattle genes were species-specific. We also showed that significant copy number variations are present in the OR repertoire of the cattle from the analysis of 10 selected OR genes. CONCLUSION: Our analysis revealed the almost complete OR gene repertoire from an individual cattle genome. Though the number of OR genes were lower than in pigs, the analysis of the genetic system of cattle ORs showed close similarities to that of the pig

Phenotypic Dissection of Bone Mineral Density Reveals Skeletal Site Specificity and Facilitates the Identification of Novel Loci in the Genetic Regulation of Bone Mass Attainment

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ~4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (re = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (re = 0.20-0.24). To explore the basis fo

Age-Related Changes in the Characteristics of the Elderly Females Using the Signal Features of an Earlobe Photoplethysmogram

Non-invasive measurement of physiological parameters and indicators, specifically among the elderly, is of utmost importance for personal health monitoring. In this study, we focused on photoplethysmography (PPG), and developed a regression model that calculates variables from the second (SDPPG) and third (TDPPG) derivatives of the PPG pulse that can observe the inflection point of the pulse wave measured by a wearable PPG device. The PPG pulse at the earlobe was measured for 3 min in 84 elderly Korean women (age: 71.19 ± 6.97 years old). Based on the PPG-based cardiovascular function, we derived additional variables from TDPPG, in addition to the aging variable to predict the age. The Aging Index (AI) from SDPPG and Sum of TDPPG variables were calculated in the second and third differential forms of PPG. The variables that significantly correlated with age were c/a, Tac, AI of SDPPG, sum of TDPPG, and correlation coefficient ‘r’ of the model. In multiple linear regression analysis, the r value of the model was 0.308, and that using deep learning on the model was 0.839. Moreover, the possibility of improving the accuracy of the model using supervised deep learning techniques, rather than the addition of datasets, was confirmed

Small molecule Y-320 stimulates ribosome biogenesis, protein synthesis, and aminoglycoside-induced premature termination codon readthrough.

Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the extent of PTC readthrough that can be achieved by aminoglycosides like G418. Using a cell-based screen, we identified a small molecule, the phenylpyrazoleanilide Y-320, that potently enhances TP53, DMD, and COL17A1 PTC readthrough by G418. Unexpectedly, Y-320 increased cellular protein levels and protein synthesis, measured by SYPRO Ruby protein staining and puromycin labeling, as well as ribosome biogenesis measured using antibodies to rRNA and ribosomal protein S6. Y-320 did not increase the rate of translation elongation and it exerted its effects independently of mTOR signaling. At the single cell level, exposure to Y-320 and G418 increased ribosome content and protein synthesis which correlated strongly with PTC readthrough. As a single agent, Y-320 did not affect translation fidelity measured using a luciferase reporter gene but it enhanced misincorporation by G418. RNA-seq data showed that Y-320 up-regulated the expression of CXC chemokines CXCL10, CXCL8, CXCL2, CXCL11, CXCL3, CXCL1, and CXCL16. Several of these chemokines exert their cellular effects through the receptor CXCR2 and the CXCR2 antagonist SB225002 reduced cellular protein levels and PTC readthrough in cells exposed to Y-320 and G418. These data show that the self-limiting nature of PTC readthrough by G418 can be compensated by Y-320, a potent enhancer of PTC readthrough that increases ribosome biogenesis and protein synthesis. They also support a model whereby increased PTC readthrough is enabled by increased protein synthesis mediated by an autocrine chemokine signaling pathway. The findings also raise the possibility that inflammatory processes affect cellular propensity to readthrough agents and that immunomodulatory drugs like Y-320 might find application in PTC readthrough therapy

Clinical Characteristics of Temporal Bone Metastases

Objectives The purposes of this study were to evaluate the clinical characteristics of temporal bone metastasis (TBM) and to determine whether the characteristics differed according to primary malignancy. Methods We retrospectively analyzed data on 20 patients diagnosed with TBM between January 2000 and January 2017. Demographics, the period from diagnosis of primary malignancy to TBM diagnosis, the period from TBM diagnosis to death, the type and staging of primary malignancy, otologic manifestations, and TBM sites were assessed. After the primary malignancies were divided into solid cancers and hematologic malignancies, each parameter was compared between the two groups. Results The most common primary malignancy with TBM was lung cancer (45%). The most common otologic symptoms and signs were facial palsy (30.5%) and hearing loss (30.5%). The temporal squama (23%) and the facial nerve (20%) were the most commonly involved. Most TBMs occurred late in the disease process after the primary malignancy first metastasized to other organs. Hematologic malignancies metastasized significantly more frequently to the external auditory canal and the middle ear/mastoid compared to solid cancers (P=0.001 and P=0.004, respectively). Conclusion If otologic manifestations such as facial palsy and hearing loss are presented in patients at advanced stages of malignancy, TBM of primary malignancy should be suspected. In addition, hematologic malignancies tend to metastasize to the external auditory canal and the middle ear cleft more commonly than solid cancers do

Desmosterolosis:An illustration of diagnostic ambiguity of cholesterol synthesis disorders

Desmosterolosis is an autosomal recessive disorder of cholesterol biosynthesis caused by biallelic mutations of DHCR24 (homozygous or compound heterozygous), which encodes 3-β-hydroxysterol Δ-24-reductase. We report two sisters homozygous for the 571G>A (E191K) DHCR24 mutation. Comparison of the propositae to other reported individuals shows that psychomotor developmental delay, failure to thrive, dysgenesis of the corpus callosum, cerebral white matter atrophy and spasticity likely constitute the minimal desmosterolosis phenotype. The nonspecific features of desmosterolosis make it difficult to suspect clinically and therefore screening for it should be entertained early in the diagnostic evaluation