162 research outputs found

    Avoidability of formulas with two variables

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    In combinatorics on words, a word ww over an alphabet Σ\Sigma is said to avoid a pattern pp over an alphabet Δ\Delta of variables if there is no factor ff of ww such that f=h(p)f=h(p) where h:Δ∗→Σ∗h:\Delta^*\to\Sigma^* is a non-erasing morphism. A pattern pp is said to be kk-avoidable if there exists an infinite word over a kk-letter alphabet that avoids pp. We consider the patterns such that at most two variables appear at least twice, or equivalently, the formulas with at most two variables. For each such formula, we determine whether it is 22-avoidable, and if it is 22-avoidable, we determine whether it is avoided by exponentially many binary words

    Association of a missense mutation in the bovine leptin gene with carcass fat content and leptin mRNA levels

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    Previously, we have shown that alleles of the BM1500 microsatellite, located 3.6 kb downstream of the leptin gene in cattle, were associated with carcass fat measures in a population of 154 unrelated beef bulls. Subsequently, a cytosine (C) to thymine (T) transition that encoded an amino acid change of an arginine to a cysteine was identified in exon 2 of the leptin gene. A PCR-RFLP was designed and allele frequencies in four beef breeds were correlated with levels of carcass fat. The T allele was associated with fatter carcasses and the C allele with leaner carcasses. The frequencies of the SNP alleles among breeds indicated that British breeds have a higher frequency of the T allele whereas the continental breeds have a higher occurrence of the C allele. A ribonuclease protection assay was developed to quantify leptin mRNA in a separate group of animals selected by genotype. Animals homozygous for thymine expressed higher levels of leptin mRNA. This may suggest that the T allele, which adds an extra cysteine to the protein, imparts a partial loss of biological function and hence could be the causative mutation

    Neuropeptide Y receptors in GtoPdb v.2023.1

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    Neuropeptide Y (NPY) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Neuropeptide Y Receptors [158]) are activated by the endogenous peptides neuropeptide Y, neuropeptide Y-(3-36), peptide YY, PYY-(3-36) and pancreatic polypeptide (PP). The receptor originally identified as the Y3 receptor has been identified as the CXCR4 chemokine recepter (originally named LESTR, [139]). The y6 receptor is a functional gene product in mouse, absent in rat, but contains a frame-shift mutation in primates producing a truncated non-functional gene [84]. Three-dimensional structures have been determined for subtype active receptors Y1, Y2 and Y4 [211, 114] and inactive antagonist bound Y1 and Y2 receptors [240, 210]. Many of the agonists exhibit differing degrees of selectivity dependent on the species examined. For example, the potency of PP is greater at the rat Y4 receptor than at the human receptor [62]. In addition, many agonists lack selectivity for individual subtypes, but can exhibit comparable potency against pairs of NPY receptor subtypes, or have not been examined for activity at all subtypes. [125I]-PYY or [125I]-NPY can be used to label Y1, Y2, Y5 and y6 subtypes non-selectively, while [125I][cPP(1-7), NPY(19-23), Ala31, Aib32, Gln34]hPP may be used to label Y5 receptors preferentially (note that cPP denotes chicken peptide sequence and hPP is the human sequence)

    Variation in the achievement of HbA1c, blood pressure and LDL cholesterol targets in type 2 diabetes in general practice and characteristics associated with risk factor control.

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    Aims To identify population, general practitioner, and practice characteristics associated with the achievement of HbA1c, blood pressure and LDL cholesterol targets, and to describe variation in the achievement of risk factor control. Methods We conducted a cross‐sectional survey of 9342 people with type 2 diabetes, 281 general practitioners and 77 general practices in Norway. Missing values (7.4%) were imputed using multiple imputation by chained equations. We used three‐level logistic regression with the achievement of HbA1c, blood pressure and LDL cholesterol targets as dependent variables, and factors related to population, general practitioners, and practices as independent variables. Results Treatment targets were achieved for HbA1c in 64%, blood pressure in 50%, and LDL cholesterol in 52% of people with type 2 diabetes, and 17% met all three targets. There was substantial heterogeneity in target achievement among general practitioners and among practices; the estimated proportion of a GPs diabetes population at target was 55–73% (10–90 percentiles) for HbA1c, 36–63% for blood pressure, and 47–57% for LDL cholesterol targets. The models explained 11%, 5% and 14%, respectively, of the total variation in the achievement of HbA1c, blood pressure and LDL cholesterol targets. Use among general practitioners of a structured diabetes form was associated with 23% higher odds of achieving the HbA1c target (odds ratio 1.23, 95% confidence interval (CI) 1.02–1.47) and 17% higher odds of achieving the LDL cholesterol target (odds ratio 1.17, 95% CI 1.01–1.35). Conclusions Clinical diabetes management is difficult, and few people meet all three risk factor control targets. The proportion of people reaching target varied among general practitioners and practices. Several population, general practitioner and practice characteristics only explained a small part of the total variation. The use of a structured diabetes form is recommended.publishedVersio

    Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

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    Thermogenic adipocytes possess a therapeutically appealing, energy-expending capacity, which is canonically cold-induced by ligand-dependent activation of ÎČ-adrenergic G protein-coupled receptors (GPCRs). Here, we uncover an alternate paradigm of GPCR-mediated adipose thermogenesis through the constitutively active receptor, GPR3. We show that the N terminus of GPR3 confers intrinsic signaling activity, resulting in continuous Gs-coupling and cAMP production without an exogenous ligand. Thus, transcriptional induction of Gpr3 represents the regulatory parallel to ligand-binding of conventional GPCRs. Consequently, increasing Gpr3 expression in thermogenic adipocytes is alone sufficient to drive energy expenditure and counteract metabolic disease in mice. Gpr3 transcription is cold-stimulated by a lipolytic signal, and dietary fat potentiates GPR3-dependent thermogenesis to amplify the response to caloric excess. Moreover, we find GPR3 to be an essential, adrenergic-independent regulator of human brown adipocytes. Taken together, our findings reveal a noncanonical mechanism of GPCR control and thermogenic activation through the lipolysis-induced expression of constitutively active GPR3.ISSN:0092-8674ISSN:1097-417

    Nonrepetitive Colouring via Entropy Compression

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    A vertex colouring of a graph is \emph{nonrepetitive} if there is no path whose first half receives the same sequence of colours as the second half. A graph is nonrepetitively kk-choosable if given lists of at least kk colours at each vertex, there is a nonrepetitive colouring such that each vertex is coloured from its own list. It is known that every graph with maximum degree Δ\Delta is cΔ2c\Delta^2-choosable, for some constant cc. We prove this result with c=1c=1 (ignoring lower order terms). We then prove that every subdivision of a graph with sufficiently many division vertices per edge is nonrepetitively 5-choosable. The proofs of both these results are based on the Moser-Tardos entropy-compression method, and a recent extension by Grytczuk, Kozik and Micek for the nonrepetitive choosability of paths. Finally, we prove that every graph with pathwidth kk is nonrepetitively O(k2)O(k^{2})-colourable.Comment: v4: Minor changes made following helpful comments by the referee
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