38 research outputs found

    Early assessment of genotypic variation in growth and nitrogen fixation in Faidherbia albida/rhizobium symbiosis

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    To enhance the benefits from N2-fixing symbiosis in low nitrogen fixers such as Faidherbia albida, knowledge is needed on how genotypes of both the host and its bacterial partner interact to influence N fixation-related traits of the host legume. A greenhouse experiment was carried out to investigate the variability of several traits with respect to provenance, rhizobial strain and their interactions. Four West African provenances of F. albida were inoculated with five proven effective strains and grown for two months. Provenance x strain interactions were significant only for shoot N concentration (%N) and total shoot N uptake but their contributions to total phenotypic variances were rather low (6-10%). Because of large differencesamong provenances in growth performance the host genotype showed the greatest contribution (70.7%) to the variability in total shoot N uptake. Variability in %N in turn was mostly related to strain effectiveness (71.2%).These results suggest that under conditions of N deficiency, growth performance and shoot N concentration provide reliable selection criteria when screening for improved N2-fixation in F. albida.Keywords: rhizobia, Faidherbia, provenance, variability, interaction, N2-fixatio

    Hijacking of transcriptional condensates by endogenous retroviruses

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    Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV derepression is associated with lethality during early development has been a mystery. Here, we report that rapid and selective degradation of the heterochromatin adapter protein TRIM28 triggers dissociation of transcriptional condensates from loci encoding super-enhancer (SE)-driven pluripotency genes and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of SE-enriched transcription factors rescued condensate localization at SEs in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA polymerase II and the Mediator coactivator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and noncoding nascent RNAs, including those produced by retrotransposons, may facilitate ‘hijacking’ of transcriptional condensates in various developmental and disease contexts

    To "Kastro" tou Lefkou Pergou

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    PPAR agonists as add-on treatment with metformin in management of type 2 diabetes:a systematic review and meta-analysis

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    The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.</p

    The inverted Gompertz-Fréchet distribution with applications

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    The probability distribution is an important aspect of probability theory because of its vast relevance in almost all human disciplines. Its applicability in finance, medicine, agriculture, actuarial science, demography, and econometrics, to mention but a few, is highly commendable. The use of probability distributions to model real-life data is an age-old practice, but most of the standard distributions are not flexible enough to model emergent real-life occurrences. This shortcoming gave birth to diverse extensions of the standard distribution. In this work, the Inverted Gompertz-Fréchet (IGoFre) distribution is developed by transforming the independent variable of Gompertz-Fréchet, and one great feature of this model is its capacity to model both positively and negatively skewed datasets with increasing and decreasing hazard rates. It is a distribution whose random variable follows the reciprocal of the Gompertz-Fréchet distribution. The proposed probability distribution is developed with the aim of modeling real data with non-monotonic failure rates. The proposed distribution does not involve the addition of extra parameters, thereby removing the difficulties encountered in deriving its properties. The statistical and mathematical properties of the new distribution, such as the survival function, hazard function, distributions of the minimum and maximum order statistics, moments, mean, median, variance, skewness, and kurtosis, and Renyi entropy are derived. The method of maximum likelihood was used to estimate the model's parameters. Tables of percentage points, which could be of immense benefit for the test of the hypothesis, were generated for different values of the parameters. The proposed distribution was applied to two real-life data sets. The results revealed that the IGoFre distribution performs better than the Gompertz-Weibull, Gompertz-Fréchet, Gompertz Bur XII, and Gompertz-Lomax distributions for the datasets. Also, it was discovered that the proposed model is suitable for modeling both positively skewed and negatively skewed datasets

    Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians

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    Expansions of amino acid repeats occur in >20 inherited human disorders, and many occur in intrinsically disordered regions (IDRs) of transcription factors (TFs). Such diseases are associated with protein aggregation, but the contribution of aggregates to pathology has been controversial. Here, we report that alanine repeat expansions in the HOXD13 TF, which cause hereditary synpolydactyly in humans, alter its phase separation capacity and its capacity to co-condense with transcriptional co-activators. HOXD13 repeat expansions perturb the composition of HOXD13-containing condensates in vitro and in vivo and alter the transcriptional program in a cell-specific manner in a mouse model of synpolydactyly. Disease-associated repeat expansions in other TFs (HOXA13, RUNX2, and TBP) were similarly found to alter their phase separation. These results suggest that unblending of transcriptional condensates may underlie human pathologies. We present a molecular classification of TF IDRs, which provides a framework to dissect TF function in diseases associated with transcriptional dysregulation
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