152 research outputs found
On the Energy Issue for a Class of Modified Higher Order Gravity Black Hole Solutions
In the case of a large class of static spherically symmetric black hole
solutions in higher order modified gravity models, an expression for the
associated energy is proposed and identified as a quantity proportional to the
constant of integration, which appears in the explicit solution. The
identification is achieved making use of derivation of the First Law of black
hole physics from the equations of motion, evaluating independently the Entropy
via Wald method and the Hawking temperature via the tunneling method. Several
non trivial examples are discussed, including a new topological higher
derivative black hole solution.Comment: 15 pages, published versio
Topological electro-vacuum solutions in extended gravity
Spherically symmetric static topological black hole solutions associated with
some extended higher order gravitational models in the presence of a
Maxwell-field are derived by means of simple Lagrangian method, based on
spherically symmetric reduction. Some new topological black hole solutions are
presented and the validity of the First Law is investigated, and in these cases
an expression for the energy is provided.Comment: 17 pages, published versio
Accelerated CCl4-Induced Liver Fibrosis in Hjv-/- Mice, Associated with an Oxidative Burst and Precocious Profibrogenic Gene Expression
Hereditary hemochromatosis is commonly associated with liver fibrosis. Likewise, hepatic iron overload secondary to chronic liver diseases aggravates liver injury. To uncover underlying molecular mechanisms, hemochromatotic hemojuvelin knockout (Hjv-/-) mice and wild type (wt) controls were intoxicated with CCl4. Hjv-/- mice developed earlier (by 2-4 weeks) and more acute liver damage, reflected in dramatic levels of serum transaminases and ferritin and the development of severe coagulative necrosis and fibrosis. These responses were associated with an oxidative burst and early upregulation of mRNAs encoding α1-(I)-collagen, the profibrogenic cytokines TGF-β1, endothelin-1 and PDGF and, notably, the iron-regulatory hormone hepcidin. Hence, CCl4-induced liver fibrogenesis was exacerbated and progressed precociously in Hjv−/− animals. Even though livers of naïve Hjv−/− mice were devoid of apparent pathology, they exhibited oxidative stress and immunoreactivity towards α-SMA antibodies, a marker of hepatic stellate cells activation. Furthermore, they expressed significantly higher (2–3 fold vs. wt, p<0.05) levels of α1-(I)-collagen, TGF-β1, endothelin-1 and PDGF mRNAs, indicative of early fibrogenesis. Our data suggest that hepatic iron overload in parenchymal cells promotes oxidative stress and triggers premature profibrogenic gene expression, contributing to accelerated onset and precipitous progression of liver fibrogenesis
Circulating microRNA (miRNA) expression profiling in plasma of patients with gestational diabetes mellitus reveals upregulation of miRNA miR-330-3p
Gestational diabetes mellitus (GDM) is characterized by insulin resistance accompanied by low/absent beta-cell compensatory adaptation to the increased insulin demand. Although the molecular mechanisms and factors acting on beta-cell compensatory response during pregnancy have been partially elucidated and reported, those inducing an impaired beta-cell compensation and function, thus evolving in GDM, have yet to be fully addressed. MicroRNAs (miRNAs) are a class of small endogenous non-coding RNAs, which negatively modulate gene expression through their sequence-specific binding to 3'UTR of mRNA target. They have been described as potent modulators of cell survival and proliferation and, furthermore, as orchestrating molecules of beta-cell compensatory response and function in diabetes. Moreover, it has been reported that miRNAs can be actively secreted by cells and found in many biological fluids (e.g., serum/plasma), thus representing both optimal candidate disease biomarkers and mediators of tissues crosstalk(s). Here, we analyzed the expression profiles of circulating miRNAs in plasma samples obtained from n = 21 GDM patients and from n = 10 non-diabetic control pregnant women (24-33 weeks of gestation) using TaqMan array microfluidics cards followed by RT-real-time PCR single assay validation. The results highlighted the upregulation of miR-330-3p in plasma of GDM vs non-diabetics. Furthermore, the analysis of miR-330-3p expression levels revealed a bimodally distributed GDM patients group characterized by high or low circulating miR-330 expression and identified as GDM-miR-330highand GDM-miR-330low. Interestingly, GDM-miR-330highsubgroup retained lower levels of insulinemia, inversely correlated to miR-330-3p expression levels, and a significant higher rate of primary cesarean sections. Finally, miR-330-3p target genes analysis revealed major modulators of beta-cell proliferation and of insulin secretion, such as the experimentally validated genes E2F1 and CDC42 as well as AGT2R2, a gene involved in the differentiation of mature beta-cells. In conclusion, we demonstrated that plasma miR-330-3p could be of help in identifying GDM patients with potential worse gestational diabetes outcome; in GDM, miR-330-3p may directly be transferred from plasma to beta-cells thus modulating key target genes involved in proliferation, differentiation, and insulin secretion
a swarm intelligence-based optimizer for molecular geometry
We present a stochastic, swarm intelligence-based optimization algorithm for
the prediction of global minima on potential energy surfaces of molecular
clusterstructures. Our optimization approach is a modification of the
artificial bee colony (ABC) algorithm which is inspired by the foraging
behavior of honey bees. We apply our modified ABC algorithm to the problem of
global geometryoptimization of molecular clusterstructures and show its
performance for clusters with 2–57 particles and different interatomic
interaction potentials
MicroRNA expression analysis of in vitro dedifferentiated human pancreatic islet cells reveals the activation of the pluripotency-related microRNA cluster miR-302s
β-cell dedifferentiation has been recently suggested as an additional mechanism contributing to type-1 and to type-2 diabetes pathogenesis. Moreover, several studies demonstrated that in vitro culture of native human pancreatic islets derived from non-diabetic donors resulted in the generation of an undifferentiated cell population. Additional evidence from in vitro human β-cell lineage tracing experiments, demonstrated that dedifferentiated cells derive from β-cells, thus representing a potential in vitro model of β-cell dedifferentiation. Here, we report the microRNA expression profiles analysis of in vitro dedifferentiated islet cells in comparison to mature human native pancreatic islets. We identified 13 microRNAs upregulated and 110 downregulated in islet cells upon in vitro dedifferentiation. Interestingly, among upregulated microRNAs, we observed the activation of microRNA miR-302s cluster, previously defined as pluripotency-associated. Bioinformatic analysis indicated that miR-302s are predicted to target several genes involved in the control of β-cell/epithelial phenotype maintenance; accordingly, such genes were downregulated upon human islet in vitro dedifferentiation. Moreover, we uncovered that cell-cell contacts are needed to maintain low/null expression levels of miR-302. In conclusion, we showed that miR-302 microRNA cluster genes are involved in in vitro dedifferentiation of human pancreatic islet cells and inhibits the expression of multiple genes involved in the maintenance of β-cell mature phenotype
MicroRNA circolanti come biomarcatori per il diabete mellito di tipo 2: avanzamenti e prospettive future
Il diabete mellito di tipo 2 (DMT2) è una malattia metabolica cronica eterogenea in costante aumento. In questa rassegna, al fine di identificare un gruppo di microRNA (miRNA) con potenziale applicazione in clinica come biomarcatori per la diagnosi, prognosi e selezione di terapie personalizzate per i pazienti con DMT2, abbiamo effettuato una ricerca sistematica di letteratura, identificando e selezionando 10 miRNA (miR-126-3p, miR-223-3p, miR-21-5p, miR-15a-5p, miR-24-3p, miR-34a-5p, miR-146a-5p, miR-148a-3p, miR-30d-5p e miR-30c-5p)
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