Detecting complex network modularity by dynamical clustering.

Based on cluster desynchronization properties of phase oscillators, we introduce an efficient method for the detection and identification of modules in complex networks. The performance of the algorithm is tested on computer generated and real-world networks whose modular structure is already known or has been studied by means of other methods. The algorithm attains a high level of precision, especially when the modular units are very mixed and hardly detectable by the other methods, with a computational effort O(KN) on a generic graph with N nodes and K links.

UVC inhibits HIF-1alpha protein translation by a DNA damage- and topoisomerase I-independent pathway.

Hypoxia inducible factor 1 (HIF-1) is a key player in cancer progression and an attractive target for cancer therapy. Several small molecule inhibitors of HIF-1alpha also induce a DNA damage response. However, whether or not DNA damage is required for or associated with the inhibition of HIF-1alpha protein accumulation is poorly understood.

Cell type-specific, topoisomerase II-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation by NSC 644221.

Purpose: The discovery and development of small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1) is an attractive, yet challenging, strategy for the development of new cancer therapeutic agents. Here, we report on a novel tricyclic carboxamide inhibitor of HIF-1alpha, NSC 644221.

Experimental Design: We investigated the mechanism by which the novel compound NSC 644221 inhibited HIF-1alpha.

Activity of Berberis aetnensis root extracts on Candida strains.

The antifungal activity of methanolic extract and alkaloidal fraction of Berberis aetnensis against Candida species was investigated. The crude extract was active against Candida species, this activity being higher than that of the alkaloidal fraction and berberine.

Hypoxic induction of an HIF-1alpha-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells.

Hypoxia is a major pathophysiological condition for the induction of angiogenesis, which is a crucial aspect of growth in solid tumors. In mammalian cells, the transcriptional response to oxygen deprivation is largely mediated by hypoxia-inducible factor 1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF-1beta subunits. However, the response of endothelial cells to hypoxia and the specific involvement of HIF-alpha subunits in this process are still poorly understood.

Efficacy and safety of bimatoprost in patients with uncontrolled glaucoma as alternative to filtration surgery.

Purpose: To evaluate the efficacy and safety of bimatoprost 0.03% as an alternative to filtration surgery in patients with uncontrolled glaucoma.

Design: Interventional study.

Topotecan blocks hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression induced by insulin-like growth factor-I in neuroblastoma cells.

The extent of angiogenesis and/or vascular endothelial growth factor (VEGF) expression in neuroblastoma tumors correlates with metastases, N-myc amplification, and poor clinical outcome. Understanding the mechanisms regulating VEGF expression in neuroblastoma cells provides additional therapeutic options to control neuroblastoma tumor growth. VEGF mRNA is controlled by growth factors and hypoxia via the transcription factor hypoxia-inducible factor (HIF-1alpha).

Accumulation of hypoxia-inducible factor-1alpha is limited by transcription-dependent depletion.

In the presence of oxygen and iron, hypoxia-inducible factor (HIF-1alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways. Given striking similarities between p53 and HIF-1alpha regulation, we previously suggested that HIF-1 transcriptionally initiates its own degradation and therefore inhibitors of transcription must induce HIF-1alpha. Under normoxia, while inducing p53, inhibitors of transcription did not induce HIF-1alpha.

Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts.

We have previously shown that topotecan, a topoisomerase I poison, inhibits hypoxia-inducible factor (HIF)-1alpha protein accumulation by a DNA damage-independent mechanism. Here, we report that daily administration of topotecan inhibits HIF-1alpha protein expression in U251-HRE glioblastoma xenografts. Concomitant with HIF-1alpha inhibition, topotecan caused a significant tumor growth inhibition associated with a marked decrease of angiogenesis and expression of HIF-1 target genes in tumor tissue.

Glassy phase in the Hamiltonian mean-field model.

We study the relaxation dynamics of a Hamiltonian system of N fully coupled XY spins. The thermodynamics of the system predicts a ferromagnetic and a paramagnetic phase. Starting from out-of-equilibrium initial conditions, the dynamics at constant energy drives the system into quasistationary states (QSSs) characterized by dynamical frustration.

Macrophage activating properties of the tryptophan catabolite picolinic acid.

Recent studies have suggested a role for aminoacid catabolites as important regulators of macrophage (Mphi) activities. We reported previously that picolinic acid (PA), a tryptophan catabolite produced under inflammatory conditions and a costimulus with IFNgamma of Mphi effector functions, is a selective inducer of the Mphi inflammatory protein-1alpha (MIP-1alpha) and -1beta (MIPs), two CC-chemokines involved in the elicitation of the inflammatory reactions and in the development of the Th1 responses. In this study, we have investigated the effects of IFNgamma on PA-induced MIPs expression and secretion by mouse Mphi as well as the regulation of MIP-1alpha/beta receptor, CCR5, by both stimuli alone or in combination.

Protection against murine endotoxemia by treatment with Ruta chalepensis L., a plant with anti-inflammatory properties.

The anti-inflammatory effect of the extract of Ruta Chalepensis L. (Rutaceae) on the course of lethal endotoxemia in BALB/c mice was studied. When administered by gavage as 1 g/kg per day starting 14 or 7 days prior to injection of 0.

Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1: mechanism and therapeutic implications.

We have shown previously that the camptothecin analogue topotecan (TPT), a topoisomerase I (Top 1) poison, inhibits hypoxia-inducible factor 1 (HIF-1) transcriptional activity and HIF-1alpha protein accumulation in hypoxia-treated U251 human glioma cells. In this article, we demonstrate that TPT does not affect HIF-1alpha protein accumulation but inhibits its translation. In addition, we demonstrate that Top 1 is required for the inhibition of HIF-1alpha protein accumulation by TPT as shown by experiments performed using camptothecin-resistant cell lines with known Top 1 alterations.

Hypoxia selectively inhibits monocyte chemoattractant protein-1 production by macrophages.

Hypoxia, a local decrease in oxygen tension occurring in inflammatory and tumor lesions, modulates gene expression in macrophages. Because macrophages are important chemokine producers, we investigated the regulatory effects of hypoxia on macrophage-derived chemokines. We demonstrated that hypoxia inhibits the production of the macrophage and T lymphocyte chemotactic and activating factor, monocyte chemoattractant protein-1 (MCP-1).

Targeting topoisomerase I to inhibit hypoxia inducible factor 1.

HIF-1 is a key factor in cancer progression. Efforts are underway to identify and develop small molecules that inhibit HIF-1 transcriptional activity. What are the best targets and the best ways to develop HIF-1 inhibitors are open questions.

Regulation of the chemokine receptor CXCR4 by hypoxia.

Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs that coordinate expression of genes involved in oxygen delivery (via angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand.

Berberis aetnensis C. Presl. extracts: antimicrobial properties and interaction with ciprofloxacin.

Previous research showed that berberine-containing Berberis species synthesise the substances 5'-methoxyhydnocarpin-D (5'-MHC-D) and pheophorbide a, which have no antimicrobial activity but inhibit the expression of multidrug resistant efflux pumps (MDRs) in Staphylococcus aureus and potentiate the action of berberine. The MDR pumps extrude synthetic and natural antimicrobials from bacterial cells. We searched for these compounds in Berberis aetnensis C.

Antibacterial activity of medicinal plant extracts against periodontopathic bacteria.

This study was performed to evaluate the antibacterial activity of Althaea officinalis L. roots, Arnica montana L. flowers, Calendula officinalis L.

Power-law time distribution of large earthquakes.

We study the statistical properties of time distribution of seismicity in California by means of a new method of analysis, the diffusion entropy. We find that the distribution of time intervals between a large earthquake (the main shock of a given seismic sequence) and the next one does not obey Poisson statistics, as assumed by the current models. We prove that this distribution is an inverse power law with an exponent mu=2.

Hyperhomocysteinemia in menopausal hypertension: an added risk factor and a dangerous association for organ damage.

Hyperhomocysteinemia is widely recognised as an emerging risk factor of endothelial dysfunction and vascular damage. In this study we wanted to verify if it, when associated to arterial hypertension--traditional risk factor--represents a higher added risk of organ damage during menopause, which is a condition connected to a higher incidence of cerebrovascular diseases. A survey of 30 postmenopausal women with similar characteristics (BMI, age, absence of relevant pathologies such as diabetes, metabolic disorders and absence of smoking) was selected (menopause had occurred from 12 to 16 months at the moment of observation).

[Measurement of carotid intima-media thickness and of pressure variability in arterial hypertension in menopause].

Forty women, with hypertension developed during menopause, were divided into two groups, depending on whether from the time of its beginning there were occurrences of clinic episodes expressing a more or less acute "organ damage" or not. In all patients a 24 hrs ambulatory blood pressure monitoring and a carotid ultrasound were carried out to evaluate the carotid intima-media thickness (IMT). The IMT resulted significantly superior in those patients presenting a vascular episode and as much significantly correlated to the pressure values, especially systolic; in particular, in "non dippers" patients there is evidence of correlations between percentages of "at risk" systolic pressure peaks, prevalence of plaques in carotidal vessels and higher IMT compared to those patients with night-time blood pressure decrease.