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The paper is devoted to the Italian-Russian diplomacy before the beginning of the First World War. The historiography debate on the entry of Italy in the conflict is more than ever open. The truth, according to historian Giorgio Petracchi, is that in all the range of time from the Agreement of Racconigi (1909) till the explosion of the First World conflict, the balance of the relations between Saint Petersburg and Rome wasn't in the whole positive. One of the reasons of this is that Italy and Russia still continued to remain \"unknown to themselves\" also due to the poor Italian diplomatic presence in the vast Russian territory, just one embassy (rather isolated) in Saint Petersburg and three consular representatives. In addition Italy remained alone in its attempt to sustain that the only way out of impasse was in Russian hands, only one capable to find an agreement between Romanians and Serbs. Thus certain mechanisms were being consolidated which would have their weight in the course of the war. England displayed no interest for the Balkan region if not strictly tied to the favorable evolution of the war; Russia showed itself very careful in \"handling\" the Adriatic policies of Serbia going inevitably in contrast with the Italian hegemony demands even in the Mediterranean area of interest. Paris also aligned itself to this policy reprimanding Rome for not respecting fully the Treaty of London. All this brought on a progressive political-diplomatic isolation of the Italian government. In syntheses we can sustain that in the diplomatic relations between Italy and Russia, at the eve and in the first years of the war, the Balkan world was in the midst of it with its complexities and its unsolved problems, which will return and explode again seventy years later with the fall of the Berlin wall.

Genetic studies have identified mutations in key regulators of the Wnt/β-catenin pathway in a variety of cancers, most frequently in colon cancers. However, whether the pathway is activated in clinical cancer samples is not easily determined, and therefore it is useful to find markers that could be surrogates to show activation of the Wnt/β-catenin pathway. Gene expression profiles were analyzed in SW620, a colon cancer cell line in which β-catenin levels are stabilized as a consequence of truncated adenomatous polyposis coli and were compared with profiles of the same cells transfected with antisense oligodeoxynucleotides. Treatment of cells with β-catenin antisense oligodeoxynucleotides resulted in a decrease in the levels of axin2 and human naked cuticle (hnkd) mRNAs. Interestingly, the proteins encoded by both of these mRNAs are known inhibitors of the β-catenin pathway. In 30 human cell lines derived from different origins, axin2 and hnkd were expressed only in human colon cancer cell lines that are known to have activating mutations in the Wnt/β-catenin pathway. Further, levels of both axin2 and hnkd mRNA were also found to be elevated in about 65% of laser microdissected cells from human colon tumors compared with laser microdissected cells of normal morphology from the same patient samples. The increased expression of axin2 and hnkd correlated with truncations in adenomatous polyposis coli in the same patient samples. These results reveal that it is possible to detect activation of a carcinogenic pathway in human cancer samples with specific markers.

The proposed site for a new solid waste disposal facility was identified by a municipal government in a north Florida area characterized by Miocene Hawthorn Group sedimentary sequences and active karst development. An evaluation of the sinkhole potential and subsurface stability was conducted with a total of 300 electrical resistivity Wenner array sounding traverses with electrode spacings extending to 30 m. Data were interpreted to identify vertical sequences of the Hawthorn Group confining layer, and the underlying Ocala Limestone. Electrical evidence identified an intermediate, discontinuous limestone layer present in limited areas, but absent in much of the area investigated. No evidence was detected to identify breeches within the confining layer over the Floridan Aquifer within the Ocala Limestone. The data were combined with lithologic logs from deep boreholes to prepare a series of continuous and interconnecting fence diagrams to portray the geologic configuration throughout the proposed site. The results demonstrate the value of electrical resistivity measurements to augment borehole data in economical investigations of sinkhole potential in karstic terrains.[PUBLICATION ABSTRACT]

We have used DNA microarrays to follow Neisseria meningitidis serogroup B (MenB) gene regulation during interaction with human epithelial cells. Host-cell contact induced changes in the expression of 347 genes, more than 30% of which encode proteins with unknown function. The upregulated genes included transporters of iron, chloride, amino acids, and sulfate, many virulence factors, and the entire pathway of sulfur-containing amino acids. Approximately 40% of the 189 upregulated genes coded for peripherally located proteins, suggesting that cell contact promoted a substantial reorganization of the cell membrane. This was confirmed by fluorescence activated cell sorting (FACS) analysis on adhering bacteria using mouse sera against twelve adhesion-induced proteins. Of the 12 adhesion-induced surface antigens, 5 were able to induce bactericidal antibodies in mice, demonstrating that microarray technology is a valid approach for identifying new vaccine candidates and nicely complements other genome mining strategies used for vaccine discovery.

Oral antibiotics, especially tetracyclines, are commonly used to treat moderate to moderately severe acne vulgaris. There are hints suggesting that a combination treatment with oral tetracyclines and topical retinoids can cause a greater and prompter improvement of acne than monotherapy with tetracyclines. We evaluated the clinical activity of a 12-week combined therapy with oral lymecycline (300mg/day for 2 weeks and then 150mg/day) and topical adapalene (gel or cream) in 419 patients with inflammatory acne. A significant reduction in the number of acne lesions was noted at 4 and 12 weeks (P<0.0001). Thereafter, 400 patients underwent a maintenance treatment with adapalene alone for 12 weeks. At week 24 a relevant improvement of acne lesions still persisted (P<0.0001) in most patients. Only 16 patients relapsed and required additional use of oral lymecycline which proved again successful. No substantial differences were noted in the magnitude of clinical response between patients treated with adapalene gel and those treated with cream formulation. Treatment was well tolerated. Local adverse reactions occurred in 11.7 % of patients and resulted in premature discontinuation of treatment in 1.4 %. Systemic (gastrointestinal) untoward effects developed in 1.2 % of patients and caused treatment interruption in 0.7 % of cases. No serious adverse events occurred.

  The infamous 1981 Winter Park sinkhole galvanized the Florida Legislature to develop wording in the state statutes designed to protect homeowners from sinkhole losses via automatic coverage in homeowner insurance policies. Although revised numerous times, the language in the statutes basically entitled policyholders to file claims for sinkhole losses if cracking or other signs of sinkhole activity occurred in their homes. Cover collapse sinkholes are less common, but occur relatively quickly (hours or days), often evolving from an earlier formed cover subsidence sinkhole. Cover collapse sinkholes are catastrophic, resulting in large, deep depressions in the ground surface and can swallow homes and buildings. This sinkhole type is usually associated with large cavities in limestone, relatively close to the ground surface. Breaches in the roof of a cavity can cause massive raveling of the overlying sand/clay, as well as collapse of the cavity itself. As The Sun editorial pointed out, \"a sinkhole industrial complex of lawyers, geologists and engineers\" emerged. Policyholders were enticed to file claims on virtually any grounds, and ensuing investigations yielding even the smallest shreds of sinkhole activity evidence were declared to be proof of a sinkhole loss.

The interplay between diet, host genetics, microbiota, and immune system has a key role in the pathogenesis of inflammatory bowel disease (IBD). Although the causal pathophysiological mechanisms remain unknown, numerous dietary nutrients have been shown to regulate gut mucosal immune function, being effective in influencing innate or adaptive immunity. Here, we proved that transient receptor potential melastatin 8 (TRPM8), a non-selective cation channel, mediates LPS- evoked Ca 2+ influx in macrophages leading to their activation. Additionally, we showed that TRPM8 is selectively blocked by the dietary flavonoid luteolin, which induced a pro-tolerogenic phenotype in pro-inflammatory macrophages. Accordingly, genetic deletion of Trpm8 in macrophages caused a deficit in the activation of pro-inflammatory metabolic and transcriptional reprogramming, leading to reduced production of key pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. The TRPM8 anti-inflammatory effect was found to be dependent on lactate which in turn induces IL-10 gene expression. Adoptive transfer of TRPM8-deficient bone marrow in wild-type mice improved intestinal inflammation in a model of colitis. Accordingly, oral administration of luteolin protected mice against colitis through an impairment in the innate immune response. Our study reveals the potential of targeting TRPM8 through specific nutrient interventions to regulate immune function in sub-clinical scenarios or to treat inflammatory diseases, primarily driven by chronic immune responses, such as IBD.