Androgens and Hypertension in Men and Women: a Unifying View.

This review was designed to revaluate the androgen role on the mechanisms of hypertension and cardiovascular risks in both men and women. Sex steroids are involved in the regulation of blood pressure, but pathophysiological mechanism is not well understood. Androgens have an important effect on metabolism, adipose and endothelial cell function, and cardiovascular risk in both men and women. A focal point in this contest is represented by the possible gender-specific regulation of different tissues and in particular of the adipose cell. Available data confirm that androgen deficiency is linked to increased prevalence of hypertension and cardiovascular diseases. Adipocyte dysfunction seems to be the main involved mechanism. Androgen replacement reduces inflammation state in man, protecting by metabolic syndrome progression. In women, androgen excess has been considered as promoting factor of cardiovascular risk. However, recent data suggest that excessive androgen production has little effect per se in inducing hypertension in young women of reproductive age. Also in postmenopausal women, data on relative androgen excess and hypertension are missing, while adrenal androgen deficiency has been associated to increased mortality. RECENT FINDINGS: Molecular mechanisms linking androgen dysregulation to hypertension are almost Unknown, but they seem to be related to increased visceral fat, promoting a chronic inflammatory state through different mechanisms. One of these may involve the recruitment and over-activation of NF-kB, a ubiquitous transcription factor also expressed in adipose cells, where it may cause the production of cytokines and other immune factors. The NF-kB signalling pathway may also influence brown adipogenesis leading to the preferential enlargement of visceral adipocytes. Chronic inflammation and adipocyte dysfunction may alter endothelial function leading to hypertension. Both in men and in women, particularly in the post-menopausal period, hypoandrogenism seems to be a major determinant of the increased prevalence of hypertension. The relationship between androgen signalling and NF-kB might explain the pathophysiological mechanism leading to the development of endothelium dysfunction and hypertension

Further Evidence on the Role of Thyroid Autoimmunity in Women with Recurrent Miscarriage

It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy

Supersymmetric particle mass measurement with invariant mass correlations

The kinematic end-point technique for measuring the masses of supersymmetric particles in R-Parity conserving models at hadron colliders is re-examined with a focus on exploiting additional constraints arising from correlations in invariant mass observables. The use of such correlations is shown to potentially resolve the ambiguity in the interpretation of quark+lepton end-points and enable discrimination between sequential two-body and three-body lepton-producing decays. The use of these techniques is shown to improve the SUSY particle mass measurement precision for the SPS1a benchmark model by at least 20-30% compared to the conventional end-point technique.Comment: 29 pages, 23 .eps figures, JHEP3 style; v2 adds some references and small clarifications to text; v3 adds some more clarifications to the tex

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis

Supersymmetric particle mass measurement with the boost-corrected contransverse mass

A modification to the contransverse mass (MCT) technique for measuring the masses of pair-produced semi-invisibly decaying heavy particles is proposed in which MCT is corrected for non-zero boosts of the centre-of-momentum (CoM) frame of the heavy states in the laboratory transverse plane. Lack of knowledge of the mass of the CoM frame prevents exact correction for this boost, however it is shown that a conservative correction can nevertheless be derived which always generates an MCT value which is less than or equal to the true value of MCT in the CoM frame. The new technique is demonstrated with case studies of mass measurement with fully leptonic ttbar events and with SUSY events possessing a similar final state.Comment: 33 pages, 33 .eps figures, JHEP3 styl

The Higgs Working Group: Summary Report (2001)

Report of the Higgs working group for the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001. It contains 7 separate sections: A. Theoretical Developments B. Higgs Searches at the Tevatron C. Experimental Observation of an invisible Higgs Boson at LHC D. Search for the Standard Model Higgs Boson using Vector Boson Fusion at the LHC E. Study of the MSSM channel $A/H \to \tau \tau$ at the LHC F. Searching for Higgs Bosons in $t\bar t H$ Production G. Studies of Charged Higgs Boson Signals for the Tevatron and the LHCComment: 120 pages, latex, many figures, proceedings of the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001, full Author list included in paper. Typos corrected, author list and acknowledgements completed. Convernors: D. Cavalli, A. Djouadi, K. Jakobs, A. Nikitenko, M. Spira, C.E.M. Wagner, W.-M. Ya

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

Higgs Boson Theory and Phenomenology

Precision electroweak data presently favors a weakly-coupled Higgs sector as the mechanism responsible for electroweak symmetry breaking. Low-energy supersymmetry provides a natural framework for weakly-coupled elementary scalars. In this review, we summarize the theoretical properties of the Standard Model (SM) Higgs boson and the Higgs sector of the minimal supersymmetric extension of the Standard Model (MSSM). We then survey the phenomenology of the SM and MSSM Higgs bosons at the Tevatron, LHC and a future e+e- linear collider. We focus on the Higgs discovery potential of present and future colliders and stress the importance of precision measurements of Higgs boson properties.Comment: 90 pages, 31 figures. Revised version. To be published in Progress in Particle and Nuclear Physics. This paper with higher resolution figures can be found at http://scipp.ucsc.edu/~haber/higgsreview/higgsrev.p

Ambient Seismic Noise Image of the Structurally Controlled Heat and Fluid Feeder Pathway at Campi Flegrei Caldera

The TIDES-COST Action (STSM-ES1401-34011) provided a travel grant to framework the research project. The Japan Society for the Promotion of Science - Short-Term Fellowship (JSPS/OF215/022) financed the work, undertaken at Tohoku University and concluded at the University of Aberdeen. We thank Giuseppe Vilardo and Eliana Bellucci Sessa for providing the geomorphological maps, and Simona Petrosino and Paola Cusano for the P- and S-wave pickings used to localise the seismicity. Informal revisions from Guido Ventura, Nick Rawlinson and Chris Kilburn helped us improving the analyses and interpretation, respectively. We acknowledge the help of Naveed Khan in parallelising the codes and two anonymous reviewers who improved the analysis, interpretation, and readibility with their comments. All data to reproduce the maps can be downloaded from the World Data Center PANGAEA data repository, permanent link https://doi.pangaea.de/10.1594/PANGAEA.890238.Peer reviewedPublisher PD

TP63 and TP73 in cancer, an unresolved “family” puzzle of complexity, redundancy and hierarchy

AbstractTP53 belongs to a small gene family that includes, in mammals, two additional paralogs, TP63 and TP73. The p63 and p73 proteins are structurally and functionally similar to p53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. p63 and p73 have important functions in embryonic development and differentiation but are also involved in tumor suppression. The biology of p63 and p73 is complex since both TP63 and TP73 genes are transcribed into a variety of different isoforms that give rise to proteins with antagonistic properties, the TA-isoforms that act as tumor-suppressors and DN-isoforms that behave as proto-oncogenes. The p53 family as a whole behaves as a signaling “network” that integrates developmental, metabolic and stress signals to control cell metabolism, differentiation, longevity, proliferation and death. Despite the progress of our knowledge, the unresolved puzzle of complexity, redundancy and hierarchy in the p53 family continues to represent a formidable challenge