Alkyphenol exposure alters steroidogenesis in male lizard podarcis siculus

Background: Nonylphenol (NP) and Octylphenol (OP) are persistent and non-biodegradable environmental contaminants classified as endocrine disruptor chemicals (EDCs). These compounds are widely used in several industrial applications and present estrogen-like properties, which have extensively been studied in aquatic organisms. The present study aimed to verify the interference of these compounds alone, and in mixture, on the reproductive cycle of the male terrestrial vertebrate Podarcis siculus, focusing mainly on the steroidogenesis process. Methods: Male lizards have been treated with different injections of both NP and OP alone and in mixture, and evaluation has been carried out using a histological approach. Results: Results obtained showed that both substances are able to alter both testis histology and localization of key steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) and P450 aromatase. Moreover, OP exerts a preponderant effect, and the P450 aromatase represents the major target of both chemicals. Conclusions: In conclusion, NP and OP inhibit steroidogenesis, which in turn may reduce the reproductive capacity of the specimens

Model-independent search strategy for the lepton-flavor-violating heavy Higgs boson decay to τμ at the LHC

In this work we present a model-independent search strategy at the LHC for heavy Higgs bosons decaying into a tau and a muon, H/ A→ τμ, showing a plausible tendency to improve the sensitivity obtained by the present experimental limits. This search strategy is performed for the Higgs boson mass range 1–5 TeV and uses as the most relevant kinematical variables, in order to discriminate signal against background, the transverse momenta of the muon and the tau together with the missing transverse energy. We estimate the exclusion limits at 95% CL and the significances for evidence and discovery at s = 14 TeV with L = 300 fb- 1, observing a growth in the sensitivities for high Higgs boson masses. Moreover, since the Higgs boson decay into a tau-lepton pair may mimic our LFV signal, we also study the impact of the ditau channel on the exclusion limits and the significances for evidence and discovery. In particular, the impact on the exclusion limits of LFV heavy Higgs boson decays is significant when the ditau rate begins to compete with the corresponding to the H/ A→ τμ decayThis work has been partially supported by CONICET and ANPCyT under projects PICT 2016-0164 (E. A., N. M., A. S.), PICT 2017-2751 (E. A., N. M., A. S.) and PICT 2017-2765 (E. A.). This work is supported by the European Union through the ITN ELUSIVES H2020-MSCA-ITN-2015//674896 and the RISE INVISIBLE-SPLUS H2020-MSCA-RISE-2015//690575, by the CICYT through the project FPA2016-78645-P, and by the Spanish MINECOs “Centro de Excelencia Severo Ochoa” Programme under Grant SEV-2016-059

Nickel and gtp modulate helicobacter pylori ureg structural flexibility

UreG is a P-loop GTP hydrolase involved in the maturation of nickel-containing urease, an essential enzyme found in plants, fungi, bacteria, and archaea. This protein couples the hydrolysis of GTP to the delivery of Ni(II) into the active site of apo-urease, interacting with other urease chaperones in a multi-protein complex necessary for enzyme activation. Whereas the conformation of Helicobacter pylori (Hp) UreG was solved by crystallography when it is in complex with two other chaperones, in solution the protein was found in a disordered and flexible form, defining it as an intrinsically disordered enzyme and indicating that the well-folded structure found in the crystal state does not fully reflect the behavior of the protein in solution. Here, isothermal titration calorimetry and site-directed spin labeling coupled to electron paramagnetic spectroscopy were successfully combined to investigate HpUreG structural dynamics in solution and the effect of Ni(II) and GTP on protein mobility. The results demonstrate that, although the protein maintains a flexible behavior in the metal and nucleotide bound forms, concomitant addition of Ni(II) and GTP exerts a structural change through the crosstalk of different protein regions

Status of coronary disease and results from early endovascular aneurysm repair after preventive percutaneous coronary revascularization

Background: The incidence of coronary artery disease (CAD) is high in patients with an aortic aneurysm but preoperative routine coronary angiography and preventive coronary revascularization are not recommended to reduce cardiac events in patients with severe CAD. Aim: This study evaluated the safeness and efficacy of preventive percutaneous coronary intervention (PCI) in patients with severe CAD scheduled for endovascular aneurysm repair (EVAR). Methods: All patients with descending thoracic aneurysm (DTA) or abdominal aortic aneurysm (AAA) scheduled for EVAR underwent preliminary coronary angiography. Based on coronary angiography results, 917 patients (40.7%) had significant CAD and were treated by percutaneous coronary intervention (PCI; CAD group) and 1337 patients (59.3%) were without or with mild/moderate CAD and were considered as controls (no‐CAD group). To evaluate the safeness and efficacy of preventive PCI in patients with severe CAD undergoing EVAR, groups were compared for hospital and 12‐month cardiac adverse events. Results: CAD was present in 1210 patients (53.6%): significant in 917 patients (38%) and mild to moderate in 293 patients (5.3%). Hospital and 12‐month cardiac events occurred in 15 (1.6%) and 13 (1.4%) CAD group patients and in 9 (0.7%) and 8 (0.4%) no‐CAD group patients (p = .05 and p = .08), respectively. Hospital and 12‐month cardiac deaths occurred in 3 (0.3%) and 2 (0.2%) CAD group patients and in 3 (0.2%) and 2 (0.2%) no‐CAD group patients (p = .9 and p = .9), respectively. Conclusion: The strategy to treat severe CAD preoperatively by PCI and early subsequent EVAR brings a similar outcome to that in patients without or with mild/ moderate CAD

Conformational selection underlies recognition of a molybdoenzyme by its dedicated chaperone

Molecular recognition is central to all biological processes. Understanding the key role played by dedicated chaperones in metalloprotein folding and assembly requires the knowledge of their conformational ensembles. In this study, the NarJ chaperone dedicated to the assembly of the membrane-bound respiratory nitrate reductase complex NarGHI, a molybdenum-iron containing metalloprotein, was taken as a model of dedicated chaperone. The combination of two techniques ie site-directed spin labeling followed by EPR spectroscopy and ion mobility mass spectrometry, was used to get information about the structure and conformational dynamics of the NarJ chaperone upon binding the N-terminus of the NarG metalloprotein partner. By the study of singly spin-labeled proteins, the E119 residue present in a conserved elongated hydrophobic groove of NarJ was shown to be part of the interaction site. Moreover, doubly spin-labeled proteins studied by pulsed double electron-electron resonance (DEER) spectroscopy revealed a large and composite distribution of inter-label distances that evolves into a single preexisting one upon complex formation. Additionally, ion mobility mass spectrometry experiments fully support these findings by revealing the existence of several conformers in equilibrium through the distinction of different drift time curves and the selection of one of them upon complex formation. Taken together our work provides a detailed view of the structural flexibility of a dedicated chaperone and suggests that the exquisite recognition and binding of the N-terminus of the metalloprotein is governed by a conformational selection mechanism

Lenvatinib for the treatment of renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) accounts for 2\u20133% of all solid tumors. Expression of the receptor for the vascular endothelial growth factor (VEGF) is one of the most common features of RCC. Areas covered: Lenvatinib is a novel multi-kinase inhibitor that has been studied in several solid tumors. It has shown promising results in the treatment of RCC, especially when combined with everolimus, In this review, we summarize the available data of lenvatinib for the treatment of advanced/metastatic renal cell carcinoma. Expert opinion: Lenvatinib in combination with everolimus has provided encouraging results in both clinical and laboratory investigations showing that blocking angiogenesis and the mTOR signalling pathway could be a remarkable approach for treating RCC. As an additive to this type of approach it would be interesting in future clinical settings testing also the combination of lenvatinib and everolimus with immune-therapy

Model-independent search strategy for the lepton-flavor-violating heavy Higgs boson decay to τμ at the LHC

In this work we present a model-independent search strategy at the LHC for heavy Higgs bosons decaying into a tau and a muon, H/A→τμ, showing a plausible tendency to improve the sensitivity obtained by the present experimental limits. This search strategy is performed for the Higgs boson mass range 1–5 TeV and uses as the most relevant kinematical variables, in order to discriminate signal against background, the transverse momenta of the muon and the tau together with the missing transverse energy. We estimate the exclusion limits at 95% CL and the significances for evidence and discovery at s√ = 14 TeV with L = 300 fb−1, observing a growth in the sensitivities for high Higgs boson masses. Moreover, since the Higgs boson decay into a tau-lepton pair may mimic our LFV signal, we also study the impact of the ditau channel on the exclusion limits and the significances for evidence and discovery. In particular, the impact on the exclusion limits of LFV heavy Higgs boson decays is significant when the ditau rate begins to compete with the corresponding to the H/A→τμ decay.Instituto de Física La Plat