Recent kinematics of the tectonic plates surrounding the Red Sea and Gulf of Aden

The Red Sea and Gulf of Aden represent two young basins that formed between Africa and Arabia since the early Oligocene, floored by oceanic crust or by transitional and thinned continental crust. While in the easternmost Gulf of Aden the rift–drift transition can be dated chron C6 (~20.1 Ma), here we show that in the Red Sea the first pulse of sea floor spreading occurred during chron C3n.2n (~4.6 Ma) around ~17.1°N (present–day coordinates) and propagated southwards from this location, separating the Danakil microplate from Arabia. It is also shown that sea floor spreading between Arabia and Nubia started later, around chron 2A (~2.58 Ma), and propagated northwards. At present, there is no magnetic evidence for the existence of a linear spreading center in the northern Red Sea at latitudes higher than ~24°N and in the southern Red Sea below ~14.8°N. The present–day plate kinematics of this region can be described with high accuracy by a network of five interacting plates (Nubia, Arabia, Somalia, Sinai, and Danakil) and six triple junctions. For times older than anomaly 2A (~2.58 Ma) and up to anomaly 3, the absence of marine magnetic anomalies between Arabia and Nubia prevents a rigorous kinematic description of the five–plates system. However, there is strong evidence that the unique changes in plate motions during the last five Myrs were a dramatic slowdown at chron C2 (~1.77 Ma) in the spreading or extension rates along the ridge and rift axes, thereby a good representation of the real plate motions can be obtained anyway by backward extension of the oldest Arabia – Nubia and Arabia – Danakil stage rotations determined on the basis of marine magnetic anomalies, respectively C2 – C2A and C2A – C3. The proposed kinematic reconstructions are accompanied by a geodynamic explanation for the genesis of large continent–continent fracture zones at the rift–drift transition and by an analysis of the strain associated with plate motions in Afar, northeastern Egypt, and Sinai

Density Distribution Maps: A Novel Tool for Subcellular Distribution Analysis and Quantitative Biomedical Imaging

open5noSubcellular spatial location is an essential descriptor of molecules biological function. Presently, super-resolution microscopy techniques enable quantification of subcellular objects distribution in fluorescence images, but they rely on instrumentation, tools and expertise not constituting a default for most of laboratories. We propose a method that allows resolving subcellular structures location by reinforcing each single pixel position with the information from surroundings. Although designed for entry-level laboratory equipment with common resolution powers, our method is independent from imaging device resolution, and thus can benefit also super-resolution microscopy. The approach permits to generate density distribution maps (DDMs) informative of both objects’ absolute location and self-relative displacement, thus practically reducing location uncertainty and increasing the accuracy of signal mapping. This work proves the capability of the DDMs to: (a) improve the informativeness of spatial distributions; (b) empower subcellular molecules distributions analysis; (c) extend their applicability beyond mere spatial object mapping. Finally, the possibility of enhancing or even disclosing latent distributions can concretely speed-up routine, large-scale and follow-up experiments, besides representing a benefit for all spatial distribution studies, independently of the image acquisition resolution. DDMaker, a Software endowed with a user-friendly Graphical User Interface (GUI), is also provided to support users in DDMs creation.openIlaria De Santis; Michele Zanoni; Chiara Arienti; Alessandro Bevilacqua; Anna TeseiIlaria De Santis; Michele Zanoni; Chiara Arienti; Alessandro Bevilacqua; Anna Tese

disrupting the pcsk9 ldlr protein protein interaction by an imidazole based minimalist peptidomimetic

We report on a tetraimidazole-based β-strand minimalist peptidomimetic as a novel inhibitor of LDLR–PCSK9 protein–protein interaction, a promising target for hypercholesterolemia

Influence of Lactobacillus kefiri on Intestinal Microbiota and Fecal IgA Content of Healthy Dogs

The increasing incidence of gastrointestinal tract pathologies in dogs and the worrisome topic of antibiotic resistance have raised the need to look for new therapeutic frontiers. Of these, the use of probiotics represents a potential therapeutic alternative. Lactobacillus kefiri (Lk) is a species of Lactobacillus isolated from kefir. Previous studies have demonstrated that its administration in mice downregulates the expression of proinflammatory mediators and increases anti-inflammatory molecules in the gut immune system. It also regulates intestinal homeostasis, incrementing immunoglobulin A (IgA) secretion. Since Lk has never been studied as a single probiotic in dogs, the aim of this study was to evaluate the safety of Lk in dogs, and its effect on IgA secretion and on intestinal microbiota composition. Ten healthy dogs without a history of gastrointestinal diseases were included. The dogs received Lk at a dose of 107 live microorganisms orally, once daily for 30 days. The fecal samples were tested before administration, in the middle, at the end, and 30 days after discontinuation. The IgA secretion concentration and the microbiota composition were evaluated on the fecal samples. The results in this study suggested that Lk did not influence the concentration of IgA, nor significant changes of the intestinal microbiota were observed during and after the treatment. Therefore, additional studies are needed to investigate if a higher daily dosage of Lk can influence the intestinal homeostasis of dogs

Metabolic Syndrome and All-Cause and Cardiovascular Mortality in an Italian Elderly Population: The Progetto Veneto Anziani (Pro.V.A.) Study

OBJECTIVE—The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population

TP53 drives abscopal effect by secretion of senescence-associated molecular signals in non small cell lung cancer

Background Recent developments in abscopal effect strongly support the use of radiotherapy for the treatment of metastatic disease. However, deeper understanding of the molecular mechanisms underlying the abscopal effect are required to best benefit a larger proportion of patients with metastasis. Several groups including ours, reported the involvement of wild-type (wt) p53 in radiation-induced abscopal effects, however very little is known on the role of wtp53 dependent molecular mechanisms. Methods We investigated through in vivo and in vitro approaches how wtp53 orchestrates radiation-induced abscopal effects. Wtp53 bearing (A549) and p53-null (H1299) NSCLC lines were xenotransplanted in nude mice, and cultured in 2D monolayers and 3D tumor spheroids. Extracellular vesicles (EVs) were isolated from medium cell culture by ultracentrifugation protocol followed by Nanoparticle Tracking Analysis. Gene expression was evaluated by RT-Real Time, digital qRT-PCR, and dot blot technique. Protein levels were determined by immunohistochemistry, confocal anlysis, western blot techniques, and immunoassay. Results We demonstrated that single high-dose irradiation (20 Gy) induces significant tumor growth inhibition in contralateral non-irradiated (NIR) A549 xenograft tumors but not in NIR p53-null H1299 or p53-silenced A549 (A549sh/p53) xenografts. We further demonstrates that irradiation of A549 cells in vitro induces a senescence-associated secretory phenotype (SASP) producing extracellular vesicles (EVs) expressing CD63 and carrying DNA:RNA hybrids and LINE-1 retrotransposon. IR-A549 EVs also hamper the colony-forming capability of recipient NIR A549 cells, induce senescent phenotype, nuclear expression of DNA:RNA hybrids, and M1 macrophage polarization. Conclusions In our models, we demonstrate that high radiation dose in wtp53 tumors induce the onset of SASP and secretion of CD63+ EVs loaded with DNA:RNA hybrids and LINE-1 retrotransposons that convey senescence messages out of the irradiation field triggering abscopal effect in NIR tumors

Sigma Receptors as Endoplasmic Reticulum Stress “Gatekeepers” and their Modulators as Emerging New Weapons in the Fight Against Cancer

Despite the interest aroused by sigma receptors (SRs) in the area of oncology, their role in tumor biology remains enigmatic. The predominant subcellular localization and main site of activity of SRs are the endoplasmic reticulum (ER). Current literature data, including recent findings on the sigma 2 receptor subtype (S2R) identity, suggest that SRs may play a role as ER stress gatekeepers. Although SR endogenous ligands are still unknown, a wide series of structurally unrelated compounds able to bind SRs have been identified. Currently, the identification of novel antiproliferative molecules acting via SR interaction is a challenging task for both academia and industry, as shown by the fact that novel anticancer drugs targeting SRs are in the preclinical-stage pipeline of pharmaceutical companies (i.e., Anavex Corp. and Accuronix). So far, no clinically available anticancer drugs targeting SRs are still available. The present review focuses literature advancements and provides a state-of-the-art overview of SRs, with emphasis on their involvement in cancer biology and on the role of SR modulators as anticancer agents. Findings from preclinical studies on novel anticancer drugs targeting SRs are presented in brief

Triple Negative Breast Cancers Have a Reduced Expression of DNA Repair Genes

DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects