Cadmium and arsenic-induced-stress differentially modulates Arabidopsis root architecture, peroxisome distribution, enzymatic activities and their nitric oxide content

In plant cells, cadmium (Cd) and arsenic (As) exert toxicity mainly by inducing oxidative stress through an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and their detoxification. Nitric oxide (NO) is a RNS acting as signalling molecule coordinating plant development and stress responses, but also as oxidative stress inducer, depending on its cellular concentration. Peroxisomes are versatile organelles involved in plant metabolism and signalling, with a role in cellular redox balance thanks to their antioxidant enzymes, and their RNS (mainly NO) and ROS. This study analysed Cd or As effects on peroxisomes, and NO production and distribution in the root system, including primary root (PR) and lateral roots (LRs). Arabidopsis thaliana wild-type and transgenic plants enabling peroxisomes to be visualized in vivo, through the expression of the 35S-cyan fluorescent protein fused to the peroxisomal targeting signal1 (PTS1) were used. Peroxisomal enzymatic activities including the antioxidant catalase, the H2O2-generating glycolate oxidase, and the hydroxypyruvate reductase, and root system morphology were also evaluated under Cd/As exposure. Results showed that Cd and As differently modulate these activities, however, catalase activity was inhibited by both. Moreover, Arabidopsis root system was altered, with the pollutants differently affecting PR growth, but similarly enhancing LR formation. Only in the PR apex, and not in LR one, Cd more than As caused significant changes in peroxisome distribution, size, and in peroxisomal NO content. By contrast, neither pollutant caused significant changes in peroxisomes size and peroxisomal NO content in the LR apex

Effectiveness of antihypertensive therapy in HIV-positive patients: evaluation to 144 weeks

Hypertension is more prevalent among HIV-infected subjects than in the general population, contributing to increased cardiovascular risk in HIV+ patients. The angiotensin II receptor blocker telmisartan is also a partial peroxisome proliferator activated receptor (PPAR)-γ agonist, with documented effects on improving hypertension, lipid metabolism and renal function. Therefore telmisartan was found to be the first choice for treatment of HIV+ hypertensive patients. Aim of this study was to evaluate the durability on 144 weeks of treatment with telmisartan in HIV+ patients. 13 HIV+ Caucasian male patients treated with combined antiretroviral therapy (cART) and discovered to be naïve hypertensive, were given 80 mg telmisartan daily. Systolic (SBP) and diastolic (DBP) blood pressure, viro-immunological, lipid and metabolic parameters, including triglycerides, cholesterol, insulin resistance (HOMA-IR), inflammatory markers, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), indexes of renal function and cardiovascular risk, microalbuminuria, cystatin C, were measured at baseline (T0), and after 24 (T24), 48 (T48), 72 (T72), 96 (T96), 120 (T120) and 144 (T144) weeks. Treatment with telmisartan decreased SBP and DBP levels during the 144 weeks of observation. We also observed improved HDL-cholesterol, HOMA-IR, microalbuminuria and cystatin C at the end of study. Triglycerides and total cholesterol significantly decreased and HDL-cholesterol significantly increased. Total cholesterol/HDL cholesterol ratio improved significantly. Throughout in the course of the trial our patients showed a significant improvement of the percentage of CD4+ and CD8+. Eventually in all 144 weeks of therapy with telmisartan 80 mg/day have not observed adverse events or dropouts. Telmisartan was effective in improving hypertension, lipid metabolism and renal function in 144 weeks of evaluation. It determines the improvement of cystatin C and microalbuminuria, markers of renal function and cardiovascular risk. Telmisartan doesn't interfere with cART, not interfering with the recovery of immunological HIV patients. Telmisartan has confirmed durability and effectiveness, excellent tolerability and an high persistance with a good blood pressure control. Therefore telmisartan reveals the first choice in the treatment of hypertension in HIV+ because of significant morbidity in this group of patients

Effects of dual renin-angiotensin system blockade on proteinuria in a hypertensive black African HIV infected patient

Kidney diseases manifesting as proteinuria or elevated creatinine are increasingly prevalent complications of HIV infection. We report the effects of dual renin-angiotensin system blockade on proteinuria in a hypertensive black African HIV-infected patient

Cumulo: A Dataset for Learning Cloud Classes

One of the greatest sources of uncertainty in future climate projections comes from limitations in modelling clouds and in understanding how different cloud types interact with the climate system. A key first step in reducing this uncertainty is to accurately classify cloud types at high spatial and temporal resolution. In this paper, we introduce Cumulo, a benchmark dataset for training and evaluating global cloud classification models. It consists of one year of 1km resolution MODIS hyperspectral imagery merged with pixel-width 'tracks' of CloudSat cloud labels. Bringing these complementary datasets together is a crucial first step, enabling the Machine-Learning community to develop innovative new techniques which could greatly benefit the Climate community. To showcase Cumulo, we provide baseline performance analysis using an invertible flow generative model (IResNet), which further allows us to discover new sub-classes for a given cloud class by exploring the latent space. To compare methods, we introduce a set of evaluation criteria, to identify models that are not only accurate, but also physically-realistic. CUMULO can be download from https://www.dropbox.com/sh/6gca7f0mb3b0ikz/AADq2lk4u7k961Qa31FwIDEpa?dl=0

A Small Molecule Inhibitor of PDK1/PLC gamma 1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs

Early detection of pleuro-pulmonary tuberculosis by bedside lung ultrasound: A case report and review of literature

We present a case in which lung ultrasound (LUS) was relevant to reach an early diagnosis of lung tuberculosis and to manage the patient in the right setting. Moreover, ultrasound allowed to detect and treat massive pleural effusion through an ultrasound-guided thoracentesis

Nasal cellularity in 183 unselected schoolchildren aged 9 to 11 years

Although rhinitis is extremely frequent in children, methods for assessing the severity of nasal inflammation produce results with wide variability and hence weak clinical significance. We designed this epidemiologic investigation to define the clinical usefulness of assessing nasal cellularity in children

Interleukin-31: a new cytokine involved in inflammation of the skin.

Cytokines affect immune functions involved inmotility, chemotaxis, phagocytosis, cytotoxicityand antigen presentation (1). Interleukins (IL) arepleiotropic cytokines with diverse receptorsignaling pathways whose expression is controlledat multiple levels (2). Interleukin receptors (ILR)have intrinsic roles in regulating and amplifyingthe inflammatory response (3-12).Skin is the largest organ of the body with thespecific immune defense and its inflammatoryconditions include atopic dermatitis, allergies,psoriasis etc. (13-19). Infiltrated lymphocytesproliferate in an activated state in the skin lesion inan autocrine and/or paracrine manner and produceTH2-type cytokines that might evoke immunologicabnormalities (20-23)...

Correlation between hormonal homeostasis and morphogenic responses in Arabidopsis thaliana seedlings growing in a Cd/Cu/Zn multi-pollution context

To date, almost no information is available in roots and shoots of the model plant Arabidopsis thaliana about the hierarchic relationship between metal accumulation, phytohormone levels, and glutathione/phytochelatin content, and how this relation affects root development. For this purpose, specific concentrations of cadmium, copper and zinc, alone or in triple combination, were supplied for 12 days to in vitro growing seedlings. The accumulation of these metals was measured in roots and shoots, and a significant competition in metal uptake was observed. Microscopic analyses revealed that root morphology was affected by metal exposure, and that the levels of trans-zeatin riboside, dihydrozeatin riboside, indole-3-acetic acid, and the auxin/cytokinin ratio varied accordingly. By contrast, under metal treatments, minor modifications in gibberellic acid and abscisic acid levels occurred. RT-PCR analysis of some genes involved in auxin and cytokinin synthesis (e.g., AtNIT in roots and AtIPT in shoots) showed on average a metal up-regulated transcription. The production of thiol-peptides was induced by all the metals, alone or in combination, and the expression of the genes involved in thiol-peptide synthesis (AtGSH1, AtGSH2, AtPCS1 and AtPCS2) was not stimulated by the metals, suggesting a full post-transcriptional control. Results show that the Cd/Cu/Zn-induced changes in root morphology are caused by a hormonal unbalance, mainly governed by the auxin/cytokinin ratio

Two PI 3-Kinases and One PI 3-Phosphatase Together Establish the Cyclic Waves of Phagosomal PtdIns(3)P Critical for the Degradation of Apoptotic Cells

Cyclic oscillations in the level of phosphatidylinositol 3-phosphate in phagosomes, regulated by two phosphoinositide kinases and one phosphatase, are critical for phagosome maturation and degradation of apoptotic cells