Transcriptional responses of durum wheat to chronic chromium exposure reveal candidate proteins involved in metal detoxification and compartmentalization

Chromium phytotoxicity results in relevant alterations to plant physiology, gene expression, and genomic DNA methylation at a transgenerational level. Herein, transcriptional responses of durum wheat (Triticum turgidum L.) to chronic chromium exposure were explored in roots and leaves by RNA-seq approach. Plants grown all the time in a hydroponic system supplemented with 2.5 and 10 mu M hexavalent chromium were compared to unstressful control plants, assessing biomass and seed yield analyses after senescence. Then, transcriptomic analysis was performed with these plants kept under 10 mu M chromium 50 days after the onset of exposure. The chromium concentrations used were considered the lowest dose sufficient to alter gene expression without impeding plant development, while the sampling time reflected the effects in the pre-harvest phase and long-lasting defense mechanisms. Root and leaf samples from plants kept under 10 mu M chromium stress and from unstressful control plants were analyzed, generating 12 RNA-seq libraries. In total, 965 and 810 transcripts were found to be differentially expressed, respectively, in roots and leaves in response to 10 mu M chromium stress. In roots, transcriptional changes were noted in the primary and secondary metabolism, redox homeostasis, protein modification, solute transport, nutrient uptake, and external stimuli responses. Meanwhile, the transcriptional changes in leaves were primarily found in the secondary metabolism, hormone-related pathways, chromatin modifications, cell division, protein modification and homeostasis, solute transport, and nutrient uptake. In particular, the metal uptake and translocation pathways were studied with greater emphasis to identify key proteins involved in chromium transport and compartmentalization. Furthermore, several genes involved in the biosynthesis of malate-derived organic acids, trace metal transport/detoxification/chelation, and vacuolar compartmentalization were linked to primary defense responses, and some of them were also associated with two putative gene clusters. Therefore, these genes and gene clusters are suggested as valuable biotechnological targets for future proof-of-concept studies aimed at genetic engineering of durum wheat to improve plant tolerance to chromium exposure

Protective Activity of Streptococcus pneumoniae Spr1875 Protein Fragments Identified Using a Phage Displayed Genomic Library

There is considerable interest in pneumococcal protein antigens capable of inducing serotype-independent immunoprotection and of improving, thereby, existing vaccines. We report here on the immunogenic properties of a novel surface antigen encoded by ORF spr1875 in the R6 strain genome. An antigenic fragment encoded by spr1875, designated R4, was identified using a Streptococcus pneumoniae phage displayed genomic library after selection with a human convalescent serum. Immunofluorescence analysis with anti-R4 antisera showed that Spr1875 was expressed on the surface of strains belonging to different serotypes. Moreover, the gene was present with little sequence variability in 27 different pneumococcal strains isolated worldwide. A mutant lacking Spr1875 was considerably less virulent than the wild type D39 strain in an intravenous mouse model of infection. Moreover, immunization with the R4 recombinant fragment, but not with the whole Spr1875 protein, induced significant protection against sepsis in mice. Lack of protection after immunization with the whole protein was related to the presence of immunodominant, non-protective epitopes located outside of the R4 fragment. In conclusion, our data indicate that Spr1875 has a role in pneumococcal virulence and is immunogenic. As the R4 fragment conferred immunoprotection from experimental sepsis, selected antigenic fragments of Spr1875 may be useful for the development of a pneumococcal protein-based vaccine

Abnormal Liver Blood Tests in Patients with Hyperthyroidism: Systematic Review and Meta-Analysis

Background: Abnormal liver blood tests (LBTs) in hyperthyroid patients are not uncommonly encountered. One major adverse event of antithyroid drug (ATD) therapy is drug-induced hepatotoxicity. Abnormal LBT in the hyperthyroidism scenario is a main diagnostic and therapeutic dilemma. We aimed to assess the prevalence and the response to ATD therapy of LBT abnormalities in newly diagnosed and uncomplicated hyperthyroidism through a systematic review and meta-analysis. Methods: A literature search was performed reporting LBTs at presentation and after ATD therapy in hyperthyroid patients. A proportion meta-analysis was performed with random-effects model. Pooled data were presented with 95% confidence intervals (CI). I2 statistic index was used to quantify the heterogeneity. Sensitivity analyses for prevalence of hyperthyroid patients with at least one abnormal LBT were performed. p-Value of <0.05 was regarded as significant. Results: The literature search yielded 2286 studies, of which 25 were included for systematic review and meta-analysis. The prevalence of untreated hyperthyroid and Graves' disease patients with at least one abnormal LBT was 55% ([CI 46-63%], I2 96%) and 60% ([CI 53-67%], I2 92%), respectively. The prevalence of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (BIL), and γ-glutamyltransferase (GGT) abnormalities in hyperthyroid patients were 33% ([CI 24-44%], I2 95%), 23% ([CI 17-29%], I2 89%), 44% ([CI 35-52%], I2 93%), 12% ([CI 7-20%], I2 92%), and 24% ([CI 16-36%], I2 95%), respectively. ATD therapy, along with euthyroidism restoration, was accompanied by normalization of LBT abnormalities in the following percentage of cases: ALT 83% ([CI 72-90%], I2 46%), AST 87% ([CI 74-94%], I2 2%), ALP 53% ([CI 32-73%], I2 76%), BIL 50% (CI cannot be calculated), and GGT 70% ([CI 47-87%], I2 74%). The sensitivity analyses showed similar results as those of the main analyses. The publication bias was not statistically significant for all outcomes, except for the prevalence of resolved BIL abnormalities that was not calculable. Conclusions: LBT abnormalities are common in newly diagnosed and untreated hyperthyroidism setting. A high chance of safely normalizing elevated transaminases, up to fivefold above the upper limit of normal, accompanies the use of ATDs in the treatment of hyperthyroidism

Preclinical carotid atherosclerosis enhances the global cardiovascular risk and increases the rate of cerebro- and cardiovascular events in a five-year follow-up

AIM: To evaluate if the intima-media thickening (IMT) and asymptomatic carotid plaque (ACP), as expression of carotid preclinical atherosclerosis (pre-ATS), can provide further information on the global cardiovascular risk (GCVR). METHODS: We studied 454 asymptomatic subjects, with a cluster of risk factors (RF), and evaluated the incidence of a first cardiovascular (CV) event in a five-year follow-up. The subjects at admission were subdivided in three groups of risk. RESULTS: Events occurred in 38% of subjects at high risk, in 13% and 6% of subjects at intermediate and low risk (p<0.003). Among evaluated parameters, carotid pre-ATS was a predictive marker of CV events (OR 2.7, 95% IC 1.4-5.1, p<0.0024). In subjects with GCVR<20% the prevalence of events was 8% for normal carotid ultrasound findings, 13% for increased IMT and 15% for ACP. CONCLUSIONS: In primary prevention, the IMT measurement can give further information for a better stratification of GCVR. The pre-ATS of carotid arteries should be considered a strong predictor of future CV events and should suggest a more aggressive treatment of RF