Syrah decline: viral or non-viral?

Declining young grapevine plants of V. vinifera variety Syrah suggesting a unique problem for this popular variety. Generally the affected vines show red canopy symptoms starting from early to late summer due to the stress caused by affecting factors

Comparison of rapid detection assays for grapevine leafroll disease associated closteroviruses

Three rapid detection assays (ELISA, dsRNA analysis and ISEM) were compared for their sensitivity, specificity, and simplicity in the detection of grapevine leafroll associated closteroviruses (GLRaV). Each was found to have advantages and disadvantages for routine testing. ELISA is sensitive and easy to use, but different antisera are needed to detect different GLRaV types. Because mixing or blending of antisera can produce good results in a single ELISA test, each antiserum does not need to be used separately unless it is important to determine the type of GLRaV present. DsRNA analysis can detect all the types of GLRaV tested but has a relatively low sensitivity and is labor intensive, which makes it unsuitable for testing large numbers of samples. Furthermore, dsRNA does not give unequivocal diagnosis of GLRaV infections. ISEM is sensitive and rapid. However, like ELISA, this technique requires an antiserum to each GLRaV type tested and an electron microscopy. Our recommendation is that ELISA should be used with multiple antisera for large scale testing programs. Samples for which ELISA results are inconclusive should be retested with ISEM and/or dsRNA. When the disease status of an individual sample must be determined conclusively, a few grams of tissue should be processed to concentrate the virus and then subjected to ELISA and examination by electron microscopy with negative staining. A dsRNA analysis should be carried out as well

Cognitive Function and Atrial Fibrillation: From the Strength of Relationship to the Dark Side of Prevention. Is There a Contribution from Sinus Rhythm Restoration and Maintenance?

Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia with an increasing prevalence over time mainly because of population aging. It is well established that the presence of AF increases the risk of stroke, heart failure, sudden death, and cardiovascular morbidity. In the last two decades several reports have shown an association between AF and cognitive function, ranging from impairment to dementia. Ischemic stroke linked to AF is a well-known risk factor and predictor of cognitive decline. In this clinical scenario, the risk of stroke might be reduced by oral anticoagulation. However, recent data suggest that AF may be a predictor of cognitive impairment and dementia also in the absence of stroke. Cerebral hypoperfusion, reduced brain volume, microbleeds, white matter hyperintensity, neuroinflammation, and genetic factors have been considered as potential mechanisms involved in the pathogenesis of AF-related cognitive dysfunction. However, a cause-effect relationship remains still controversial. Consequently, no therapeutic strategies are available to prevent AF-related cognitive decline in stroke-free patients. This review will analyze the potential mechanisms leading to cognitive dysfunction in AF patients and examine the available data on the impact of a sinus rhythm restoration and maintenance strategy in reducing the risk of cognitive decline

Molecular analysis of a California strain of Rupestris stem pitting-associated virus isolated from declining Syrah grapevines

The sequence of the genome of a Rupestris stem pitting-associated virus (RSPaV) isolated from a declining Syrah grapevine in California, designated the Syrah strain (RSPaV-SY) was determined. The genome of this strain had an overall nucleotide identity os 77% in comparison with RSPaV sequences in GenBank; the coat protein was the most conservd gene among RSPaV sequences among replicase was the least conserved gene. Phylogenetic analysis of partial coat protein and replicase gene sequences showed RSPaV-SY clustrd independently from the majority of RSPaV isolates

Unusual sesquiterpene glucosides from Amaranthus retroflexus

Abstract—Implementing the phytochemical study of the weed Amaranthus retroflexus, four new sesquiterpene glucosides were isolated from the methanolic extract of the plant. The structures of these metabolites are determined on the basis of the mass spectrometry, and 1D and 2D NMR spectroscopies (DQ-COSY, TOCSY, HSQC, HSQC–TOCSY, HMBC, and NOESY). Two compounds are characterized by a new aglycone and differed from the site of glucosylation. The other two compounds are dimeric diastereoisomers. All the glucoside sesquiterpenes were tested on the wild species Taraxacum officinale to evaluate the role of this weed in the habitat and on the seed of A. retroflexus to verify the potential autotoxic effect of the plant

IBtkα Activates the β‐Catenin‐Dependent Transcription of MYC through Ubiquitylation and Proteasomal Degradation of GSK3βin Cancerous B Cells

The IBTK gene encodes the IBtkα protein that is a substrate receptor of E3 ubiquitin ligase, Cullin 3. We have previously reported the pro‐tumorigenic activity of Ibtk in MYC‐dependent B‐ lymphomagenesis observed in Eμ‐myc transgenic mice. Here, we provide mechanistic evidence of the functional interplay between IBtkα and MYC. We show that IBtkα, albeit indirectly, activates the β‐catenin‐dependent transcription of the MYC gene. Of course, IBtkαassociates with GSK3β and promotes its ubiquitylation, which is associated with proteasomal degradation. This event increases the protein level of β‐catenin, a substrate of GSK3β, and results in the transcriptional activation of the MYC and CCND1 target genes of β‐catenin, which are involved in the control of cell division and apoptosis. In particular, we found that in Burkitt’s lymphoma cells, IBtkα silencing triggered the downregulation of both MYC mRNA and protein expression, as well as a strong decrease of cell survival, mainly through the induction of apoptotic events, as assessed by using flow cytometry‐based cell cycle and apoptosis analysis. Collectively, our results shed further light on the complex puzzle of IBtkα interactome and highlight IBtkα as a potential novel therapeutic target to be employed in the strategy for personalized therapy of B cell lymphoma

Serotonin Antagonism Improves Platelet Inhibition in Clopidogrel Low-Responders after Coronary Stent Placement: An In Vitro Pilot Study

Increased residual platelet reactivity remains a burden for coronary artery disease (CAD) patients who received a coronary stent and do not respond sufficiently to treatment with acetylsalicylic acid and clopidogrel. We hypothesized that serotonin antagonism reduces high on-treatment platelet reactivity. Whole blood impedance aggregometry was performed with arachidonic acid (AA, 0.5 mM) and adenosine diphosphate (ADP, 6.5 µM) in addition to different concentrations of serotonin (1–100 µM) in whole blood from 42 CAD patients after coronary stent placement and 10 healthy subjects. Serotonin increased aggregation dose-dependently in CAD patients who responded to clopidogrel treatment: After activation with ADP, aggregation increased from 33.7±1.3% to 40.9±2.0% in the presence of 50 µM serotonin (p<0.05) and to 48.2±2.0% with 100 µM serotonin (p<0.001). The platelet serotonin receptor antagonist ketanserin decreased ADP-induced aggregation significantly in clopidogrel low-responders (from 59.9±3.1% to 37.4±3.5, p<0.01), but not in clopidogrel responders. These results were confirmed with light transmission aggregometry in platelet-rich plasma in a subset of patients. Serotonin hence increased residual platelet reactivity in patients who respond to clopidogrel after coronary stent placement. In clopidogrel low-responders, serotonin receptor antagonism improved platelet inhibition, almost reaching responder levels. This may justify further investigation of triple antiplatelet therapy with anti-serotonergic agents

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients

Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p &lt; 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM

Lipid Accumulation in Hearts Transplanted From Nondiabetic Donors to Diabetic Recipients

Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM

Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts

Background: The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment. Methods: We evaluated 77 first HTX recipients (40 and 37 patients with and without diabetes, respectively). Among the recipients with diabetes, 17 (45.9%) were receiving SGLT2i treatment. HTX recipients underwent standard clinical evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsy). In the biopsy samples, we evaluated JunD, insulin receptor substrates 1 and 2 (IRS1 and IRS2), peroxisome proliferator-activated receptor-γ (PPAR-γ), and ceramide levels using real-time polymerase chain reaction and immunofluorescence. The biopsy evaluations in this study were performed at 1–4 weeks (basal), 5–12 weeks (intermediate), and up to 48 weeks (final, end of 12-month follow-up) after HTX. Results: There was a significant early and progressive increase in the cardiac expression of JunD/PPAR-γ and ceramide levels, along with a significant decrease in IRS1 and IRS2 in recipients with diabetes but not in those without diabetes. These molecular changes were blunted in patients with diabetes receiving SGLT2i treatment. Conclusion: Early pathogenesis in human diabetic cardiomyopathy is associated with JunD/PPAR-γ overexpression and lipid accumulation following HTX in recipients with diabetes. Remarkably, this phenomenon was reduced by concomitant therapy with SGLT2i, which acted directly on diabetic hearts