Scion genotypes exert long distance control over rootstock transcriptome responses to low phosphate in grafted grapevine.

BACKGROUND: Grafting is widely used in horticulture and rootstocks are known to modify scion growth and adaptation to soil conditions. However, the role of scion genotype in regulating rootstock development and functioning has remained largely unexplored. In this study, reciprocal grafts of two grapevine genotypes were produced as well as the corresponding homo-graft controls. These plants were subjected to a low phosphate (LP) treatment and transcriptome profiling by RNA sequencing was done on root samples collected 27 h after the onset of the LP treatment. RESULTS: A set of transcripts responsive to the LP treatment in all scion/rootstock combinations was identified. Gene expression patterns associated with genetic variation in response to LP were identified by comparing the response of the two homo-grafts. In addition, the scion was shown to modify root transcriptome responses to LP in a rootstock dependent manner. A weighted gene co-expression network analysis identified modules of correlated genes; the analysis of the association of these modules with the phosphate treatment, and the scion and rootstock genotype identified potential hub genes. CONCLUSIONS: This study provides insights into the response of grafted grapevine to phosphate supply and identifies potential shoot-to-root signals that could vary between different grapevine genotypes.

Merging genotypes: graft union formation and scion-rootstock interactions.

Grafting has been utilised for at least the past 7000 years. Historically, grafting has been developed by growers without particular interest beyond the agronomical and ornamental effects, and thus knowledge about grafting has remained largely empirical. Much of the commercial production of fruit, and increasingly vegetables, relies upon grafting with rootstocks to provide resistance to soil-borne pathogens and abiotic stresses as well as to influence scion growth and performance. Although there is considerable agronomic knowledge about the use and selection of rootstocks for many species, we know little of the molecular mechanisms underlying rootstock adaptation to different soil environments and rootstock-conferred modifications of scion phenotypes. Furthermore, the processes involved in the formation of the graft union and graft compatibility are poorly understood despite over a hundred years of scientific study. In this paper, we provide an overview of what is known about grafting and the mechanisms underlying rootstock-scion interactions. We highlight recent studies that have advanced our understanding of graft union formation and outline subjects that require further development.

Genome-Wide Association Study of Acute Renal Graft Rejection.

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium.

Novel inhibitors of the Plasmodium falciparum electron transport chain.

Due to an increased need for new antimalarial chemotherapies that show potency against Plasmodium falciparum, researchers are targeting new processes within the parasite in an effort to circumvent or delay the onset of drug resistance. One such promising area for antimalarial drug development has been the parasite mitochondrial electron transport chain (ETC). Efforts have been focused on targeting key processes along the parasite ETC specifically the dihydroorotate dehydrogenase (DHOD) enzyme, the cytochrome bc 1 enzyme and the NADH type II oxidoreductase (PfNDH2) pathway. This review summarizes the most recent efforts in antimalarial drug development reported in the literature and describes the evolution of these compounds.

Involvement of the cytoskeleton in the effect of PGE2 on ion transport in the rat distal colon.

This work aimed at studying the effect of PGE2 on water and chloride absorption from the rat distal colon and at investigating the involvement of the cytoskeleton in the modulation of colonic transporters. PGE2 increased significantly net water and chloride absorption. It increased also the activity of the Na+K+-ATPase and the expression of the Na+K+2Cl- cotransporter. The increase in pump activity was ascribed to its phosphorylation by PKA or PKC when activated upon binding of PGE2 to its receptors, and was deemed responsible for the increase in Cl- absorption. Cytochalasin B (CytoB), a disrupter of microfilaments, decreased net water and chloride absorption in presence or absence of PGE2. Furthermore it down-regulated both pump and cotransporter, and lowered Na+K+-ATPase activity. It was suggested that an intact actin cytoskeleton is required for the basal and the PGE2-elicited trafficking of both transporters. On the other hand, colchicine, an inhibitor of microtubule polymerization, had no effect on the absorption of water and chloride but abrogated the stimulatory effect of PGE2. Colchicine exerted a similar effect to that of cytochlasin on the expression of both pump and cotransporter in presence or absence of PGE2 except for the basal activity of the pump which was not altered by microtubule disruption. It was concluded that both microfilament and microtubular networks are involved in the basal and PGE2-elicited increase in colonic ion absorption.

Contemporary Use of Oral Antithrombotic Agents: Focus on Dual and Triple Therapeutic Approaches.

Atherosclerotic cardiovascular disease (ASCVD) represents a long-standing health care burden in most industrialized countries. Management of ASCVD is multifaceted, and utilization of antithrombotic agents is a key component of care to reduce vascular events. Minimizing thrombotic risk can be accomplished via antiplatelet or anticoagulant drugs; however, combination therapy is warranted for some indications. Although reducing thrombotic complications is important, it is equally vital to consider the safety of combination regimens. Thus clinicians must effectively balance both individualized thrombotic and bleeding risks when using this strategy. Scenarios occur in practice when determining the role for combination therapy is not clear, especially for patients with ASCVD who require both dual antiplatelet therapy plus anticoagulation. The aim of this review is to discuss the role of dual or triple antithrombotic therapies across the spectrum of thrombotic disease states. In addition to critiquing relevant research studies and evaluating key recommendations from nationally published guidelines and consensus statements involving the use of these agents, we offer practical considerations that can be utilized when managing patients with ASCVD.

The role of academic pharmacy in tobacco cessation and control.

Despite decades of public health initiatives, tobacco use remains the leading known preventable cause of death in the United States. Clinicians have a proven, positive effect on patients' ability to quit, and pharmacists are strategically positioned to assist patients with quitting. The American Association of Colleges of Pharmacy recognizes health promotion and disease prevention as a key educational outcome; as such, tobacco cessation education should be a required component of pharmacy curricula to ensure that all pharmacy graduates possess the requisite evidence-based knowledge and skills to intervene with patients who use tobacco. Faculty members teaching tobacco cessation-related content must be knowledgeable and proficient in providing comprehensive cessation counseling, and all preceptors and practicing pharmacists providing direct patient care should screen for tobacco use and provide at least minimal counseling as a routine component of care. Pharmacy organizations should establish policies and resolutions addressing the profession's role in tobacco cessation and control, and the profession should work together to eliminate tobacco sales in all practice settings where pharmacy services are rendered.

Drug-induced heart failure.

PURPOSE: The published evidence on the role of various drugs and medication classes in causing or exacerbating heart failure (HF) is reviewed, with discussion of precautions and management strategies for use in clinical practice. SUMMARY: A literature search was conducted to identify reports of new-onset HF and exacerbations of HF associated with medication use published from 1960 to January 2011. A large body of evidence from controlled clinical trials has led to an improved understanding of well-established causes of drug-induced HF symptoms (e.g., thiazolidinediones, certain older chemotherapy agents) while implicating a wide range of other commonly used drugs and drug classes (e.g., tyrosine kinase inhibitors, biological response modifiers) as having causal or contributory roles. Among the various medications cited in cases of drug-induced HF, some have been linked to significantly increased risks of stroke, myocardial infarction, and death, particularly in patients with existing cardiovascular (CV) disorders or CV risk factors. In recent years, postmarketing and surveillance data have linked a number of newer medications--including the antiarrhythmic dronedarone, the antifungal itraconazole, and the anti-cancer drugs trastuzumab, lapatinib, and bevacizumab--to serious cardiac effects not reported during clinical trials. CONCLUSION: A variety of agents have been associated with drug-induced HF. Patients receiving agents that have been implicated in cases of new-onset HF or exacerbations of HF should be monitored for signs and symptoms of CV effects.

SUPRAVALVULAR PULMONARY STENOSIS IN LEVO TRANSPOSITION AND "SINGLE" VENTRICLE.

A case of supravalvular and valvular pulmonary stenosis in an L-transposition of the great arteries and "single" or double inlet left ventricle is described. Supravalvular pulmonary stenosis has not heretofore been reported in transposition of the great arteries. The clinical, hemodynamic and angiographic features are described. Surgical correction has many problems.