Separate loci underlie resistance to root infection and leaf scorch during soybean sudden death syndrome

Soybean [Glycine max (L.) Merr.] cultivars show differences in their resistance to both the leaf scorch and root rot of sudden death syndrome (SDS). The syndrome is caused by root colonization by Fusarium virguliforme (ex. F. solani f. sp. glycines). Root susceptibility combined with reduced leaf scorch resistance has been associated with resistance to Heterodera glycines HG Type 1.3.6.7 (race 14) of the soybean cyst nematode (SCN). In contrast, the rhg1 locus underlying resistance to Hg Type 0 was found clustered with three loci for resistance to SDS leaf scorch and one for root infection. The aims of this study were to compare the inheritance of resistance to leaf scorch and root infection in a population that segregated for resistance to SCN and to identify the underlying quantitative trait loci (QTL). “Hartwig”, a cultivar partially resistant to SDS leaf scorch, F. virguliforme root infection and SCN HG Type 1.3.6.7 was crossed with the partially susceptible cultivar “Flyer”. Ninety-two F5-derived recombinant inbred lines and 144 markers were used for map development. Four QTL found in earlier studies were confirmed. One contributed resistance to leaf scorch on linkage group (LG) C2 (Satt277; P = 0.004, R 2 = 15%). Two on LG G underlay root infection at R8 (Satt038; P = 0.0001 R 2 = 28.1%; Satt115; P = 0.003, R 2 = 12.9%). The marker Satt038 was linked to rhg1 underlying resistance to SCN Hg Type 0. The fourth QTL was on LG D2 underlying resistance to root infection at R6 (Satt574; P = 0.001, R 2 = 10%). That QTL was in an interval previously associated with resistance to both SDS leaf scorch and SCN Hg Type 1.3.6.7. The QTL showed repulsion linkage with resistance to SCN that may explain the relative susceptibility to SDS of some SCN resistant cultivars. One additional QTL was discovered on LG G underlying resistance to SDS leaf scorch measured by disease index (Satt130; P = 0.003, R 2 = 13%). The loci and markers will provide tagged alleles with which to improve the breeding of cultivars combining resistances to SDS leaf scorch, root infection and SCN HG Type 1.3.6.7

Mitochondrial Pathway Mediates the Antileukemic Effects of Hemidesmus Indicus, a Promising Botanical Drug

Although cancers are characterized by the deregulation of multiple signalling pathways, most current anticancer therapies involve the modulation of a single target. Because of the enormous biological diversity of cancer, strategic combination of agents targeted against the most critical of those alterations is needed. Due to their complex nature, plant products interact with numerous targets and influence several biochemical and molecular cascades. The interest in further development of botanical drugs has been increasing steadily and the FDA recently approved the first new botanical prescription drug. The present study is designed to explore the potential antileukemic properties of Hemidesmus indicus with a view to contributing to further development of botanical drugs. Hemidesmus was submitted to an extensive in vitro preclinical evaluation.A variety of cellular assays and flow cytometry, as well as a phytochemical screening, were performed on different leukemic cell lines. We have demonstrated that Hemidesmus modulated many components of intracellular signaling pathways involved in cell viability and proliferation and altered the protein expression, eventually leading to tumor cell death, mediated by a loss of mitochondrial transmembrane potential and increased Bax/Bcl-2 ratio. ADP, adenine nucleotide translocator and mitochondrial permeability transition pore inhibitors did not reverse Hemidesmus-induced mitochondrial depolarization. Hemidesmus induced a significant [Ca(2+)](i) raise through the mobilization of intracellular Ca(2+) stores. Moreover, Hemidesmus significantly enhanced the antitumor activity of three commonly used chemotherapeutic drugs (methotrexate, 6-thioguanine, cytarabine). A clinically relevant observation is that its cytotoxic activity was also recorded in primary cells from acute myeloid leukemic patients.These results indicate the molecular basis of the antileukemic effects of Hemidesmus and identify the mitochondrial pathways and [Ca(2+)](i) as crucial actors in its anticancer activity. On these bases, we conclude that Hemidesmus can represent a valuable tool in the anticancer pharmacology, and should be considered for further investigations

BAMBI Regulates Angiogenesis and Endothelial Homeostasis through Modulation of Alternative TGFβ Signaling

BACKGROUND: BAMBI is a type I TGFβ receptor antagonist, whose in vivo function remains unclear, as BAMBI(-/-) mice lack an obvious phenotype. METHODOLOGY/PRINCIPAL FINDINGS: Identifying BAMBI's functions requires identification of cell-specific expression of BAMBI. By immunohistology we found BAMBI expression restricted to endothelial cells and by electron microscopy BAMBI(-/-) mice showed prominent and swollen endothelial cells in myocardial and glomerular capillaries. In endothelial cells over-expression of BAMBI reduced, whereas knock-down enhanced capillary growth and migration in response to TGFβ. In vivo angiogenesis was enhanced in matrigel implants and in glomerular hypertrophy after unilateral nephrectomy in BAMBI(-/-) compared to BAMBI(+/+) mice consistent with an endothelial phenotype for BAMBI(-/-) mice. BAMBI's mechanism of action in endothelial cells was examined by canonical and alternative TGFβ signaling in HUVEC with over-expression or knock-down of BAMBI. BAMBI knockdown enhanced basal and TGFβ stimulated SMAD1/5 and ERK1/2 phosphorylation, while over-expression prevented both. CONCLUSIONS/SIGNIFICANCE: Thus we provide a first description of a vascular phenotype for BAMBI(-/-) mice, and provide in vitro and in vivo evidence that BAMBI contributes to endothelial and vascular homeostasis. Further, we demonstrate that in endothelial cells BAMBI interferes with alternative TGFβ signaling, most likely through the ALK 1 receptor, which may explain the phenotype observed in BAMBI(-/-) mice. This newly described role for BAMBI in regulating endothelial function has potential implications for understanding and treating vascular disease and tumor neo-angiogenesis

One-year clinical outcome of patients with nonvalvular atrial fibrillation: Insights from KERALA-AF registry.

BackgroundWe report patient characteristics, treatment pattern and one-year clinical outcome of nonvalvular atrial fibrillation (NVAF) from Kerala, India. This cohort forms part of Kerala Atrial Fibrillation (KERALA-AF) registry which is an ongoing large prospective study.MethodsKERALA-AF registry collected data of adults with previously or newly diagnosed atrial fibrillation (AF) during April 2016 to April 2017. A total of 3421 patients were recruited from 53 hospitals across Kerala state. We analysed one-year follow-up outcome of 2507 patients with NVAF.ResultsMean age at recruitment was 67.2 years (range 18-98) and 54.8% were males. Main co-morbidities were hypertension (61.2%), hyperlipidaemia (46.2%) and diabetes mellitus (37.2%). Major co-existing diseases were chronic kidney disease (42.1%), coronary artery disease (41.6%), and chronic heart failure (26.4%). Mean CHA2DS2-VASc score was 3.18 (SD ± 1.7) and HAS-BLED score, 1.84 (SD ± 1.3). At baseline, use of oral anticoagulants (OAC) was 38.6% and antiplatelets 32.7%. On one-month follow-up use of OAC increased to 65.8% and antiplatelets to 48.3%. One-year all-cause mortality was 16.48 and hospitalization 20.65 per 100 person years. The main causes of death were cardiovascular (75.0%), stroke (13.1%) and others (11.9%). The major causes of hospitalizations were acute coronary syndrome (35.0%), followed by arrhythmia (29.5%) and heart failure (8.4%).ConclusionsDespite high risk profile of patients in this registry, use of OAC was suboptimal, whereas antiplatelets were used in nearly half of patients. A relatively high rate of annual mortality and hospitalization was observed in patients with NVAF in Kerala AF Registry

Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes

Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses

Coronary artery calcium screening: current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging

Current guidelines and literature on screening for coronary artery calcium for cardiac risk assessment are reviewed for both general and special populations. It is shown that for both general and special populations a zero score excludes most clinically relevant coronary artery disease. The importance of standardization of coronary artery calcium measurements by multi-detector CT is discussed

Dry Sliding-Friction and Wear Behavior of Hot-Extruded Al6061/Si3N4/Cf Hybrid Metal Matrix Composite.

The effects of reinforcement addition and hot extrusion on the microstructures, micro hardness, friction, and wear behavior of aluminium (Al) hybrid composite were investigated. Al6061 dispersed with electroless nickel-coated Si3N4 (6wt.%) and copper-coated carbon fiber (Cf) (1wt.%) hybrid composites was developed through stir casting followed by hot extrusion. Optical micro structural studies confirmed that the size of reinforcements decreased, and their orientations were in the extrusion direction. The decrease in the grain size (29%) of hybrid composites was larger than that in the grain size of matrix alloys under hot-extruded conditions. The synthesized hot-extruded Al6061 hybrid composite exhibited a lower coefficient of friction (51%) and high wear resistance (39%) compared with the hotextruded Al6061base alloy

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe