Highlights of the 2nd International Symposium on Tribbles and Diseases: Tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

The Tribbles (TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2nd International Symposium on Tribbles and Diseases held on May 7‒9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases

Chronic hyperglycemia induces trans-differentiation of human pancreatic stellate cells and enhances the malignant molecular communication with human pancreatic cancer cells

BACKGROUND: Diabetes mellitus is linked to pancreatic cancer. We hypothesized a role for pancreatic stellate cells (PSC) in the hyperglycemia induced deterioration of pancreatic cancer and therefore studied two human cell lines (RLT-PSC, T3M4) in hyperglycemic environment. METHODOLOGY/PRINCIPAL FINDINGS: The effect of chronic hyperglycemia (CHG) on PSCs was studied using mRNA expression array with real-time PCR validation and bioinformatic pathway analysis, and confirmatory protein studies. The stress fiber formation (IC: αSMA) indicated that PSCs tend to transdifferentiate to a myofibroblast-like state after exposure to CHG. The phosphorylation of p38 and ERK1/2 was increased with a consecutive upregulation of CDC25, SP1, cFOS and p21, and with downregulation of PPARγ after PSCs were exposed to chronic hyperglycemia. CXCL12 levels increased significantly in PSC supernatant after CHG exposure independently from TGF-β1 treatment (3.09-fold with a 2.73-fold without TGF-β1, p<0.05). The upregualtion of the SP1 transcription factor in PSCs after CHG exposure may be implicated in the increased CXCL12 and IGFBP2 production. In cancer cells, hyperglycemia induced an increased expression of CXCR4, a CXCL12 receptor that was also induced by PSC's conditioned medium. The receptor-ligand interaction increased the phosphorylation of ERK1/2 and p38 resulting in activation of MAP kinase pathway, one of the most powerful stimuli for cell proliferation. Certainly, conditioned medium of PSC increased pancreatic cancer cell proliferation and this effect could be partially inhibited by a CXCR4 inhibitor. As the PSC conditioned medium (normal glucose concentration) increased the ERK1/2 and p38 phosphorylation, we concluded that PSCs produce other factor(s) that influence(s) pancreatic cancer behaviour. CONCLUSIONS: Hyperglycemia induces increased CXCL12 production by the PSCs, and its receptor, CXCR4 on cancer cells. The ligand-receptor interaction activates MAP kinase signaling that causes increased cancer cell proliferation and migration

Quantitative trait loci and candidate gene mapping of aluminum tolerance in diploid alfalfa

Aluminum (Al) toxicity in acid soils is a major limitation to the production of alfalfa (Medicago sativa subsp. sativa L.) in the USA. Developing Al-tolerant alfalfa cultivars is one approach to overcome this constraint. Accessions of wild diploid alfalfa (M. sativa subsp. coerulea) have been found to be a source of useful genes for Al tolerance. Previously, two genomic regions associated with Al tolerance were identified in this diploid species using restriction fragment length polymorphism (RFLP) markers and single marker analysis. This study was conducted to identify additional Al-tolerance quantitative trait loci (QTLs); to identify simple sequence repeat (SSR) markers that flank the previously identified QTLs; to map candidate genes associated with Al tolerance from other plant species; and to test for co-localization with mapped QTLs. A genetic linkage map was constructed using EST-SSR markers in a population of 130 BC(1)F(1) plants derived from the cross between Al-sensitive and Al-tolerant genotypes. Three putative QTLs on linkage groups LG I, LG II and LG III, explaining 38, 16 and 27% of the phenotypic variation, respectively, were identified. Six candidate gene markers designed from Medicago truncatula ESTs that showed homology to known Al-tolerance genes identified in other plant species were placed on the QTL map. A marker designed from a candidate gene involved in malic acid release mapped near a marginally significant QTL (LOD 2.83) on LG I. The SSR markers flanking these QTLs will be useful for transferring them to cultivated alfalfa via marker-assisted selection and for pyramiding Al tolerance QTLs

Fungal Planet description sheets : 951–1041

Novel species of fungi described in this study include those from various countries as follows: Antarctica,Apenidiella antarctica from permafrost, Cladosporium fildesense from an unidentified marine sponge. Argentina,Geastrum wrightii on humus in mixed forest. Australia, Golovinomyces glandulariae on Glandularia aristigera,Neoanungitea eucalyptorum on leaves of Eucalyptus grandis, Teratosphaeria corymbiicola on leaves of Corymbiaficifolia, Xylaria eucalypti on leaves of Eucalyptus radiata. Brazil, Bovista psammophila on soil, Fusarium awaxy onrotten stalks of Zea mays, Geastrum lanuginosum on leaf litter covered soil, Hermetothecium mikaniae-micranthae(incl. Hermetothecium gen. nov.) on Mikania micrantha, Penicillium reconvexovelosoi in soil, Stagonosporopsis vannacciifrom pod of Glycine max. British Virgin Isles, Lactifluus guanensis on soil. Canada, Sorocybe oblongisporaon resin of Picea rubens. Chile, Colletotrichum roseum on leaves of Lapageria rosea. China, Setophoma cavernafrom carbonatite in Karst cave. Colombia, Lareunionomyces eucalypticola on leaves of Eucalyptus grandis. CostaRica, Psathyrella pivae on wood. Cyprus, Clavulina iris on calcareous substrate. France, Chromosera ambiguaand Clavulina iris var. occidentalis on soil. French West Indies, Helminthosphaeria hispidissima on dead wood.Guatemala, Talaromyces guatemalensis in soil. Malaysia, Neotracylla pini (incl. Tracyllales ord. nov. and Neotracyllagen. nov.) and Vermiculariopsiella pini on needles of Pinus tecunumanii. New Zealand, Neoconiothyriumviticola on stems of Vitis vinifera, Parafenestella pittospori on Pittosporum tenuifolium, Pilidium novae-zelandiaeon Phoenix sp. Pakistan, Russula quercus-floribundae on forest floor. Portugal, Trichoderma aestuarinum fromsaline water. Russia, Pluteus liliputianus on fallen branch of deciduous tree, Pluteus spurius on decaying deciduous wood or soil. South Africa, Alloconiothyrium encephalarti, Phyllosticta encephalarticola and Neothyrostromaencephalarti (incl. Neothyrostroma gen. nov.) on leaves of Encephalartos sp., Chalara eucalypticola on leaf spots ofEucalyptus grandis x urophylla, Clypeosphaeria oleae on leaves of Olea capensis, Cylindrocladiella postalofficiumon leaf litter of Sideroxylon inerme, Cylindromonium eugeniicola (incl. Cylindromonium gen. nov.) on leaf litter ofEugenia capensis, Cyphellophora goniomatis on leaves of Gonioma kamassi, Nothodactylaria nephrolepidis (incl.Nothodactylaria gen. nov. and Nothodactylariaceae fam. nov.) on leaves of Nephrolepis exaltata, Falcocladiumeucalypti and Gyrothrix eucalypti on leaves of Eucalyptus sp., Gyrothrix oleae on leaves of Olea capensis subsp.macrocarpa, Harzia metro-sideri on leaf litter of Metrosideros sp., Hippopotamyces phragmitis (incl. Hippopotamycesgen. nov.) on leaves of Phragmites australis, Lectera philenopterae on Philenoptera violacea, Leptosilliamayteni on leaves of Maytenus heterophylla, Lithohypha aloicola and Neoplatysporoides aloes on leaves of Aloesp., Millesimomyces rhoicissi (incl. Millesimomyces gen. nov.) on leaves of Rhoicissus digitata, Neodevriesiastrelitziicola on leaf litter of Strelitzia nicolai, Neokirramyces syzygii (incl. Neokirramyces gen. nov.) on leaf spots of Syzygium sp., Nothoramichloridium perseae (incl. Nothoramichloridium gen. nov. and Anungitiomycetaceae fam.nov.) on leaves of Persea americana, Paramycosphaerella watsoniae on leaf spots of Watsonia sp., Penicilliumcuddlyae from dog food, Podocarpomyces knysnanus (incl. Podocarpomyces gen. nov.) on leaves of Podocarpusfalcatus, Pseudocercospora heteropyxidicola on leaf spots of Heteropyxis natalensis, Pseudopenidiella podocarpi,Scolecobasidium podocarpi and Ceramothyrium podocarpicola on leaves of Podocarpus latifolius, Scolecobasidiumblechni on leaves of Blechnum capense, Stomiopeltis syzygii on leaves of Syzygium chordatum, Strelitziomycesknysnanus (incl. Strelitziomyces gen. nov.) on leaves of Strelitzia alba, Talaromyces clemensii from rotting wood ingoldmine, Verrucocladosporium visseri on Carpobrotus edulis. Spain, Boletopsis mediterraneensis on soil, Calycinacortegadensisi on a living twig of Castanea sativa, Emmonsiellopsis tuberculata in fluvial sediments, Mollisia cortegadensison dead attached twig of Quercus robur, Psathyrella ovispora on soil, Pseudobeltrania lauri on leaf litterof Laurus azorica, Terfezia dunensis in soil, Tuber lucentum in soil, Venturia submersa on submerged plant debris.Thailand, Cordyceps jakajanicola on cicada nymph, Cordyceps kuiburiensis on spider, Distoseptispora caricis onleaves of Carex sp., Ophiocordyceps khonkaenensis on cicada nymph. USA, Cytosporella juncicola and Davidiellomycesjuncicola on culms of Juncus effusus, Monochaetia massachusettsianum from air sample, Neohelicomycesmelaleucae and Periconia neobrittanica on leaves of Melaleuca styphelioides x lanceolata, Pseudocamarosporiumeucalypti on leaves of Eucalyptus sp., Pseudogymnoascus lindneri from sediment in a mine, Pseudogymnoascusturneri from sediment in a railroad tunnel, Pulchroboletus sclerotiorum on soil, Zygosporium pseudomasonii onleaf of Serenoa repens. Vietnam, Boletus candidissimus and Veloporphyrellus vulpinus on soil. Morphological andculture characteristics are supported by DNA barcodes

Heterogeneous catalysis for sustainable biodiesel production via esterification and transesterification

Concern over the economics of accessing fossil fuel reserves, and widespread acceptance of the anthropogenic origin of rising CO2 emissions and associated climate change from combusting such carbon sources, is driving academic and commercial research into new routes to sustainable fuels to meet the demands of a rapidly rising global population. Here we discuss catalytic esterification and transesterification solutions to the clean synthesis of biodiesel, the most readily implemented and low cost, alternative source of transportation fuels to meet future societal demands

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Peg Biology: Deciphering the Molecular Regulations Involved During Peanut Peg Development.

Peanut or groundnut is one of the most important legume crops with high protein and oil content. The high nutritional qualities of peanut and its multiple usage have made it an indispensable component of our daily life, in both confectionary and therapeutic food industries. Given the socio-economic significance of peanut, understanding its developmental biology is important in providing a molecular framework to support breeding activities. In peanut, the formation and directional growth of a specialized reproductive organ called a peg, or gynophore, is especially relevant in genetic improvement. Several studies have indicated that peanut yield can be improved by improving reproductive traits including peg development. Therefore, we aim to identify unifying principles for the genetic control, underpinning molecular and physiological basis of peg development for devising appropriate strategy for peg improvement. This review discusses the current understanding of the molecular aspects of peanut peg development citing several studies explaining the key mechanisms. Deciphering and integrating recent transcriptomic, proteomic, and miRNA-regulomic studies provide a new perspective for understanding the regulatory events of peg development that participate in pod formation and thus control yield

Multi-scale genomic, transcriptomic and proteomic analysis of colorectal cancer cell lines to identify novel biomarkers

This work was partially funded by the Strategic Educational Pathways Scholarship (Malta). The scholarship is part-financed by the European Union – European Social Fund (ESF) under Operational Programme II – Cohesion Policy 2007-2013, “Empowering People for More Jobs and a Better Quality of Life”. This project was additionally funded by Medical Research Scotland.Selecting colorectal cancer (CRC) patients likely to respond to therapy remains a clinical challenge. The objectives of this study were to establish which genes were differentially expressed with respect to treatment sensitivity and relate this to copy number in a panel of 15 CRC cell lines. Copy number variations of the identified genes were assessed in a cohort of CRCs. IC50’s were measured for 5-fluorouracil, oxaliplatin, and BEZ-235, a PI3K/mTOR inhibitor. Cell lines were profiled using array comparative genomic hybridisation, Illumina gene expression analysis, reverse phase protein arrays, and targeted sequencing of KRAS hotspot mutations. Frequent gains were observed at 2p, 3q, 5p, 7p, 7q, 8q, 12p, 13q, 14q, and 17q and losses at 2q, 3p, 5q, 8p, 9p, 9q, 14q, 18q, and 20p. Frequently gained regions contained EGFR, PIK3CA, MYC, SMO, TRIB1, FZD1, and BRCA2, while frequently lost regions contained FHIT and MACROD2. TRIB1 was selected for further study. Gene enrichment analysis showed that differentially expressed genes with respect to treatment response were involved in Wnt signalling, EGF receptor signalling, apoptosis, cell cycle, and angiogenesis. Stepwise integration of copy number and gene expression data yielded 47 candidate genes that were significantly correlated. PDCD6 was differentially expressed in all three treatment responses. Tissue microarrays were constructed for a cohort of 118 CRC patients and TRIB1 and MYC amplifications were measured using fluorescence in situ hybridisation. TRIB1 and MYC were amplified in 14.5% and 7.4% of the cohort, respectively, and these amplifications were significantly correlated (p≤0.0001). TRIB1 protein expression in the patient cohort was significantly correlated with pERK, Akt, and Caspase 3 expression. In conclusion, a set of candidate predictive biomarkers for 5-fluorouracil, oxaliplatin, and BEZ235 are described that warrant further study. Amplification of the putative oncogene TRIB1 has been described for the first time in a cohort of CRC patients.Publisher PDFPeer reviewe