HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

Increased Postprandial Nonesterified Fatty Acid Appearance and Oxidation in Type 2 Diabetes Is Not Fully Established in Offspring of Diabetic Subjects

BACKGROUND: It has been proposed that abnormal postprandial plasma nonesterified fatty acid (NEFA) metabolism may participate in the development of tissue lipotoxicity and type 2 diabetes (T2D). We previously found that non-diabetic offspring of two parents with T2D display increased plasma NEFA appearance and oxidation rates during intravenous administration of a fat emulsion. However, it is currently unknown whether plasma NEFA appearance and oxidation are abnormal during the postprandial state in these subjects at high-risk of developing T2D. METHODOLOGY: Palmitate appearance and oxidation rates and glycerol appearance rate were determined in eleven healthy offspring of two parents with T2D (positive family history, FH+), 13 healthy subjects without first-degree relatives with T2D (FH-) and 12 subjects with T2D at fasting, during normoglycemic hyperinsulinemic clamp and during continuous oral intake of a standard liquid meal to achieve steady postprandial NEFA and triacylglycerols (TG) without and with insulin infusion to maintain similar glycemia in all three groups. PRINCIPAL FINDINGS: Plasma palmitate appearance and oxidation were higher at fasting and during the clamp conditions in the T2D group (all P<0.05). In the postprandial state, palmitate appearance, oxidative and non oxidative rates were all elevated in T2D (all P<0.05) but not in FH+. Both T2D and FH+ displayed elevated postprandial TG vs. FH- (P<0.001). Acute correction of hyperglycemia during the postprandial state did not affect these group differences. Increased waist circumference and BMI were positively associated with elevated postprandial plasma palmitate appearance and oxidation. CONCLUSIONS/SIGNIFICANCE: Postprandial plasma NEFA intolerance observed in subjects with T2D is not fully established in non-diabetic offspring of both parents with T2D, despite the presence of increased postprandial plasma TG in the later. Elevated postprandial plasma NEFA appearance and oxidation in T2D is observed despite acute correction of the exaggerated glycemic excursion in this group

Comparison study of microarray meta-analysis methods

<p>Abstract</p> <p>Background</p> <p>Meta-analysis methods exist for combining multiple microarray datasets. However, there are a wide range of issues associated with microarray meta-analysis and a limited ability to compare the performance of different meta-analysis methods.</p> <p>Results</p> <p>We compare eight meta-analysis methods, five existing methods, two naive methods and a novel approach (mDEDS). Comparisons are performed using simulated data and two biological case studies with varying degrees of meta-analysis complexity. The performance of meta-analysis methods is assessed via ROC curves and prediction accuracy where applicable.</p> <p>Conclusions</p> <p>Existing meta-analysis methods vary in their ability to perform successful meta-analysis. This success is very dependent on the complexity of the data and type of analysis. Our proposed method, mDEDS, performs competitively as a meta-analysis tool even as complexity increases. Because of the varying abilities of compared meta-analysis methods, care should be taken when considering the meta-analysis method used for particular research.</p

Ecological impacts of non-native Pacific oysters (Crassostrea gigas) and management measures for protected areas in Europe

Pacific oysters are now one of the most ‘globalised’ marine invertebrates. They dominate bivalve aquaculture production in many regions and wild populations are increasingly becoming established, with potential to displace native species and modify habitats and ecosystems. While some fishing communities may benefit from wild populations, there is now a tension between the continued production of Pacific oysters and risk to biodiversity, which is of particular concern within protected sites. The issue of the Pacific oyster therefore locates at the intersection between two policy areas: one concerning the conservation of protected habitats, the other relating to livelihoods and the socio-economics of coastal aquaculture and fishing communities. To help provide an informed basis for management decisions, we first summarise evidence for ecological impacts of wild Pacific oysters in representative coastal habitats. At local scales, it is clear that establishment of Pacific oysters can significantly alter diversity, community structure and ecosystem processes, with effects varying among habitats and locations and with the density of oysters. Less evidence is available to evaluate regional-scale impacts. A range of management measures have been applied to mitigate negative impacts of wild Pacific oysters and we develop recommendations which are consistent with the scientific evidence and believe compatible with multiple interests. We conclude that all stakeholders must engage in regional decision making to help minimise negative environmental impacts, and promote sustainable industry development

Advances in heterometallic ring-opening (co)polymerisation catalysis

Truly sustainable plastics require renewable feedstocks coupled with efficient production and end-of-life degradation/recycling processes. Some of the most useful degradable materials are aliphatic polyesters, polycarbonates and polyamides, which are often prepared via ring-opening (co)polymerisation (RO(CO)P) using an organometallic catalyst. While there has been extensive research into ligand development, heterometallic cooperativity offers an equally promising yet underexplored strategy to improve catalyst performance, as heterometallic catalysts often exhibit significant activity and selectivity enhancements compared to their homometallic counterparts. This review describes advances in heterometallic RO(CO)P catalyst design, highlighting the overarching structure-activity trends and reactivity patterns to inform future catalyst design

A histomorphometric meta-analysis of sinus elevation with various grafting materials

Several grafting materials have been used in sinus augmentation procedures including autogenous bone, demineralized freeze-dried bone (DFDBA), hydroxyapatite, β-tricalcium phosphate (β-TCP), anorganic deproteinized bovine bone and combination of these and others. Up to now a subject of controversy in maxillofacial surgery and dentistry is, what is the most appropriate graft material for sinus floor augmentation

Classification of Plant Associated Bacteria Using RIF, a Computationally Derived DNA Marker

A DNA marker that distinguishes plant associated bacteria at the species level and below was derived by comparing six sequenced genomes of Xanthomonas, a genus that contains many important phytopathogens. This DNA marker comprises a portion of the dnaA replication initiation factor (RIF). Unlike the rRNA genes, dnaA is a single copy gene in the vast majority of sequenced bacterial genomes, and amplification of RIF requires genus-specific primers. In silico analysis revealed that RIF has equal or greater ability to differentiate closely related species of Xanthomonas than the widely used ribosomal intergenic spacer region (ITS). Furthermore, in a set of 263 Xanthomonas, Ralstonia and Clavibacter strains, the RIF marker was directly sequenced in both directions with a success rate approximately 16% higher than that for ITS. RIF frameworks for Xanthomonas, Ralstonia and Clavibacter were constructed using 682 reference strains representing different species, subspecies, pathovars, races, hosts and geographic regions, and contain a total of 109 different RIF sequences. RIF sequences showed subspecific groupings but did not place strains of X. campestris or X. axonopodis into currently named pathovars nor R. solanacearum strains into their respective races, confirming previous conclusions that pathovar and race designations do not necessarily reflect genetic relationships. The RIF marker also was sequenced for 24 reference strains from three genera in the Enterobacteriaceae: Pectobacterium, Pantoea and Dickeya. RIF sequences of 70 previously uncharacterized strains of Ralstonia, Clavibacter, Pectobacterium and Dickeya matched, or were similar to, those of known reference strains, illustrating the utility of the frameworks to classify bacteria below the species level and rapidly match unknown isolates to reference strains. The RIF sequence frameworks are available at the online RIF database, RIFdb, and can be queried for diagnostic purposes with RIF sequences obtained from unknown strains in both chromatogram and FASTA format