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

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Cell-based screen for altered nuclear phenotypes reveals senescence progression in polyploid cells after Aurora kinase B inhibition.

Cellular senescence is a widespread stress response and is widely considered to be an alternative cancer therapeutic goal. Unlike apoptosis, senescence is composed of a diverse set of subphenotypes, depending on which of its associated effector programs are engaged. Here we establish a simple and sensitive cell-based prosenescence screen with detailed validation assays. We characterize the screen using a focused tool compound kinase inhibitor library. We identify a series of compounds that induce different types of senescence, including a unique phenotype associated with irregularly shaped nuclei and the progressive accumulation of G1 tetraploidy in human diploid fibroblasts. Downstream analyses show that all of the compounds that induce tetraploid senescence inhibit Aurora kinase B (AURKB). AURKB is the catalytic component of the chromosome passenger complex, which is involved in correct chromosome alignment and segregation, the spindle assembly checkpoint, and cytokinesis. Although aberrant mitosis and senescence have been linked, a specific characterization of AURKB in the context of senescence is still required. This proof-of-principle study suggests that our protocol is capable of amplifying tetraploid senescence, which can be observed in only a small population of oncogenic RAS-induced senescence, and provides additional justification for AURKB as a cancer therapeutic target.This work was supported by the University of Cambridge, Cancer Research UK, Hutchison Whampoa; Cancer Research UK grants A6691 and A9892 (M.N., N.K., C.J.T., D.C.B., C.J.C., L.S.G, and M.S.); a fellowship from the Uehara Memorial Foundation (M.S.).This is the author accepted manuscript. The final version is available from the American Society for Cell Biology via http://dx.doi.org/10.1091/mbc.E15-01-000

Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries

TRY plant trait database - enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Prospective Trial of Recombinant Leukocyte Interferon in Chronic Hepatitis-b - a 10-month Follow-up-study

Twenty-one adult patients with chronic hepatitis B and active viral replication as indicated by the presence of hepatitis Be antigen (HBeAg), increased DNA polymerase (DNAp) and positive hepatitis B virus DNA (HBV-DNA) for more than 6 months, were entered into a prospective trial of recombinant human interferon therapy. Ten patients had chronic persistent or chronic lobular hepatitis, 8 chronic active hepatitis and 3 postnecrotic cirrhosis. All cases were treated with 5 x 10(6) units of recombinant interferon alfa-2B given subcutaneously every other day for 12 weeks. During treatment, 18 patients (86%) showed a significant reduction of DNAp levels, which reached normal values in 10 patients (48%). Viral replication was controlled over a 10-month follow-up period in 7 out of 21 patients (33%). Of these 7, five patients became HBeAg negative and HBeAb positive. HBsAg disappeared in one patient. The only serious adverse effect was thrombocytopenia in one patient in whom rapid recovery occurred when interferon was withdrawn. Treatment was also terminated in a second patient because of local reactions at the injection sites occurring after 10 weeks of therapy. Our data indicate that relatively small doses of recombinant alfa-2B interferon given during a 12-week period induce a significant reduction in viral replication and might approximately triple the spontaneous seroconversion rate observed in patients with chronic hepatitis B