Bub1 as a recruitment platform for Spindle Assembly Checkpoint components

Motivation: The Spindle Assembly Checkpoint (SAC) is a safeguard mechanism conserved in all the eukaryotes that ensures the correct chromosome segregation in mitosis by preventing the premature mitotic exit in condition of unattached kinetochores. SAC defects lead to chromosome mis-segregation provoking aneuploidies that has been widely associated with cancer. Kinase Bub1 is a key player in SAC function because it maintains a proper centromeric cohesion and serves as a platform for other SAC components such as Mad1, Mad2 and Mad3. In this study, we are characterizing a bub1 mutant allele which exhibits an impaired SAC function. The phenotype shown by this mutant has not been previously described. This mutant can provide new insights about the Bub1-dependent recruitment of SAC components to the kinetochores and the mechanism of mitosis arrest.Methods: We made use of live imaging techniques to study SAC function by using GFP-tagged alleles of the main SAC components (like Mad1, Mad2 and Mad3), comparing the wild type background versus the bub1 mutant allele. Furthermore, we have used a cold sensitive tubulin mutant that allows us to test SAC activity; in response to microtubules damage induced by this mutant, cells activate the SAC and arrest in metaphase. We have also tested Bub1 protein levels in a wild-type and in the Bub1-mutant by Western Blot. Finally, we are performing a two-hybrid screening using a S. pombe library-strain to detect differences in the interactome of the Bub1-mutant compared with the wild-type. Results: We have demonstrated that in the Bub1-mutant background, Mad1 correctly localizes at the kinetochores meanwhile Mad2 does not. Bub1 protein levels turned out to be quite similar in both strain. Additionally, we have observed that the SAC defects notice in the Bub1-mutant in the cold sensitive background partially phenocopies the one seen in the Bub1-deleted cells.Conclusions: Our Bub1-mutant is unable to maintain a proper metaphase block in the cold-sensitive tubulin background and exhibit a SAC failure. We are working in a model where Bub1 could be regulating SAC activity by promoting Mad2 recruitment to kinetochores

Dynamical simulation of the injection of vortices into a Majorana edge mode

The chiral edge modes of a topological superconductor can transport fermionic quasiparticles, with Abelian exchange statistics, but they can also transport non-Abelian anyons: Majorana zero-modes bound to a {\pi}-phase domain wall that propagates along the boundary. Such an edge vortex is injected by the application of an h/2e flux bias over a Josephson junction. Existing descriptions of the injection process rely on the instantaneous scattering approximation of the adiabatic regime, where the internal dynamics of the Josephson junction is ignored. Here we go beyond that approximation in a time-dependent many-body simulation of the injection process, followed by a braiding of the mobile edge vortex with an immobile Abrikosov vortex in the bulk of the superconductor. Our simulation sheds light on the properties of the Josephson junction needed for a successful implementation of a flying Majorana qubit.Comment: 13 pages 12 figure

Exchange Effects in the Invar Hardening: Fe0.65Ni0.35Fe_{0.65}Ni_{0.35} as a test case

An increase of the critical resolved shear stress of Invar alloys (Invar hardening) with a lowering temperature is explained. The effect is caused by a growth of the exchange interaction between dangling $d$-electron states of dislocation cores and paramagnetic obstacles (e.g., Ni atoms in FeNi alloys) which occurs below the Curie temperature. The spins of the two electrons align along the magnetization due to the exchange interaction with the surrounding atoms of the ferromagnetic. The exchange interaction between the dislocations and obstacles is enhanced in Invars due to a strong growth of the magnetic moments of atoms under the action of elastic strains near the dislocation cores. Parameters characterizing the exchange interaction are determined for the case of the Fe$_{0.65}$Ni$_{0.35}$ Invar. The influence of the internal magnetic field on the dislocation detachment from the obstacles is taken into account. The obtained temperature dependence of the critical resolved shear stress in the Fe$_{0.65}$Ni$_{0.35}$ Invar agrees well with the available experimental data. Experiments facilitating a further check of the theoretical model are suggested.Comment: 8 pages, 2 figure

Training in Spanish organizations : trends and future perspectives

Purpose: This study aims to identify training trends in Spanish organizations. Design/methodology/approach: A survey methodology is conducted and the questionnaire is the strategy to collect information. In order to construct the sample, a previous selection of enterprises was done out of the 50 000 enterprises registered at DICODI (Data base of main Spanish societies 2004/2005). The sampling was done by quotas. The quotas or categories selected were: the enterprises' activity sector, gender and job position. Findings: The research describes the actual state of training trends and the changes that seem to glimpse out of the considered dimensions: training planning, goals, recipients, modalities, resources, evaluation, training professionals and outsourcing. Research limitations: The study was carried out through a not randomized sample, so the results cannot be generalized. Practical implications: Organizations can make future proposals from the facts exposed in our research. Originality/value: Is the first time in our context that a research of this type is performed, showing significant matches in the results with other studies of international reference

Differential analysis of genome-wide methylation and gene expression in mesenchymal stemcells of patients with fractures and osteoarthritis

Insufficient activity of the bone-forming osteoblasts leads to low bone mass and predisposes to fragility fractures. The functional capacity of human mesenchymal stem cells (hMSCs), the precursors of osteoblasts, may be compromised in elderly individuals, in relation with the epigenetic changes associated with aging. However, the role of hMSCs in the pathogenesis of osteoporosis is still unclear. Therefore, we aimed to characterize the genome-wide methylation and gene expression signatures and the differentiation capacity of hMSCs from patients with hip fractures. We obtained hMSCs from the femoral heads of women undergoing hip replacement due to hip fractures and controls with hip osteoarthritis. DNA methylation was explored with the Infinium 450K bead array. Transcriptome analysis was done by RNA sequencing. The genomic analyses revealed that most differentially methylated loci were situated in genomic regions with enhancer activity, distant from gene bodies and promoters. These regions were associated with differentially expressed genes enriched in pathways related to hMSC growth and osteoblast differentiation. hMSCs from patients with fractures showed enhanced proliferation and upregulation of the osteogenic drivers RUNX2/OSX. Also, they showed some signs of accelerated methylation aging. When cultured in osteogenic medium, hMSCs from patients with fractures showed an impaired differentiation capacity, with reduced alkaline phosphatase activity and poor accumulation of a mineralized matrix. Our results point to 2 areas of potential interest for discovering new therapeutic targets for low bone mass disorders and bone regeneration: the mechanisms stimulating MSCs proliferation after fracture and those impairing their terminal differentiation

Characteristics and outcome of adult patients with acute promyelocytic leukemia and increased body mass index treated with the PETHEMA Protocols

Objective The obesity/overweight may have an influence on APL outcomes. Methods This is the biggest multicentre analysis on 1320 APL patients treated with AIDA-induction and risk-adapted consolidation between 1996 and 2012. Patients body mass index (BMI) was classified as underweight (= 30 kg/m(2)) according to the World Health Organization (WHO) criteria. Results and conclusions Relationship between male gender, older age, and other known laboratory abnormalities in overweight/obese patients was significant. The induction mortality rate was significantly higher in APL with BMI >= 25 vs BMI = 25 had a trend to lower OS (74% vs 80%; P = .06). However, in the multivariate analysis, BMI did not retain the independent predictive value (P = .46). There was no higher incidence of differentiation syndrome with BMI >= 25, but there was a trend in obese. There was no difference in relapse rate according to the BMI. In summary, overweight/obesity does not represent an independent risk factor for APL outcomes. The influence of obesity in APL patients treated with chemotherapy-free regimens remains to be established

Selected reactive oxygen species and antioxidant enzymes in common bean after Pseudomonas syringae pv. phaseolicola and Botrytis cinerea infection

Phaseolus vulgaris cv. Korona plants were inoculated with the bacteria Pseudomonas syringae pv. phaseolicola (Psp), necrotrophic fungus Botrytis cinerea (Bc) or with both pathogens sequentially. The aim of the experiment was to determine how plants cope with multiple infection with pathogens having different attack strategy. Possible suppression of the non-specific infection with the necrotrophic fungus Bc by earlier Psp inoculation was examined. Concentration of reactive oxygen species (ROS), such as superoxide anion (O2 -) and H2O2 and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were determined 6, 12, 24 and 48 h after inoculation. The measurements were done for ROS cytosolic fraction and enzymatic cytosolic or apoplastic fraction. Infection with Psp caused significant increase in ROS levels since the beginning of experiment. Activity of the apoplastic enzymes also increased remarkably at the beginning of experiment in contrast to the cytosolic ones. Cytosolic SOD and guaiacol peroxidase (GPOD) activities achieved the maximum values 48 h after treatment. Additional forms of the examined enzymes after specific Psp infection were identified; however, they were not present after single Bc inoculation. Subsequent Bc infection resulted only in changes of H2O2 and SOD that occurred to be especially important during plant–pathogen interaction. Cultivar Korona of common bean is considered to be resistant to Psp and mobilises its system upon infection with these bacteria. We put forward a hypothesis that the extent of defence reaction was so great that subsequent infection did not trigger significant additional response

Genetics of Resistance to the Rust Fungus Coleosporium ipomoeae in Three Species of Morning Glory (Ipomoea)

We examined the genetic basis of resistance to the rust pathogen Coleosporium ipomoea in three host species: Ipomoea purpurea, I. hederacea, and I. coccinea (Convolvulaceae). In crosses between resistant and susceptible individuals, second-generation selfed offspring segregated in ratios that did not differ statistically from the 3∶1 ratio indicative of single-gene resistance with the resistant allele dominant. One out of three crosses between resistant individuals from two different populations revealed that resistance loci differed in the two populations, as evidenced by the production of susceptible individuals among the S2 generation. These results suggest that gene-for-gene interactions contribute substantially to the dynamics of coevolution in this natural pathosystem. They also suggest that evolution of resistance to the same pathogen strain may involve different loci in different Ipomoea populations