The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling.     

Application of ZFN for Site Directed Mutagenesis of Rice <Emphasis Type="Italic">SSIVa</Emphasis> Gene

Many successful studies on genome editing in plants have been reported and one of the popular genome editing technology used in plants is Zinc Finger Nucleases (ZFN), which are chimeric proteins composed of synthetic zinc finger-based DNA binding domain and a DNA cleavage domain. The objective of this research was to utilize ZFNs to induce a double-stranded break in SSIVa, a soluble starch synthase involved in starch biosynthesis pathway, leading to the regulation of the SSIVa expression. The isoform SSIVa is not yet well studied, thus, by modifying the endogenous loci in SSIVa, we can explore on the specific roles of this gene in starch biosynthesis and other possible functions it might play. In this study, we used ZFN-mediated targeted gene disruption in the coding sequence of the SSIVa rice gene in an effort to elucidate the functional role of the gene. Generation of transgenic plants carrying premature stop codons and substitution events, revealed no SSIVa mRNA expression, low starch contents and dwarf phenotypes. Remarkably, based on our analysis SSIVa gene disruption had no effect on other starch synthesis related genes as their expression remained at wild type levels. Therefore, the engineered ZFNs can efficiently cleave and stimulate mutations at SSIVa locus in rice to     

Quantitative Evaluation of Performance in Interventional Neuroradiology: An Integrated Curriculum Featuring Theoretical and Practical Challenges

Purpose

We sought to develop a standardized curriculum capable of assessing key competencies in Interventional Neuroradiology by the use of models and simulators in an objective, quantitative, and efficient way. In this evaluation we analyzed the associations between the practical experience, theoretical knowledge, and the skills lab performance of interventionalists.

Materials and Methods

We evaluated the endovascular skills of 26 participants of the Advanced Course in Endovascular Interventional Neuroradiology of the European Society of Neuroradiology with a set of three tasks (aneurysm coiling and thrombectomy in a virtual simulator and placement of an intra-aneurysmal flow disruptor in a flow model). Practical experience was assessed by a survey. Participants completed a written and oral examination to evaluate theoretical knowledge. Bivariate and multivariate analyses were performed.

Results

In multivariate analysis knowledge of materials and techniques in Interventional Neuroradiology was moderately associated with skills in aneurysm coiling and thrombectomy. Experience in mechanical thrombectomy was moderately associated with thrombectomy skills, while age was negatively associated with thrombectomy skills. We found no significant association between age, sex, or work experience and skills in aneurysm coiling.

Conclusion

Our study gives an example of how an integrated curriculum for reasonable and cost-effective assessment of key competences of an interventional neuroradiologist could look. In addition to traditional assessment of theoretical knowledge practical skills are measured by the use of endovascular simulators yielding objective, quantitative, and constructive data for the evaluation of the current performance status of participants as well as the evolution of their technical competency over time.     

Towards a better understanding of the role of psychological variables in arthritis outcome research

In the previous issue of Arthritis Research and Therapy, Brionez and colleagues show that helplessness, depression, and passive coping account for significant variability in self-reported functional limitations in patients with ankylosing spondylitis, beyond the effect of age, inflammation and radiographic damage. Since the perspective of the patients in the experience of health is increasingly important, insight into the type of psychological variables, the pathways by which they influence health and the approaches for how to deal with these variables are challenging.     

Contribution to the quantitative and enantioselective determination of kavapyrones by high-performance liquid chromatography on ChiraSpher NT material

A simultaneous HPLC separation of the enantiomers of kavain, dihydrokavain, methysticin and dihydromethysticin, as well as the achiral dienolides yangonin and desmethoxyyangonin was carried out on a ChiraSpher NT column. For quantitative determinations, calibration curves with correlation coefficients between 0.9982 and 0.9996 were established for the genuine kavapyrones. Detection limits between 0.25 μg and 0.5 μg per injection were measured at 240 nm. The defined scopes of work corresponded with the different kavapyrone amounts, depending on growth factors of distinct plant locations. The precision of the method was verified by analysing a phytopharmacon with a nominal value of 40 mg kavapyrones per tablet. The evaluation revealed 39.62 mg per tablet by the sum of single calculated kavapyrones. Relative standard deviations between 1.06% and 2.39% were found for the compounds under investigation. The accuracy of the method was proved by a recovery of 99.7%. To simplify the determination of the total kavapyrone amount, response factors and correlation factors for (+)-dihydrokavain, (+)-methysticin, (+)-dihydromethysticin, yangonin and desmethoxyyangonin were calculated relative to (+)-kavain.     

Institutional Delivery and Satisfaction among Indigenous and Poor Women in Guatemala,Mexico, and Panama

Indigenous women in Mesoamerica experience disproportionately high maternal mortality rates and are less likely to have institutional deliveries. Identifying correlates of institutional delivery, and satisfaction with institutional deliveries, may help improve facility utilization and health outcomes in this population. We used baseline surveys from the Salud Mesoamérica Initiative to analyze data from 10,895 indigenous and non-indigenous women in Guatemala and Mexico (Chiapas State) and indigenous women in Panama. We created multivariable Poisson regression models for indigenous (Guatemala, Mexico, Panama) and non-indigenous (Guatemala, Mexico) women to identify correlates of institutional delivery and satisfaction. Compared to their non-indigenous peers, indigenous women were substantially less likely to have an institutional delivery (15.2% vs. 41.5% in Guatemala (P<0.001), 29.1% vs. 73.9% in Mexico (P<0.001), and 70.3% among indigenous Panamanian women). Indigenous women who had at least one antenatal care visit were more than 90% more likely to have an institutional delivery (adjusted risk ratio (aRR) = 1.94, 95% confidence interval (CI): 1.44–2.61), compared to those who had no visits. Indigenous women who were advised to give birth in a health facility (aRR = 1.46, 95% CI: 1.18–1.81), primiparous (aRR = 1.44, 95% CI: 1.24–1.68), informed that she should have a Caesarean section (aRR = 1.41, 95% CI: 1.21–1.63), and had a secondary or higher level of education (aRR = 1.36, 95% CI: 1.04–1.79) also had substantially higher likelihoods of institutional delivery. Satisfaction among indigenous women was associated with being able to be accompanied by a community health worker (aRR = 1.15, 95% CI: 1.05–1.26) and facility staff speaking an indigenous language (aRR = 1.10, 95% CI: 1.02–1.19). Additional effort should be exerted to increase utilization of birthing facilities by indigenous and poor women in the region. Improving access to antenatal care and opportunities for higher-level education may increase institutional delivery rates, and providing culturally adapted services may improve satisfaction.     

Clonality and Evolutionary History of Rhabdomyosarcoma

To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS.