The Drosophila IKK-related kinase (Ik2) and Spindle-F proteins are part of a complex that regulates cytoskeleton organization during oogenesis

<p>Abstract</p> <p>Background</p> <p>IkappaB kinases (IKKs) regulate the activity of Rel/NF-kappaB transcription factors by targeting their inhibitory partner proteins, IkappaBs, for degradation. The <it>Drosophila </it>genome encodes two members of the IKK family. Whereas the first is a kinase essential for activation of the NF-kappaB pathway, the latter does not act as IkappaB kinase. Instead, recent findings indicate that Ik2 regulates F-actin assembly by mediating the function of nonapoptotic caspases via degradation of DIAP1. Also, it has been suggested that <it>ik2 </it>regulates interactions between the minus ends of the microtubules and the actin-rich cortex in the oocyte. Since <it>spn-F </it>mutants display oocyte defects similar to those of <it>ik2 </it>mutant, we decided to investigate whether Spn-F could be a direct regulatory target of Ik2.</p> <p>Results</p> <p>We found that Ik2 binds physically to Spn-F, biomolecular interaction analysis of Spn-F and Ik2 demonstrating that both proteins bind directly and form a complex. We showed that Ik2 phosphorylates Spn-F and demonstrated that this phosphorylation does not lead to Spn-F degradation. Ik2 is localized to the anterior ring of the oocyte and to punctate structures in the nurse cells together with Spn-F protein, and both proteins are mutually required for their localization.</p> <p>Conclusion</p> <p>We conclude that Ik2 and Spn-F form a complex, which regulates cytoskeleton organization during <it>Drosophila </it>oogenesis and in which Spn-F is the direct regulatory target for Ik2. Interestingly, Ik2 in this complex does not function as a typical IKK in that it does not direct SpnF for degradation following phosphorylation.</p

Assessing the psychological response to the COVID-19: a response to Bitan et al. "Fear of COVID-19 scale: psychometric characteristics, reliability and validity in the Israeli population"

202007 bcwhNot applicablePublished12 month

The Influence of Managers’ Personality on Innovation Deployment: Evidence from Small Business

The firm’s involvement in innovation became a necessary attribute in order to remain competitive and successful. Not surprisingly, the adop-tion of innovations has emerged as one of the dominant research topics in the management of innovations in organizations, though investigations often yield mixed results. However, innovation is still considered a hallmark of big companies only. This study aims to hint the gap of knowledge related to the association between the owners and managers’ personality traits and innovation orientation of small business. The empirical research includes data from two hundred small businesses in different branches of industry. The results interestingly showed that high levels of both conscientiousness and extraversion among owners/managers have positive, but insignificant, impacts on the performance of their small enterprises. The knowledge acquired is critical to organizational innovation and yields lessons that can be used to transform how individual contributors are leveraged within organizations. Implications for practice are also discussed

Asymmetric Microtubule Function Is an Essential Requirement for Polarized Organization of the Drosophila Bristle▿ †

While previous studies have shown that microtubules (MTs) are essential for maintaining the highly biased axial growth of the Drosophila bristle, the mechanism for this process has remained vague. We report that the MT minus-end marker, Nod-KHC, accumulates at the bristle tip, suggesting that the MT network in the bristle is organized minus end out. Potential markers for studying the importance of properly polarized MTs to bristle axial growth are Ik2 and Spindle-F (Spn-F), since mutations in spn-F and ik2 affect bristle development. We demonstrate that Spn-F and Ik2 are localized to the bristle tip and that mutations in ik2 and spn-F affect bristle MT and actin organization. Specifically, mutation in ik2 affects polarized bristle MT function. It was previously found that the hook mutant exhibited defects in bristle polarity and that hook is involved in endocytic trafficking. We found that Hook is localized at the bristle tip and that this localization is affected in ik2 mutants, suggesting that the contribution of MTs within the bristle shaft is important for correct endocytic trafficking. Thus, our results show that MTs are organized in a polarized manner within the highly elongated bristle and that this organization is essential for biased bristle axial growth

Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age

Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for year after allogeneic myeloablative HCT for hematologic malignancy at &lt;3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P=.0018). Thirty percent of patients experienced &gt;= 1 organ toxicity/late effect &gt;1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P &lt;.001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P &lt;.001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P &lt;.001). In summary, those who survived relapse free year after HCT for hematologic malignancy at &lt;3 years of age had favorable overall survival. Chronic graft-versus host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age

Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases

Advances in allogeneic hematopoietic cell transplantation for sickle cell disease have improved outcomes, but there is limited analysis of healthcare utilization in this setting. We hypothesized that, compared to late transplantation, early transplantation (at age &lt; 10 years) improves outcomes and decreases healthcare utilization. We performed a retrospective study of children transplanted for sickle cell disease in the USA during 2000-2013 using two large databases. Univariate and Cox models were used to estimate associations of demographics, sickle cell disease severity, and transplant-related variables with mortality and chronic graft-versus-host disease, while Wilcoxon, Kruskal-Wallis, or linear trend tests were applied for the estimates of healthcare utilization. Among 161 patients with a 2-year overall survival rate of 90% (95% confidence interval [CI] 85-95%) mortality was significantly higher in those who underwent late transplantation versus early (hazard ratio (HR) 21, 95% CI 2.8-160.8, P=0.003) and unrelated compared to matched sibling donor transplantation (HR 5.9, 95% CI 1.7-20.2, P=0.005). Chronic graftversus host disease was significantly more frequent among those translanted late (HR 1.9, 95% CI 1.0-3.5, P=0.034) and those who received an unrelated graft (HR 2.5, 95% CI 1.2-5.4; P=0.017). Merged data for 176 patients showed that the median total adjusted transplant cost per patient was $467,747 (range:$344,029-$ 799,219). Healthcare utilization was lower among recipients of matched sibling donor grafts and those with low severity disease compared to those with other types of donor and disease severity types (P&lt;0.001 and P=0.022, respectively); no association was demonstrated with late transplantation (P=0.775). Among patients with 2-year pre-and post-transplant data (n=41), early transplantation was associated with significant reductions in admissions (P&lt;0.001), length of stay (P&lt;0.001), and cost (P=0.008). Early transplant outcomes need to be studied prospectively in young children without severe disease and an available matched sibling to provide conclusive evidence for the superiority of this approach. Reduced post-transplant healthcare utilization inpatient care indicates that transplantation may provide a sustained decrease in healthcare costs over time