The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90β, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect

Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room

Correction to: First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma

Following publication of the original article [1], the authors reported an error in the spelling of one of the author names. In this Correction the incorrect and correct author names are indicated and the author name has been updated in the original publication. The authors also reported an error in the Methods section of the original article. In this Correction the incorrect and correct versions of the affected sentence are indicated. The original article has not been updated with regards to the error in the Methods section.https://deepblue.lib.umich.edu/bitstream/2027.42/144529/1/12967_2018_Article_1552.pd

Comparative Composition, Diversity and Trophic Ecology of Sediment Macrofauna at Vents, Seeps and Organic Falls

Sediments associated with hydrothermal venting, methane seepage and large organic falls such as whale, wood and plant detritus create deep-sea networks of soft-sediment habitats fueled, at least in part, by the oxidation of reduced chemicals. Biological studies at deep-sea vents, seeps and organic falls have looked at macrofaunal taxa, but there has yet to be a systematic comparison of the community-level attributes of sediment macrobenthos in various reducing ecosystems. Here we review key similarities and differences in the sediment-dwelling assemblages of each system with the goals of (1) generating a predictive framework for the exploration and study of newly identified reducing habitats, and (2) identifying taxa and communities that overlap across ecosystems. We show that deep-sea seep, vent and organic-fall sediments are highly heterogeneous. They sustain different geochemical and microbial processes that are reflected in a complex mosaic of habitats inhabited by a mixture of specialist (heterotrophic and symbiont-associated) and background fauna. Community-level comparisons reveal that vent, seep and organic-fall macrofauna are very distinct in terms of composition at the family level, although they share many dominant taxa among these highly sulphidic habitats. Stress gradients are good predictors of macrofaunal diversity at some sites, but habitat heterogeneity and facilitation often modify community structure. The biogeochemical differences across ecosystems and within habitats result in wide differences in organic utilization (i.e., food sources) and in the prevalence of chemosynthesis-derived nutrition. In the Pacific, vents, seeps and organic-falls exhibit distinct macrofaunal assemblages at broad-scales contributing to ß diversity. This has important implications for the conservation of reducing ecosystems, which face growing threats from human activities

Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: a retrospective multicohort analysis

PURPOSE: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. METHODS: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. RESULTS: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. CONCLUSION: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence

Therapeutic Impact of Cytoreductive Surgery and Irradiation of Posterior Fossa Ependymoma in the Molecular Era: A Retrospective Multicohort Analysis

Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known

Fashion retailing – past, present and future

This issue of Textile Progress reviews the way that fashion retailing has developed as a result of the application of the World Wide Web and information and communications technology (ICT) by fashion-retail companies. The review therefore first considers how fashion retailing has evolved, analysing retail formats, global strategies, emerging and developing economies, and the factors that are threatening and driving growth in the fashion-retail market. The second part of the review considers the emergence of omni-channel retailing, analysing how retail has progressed and developed since the adoption of the Internet and how ICT initiatives such as mobile commerce (m-commerce), digital visualisation online, and in-store and self-service technologies have been proven to support the progression and expansion of fashion retailing. The paper concludes with recommendations on future research opportunities for gaining a better understanding of the impacts of ICT and omni-channel retailing, through which it may be possible to increase and develop knowledge and understanding of the way the sector is developing and provide fresh impetus to an already-innovative and competitive industr