Glial βii spectrin contributes to paranode formation and maintenance

Action potential conduction along myelinated axons depends on high densities of voltage-gated Na channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes intheCNS. Paranodal junctions contribute to both no deassembly and maintenance. Despitetheir importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions.Fil: Susuki, Keiichiro. Baylor College of Medicine; Estados UnidosFil: Zollinger, Daniel R.. Baylor College of Medicine; Estados UnidosFil: Chang, Kae Jiun. Baylor College of Medicine; Estados UnidosFil: Zhang, Chuansheng. Baylor College of Medicine; Estados UnidosFil: Huang, Claire Yu Mei. Baylor College of Medicine; Estados UnidosFil: Tsai, Chang Ru. Baylor College of Medicine; Estados UnidosFil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine; Estados UnidosFil: Liu, Yanhong. Baylor College of Medicine; Estados UnidosFil: Benusa, Savannah D.. Virginia Commonwealth University; Estados UnidosFil: Yermakov, Leonid M.. Wright State University; Estados UnidosFil: Griggs, Ryan B.. Wright State University; Estados UnidosFil: Dupree, Jeffrey L.. Virginia Commonwealth University; Estados UnidosFil: Rasband, Matthew N.. Baylor College of Medicine; Estados Unido

Droplet Size Impact on Efficacy of a Dicamba-plus-Glyphosate Mixture

Chemical weed control remains a widely used component of integrated weed management strategies because of its cost-effectiveness and rapid removal of crop pests. Additionally, dicamba-plus-glyphosate mixtures are a commonly recommended herbicide combination to combat herbicide resistance, specifically in recently commercially released dicamba-tolerant soybean and cotton. However, increased spray drift concerns and antagonistic interactions require that the application process be optimized to maximize biological efficacy while minimizing environmental contamination potential. Field research was conducted in 2016, 2017, and 2018 across three locations (Mississippi, Nebraska, and North Dakota) for a total of six site-years. The objectives were to characterize the efficacy of a range of droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)] using a dicamba-plus-glyphosate mixture and to create novel weed management recommendations utilizing pulse-width modulation (PWM) sprayer technology. Results across pooled site-years indicated that a droplet size of 395 μm (Coarse) maximized weed mortality from a dicamba-plus-glyphosate mixture at 94 L ha–1. However, droplet size could be increased to 620 μm (Extremely Coarse) to maintain 90% of the maximum weed mortality while further mitigating particle drift potential. Although generalized droplet size recommendations could be created across site-years, optimum droplet sizes within each site-year varied considerably and may be dependent on weed species, geographic location, weather conditions, and herbicide resistance(s) present in the field. The precise, site-specific application of a dicamba-plus-glyphosate mixture using the results of this research will allow applicators to more effectively utilize PWM sprayers, reduce particle drift potential, maintain biological efficacy, and reduce the selection pressure for the evolution of herbicide-resistant weeds

GIFTS EDU Ground-based Measurement Experiment

Geosynchronous Imaging Fourier Transform Spectrometer (GIFTS) Engineering Demonstration Unit (EDU) is an imaging infrared spectrometer designed for atmospheric soundings. The EDU groundbased measurement experiment was held in Logan, Utah during September 2006 to demonstrate its extensive capabilities for geosynchronous and other applications

Molecular residual disease detection in resected, muscle-invasive urothelial cancer with a tissue-based comprehensive genomic profiling–informed personalized monitoring assay

IntroductionCirculating tumor DNA (ctDNA) detection postoperatively may identify patients with urothelial cancer at a high risk of relapse. Pragmatic tools building off clinical tumor next-generation sequencing (NGS) platforms could have the potential to increase assay accessibility.MethodsWe evaluated the widely available Foundation Medicine comprehensive genomic profiling (CGP) platform as a source of variants for tracking of ctDNA when analyzing residual samples from IMvigor010 (ClinicalTrials.gov identifier NCT02450331), a randomized adjuvant study comparing atezolizumab with observation after bladder cancer surgery. Current methods often involve germline sampling, which is not always feasible or practical. Rather than performing white blood cell sequencing to filter germline and clonal hematopoiesis (CH) variants, we applied a bioinformatic approach to select tumor (non-germline/CH) variants for molecular residual disease detection. Tissue-informed personalized multiplex polymerase chain reaction–NGS assay was used to detect ctDNA postsurgically (Natera).ResultsAcross 396 analyzed patients, prevalence of potentially actionable alterations was comparable with the expected prevalence in advanced disease (13% FGFR2/3, 20% PIK3CA, 13% ERBB2, and 37% with elevated tumor mutational burden ≥10 mutations/megabase). In the observation arm, 66 of the 184 (36%) ctDNA-positive patients had shorter disease-free survival [DFS; hazard ratio (HR) = 5.77; 95% confidence interval (CI), 3.84–8.67; P < 0.0001] and overall survival (OS; HR = 5.81; 95% CI, 3.41–9.91; P < 0.0001) compared with ctDNA-negative patients. ctDNA-positive patients had improved DFS and OS with atezolizumab compared with those in observation (DFS HR = 0.56; 95% CI, 0.38–0.83; P = 0.003; OS HR = 0.66; 95% CI, 0.42–1.05). Clinical sensitivity and specificity for detection of postsurgical recurrence were 58% (60/103) and 93% (75/81), respectively.ConclusionWe present a personalized ctDNA monitoring assay utilizing tissue-based FoundationOne® CDx CGP, which is a pragmatic and potentially clinically scalable method that can detect low levels of residual ctDNA in patients with resected, muscle-invasive bladder cancer without germline sampling

The IceCube Neutrino Observatory, the Pierre Auger Observatory and the Telescope Array: Joint Contribution to the 34th International Cosmic Ray Conference (ICRC 2015)

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube `high-energy starting events' sample and the other with 16 high-energy `track events'. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values $3^\circ$, $6^\circ$ and $9^\circ$ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches.Comment: one proceeding, the 34th International Cosmic Ray Conference, 30 July - 6 August 2015, The Hague, The Netherlands; will appear in PoS(ICRC2015