Cleaved TMEM106B forms amyloid aggregates in central and peripheral nervous systems

Filaments made of residues 120-254 of transmembrane protein 106B (TMEM106B) form in an age-dependent manner and can be extracted from the brains of neurologically normal individuals and those of subjects with a variety of neurodegenerative diseases. TMEM106B filament formation requires cleavage at residue 120 of the 274 amino acid protein; at present, it is not known if residues 255-274 form the fuzzy coat of TMEM106B filaments. Here we show that a second cleavage appears likely, based on staining with an antibody raised against residues 263-274 of TMEM106B. We also show that besides the brain TMEM106B inclusions form in dorsal root ganglia and spinal cord, where they were mostly found in non-neuronal cells. We confirm that in the brain, inclusions were most abundant in astrocytes. No inclusions were detected in heart, liver, spleen or hilar lymph nodes. Based on their staining with luminescent conjugated oligothiophenes, we confirm that TMEM106B inclusions are amyloids. By in situ immunoelectron microscopy, TMEM106B assemblies were often found in structures resembling endosomes and lysosomes.</p

Is there a compact companion orbiting the late O-type binary star HD 164816?

We present a multi-wavelength (X-ray, $\gamma$-ray, optical and radio) study of HD 194816, a late O-type X-ray detected spectroscopic binary. X-ray spectra are analyzed and the X-ray photon arrival times are checked for pulsation. In addition, newly obtained optical spectroscopic monitoring data on HD 164816 are presented. They are complemented by available radio data from several large scale surveys as well as the \emph{FERMI} $\gamma$-ray data from its \emph{Large Area Telescope}. We report the detection of a low energy excess in the X-ray spectrum that can be described by a simple absorbed blackbody model with a temperature of $\sim$ 50 eV as well as a 9.78 s pulsation of the X-ray source. The soft X-ray excess, the X-ray pulsation, and the kinematical age would all be consistent with a compact object like a neutron star as companion to HD 164816. The size of the soft X-ray excess emitting area is consistent with a circular region with a radius of about 7 km, typical for neutron stars, while the emission measure of the remaining harder emission is typical for late O-type single or binary stars. If HD 164816 includes a neutron star born in a supernova, this supernova should have been very recent and should have given the system a kick, which is consistent with the observation that the star HD 164816 has a significantly different radial velocity than the cluster mean. In addition we confirm the binarity of HD 164816 itself by obtaining an orbital period of 3.82 d, projected masses $m_1 {\rm sin}^{3} i$ = 2.355(69) M$_\odot$, $m_2 {\rm sin}^{3} i$ = 2.103(62) M$_\odot$ apparently seen at low inclination angle, determined from high-resolution optical spectra.Comment: Accepted for publication by MNRAS, 11 pages, 6 figures, 4 table

Diverse Macrophage Populations Contribute to the Inflammatory Microenvironment in Premalignant Lesions During Localized Invasion.

Myeloid cell heterogeneity remains poorly studied in breast cancer, and particularly in premalignancy. Here, we used single cell RNA sequencing to characterize macrophage diversity in mouse pre-invasive lesions as compared to lesions undergoing localized invasion. Several subpopulations of macrophages with transcriptionally distinct profiles were identified, two of which resembled macrophages in the steady state. While all subpopulations expressed tumor-promoting genes, many of the populations expressed pro-inflammatory genes, differing from reports in tumor-associated macrophages. Gene profiles of the myeloid cells were similar between early and late stages of premalignancy, although expansion of some subpopulations occurred. These results unravel macrophage heterogeneity in early progression and may provide insight into early intervention strategies that target macrophages

X-ray emission from the giant molecular clouds in the Galactic Center region and the discovery of new X-ray sources

We report the results of X-ray (2-10 keV) observations of the giant molecular clouds SgrB, SgrC and SgrD in the Galactic Center region, together with the discovery of the point-like source SAXJ1748.2-2808. The data have been obtained with the MECS instrument on the BeppoSAX satellite. The core of SgrB2 has an X-ray luminosity of 6x10^34 erg/s and its spectrum is characterized by a strong Fe emission line at 6.5 keV with an equivalent width of 2 keV. Faint diffuse X-ray emission is detected from SgrC and from the SNR G1.05-0.15 (SgrD). A new, unresolved source with a strong Fe line has been discovered in the SgrD region. This source, SAXJ1748.2-2808, is probably associated with a SiO and OH maser source at the Galactic Center distance. If so, its luminosity is 10^34 erg/s. We propose that the X-ray emission from SAX J1748.2-2808 is produced either by protostars or by a giant molecular cloud core. Emission from sources similar to SAX J1748.2-2808 could have an impact on the expected contribution on the observed Fe line emission from the Galactic ridge.Comment: 12 pages, 8 figures, accepted for publication in Astronomy & Astrophysics Main Journa

Genes, gene flow and adaptation of Diabrotica virgifera virgifera

Diabrotica virgifera virgifera has emerged as a major pest of cultivated maize, due to a combination of its high capacity to inflict economic damage, adaptability to pest management techniques and invasiveness. This review presents a survey of the current state of knowledge about the genetics of D. v. virgifera. In addition, the tools and resources currently available to Diabrotica geneticists are identified, as are areas where knowledge is lacking and research should be prioritized. A substantial amount of information has been published concerning the molecular phylogenetic relationships of D. v. virgifera to other chrysomelids. There is a growing literature focused on the population genetics and evolution of the species. Several adaptations to anthropogenic selection pressure have been studied, with resistance to synthetic insecticides providing some particularly well-characterized examples. A notable deficiency is a lack of studies directed toward the formal genetics of D. v. virgifera

Chemical and Biological Aspects of Nutritional Immunity - Perspectives for New Anti-infectives Targeting Iron Uptake Systems : Perspectives for New Anti-infectives Targeting Iron Uptake Systems

Upon bacterial infection, one of the defense mechanisms of the host is the withdrawal of essential metal ions, in particular iron, which leads to "nutritional immunity". However, bacteria have evolved strategies to overcome iron starvation, for example, by stealing iron from the host or other bacteria through specific iron chelators with high binding affinity. Fortunately, these complex interactions between the host and pathogen that lead to metal homeostasis provide several opportunities for interception and, thus, allow the development of novel antibacterial compounds. This Review focuses on iron, discusses recent highlights, and gives some future perspectives which are relevant in the fight against antibiotic resistance

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Science DMZ track lecture for ACI-REF virtual residency

Presented at the Advanced Cyberinfrastructure Research & Education Facilitators Virtual Residency 2015, June 1, 2015.Advanced Cyberinfrastructure Research & Education Facilitators Virtual Residency 2015 University of Oklahoma Supercomputing Center for Education and Research (OSCER) University of Oklahoma Dept. of Information TechnologyN

A Day in the Life of a Networking Professional

Presentation given by Zane Gray at 12:30pm on Wednesday, October 10, 2013, to the Oklahoma City Community College OCCC Cyber Club. Zane Gray, Manager, Data and Telecommunications, UNIVERSITY OF OKLAHOMA Partially supported by the National Science Foundation. Presented under Oklahoma’s NSF EPSCoR CyberConnectivity Grant. Zane Gray is the Data and Telecommunications Manager for the University of Oklahoma’s Norman Campus. He received his Bachelor of Science in Chemical Engineering from the University of Oklahoma in 1996 . Before returning to the University of Oklahoma as a network engineer, he was employed as a civilian with the United States Air Force, and deployed computer networks throughout the United States. At the University of Oklahoma, he collaborates with a team of highly talented network associates, oversees the daily operations and maintenance of the campus computer network; charts the direction of a network design that supports tens of thousands of devices; interacts with other IT professionals, faculty, and students; and faces the day to day challenges of change with a smile. Outside of work, he spends quality time with his wife and nine children, and is putting to practice his experience with the Net Zero Energy Footprint initiative in hopes of making the world a better place for his grandchildrenWhat is it like to be a network professional? What are the day to day experiences? What issues of professionalism, customer service, project management, and culture does a network professional encounter? How can you prepare yourself to be a more attractive job candidate, and what do network professionals look for in prospective employees? What is the structure of the network design at a large institution like at the University of Oklahoma?National Science Foundation under Oklahoma’s NSF EPSCoR CyberConnectivity Grant Data and Telecommunications, UNIVERSITY OF OKLAHOMA University of Oklahoma Supercomputing Center for Education & Research (OSCER) Oklahoma SteN

Synergistic Opportunities for Computational Resource Providers and Local IT

Biography Zane Gray is the Data and Telecommunications Manager for the University of Oklahoma's Norman Campus. He received his Bachelor of Science in Chemical Engineering from OU in 1996. Before returning to OU as a network engineer, he was employed as a civilian with the United States Air Force, and deployed computer networks throughout the United States. At OU, he collaborates with a team of highly talented network associates; oversees the daily operations and maintenance of the campus computer network; charts the direction of a network design that supports tens of thousands of devices; interacts with other IT professionals, faculty, and students; and faces the day to day challenges of change with a smile.Talk Abstract How do high-speed data paths benefit research computing, and should you care? This talk explores the means of engaging local Information Technology resources to build two-way, collaborative partnerships that enable the achievement of research goals. We will discuss examples of how this relationship benefits local IT through exposure to cutting edge technologies prior to introduction into the campus or enterprise environment — a selling point in an affiliation that has traditionally been more "take" than "give." We will also discuss when circuit services, Science DMZ's, and Research and Education Networks are appropriate enough to warrant engagement with local or regional IT resources.University of Oklahoma University of Oklahoma Supercomputing Center for Education & Research (OSCER) Oklahoma Supercomputing Symposium 2014N