Granulins as Inflammatory Mediators in Alzheimer Disease

Alzheimer disease (AD) is a neurodegenerative disorder characterized by severe memory deficit and cognitive decline among the elderly. This degeneration is caused by the aggregation and deposition of a protein called amyloid-β (Aβ) in the brain. Aggregation of Aβ causes neuroinflammation in addition to other toxic events. However, it is unclear whether inflammation from an external source, such as from a traumatic brain injury (TBI), could trigger Aβ aggregation. In this context, several pro-inflammatory mediators such as cytokines and chemokines have been suspects. It is now hypothesized that a group of proteins called granulins (Grns) are unique inflammatory mediators that can interact and modulate Aβ aggregation. Grns are a family of seven (A-G) small, cysteine-rich proteins that are proteolytically cleaved from a precursor protein called progranulin (PGrn) during neuroinflammation. Grns have been implicated in both AD and frontotemporal lobar degeneration (FTLD). Among the seven Grns, my work is primarily focused on GrnE. GrnE was recombinantly expressed in E. coli and purified using affinity chromatography. The structural characteristics were studied using several biochemical and biophysical techniques, such as sodium dodecyl sulfate (SDS) and native gel electrophoresis, circular dichroism (CD), and fluorescence spectroscopy. The collective data suggest that GrnE is an intrinsically disordered protein (IDP) and is able to dimerize at high concentrations. This is a novel finding because GrnE is not expected to be disordered due to its high degree of intramolecular disulfide bonds. Additionally, Grns C and F have been successfully expressed in E. coli

Annual Report of Hail Studies

published or submitted for publicationis peer reviewedOpe

Oceanographic drivers of deep-sea coral species distribution and community assembly on seamounts, islands, atolls, and reefs within the Phoenix Islands Protected Area

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Auscavitch, S. R., Deere, M. C., Keller, A. G., Rotjan, R. D., Shank, T. M., & Cordes, E. E. Oceanographic drivers of deep-sea coral species distribution and community assembly on seamounts, islands, atolls, and reefs within the Phoenix Islands Protected Area. Frontiers in Marine Science, 7, (2020): 42, doi:10.3389/fmars.2020.00042.The Phoenix Islands Protected Area, in the central Pacific waters of the Republic of Kiribati, is a model for large marine protected area (MPA) development and maintenance, but baseline records of the protected biodiversity in its largest environment, the deep sea (>200 m), have not yet been determined. In general, the equatorial central Pacific lacks biogeographic perspective on deep-sea benthic communities compared to more well-studied regions of the North and South Pacific Ocean. In 2017, explorations by the NOAA ship Okeanos Explorer and R/V Falkor were among the first to document the diversity and distribution of deep-water benthic megafauna on numerous seamounts, islands, shallow coral reef banks, and atolls in the region. Here, we present baseline deep-sea coral species distribution and community assembly patterns within the Scleractinia, Octocorallia, Antipatharia, and Zoantharia with respect to different seafloor features and abiotic environmental variables across bathyal depths (200–2500 m). Remotely operated vehicle (ROV) transects were performed on 17 features throughout the Phoenix Islands and Tokelau Ridge Seamounts resulting in the observation of 12,828 deep-water corals and 167 identifiable morphospecies. Anthozoan assemblages were largely octocoral-dominated consisting of 78% of all observations with seamounts having a greater number of observed morphospecies compared to other feature types. Overlying water masses were observed to have significant effects on community assembly across bathyal depths. Revised species inventories further suggest that the protected area it is an area of biogeographic overlap for Pacific deep-water corals, containing species observed across bathyal provinces in the North Pacific, Southwest Pacific, and Western Pacific. These results underscore significant geographic and environmental complexity associated with deep-sea coral communities that remain in under-characterized in the equatorial central Pacific, but also highlight the additional efforts that need to be brought forth to effectively establish baseline ecological metrics in data deficient bathyal provinces.Funding for this work was provided by NOAA Office of Ocean Exploration and Research (Grant No. NA17OAR0110083) to RR, EC, TS, and David Gruber

Neuropilin-1 Controls Endothelial Homeostasis by Regulating Mitochondrial Function and Iron-Dependent Oxidative Stress.

The transmembrane protein neuropilin-1 (NRP1) promotes vascular endothelial growth factor (VEGF) and extracellular matrix signaling in endothelial cells (ECs). Although it is established that NRP1 is essential for angiogenesis, little is known about its role in EC homeostasis. Here, we report that NRP1 promotes mitochondrial function in ECs by preventing iron accumulation and iron-induced oxidative stress through a VEGF-independent mechanism in non-angiogenic ECs. Furthermore, NRP1-deficient ECs have reduced growth and show the hallmarks of cellular senescence. We show that a subcellular pool of NRP1 localizes in mitochondria and interacts with the mitochondrial transporter ATP-binding cassette B8 (ABCB8). NRP1 loss reduces ABCB8 levels, resulting in iron accumulation, iron-induced mitochondrial superoxide production, and iron-dependent EC senescence. Treatment of NRP1-deficient ECs with the mitochondria-targeted antioxidant compound mitoTEMPO or with the iron chelator deferoxamine restores mitochondrial activity, inhibits superoxide production, and protects from cellular senescence. This finding identifies an unexpected role of NRP1 in EC homeostasis

Karakteristik Massa Air Lapisan Tercampur Dan Lapisan Termoklin Di Selat Lombok Pada Bulan November 2015

Penelitian ini bertujuan untuk mengetahui karakteristik massa air di lapisan tercampur dan lapisan termoklin. Karakteristik yang dimaksud adalah suhu, salinitas, densitas, stabilitas statik dan tipe massa air.Penelitian ini menggunakan data suhu, salinitas, densitas dan kedalaman yang diakuisisi dari instrumen CTD. Data suhu dan salinitas digunakan untuk menentukan tipe massa air dengan diagram T-S (Temperatur-Salinitas) yang mengacu pada klasifikasi Wyrtki, sedangkan data densitas dan kedalaman digunakan untuk menentukan stabilitas statik massa air. Stratifikasi massa air ditentukan dengan dengan kriteria ambang lapisan piknoklin >0,125 kg/m3 dari densitas permukaan dan lapisan termoklin >0,5oC dari suhu permukaan. Hasil penelitian menunjukkan adanya stratifikasi lapisan massa air bervariasi secara vertikal dengan kedalaman lapisan tercampur bervariasi dari 0-43 m berdasarkan temperatur dan 0-45 m berdasarkan densitas, lapisan termoklin berada diantara kedalaman 3-412 m. Stabilitas massa air menunjukkan nilai bervariasi dari -15 sampai 30 siklus/jam, nilai Frekuensi Brunt-Vӓїsӓlӓ yang tinggi ditemukan di lapisan termoklin. Hasil diagram T-S menunjukkan adanya empat massa air yang teridentifikasi yaitu massa air North Pacific Intermediate Water (NPIW) yang dicirikan salinitas minimum, massa air North Pacific Subtropical Water (NPSW) dengan karakter salinitas maksimum, massa air North Indian Subtropical Water (NISW) dicirikan salinitas maksimum dan massa air Australasian Mediterranean Water (AAMW) yang dicirikan oleh salinitas maksimum

Comparison of coupled and uncoupled load simulations on a jacket support structure

AbstractIn this article, a comparison of the moments and forces at the joints of a jacket structure is made between fully coupled aero-hydro-elastic simulations in HAWC2 and uncoupled load predictions in the finite element software Abaqus. The jacket sub structure is modelled in moderate deep waters of 50m and designed for the 5MW NREL baseline wind turbine. External conditions are based on wind and wave joint distribution for a site in the North Sea. The turbulent wind field in HAWC2 is generated by random values, defined by the Mann Turbulence model, for each operational mean wind speed. A four-legged jacket structure similar to the Upwind reference jacket is developed in the Abaqus environment, to which is added the transition piece and tower. The aeroelastic loads determined in normal operating conditions of the turbine is integrated and centralized as nodal forces and moments acting at the tower top of the finite element model. Hydrodynamic loads from the incoming waves are computed using the Morison equation and based on a nonlinear irregular wave field. Velocities, accelerations and amplitudes of the wave field as well as tower top forces and moments are used as inputs for the structural analysis in Abaqus. The fully coupled simulation is implemented and performed in HAWC2. In the uncoupled case, the loads (wave loads and tower base loads) are analysed by an implicit structural Finite Element Analysis (Abaqus 6.11-1). A subroutine is used as a preprocessor generating a beam element model and linking the loads to the components as nodal forces. In both simulation cases, the integrated loads acting on the jacket legs are computed as time series and as damage equivalent loading. The analysis and comparison of the fully coupled and decoupled simulation method show that the results vary depending on the structural stiffness and the applied wave loads. Variation in the amplitudes of the moments and forces on the jacket legs up to 25% was observed between the results obtained from coupled and uncoupled simulations

Addressing Intimate Partner Violence: Development of a Trauma Informed Workforce

Abstract available through the Annals of Behavioral Medicine