Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n = 4) and age-matched typically developing (TD) individuals (n = 4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders

Investigating the physical properties of transiting hot Jupiters with the 1.5-m Kuiper Telescope

We present new photometric data of 11 hot Jupiter transiting exoplanets (CoRoT-12b, HAT-P-5b, HAT-P-12b, HAT-P-33b, HAT-P-37b, WASP-2b, WASP-24b, WASP-60b, WASP-80b, WASP-103b, XO-3b) in order to update their planetary parameters and to constrain information about their atmospheres. These observations of CoRoT-12b, HAT-P-37b and WASP-60b are the first follow-up data since their discovery. Additionally, the first near-UV transits of WASP-80b and WASP-103b are presented. We compare the results of our analysis with previous work to search for transit timing variations (TTVs) and a wavelength dependence in the transit depth. TTVs may be evidence of a third body in the system and variations in planetary radius with wavelength can help constrain the properties of the exoplanet's atmosphere. For WASP-103b and XO-3b, we find a possible variation in the transit depths that may be evidence of scattering in their atmospheres. The B-band transit depth of HAT-P-37b is found to be smaller than its near-IR transit depth and such a variation may indicate TiO/VO absorption. These variations are detected from 2-4.6$\sigma$, so follow-up observations are needed to confirm these results. Additionally, a flat spectrum across optical wavelengths is found for 5 of the planets (HAT-P-5b, HAT-P-12b, WASP-2b, WASP-24b, WASP-80b), suggestive that clouds may be present in their atmospheres. We calculate a refined orbital period and ephemeris for all the targets, which will help with future observations. No TTVs are seen in our analysis with the exception of WASP-80b and follow-up observations are needed to confirm this possible detection.Comment: 18 pages, 7 figures, 9 Tables. Light Curves available online. Accepted to MNRAS (2017 August 25

Fingerprinting the Cretaceous-Paleogene boundary impact with Zn isotopes

Numerous geochemical anomalies exist at the K-Pg boundary that indicate the addition of extraterrestrial materials; however, none fingerprint volatilization, a key process that occurs during large bolide impacts. Stable Zn isotopes are an exceptional indicator of volatility-related processes, where partial vaporization of Zn leaves the residuum enriched in its heavy isotopes. Here, we present Zn isotope data for sedimentary rock layers of the K-Pg boundary, which display heavier Zn isotope compositions and lower Zn concentrations relative to surrounding sedimentary rocks, the carbonate platform at the impact site, and most carbonaceous chondrites. Neither volcanic events nor secondary alteration during weathering and diagenesis can explain the Zn concentration and isotope signatures present. The systematically higher Zn isotope values within the boundary layer sediments provide an isotopic fingerprint of partially evaporated material within the K-Pg boundary layer, thus earmarking Zn volatilization during impact and subsequent ejecta transport associated with an impact at the K-Pg

Development and Application of STORMTOOLS Design Load (SDL) Maps

Under the STORMTOOLS initiative, maps of the impact of sea level rise (SLR) (0 to 12 ft), nuisance flooding (1–10 yr), 25, 50, and 100 yr storms, and hindcasts of the four top ranked tropical storms have been developed for the coastal waters of Rhode Island (RI). Estimates of the design elevations, expressed in terms of the Base Flood Elevation (BFE) and thus incorporating surge and associated wave conditions, have also been developed, including the effects of SLR to facilitate structural design. Finally, Coastal Environmental Risk Index (CERI) maps have been developed to estimate the risk to individual structures and infrastructure. CERI employs the BFE maps in concert with damage curves for residential and commercial structures to make estimates of damage to individual structures. All maps are available via an ArcGIS Hub. The objective of this senior design capstone project was to develop STORMTOOLS Design Load maps (SDL) with a goal of estimating the hydrostatic, hydrodynamic, wave, and debris loading, based on ASCE/SEI 7–16 Minimum Design Standards methods, on residential structures in the RI coastal floodplain. The resulting maps display the unitized loads and thus can be scaled for any structure of interest. The goal of the maps is to provide environmental loads that support the design of structures, and reduce the time and cost required in performing the design and the permitting process, while also improving the accuracy and consistency of the designs. SDL maps were generated for all loads, including the effects of SLR for a test case: the Watch Hill/Misquamicut Beach, Westerly, along the southern RI coast. The Autodesk Professional Robot Structural Analysis software, along with SDL loading, was used to evaluate the designs for selected on-grade and pile-elevated residential structures. Damage curves were generated for each and shown to be consistent with the US Army Corps of Engineers empirical damage curves currently used in CERI

Water and Metasomatism in the Slave Cratonic Lithosphere (Canada): An FTIR Study

Water in the mantle influences melting, viscosity, seismic velocity, and electrical conductivity. The role played by water in the long-term stabilization of cratonic roots is currently being debated. This study focuses on water contents of mantle minerals (olivine, pyroxene and garnet) from xenoliths found in kimberlites of the Archean Slave craton. 19 mantle xenoliths from central Lac de Gras, and 10 from northern Jericho were analyzed by FTIR for water, and their equilibration depths span the several compositional layers identified beneath the region. At both locations, the shallow peridotites have lower water contents in their olivines (11-30 ppm H2O) than those from the deeper layers (28-300 ppm H2O). The driest olivines, however, are not at the base of the cratonic lithosphere (>6 GPa) as in the Kaapvaal craton. Instead, the deepest olivines are hydrous (31-72 ppm H2O at Lac de Gras and 275 ppm H2O at Jericho). Correlations of water in clinopyroxene and garnet with their other trace element contents are consistent with water being added by metasomatism by melts resembling kimberlite precursors in the mantle approx.0.35 Ga ago beneath Lac de Gras. The northern Jericho xenoliths are derived from a region of the Slave craton that is even more chemically stratified, and was affected at depth by the 1.27 Ga Mackenzie igneous events. Metasomatism at Jericho may be responsible for the particularly high olivine water contents (up to 300 ppm H2O) compared to those at Lac de Gras, which will be investigated by acquiring trace-element data on these xenoliths. These data indicate that several episodes of metasomatic rehydration occurred in the deep part of the Slave craton mantle lithosphere, with the process being more intense in the northern part beneath Jericho, likely related to a translithospheric suture serving as a channel to introduce fluids and/or melts in the northern region. Consequently, rehydration of the lithosphere does not necessarily cause cratonic root delamination and these peridotites may represent localized metasomatic zones - the wall rocks to kimberlite magma passage

Peripheral and central compensatory mechanisms for impaired vagus nerve function during peripheral immune activation

Background Determining the etiology and possible treatment strategies for numerous diseases requires a comprehensive understanding of compensatory mechanisms in physiological systems. The vagus nerve acts as a key interface between the brain and the peripheral internal organs. We set out to identify mechanisms compensating for a lack of neuronal communication between the immune and the central nervous system (CNS) during infection. Methods We assessed biochemical and central neurotransmitter changes resulting from subdiaphragmatic vagotomy and whether they are modulated by intraperitoneal infection. We performed a series of subdiaphragmatic vagotomy or sham operations on male Wistar rats. Next, after full, 30-day recovery period, they were randomly assigned to receive an injection of Escherichia coli lipopolysaccharide or saline. Two hours later, animal were euthanized and we measured the plasma concentration of prostaglandin E2 (with HPLC-MS), interleukin-6 (ELISA), and corticosterone (RIA). We also had measured the concentration of monoaminergic neurotransmitters and their metabolites in the amygdala, brainstem, hippocampus, hypothalamus, motor cortex, periaqueductal gray, and prefrontal medial cortex using RP-HPLC-ED. A subset of the animals was evaluated in the elevated plus maze test immediately before euthanization. Results The lack of immunosensory signaling of the vagus nerve stimulated increased activity of discrete inflammatory marker signals, which we confirmed by quantifying biochemical changes in blood plasma. Behavioral results, although preliminary, support the observed biochemical alterations. Many of the neurotransmitter changes observed after vagotomy indicated that the vagus nerve influences the activity of many brain areas involved in control of immune response and sickness behavior. Our studies show that these changes are largely eliminated during experimental infection. Conclusions Our results suggest that in vagotomized animals with blocked CNS, communication may transmit via a pathway independent of the vagus nerve to permit restoration of CNS activity for peripheral inflammation control