Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

In early Alzheimer's disease (AD) spatial navigation is impaired; however, the precise cause of this impairment is unclear. Recent evidence suggests that getting lost is one of the first impairments to emerge in AD. It is possible that getting lost represents a failure to use distal cues to get oriented in space. Therefore, we set out to look for impaired use of distal cues for spatial orientation in a mouse model of amyloidosis (3xTg-AD). To do this, we trained mice to shuttle to the end of a track and back to an enclosed start box to receive a water reward. Then, mice were trained to stop in an unmarked reward zone to receive a brain stimulation reward. The time required to remain in the zone for a reward was increased across training, and the track was positioned in a random start location for each trial. We found that 6-month female, but not 3-month female, 6-month male, or 12-month male, 3xTg-AD mice were impaired. 6-month male and female mice had only intracellular pathology and male mice had less pathology, particularly in the dorsal hippocampus. Thus, AD may cause spatial disorientation as a result of impaired use of landmarks

The AIMSS Project, III : the stellar populations of compact stellar systems

In recent years, a growing zoo of compact stellar systems (CSSs) have been found whose physical properties (mass, size, velocity dispersion) place them between classical globular clusters (GCs) and true galaxies, leading to debates about their nature. Here we present results using a so far underutilized discriminant, their stellar population properties. Based on new spectroscopy from 8-10m telescopes, we derive ages, metallicities, and [α/Fe] of 29 CSSs. These range from GCs with sizes of merely a few parsec to compact ellipticals (cEs) larger than M32. Together with a literature compilation, this provides a panoramic view of the stellar population characteristics of early-type systems. We find that the CSSs are predominantly more metal rich than typical galaxies at the same stellar mass. At high mass, the cEs depart from the mass-metallicity relation of massive early-type galaxies, which forms a continuous sequence with dwarf galaxies. At lower mass, the metallicity distribution of ultracompact dwarfs (UCDs) changes at a few times 10^7 M⊙, which roughly coincides with the mass where luminosity function arguments previously suggested the GC population ends. The highest metallicities in CSSs are paralleled only by those of dwarf galaxy nuclei and the central parts of massive early types. These findings can be interpreted as CSSs previously being more massive and undergoing tidal interactions to obtain their current mass and compact size. Such an interpretation is supported by CSSs with direct evidence for tidal stripping, and by an examination of the CSS internal escape velocities.Fil: Janz, Joachin. Swinburne University; AustraliaFil: Norris, Mark A.. Gobierno de la Republica Federal de Alemania. Max Planck Institut Fur Astrophysik; AlemaniaFil: Forbes, Duncan A.. Swinburne University; AustraliaFil: Huxor, Avon. Universität Heidelberg; AlemaniaFil: Romanowsky, Aaron. San José State University; Estados UnidosFil: Frank, Matthias. Universität Heidelberg; AlemaniaFil: Escudero, Carlos Gabriel. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica la Plata; ArgentinaFil: Faifer, Favio Raúl. Universidad Nacional de la Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica la Plata; ArgentinaFil: Forte, Juan Carlos. Gobierno de la Ciudad de Buenos Aires. Secretaria de Cultura. Subsecretaria de Patrimonio Cultural. Planetario ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Kannappan, Sheila J.. University of North Carolina; Estados UnidosFil: Maraston, Claudia. Institute of Cosmology snd Gravitation; Estados UnidosFil: Brodie, Jean. University of California; Estados UnidosFil: Strader, Jay. Michigan State University; Estados UnidosFil: Thompson, Bradley. San José State University; Estados Unido

Peptidylarginine deiminase 1-catalyzed histone citrullination is essential for early embryo development

Peptidylarginine deiminase (PADI) enzymes are increasingly being associated with the regulation of chromatin structure and gene activity via histone citrullination. As one of the PADI family members, PADI1 has been mainly reported to be expressed in the epidermis and uterus, where the protein in keratinocytes is thought to promote differentiation by citrullinating filament proteins. However, the roles of PADI1 in preimplantation development have not been addressed. Using a PADI1-specific inhibitor and Padi1-morpholino knockdown, we found that citrullination of histone tails at H4R3 and H3R2/8/17 were markedly reduced in the 2- and 4-cell embryos. Consistent with this observation, early embryo development was also arrested at the 4-cell stage upon depletion of PADI1 or inhibition of PADI1 enzyme activity. Additionally, by employing 5-ethynyl uridine (EU) incorporation analysis, ablation of PADI1 function led to a dramatic decrease in overall transcriptional activity, correlating well with the reduced levels of phosphorylation of RNA Pol II at Ser2 observed at 2- or 4-cell stage of embryos under Padi1 knockdown or inhibiting PADI1. Thus, our data reveal a novel function of PADI1 during early embryo development transitions by catalyzing histone tail citrullination, which facilitates early embryo genome transactivation

Ocean Bottom Seismometer Augmentation in the North Pacific (OBSANP) - cruise report

The Ocean Bottom Seismometer Augmentation in the North Pacific Experiment (OBSANP, June-July, 2013, R/V Melville) addresses the coherence and depth dependence of deep-water ambient noise and signals. During the 2004 NPAL Experiment in the North Pacific Ocean, in addition to predicted ocean acoustic arrivals and deep shadow zone arrivals, we observed "deep seafloor arrivals" (DSFA) that were dominant on the seafloor Ocean Bottom Seismometer (OBS) (at about 5000m depth) but were absent or very weak on the Distributed Vertical Line Array (DVLA) (above 4250m depth). At least a subset of these arrivals correspond to bottomdiffracted surface-reflected (BDSR) paths from an out-of-plane seamount. BDSR arrivals are present throughout the water column, but at depths above the conjugate depth are obscured by ambient noise and PE predicted arrivals. On the 2004 NPAL/LOAPEX experiment BDSR paths yielded the largest amplitude seafloor arrivals for ranges from 500 to 3200km. The OBSANP experiment tests the hypothesis that BDSR paths contribute to the arrival structure on the deep seafloor even at short ranges (from near zero to 4-1/2CZ). The OBSANP cruise had three major research goals: a) identification and analysis of DSFA and BDSR arrivals occurring at short (1/2CZ) ranges in the 50 to 400Hz band, b) analysis of deep sea ambient noise in the band 0.03 to 80Hz, and c) analysis of the frequency dependence of BR and SRBR paths. On OBSANP we deployed a 32 element VLA from 12 to 1000m above the seafloor, eight short-period OBSs and four long-period OBSs and carried out a 15day transmission program using a J15-3 acoustic source.Funding was provided by the Office of Naval Research under contract #'s N00014-10-1-0987 and N00014-10-1-051

Age and growth of an outbreaking Acanthaster cf. solaris population within the Great Barrier Reef

Despite having been studied for more than 40 years, much about the basic life history of crown-of-thorns starfish (CoTS; Acanthaster spp.) remains poorly understood. Size at age-a key metric of productivity for any animal population-has yet to be clearly defined, primarily due to difficulties in obtaining validated ages and potentially indeterminate growth due to factors such as starvation; within-population variability is entirely unknown. Here we develop age and growth estimates for an outbreaking CoTS population in Australian waters by integrating prior information with data from CoTS collected from multiple outbreaking reefs. Age estimates were made from un-validated band counts of 2038 individual starfish. Results from our three-parameter von Bertalanffy Bayesian hierarchical model show that, under 2013-2014 outbreak conditions, CoTS on the GBR grew to a 349 ( 326, 380) mm (posterior median (95% uncertainty interval)) total diameter at a 0.54 (0.43, 0.66) intrinsic rate of increase. However, we also found substantial evidence (Delta DIC > 200) for inter-reef variability in both maximum size (SD 38 (19, 76)) and intrinsic rate of increase (SD 0.32 (0.20, 0.49)) within the CoTS outbreak initiation area. These results suggest that CoTS demography can vary widely with reef-scale environmental conditions, supporting location-based mechanisms for CoTS outbreaks generally. These findings should help improve population and metapopulation models of CoTS dynamics and better predict the potential damage they may cause in the future

Iron (Oxyhydr)Oxides Serve as Phosphate Traps in Tundra and Boreal Peat Soils

Arctic and boreal ecosystems are experiencing pronounced warming that is accelerating decomposition of soil organic matter and releasing greenhouse gases to the atmosphere. Future carbon storage in these ecosystems depends on the balance between microbial decomposition and primary production, both of which can be regulated by nutrients such as phosphorus. Phosphorus cycling in tundra and boreal regions is often assumed to occur through biological pathways with little interaction with soil minerals; that is, phosphate released from organic molecules is rapidly assimilated by plants or microorganisms. In contrast to this prevailing conceptual model, we use sequential extractions and spectroscopic techniques to demonstrate that iron (oxyhydr)oxides sequester approximately half of soil phosphate in organic soils from four arctic and boreal sites. Iron (III) (oxyhydr)oxides accumulated in shallow soils of low‐lying, saturated areas where circumneutral pH and the presence of a redox interface promoted iron oxidation and hydrolysis. Soils enriched in short‐range ordered iron oxyhydroxides, which are susceptible to dissolution under anoxic conditions, had high phosphate sorption capacities and maintained low concentrations of soluble phosphate relative to soils containing mostly organic‐bound iron or crystalline iron oxides. Thus, substantial quantities of phosphorus in these organic soils were associated with minerals that could reduce bioavailability but potentially also serve as phosphorus sources under anoxic conditions. The implication of this finding is that mineral surfaces effectively compete with biological processes for phosphate and must be considered as a nutrient regulator in these sensitive ecosystems

Synergistic drug combinations from electronic health records and gene expression.

ObjectiveUsing electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding.MethodWe applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis.ResultsFrom EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence.ConclusionsThis is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing

Construction and Analysis of an Ozone Profile Climatology Over Houston, Texas

Since the summer of 2004, over 200 ozonesondes have been launched from the campuses of Rice University or the University of Houston (29.7 N, 95.3 W), each about 3 miles from downtown Houston. These sounding launches have been sponsored by NASA, the Shell Center for Sustainability of Rice University, and the Texas Commissions for Environmental Quality as part of a large effort to understand Houston’s ozone problem. Data from these soundings have provided valuable insight into the seasonal and diurnal variations of the vertical ozone distribution and their relationship to changes in atmospheric conditions. In this presentation, we show annual and seasonal variability in the ozone profile, evidence for the impact of meteorological factors on the ozone profile, and comparisons of the ozonesonde data with TES and OMI retrievals