A spatial covariance (123)I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) single photon emission computed tomography to investigate spatial covariance of α4β2 nicotinic acetylcholine receptors in AD and healthy controls. Thirteen AD and 16 controls underwent 1235IA-85380 and regional cerebral blood flow (99mTc-exametazime) single photon emission computed tomography scanning. We applied voxel principal component (PC) analysis, generating series of principal component images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 and regional cerebral blood flow covariance patterns that differentiated AD from controls. The α4β2 pattern showed relative decreased uptake in numerous brain regions implicating several networks including default mode, salience, and Papez hubs. Thus, as well as basal forebrain and brainstem cholinergic system dysfunction, cholinergic deficits mediated through nicotinic acetylcholine receptors could be evident within key networks in AD. These findings may be important for the pathophysiology of AD and its associated cognitive and behavioral phenotypes

What does the occurrence of Sporormiella (Preussia) spores mean in Australian fossil sequences?

Understanding the loss of the final few species of Australian megafauna is beset by a paucity of data on human arrival, well-provenanced megafauna, human/megafauna population range and distribution (coexistence and interaction), and the range, scale and impact of environmental changes spanning the human-megafauna period. To overcome these shortcomings, the occurrence and decline of coprophilous fungal spores of Sporormiella in sediments have been used as a proxy for extinct megaherbivores. The Sporormiella evidence is presented as the key indicator of extinction timing and these reports are often from locations where there is no known archaeological record or megafauna remains. However, interpreting fungal spore occurrence is not straightforward, as demonstrated by studies investigating taphonomy, taxonomy and the types of animal dung where Sporormiella occurs. No detailed studies on these problems exist for Australia and no evidence supporting the use of Sporormiella as a valid proxy has been reported. Here we examine the occurrence of Sporormiella spores from Cuddie Springs in south-eastern Australia. Despite a well-preserved suite of megafauna fossils, Sporormiella occurrence is sporadic and frequencies are low. We conclude that using Sporormiella alone as an indicator for the presence of megafauna is premature for the Australian context. Copyright (C) 2018 John Wiley & Sons, Ltd

Observation of playa salts as nuclei in orographic wave clouds

During the Ice in Clouds Experiment-Layer Clouds (ICE-L), dry lakebed, or playa, salts from the Great Basin region of the United States were observed as cloud nuclei in orographic wave clouds over Wyoming. Using a counterflow virtual impactor in series with a single-particle mass spectrometer, sodium-potassium-magnesium-calcium-chloride salts were identified as residues of cloud droplets. Importantly, these salts produced similar mass spectral signatures to playa salts with elevated cloud condensation nuclei (CCN) efficiencies close to sea salt. Using a suite of chemical characterization instrumentation, the playa salts were observed to be internally mixed with oxidized organics, presumably produced by cloud processing, as well as carbonate. These salt particles were enriched as residues of large droplets (>19 μm) compared to smaller droplets (>7 μm). In addition, a small fraction of silicate-containing playa salts were hypothesized to be important in the observed heterogeneous ice nucleation processes. While the high CCN activity of sea salt has been demonstrated to play an important role in cloud formation in marine environments, this study provides direct evidence of the importance of playa salts in cloud formation in continental North America has not been shown previously. Studies are needed to model and quantify the impact of playas on climate globally, particularly because of the abundance of playas and expected increases in the frequency and intensity of dust storms in the future due to climate and land use changes

Assessing direct contributions of morphological awareness and prosodic sensitivity to children’s word reading and reading comprehension

We examined the independent contributions of prosodic sensitivity and morphological awareness to word reading, text reading accuracy, and reading comprehension. We did so in a longitudinal study of English-speaking children (N = 70). At 5 to 7 years of age, children completed the metalinguistic measures along with control measures of phonological awareness and vocabulary. Children completed the reading measures two years later. Morphological awareness, but not prosodic sensitivity made a significant independent contribution to word reading, text reading accuracy and reading comprehension. The effects of morphological awareness on reading comprehension remained after controls for word reading. These results suggest that morphological awareness needs to be considered seriously in models of reading development and that prosodic sensitivity might have primarily indirect relations to reading outcomes. Keywords: Morphological Awareness; Prosody; Word Reading; Reading Comprehension

Zampanolide, a Microtubule-Stabilizing Agent, Is Active in Resistant Cancer Cells and Inhibits Cell Migration.

Zampanolide, first discovered in a sponge extract in 1996 and later identified as a microtubule-stabilizing agent in 2009, is a covalent binding secondary metabolite with potent, low nanomolar activity in mammalian cells. Zampanolide was not susceptible to single amino acid mutations at the taxoid site of β-tubulin in human ovarian cancer 1A9 cells, despite evidence that it selectively binds to the taxoid site. As expected, it did not synergize with other taxoid site microtubule-stabilizing agents (paclitaxel, ixabepilone, discodermolide), but surprisingly also did not synergize in 1A9 cells with laulimalide/peloruside binding site agents either. Efforts to generate a zampanolide-resistant cell line were unsuccessful. Using a standard wound scratch assay in cell culture, it was an effective inhibitor of migration of human umbilical vein endothelial cells (HUVEC) and fibroblast cells (D551). These properties of covalent binding, the ability to inhibit cell growth in paclitaxel and epothilone resistant cells, and the ability to inhibit cell migration suggest that it would be of interest to investigate zampanolide in preclinical animal models to determine if it is effective in vivo at preventing tumor growth and metastasis

Ultralow-Temperature Measurements of Submicron Devices

Contains research summary.Joint Services Electronics Program (Contract DAALO03-86-K-0002

Ultralow Temperature Studies of Nanometer Size Semiconductor Devices

Contains report on one research project.Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAAL03-89-C-0001

Ultralow-Temperature Measurements of Submicron Devices Nanometer-Scale Semiconductor Devices

Contains project goals.Joint Services Electronics Program (Contract DAALO3-86-K-0002

Dietary responses of Sahul (Pleistocene Australia-New Guinea) megafauna to climate and environmental change

Throughout the late Quaternary, the Sahul (Pleistocene Australia-New Guinea) vertebrate fauna was dominated by a diversity of large mammals, birds, and reptiles, commonly referred to as megafauna. Since ca. 450-400 Ka, approximately 88 species disappeared in Sahul, including kangaroos exceeding 200 kg in size, wombat-like animals the size of hippopotamuses, flightless birds, and giant monitor lizards that were likely venomous. Ongoing debates over the primary cause of these extinctions have typically favored climate change or human activities. Improving our understanding of the population biology of extinct megafauna as more refined paleoenvironmental data sets become available will assist in identifying their potential vulnerabilities. Here, we apply a multiproxy approach to analyze fossil teeth from deposits dated to the middle and late Pleistocene at Cuddie Springs in southeastern Australia, assessing relative aridity via oxygen isotopes as well as vegetation and megafaunal diets using both carbon isotopes and dental microwear texture analyses. We report that the Cuddie Springs middle Pleistocene fauna was largely dominated by browsers, including consumers of C4 shrubs, but that by late Pleistocene times the C4 dietary component was markedly reduced. Our results suggest dietary restriction in more arid conditions. These dietary shifts are consistent with other independently derived isotopic data from eggshells and wombat teeth that also suggest a reduction in C4 vegetation after ∼ 45 Ka in southeastern Australia, coincident with increasing aridification through the middle to late Pleistocene. Understanding the ecology of extinct species is important in clarifying the primary drivers of faunal extinction in Sahul. The results presented here highlight the potential impacts of aridification on marsupial megafauna. The trend to increasingly arid conditions through the middle to late Pleistocene (as identified in other paleoenvironmental records and now also observed, in part, in the Cuddie Springs sequence) may have stressed the most vulnerable animals, perhaps accelerating the decline of late Pleistocene megafauna in Australia

Cascading Disturbances in Florida Bay, USA: Cyanobacteria Blooms, Sponge Mortality, And Implications For Juvenile Spiny Lobsters Panulirus Argus

Florida Bay, the shallow lagoon separating mainland Florida and the Florida Keys, USA, is experiencing an unprecedented series of ecological disturbances. In 1991, following reports of other ecosystem perturbations, we observed widespread and persistent blooms of cyanobacteria that coincided with the decimation of sponge communities over hundreds of square kilometers. Juvenile Caribbean spiny lobsters Panulirus argus, among other animals, rely on sponges for shelter; the impact of sponge loss on the abundance of lobsters and their use of shelter, in particular, has been dramatic. The loss of sponges on 27 experimental sites in hard bottom habitat in central Florida Bay resulted in the redistribution of juvenile lobsters among the remaining shelters, an influx of lobsters into sites where artificial shelters were present, and a decline in lobster abundances on sites without artificial shelters. Diver surveys of sponge damage at additional sites in central Florida Bay confirmed that the sponge die-off was widespread and its occurrence coincided with areas that had been exposed to the cyanobacteria bloom. This cascade of disturbances has dramatically altered the community structure of affected hard bottom areas and demonstrates the coupled dynamics of this shallow marine ecosystem