The new-generation antipsychotics -integrating the neuropathology and pharmacology of schizophrenia

No Abstract

THE COGNITIVE OVERRIDE OF ANXIETY IS ACCOMPLISHED BY SOCIAL FAMILIARITY AND IS MEDIATED BY THE MEDIAL PREFRONTAL CORTEX.

poster abstractIn rats, social familiarity can alleviate anxiety-like behavior observed in the social interaction test. We propose that a neural circuit that includes the medial Prefrontal Cortex (mPFC) and Basolateral Amygdala (BLA), in which the mPFC processes social cues of familiarity and suppresses BLA outputs that lead to anxiety-like behavior, regulate this social familiarity effect. To investigate the effect of social familiarity on anxiety, we developed the Social Interaction-Habituation (SI-h) paradigm, consisting of a 5 min social interaction test repeated daily with the experimental rat exposed to the same partner rat on each test day. As the experimental rat becomes “familiar” with the partner rat, a significant increase in SI time is observed by day 5 compared to day 1, producing a SI-familiarity effect (SI-f). This SI-f effect is dependent on the presence of an anxiogenic stimulus (bright light), and familiarity to a partner rat. No increases in SI times were observed in rats when the SI-h test was performed under dark conditions or when exposed to novel partners on days 1-5. After establishing SI-f, exposure to a novel partner significantly reduces SI times, suggesting the SI-f effect is a result of recognition of the familiar partner rat. Re-exposure to the original partner in a new environment produces an enhanced SI-f effect; SI time significantly increases from day 1 by day 3. Bilateral inhibition of the mPFC with a GABAA agonist blocks the anxiolytic SI-f effect. Exposure to the same partner 24 hours following mPFC inhibition, SI times increase significantly higher than day 1. These data indicate that the mPFC activity is necessary for expression of the SI-f effect

Identification of the Emergent Leaders within a CSE Professional Development Program

The need for high quality, sustainable Computer Science Education (CSE) professional development (PD) at the grades K-12 level is essential to the success of the global CSE initiatives. This study investigates the use of Social Network Analysis (SNA) to identify emergent teacher leaders within a high quality CSE PD program. The CSE PD program was designed and implemented through collaboration between the computer science and teacher education units at a Midwestern metropolitan university in North America. A unique feature of this specific program is in the intentional development of a social network. This study discusses the importance of social networks, the development of social capital, and its impact on the sustainability of the goals of the CSE PD program. The role of emergent teacher leaders in the development of the social capital of the CSE PD cohort is investigated using SNA techniques. The cohort consisted of 16 in-service teachers in grades 6-12 representing seven districts and four distinct content areas. The instruments used involved a questionnaire and the results of a CSE PD program online course. The findings suggest a correlation between the emergent teacher leaders, the online course results, and the overall cohort social capital. Future uses of SNA within professional development programs are also discussed

Sister chromatid telomere fusions, but not NHEJ-mediated inter-chromosomal telomere fusions, occur independently of DNA ligases 3 and 4

Telomeres shorten with each cell division and can ultimately become substrates for non-homologous end-joining repair, leading to large-scale genomic rearrangements of the kind frequently observed in human cancers. We have characterised over 1400 telomere fusion events at the single-molecule level, using a combination of high-throughput sequence analysis together with experimentally-induced telomeric double-stranded DNA breaks. We show that a single chromosomal dysfunctional telomere can fuse with diverse non-telomeric genomic loci, even in the presence of an otherwise stable genome, and that fusion predominates in coding regions. Fusion frequency was markedly increased in the absence of TP53 checkpoint control and significantly modulated by the cellular capacity for classical, versus alternative, non-homologous end joining (NHEJ). We observed a striking reduction in inter-chromosomal fusion events in cells lacking DNA ligase 4, in contrast to a remarkably consistent profile of intra-chromosomal fusion in the context of multiple genetic knockouts, including DNA ligase 3 and 4 double-knockouts. We reveal distinct mutational signatures associated with classical NHEJ-mediated inter-chromosomal, as opposed to alternative NHEJ-mediated intra-chromosomal telomere fusions and evidence an unanticipated sufficiency of DNA ligase 1 for these intra-chromosomal events. Our findings have implications for mechanisms driving cancer genome evolution

Forest Carbon Storage in the Western United States: Distribution, Drivers, and Trends

Abstract: Forests are a large carbon sink and could serve as natural climate solutions that help moderate future warming. Thus, establishing forest carbon baselines is essential for tracking climate‐mitigation targets. Western US forests are natural climate solution hotspots but are profoundly threatened by drought and altered disturbance regimes. How these factors shape spatial patterns of carbon storage and carbon change over time is poorly resolved. Here, we estimate live and dead forest carbon density in 19 forested western US ecoregions with national inventory data (2005–2019) to determine: (a) current carbon distributions, (b) underpinning drivers, and (c) recent trends. Potential drivers of current carbon included harvest, wildfire, insect and disease, topography, and climate. Using random forests, we evaluated driver importance and relationships with current live and dead carbon within ecoregions. We assessed trends using linear models. Pacific Northwest (PNW) and Southwest (SW) ecoregions were most and least carbon dense, respectively. Climate was an important carbon driver in the SW and Lower Rockies. Fire reduced live and increased dead carbon, and was most important in the Upper Rockies and California. No ecoregion was unaffected by fire. Harvest and private ownership reduced carbon, particularly in the PNW. Since 2005, live carbon declined across much of the western US, likely from drought and fire. Carbon has increased in PNW ecoregions, likely recovering from past harvest, but recent record fire years may alter trajectories. Our results provide insight into western US forest carbon function and future vulnerabilities, which is vital for effective climate change mitigation strategies

Dimensionally Dependent Tensor Identities by Double Antisymmetrisation

Some years ago, Lovelock showed that a number of apparently unrelated familiar tensor identities had a common structure, and could all be considered consequences in n-dimensional space of a pair of fundamental identities involving trace-free (p,p)-forms where 2p >= n$. We generalise Lovelock's results, and by using the fact that associated with any tensor in n-dimensional space there is associated a fundamental tensor identity obtained by antisymmetrising over n+1 indices, we establish a very general 'master' identity for all trace-free (k,l)-forms. We then show how various other special identities are direct and simple consequences of this master identity; in particular we give direct application to Maxwell, Lanczos, Ricci, Bel and Bel-Robinson tensors, and also demonstrate how relationships between scalar invariants of the Riemann tensor can be investigated in a systematic manner.Comment: 17 pages, 2 figure

The effect of high [K(+)]o on spontaneous Ca(2+) waves in freshly isolated interstitial cells of Cajal from the rabbit urethra.

Interstitial cells of Cajal (ICC) act as putative pacemaker cells in the rabbit urethra. Pacemaker activity in ICC results from spontaneous global Ca(2+) waves that can be increased in frequency by raising external [K(+)]. The purpose of this study was to elucidate the mechanism of this response. Intracellular [Ca(2+)] was measured in fluo-4-loaded smooth muscle cells (SMCs) and ICC using a Nipkow spinning disk confocal microscope. Increasing [K(+)]o to 60 mmol/L caused an increase in [Ca(2+)]i accompanied by contraction in SMCs. Raising [K(+)]o did not cause contraction in ICC, but the frequency of firing of spontaneous calcium waves increased. Reducing [Ca(2+)]o to 0 mmol/L abolished the response in both cell types. Nifedipine of 1 μmol/L blocked the response of SMC to high [K(+)]o, but did not affect the increase in firing in ICC. This latter effect was blocked by 30 μmol/L NiCl2 but not by the T-type Ca(2+) channel blocker mibefradil (300 nmol/L). However, inhibition of Ca(2+) influx via reverse-mode sodium/calcium exchange (NCX) using either 1 μmol/L SEA0400 or 5 μmol/L KB-R7943 did block the effect of high [K(+)]o on ICC. These data suggest that high K(+) solution increases the frequency of calcium waves in ICC by increasing Ca(2+) influx through reverse-mode NCX

The Spitzer Survey of Interstellar Clouds in the Gould Belt. III. A Multi-Wavelength View of Corona Australis

We present Spitzer Space Telescope IRAC and MIPS observations of a 0.85 deg^2 field including the Corona Australis (CrA) star-forming region. At a distance of 130 pc, CrA is one of the closest regions known to be actively forming stars, particularly within its embedded association, the Coronet. Using the Spitzer data, we identify 51 young stellar objects (YSOs) in CrA which include sources in the well-studied Coronet cluster as well as distributed throughout the molecular cloud. Twelve of the YSOs discussed are new candidates, one of which is located in the Coronet. Known YSOs retrieved from the literature are also added to the list, and a total of 116 candidate YSOs in CrA are compiled. Based on these YSO candidates, the star formation rate is computed to be 12 M_o Myr^-1, similar to that of the Lupus clouds. A clustering analysis was also performed, finding that the main cluster core, consisting of 68 members, is elongated (having an aspect ratio of 2.36), with a circular radius of 0.59 pc and mean surface density of 150 pc^-2. In addition, we analyze outflows and jets in CrA by means of new CO and H_2 data. We present 1.3 mm interferometric continuum observations made with the Submillimeter Array (SMA) covering R CrA, IRS 5, IRS 7, and IRAS 18595-3712 (IRAS 32). We also present multi-epoch H_2 maps and detect jets and outflows, study their proper motions, and identify exciting sources. The Spitzer and ISAAC/VLT observations of IRAS 32 show a bipolar precessing jet, which drives a CO (2-1) outflow detected in the SMA observations. There is also clear evidence for a parsec-scale precessing outflow, E-W oriented, and originating in the SMA 2 region, likely driven by SMA 2 or IRS 7A.Comment: Accepted for publication in ApJS. 112 pages, 42 figures (quality reduced), 13 tables. Full resolution version can be found at http://www.cfa.harvard.edu/~dpeterson/CrA/CrA_highres.pd

Insights from wildfire science: A resource for fire policy discussions

Record blazes swept across parts of the US in 2015, burning more than 10 million acres. The four biggest fire seasons since 1960 have all occurred in the last 10 years, leading to fears of a ‘new normal’ for wildfire. Fire fighters and forest managers are overwhelmed, and it is clear that the policy and management approaches of the past will not suffice under this new era of western wildfires. In recent decades, state and federal policymakers, tribes, and others are confronting longer fire seasons (Jolly et al. 2015), more large fires (Dennison et al. 2014), a tripling of homes burned, and a doubling of firefighter deaths (Rasker 2015). Federal agencies now spend $2 to$3 billion annually fighting fires (and in the case of the US Forest Service, over 50% of their budget), and the total cost to society may be up to 30 times more than the direct cost of firefighting. If we want to contain these costs and reduce risks to communities, economies, and natural systems, we can draw on the best available science when designing fire management strategies, as called for in the recent federal report on Wildland Fire Science and Technology. Here, we highlight key science insights that can contribute to the public discourse on wildfire policy and associated management of forests, woodlands, and shrublands. This information is fundamental to decisions that will promote resilient communities and landscapes facing more fire in the future