Balancing proliferation and connectivity in PTEN -associated Autism Spectrum Disorder

Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway—controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator

NASA Planetary Mission Concept Study: Assessing: Dwarf Planet Ceres' past and Present Habitability Potential

The Dawn mission revolutionized our understanding of Ceres during the same decade that has also witnessed the rise of ocean worlds as a research and exploration focus. We will report progress on the Planetary Mission Concept Study (PMCS) on the future exploration of Ceres under the New Frontiers or Flagship program that was selected for NASA funding in October 2019. At the time this writing, the study was just kicked off, hence this abstract reports the study plan as presented in the proposal

Antidepressants for cognitive impairment in schizophrenia - A systematic review and meta-analysis

Background: Cognitive impairment in schizophrenia is disabling, but current treatment options remain limited. Objective: To meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia. Data sources and study selection: PubMed, MEDLINE, PsycINFO, and Cochrane Library databases were searched until 12/2013 for randomized controlled trials comparing antidepressant augmentation of antipsychotics with placebo regarding effects on cognitive functioning in schizophrenia. Data extraction: Two authors independently extracted data. Standardized mean differences (SMDs) were calculated for continuous outcomes and risk ratios for categorical outcomes. SMDs of individual cognitive tests were pooled on a study level within domains (primary outcome) and across domains. When results were heterogeneous, random instead of fixed effects models were used. Results: We meta-analyzed 11 studies (duration=8.7 +/- 3.7 weeks) including 568 patients (mean age=39.5 +/- 6.9 years, males=67.2%, illness duration=12.5 +/- 8.0 years). Antidepressants included mirtazapine (4 studies; n=126), citalopram (2 studies; n=231), fluvoxamine (1 study; n=47), duloxetine (1 study; n=40), mianserin (1 study; n=30), bupropion (1 study; n=61), and reboxetine (1 study; n=33). Statistically significant, but clinically negligible, advantages were found for pooled antidepressants compared to placebo in executive function (Hedges\u27 g=0.17, p=0.02) and a composite cognition score (Hedges\u27 g=0.095, p=0.012). Depression improved with serotonergic antidepressants (p=0.0009) and selective serotonin reuptake inhibitors (p=0.009), but not with pooled antidepressants (p=0.39). Sedation was more common with pooled antidepressants (p=0.04). Conclusion: Adjunctive antidepressants do not demonstrate clinically significant effects on cognition in schizophrenia patients, however, larger studies, preferably in euthymic schizophrenia patients and using full neurocognitive batteries, are needed to confirm this finding. (C) 2014 Elsevier B. V. All rights reserved

Nurses\u27 Alumnae Association Bulletin, June 1970

Alumnae President\u27s Message Congratulations Alumni Association Portrait of Samuel D. Gross Officers and Chairmen of Committees Financial Report Progress of Jefferson 1969-1970 School of Nursing Annual Report School of Practical Nursing Report Emergency Department Patient Services Department Annual Luncheon Pictures Committee Reports Progress of the Alumnae Association Crossword Puzzle Missing Graduates Resume of Alumnae Meetings Minutes Class News Student Nurses Section Crossword Puzzle Answers Notice

Nurses\u27 Alumnae Association Bulletin, June 1969

Alumnae President\u27s Message Officers and Chairmen Financial Report Progressive Changes at Jefferson School of Nursing Report Student Activities School of Practical Nursing Report Jefferson Expansion Report Clerk-Typist Report Committee Reports Resume of Alumnae Meetings Class News 1969 CLINIC Correspondence Notice

Reading sentences with a late closure ambiguity: does semantic information help?

Stowe (1989) reported that semantic information eliminates garden paths in sentences with the direct-object vs. subject ambiguity, such as Even before the police stopped the driver was very frightened. Three experiments are presented which addressed some methodological problems in Stowe's study. Experiment 1, using a word-by-word, self-paced reading task with grammaticality judgements, manipulated animacy of the first subject noun while controlling for the plausibility of the transitive action. The results suggest that initial sentence analysis is not guided by animacy. Experiment 2 and 3, using the self-paced task with grammaticality judgements and eye-tracking, varied the plausibility of the direct-object nouns to test revision effects. Plausibility was found to facilitate revision without fully eliminating garden paths, in line with various revision models. The findings support the view of a sentence processing system relying heavily on syntactic information, with semantic information playing a weaker role both in initial analysis and during revision, thus supporting serial, syntax-first models and ranked-parallel models relying on structural criteria

Parity Violation in Elastic Electron-Proton Scattering and the Proton's Strange Magnetic Form Factor

We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A=-4.92 +- 0.61 +- 0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections.Comment: 4 pages, 3 figures, submitted to Physical Review Letters, Sept 199

On the well-posedness for the Ideal MHD equations in the Triebel-Lizorkin spaces

In this paper, we prove the local well-posedness for the Ideal MHD equations in the Triebel-Lizorkin spaces and obtain blow-up criterion of smooth solutions. Specially, we fill a gap in a step of the proof of the local well-posedness part for the incompressible Euler equation in \cite{Chae1}.Comment: 16page

Multiscale fluctuations in nuclear response

The nuclear collective response is investigated in the framework of a doorway picture in which the spreading width of the collective motion is described as a coupling to more and more complex configurations. It is shown that this coupling induces fluctuations of the observed strength. In the case of a hierarchy of overlapping decay channels, we observe Ericson fluctuations at different scales. Methods for extracting these scales and the related lifetimes are discussed. Finally, we show that the coupling of different states at one level of complexity to some common decay channels at the next level, may produce interference-like patterns in the nuclear response. This quantum effect leads to a new type of fluctuations with a typical width related to the level spacing.Comment: 34 Latex pages including 6 figures (submitted to Phys. Rev. C