A Non-Canonical Role for Choline Acetyltransferase in Chromatin Organization and the Response to Beta-Amyloid

The three-dimensional structure of chromatin is essential for context-dependent regulation of gene expression in post-mitotic neurons. Chromosomal rearrangements have been observed in the aging brain, and proteins involved in chromatin organization have altered expression and/or localization in Alzheimer’s disease (AD). A human- and primate-specific transcript of choline acetyltransferase produces an 82-kDa protein (82-kDa ChAT) that is localized to the nucleus of cholinergic neurons, but is found in the cytoplasm in individuals with mild cognitive impairment (MCI) and AD. The function of the 82-kDa ChAT protein is unknown, though recent evidence suggests it has a role in gene expression changes in response to cellular perturbations. In the present study, we explore whether 82-kDa ChAT is involved in global chromatin organization and an epigenetic response to cytotoxic amyloid-β(Aβ) exposure. We show that 82-kDa ChAT associates with chromatin in human SH-SY5Y neural cells using chromatin immunoprecipitation with next-generation sequencing (ChIP-seq), finding that acute exposure of cells to oligomeric Aβ1–42 increases 82-kDa ChAT associations with gene promoters and introns. Following Aβ1–42-exposure, 82-kDa ChAT co-localizes in nuclear aggregates with special AT-rich binding protein 1 (SATB1), which anchors DNA to scaffolding/matrix attachment regions (S/MARs). SATB1 has similar increases in genic associations following Aβ1–42-exposure, and both SATB1 and 82-kDa ChAT associate with synapse-related genes. The 82-kDa ChAT and SATB1 proteins have patterned genomic associations at regions enriched with S/MAR binding motifs, preventing an Aβ1–42-induced increase in an isoform-specific APP mRNA transcript. Finally, we show that 82-kDa ChAT expression during cholinergic differentiation of SH-SY5Y cells increases the steady-state levels of proteins related to synapse formation, resulting in increased neurite complexity. These results demonstrate that 82-kDa ChAT and SATB1 regulate chromatin organization at S/MARs, resulting in context-dependent gene expression changes in cholinergic cells and increased expression of synapse formation-related proteins during cholinergic differentiation. Cholinergic synapse dysfunction and degeneration is observed early in AD progression and 82-kDa ChAT is mislocalized in AD, therefore the loss of both the epigenetic response to Aβ and gene expression changes related to synapse formation and maintenance may have implications for the etiology or progression of MCI and AD

Community rotorcraft air transportation benefits and opportunities

Information about rotorcraft that will assist community planners in assessing and planning for the use of rotorcraft transportation in their communities is provided. Information useful to helicopter researchers, manufacturers, and operators concerning helicopter opportunities and benefits is also given. Three primary topics are discussed: the current status and future projections of rotorcraft technology, and the comparison of that technology with other transportation vehicles; the community benefits of promising rotorcraft transportation opportunities; and the integration and interfacing considerations between rotorcraft and other transportation vehicles. Helicopter applications in a number of business and public service fields are examined in various geographical settings

Empirical Storm-Time Correction to the International Reference Ionosphere Model E-Region Electron and Ion Density Parameterizations Using Observations from TIMED/SABER

The response of the ionospheric E-region to solar-geomagnetic storms can be characterized using observations of infrared 4.3 micrometers emission. In particular, we utilize nighttime TIMED/SABER measurements of broadband 4.3 micrometers limb emission and derive a new data product, the NO+(v) volume emission rate, which is our primary observation-based quantity for developing an empirical storm-time correction the IRI E-region electron density. In this paper we describe our E-region proxy and outline our strategy for developing the empirical storm model. In our initial studies, we analyzed a six day storm period during the Halloween 2003 event. The results of this analysis are promising and suggest that the ap-index is a viable candidate to use as a magnetic driver for our model

Ionospheric E-Region Response to Solar-Geomagnetic Storms Observed by TIMED/SABER and Application to IRI Storm-Model Development

The large thermospheric infrared radiance enhancements observed from the TIMED/SABER experiment during recent solar storms provide an exciting opportunity to study the influence of solar-geomagnetic disturbances on the upper atmosphere and ionosphere. In particular, nighttime enhancements of 4.3 um emission, due to vibrational excitation and radiative emission by NO+, provide an excellent proxy to study and analyze the response of the ionospheric E-region to auroral electron dosing and storm-time enhancements to the E-region electron density. In this paper we give a status report of on-going work on model and data analysis methodologies of deriving NO+ 4.3 um volume emission rates, a proxy for the storm-time E-region response, and the approach for deriving an empirical storm-time correction to International Reference Ionosphere (IRI) E-region NO+ and electron densities

The biosocial event : responding to innovation in the life sciences

Innovation in the life sciences calls for reflection on how sociologies separate and relate life processes and social processes. To this end we introduce the concept of the ‘biosocial event’. Some life processes and social processes have more mutual relevance than others. Some of these relationships are more negotiable than others. We show that levels of relevance and negotiability are not static but can change within existing relationships. Such changes, or biosocial events, lie at the heart of much unplanned biosocial novelty and much deliberate innovation. We illustrate and explore the concept through two examples – meningitis infection and epidemic, and the use of sonic ‘teen deterrents’ in urban settings. We then consider its value in developing sociological practice oriented to critically constructive engagement with innovation in the life sciences

Influence of Solar-Geomagnetic Disturbances on SABER Measurements of 4.3 Micrometer Emission and the Retrieval of Kinetic Temperature and Carbon Dioxide

Thermospheric infrared radiance at 4.3 micrometers is susceptible to the influence of solar-geomagnetic disturbances. Ionization processes followed by ion-neutral chemical reactions lead to vibrationally excited NO(+) (i.e., NO(+)(v)) and subsequent 4.3 micrometer emission in the ionospheric E-region. Large enhancements of nighttime 4.3 m emission were observed by the TIMED/SABER instrument during the April 2002 and October-November 2003 solar storms. Global measurements of infrared 4.3 micrometer emission provide an excellent proxy to observe the nighttime E-region response to auroral dosing and to conduct a detailed study of E-region ion-neutral chemistry and energy transfer mechanisms. Furthermore, we find that photoionization processes followed by ion-neutral reactions during quiescent, daytime conditions increase the NO(+) concentration enough to introduce biases in the TIMED/SABER operational processing of kinetic temperature and CO2 data, with the largest effect at summer solstice. In this paper, we discuss solar storm enhancements of 4.3 micrometer emission observed from SABER and assess the impact of NO(+)(v) 4.3 micrometer emission on quiescent, daytime retrievals of Tk/CO2 from the SABER instrument

Rubella metapopulation dynamics and importance of spatial coupling to the risk of congenital rubella syndrome in Peru

Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Consequently, understanding the age-structured dynamics of this infection has considerable public health value. Vaccination short of the threshold for local elimination of transmission will increase the average age of infection. Accordingly, the classic concern for this infection is the potential for vaccination to increase incidence in individuals of childbearing age. A neglected aspect of rubella dynamics is how age incidence patterns may be moulded by the spatial dynamics inherent to epidemic metapopulations. Here, we use a uniquely detailed dataset from Peru to explore the implications of this for the burden of CRS. Our results show that the risk of CRS may be particularly severe in small remote regions, a prediction at odds with expectations in the endemic situation, and with implications for the outcome of vaccination. This outcome results directly from the metapopulation context: specifically, extinction–re-colonization dynamics are crucial because they allow for significant leakage of susceptible individuals into the older age classes during inter-epidemic periods with the potential to increase CRS risk by as much as fivefold

Permanent magnet undulator for SPEAR

A 30 period permanent magnet (SmCo/sub 5/) undulator has been designed, built and tested. The period is 6.1 cm, overall length is 1.95 m, and the gap is variable from 2.7 cm to 6.0 cm. Magnetic measurements at the midplane with a 2.7 cm gap show that the field is sinusoidal with a peak value of .28 T. Construction details and magnetic measurements are presented along with the spectral distribution of radiation produced by 3.0 GeV electrons traversing the undulator

Synchrotron radiation from a charge moving along a helical orbit inside a dielectric cylinder

The radiation emitted by a charged particle moving along a helical orbit inside a dielectric cylinder immersed into a homogeneous medium is investigated. Expressions are derived for the electromagnetic potentials, electric and magnetic fields, and for the spectral-angular distribution of radiation in the exterior medium. It is shown that under the Cherenkov condition for dielectric permittivity of the cylinder and the velocity of the particle image on the cylinder surface, strong narrow peaks are present in the angular distribution for the number of radiated quanta. At these peaks the radiated energy exceeds the corresponding quantity for a homogeneous medium by some orders of magnitude. The results of numerical calculations for the angular distribution of radiated quanta are presented and they are compared with the corresponding quantities for radiation in a homogeneous medium. The special case of relativistic charged particle motion along the direction of the cylinder axis with non-relativistic transverse velocity (helical undulator) is considered in detail. Various regimes for the undulator parameter are discussed. It is shown that the presence of the cylinder can increase essentially the radiation intensity.Comment: 18 pages, 8 EPS figure

Affirming Basic Psychological Needs Promotes Mental Well-Being During the COVID-19 Outbreak

We tested if challenges to basic psychological needs (BPN) for autonomy, competence, and relatedness during the COVID-19 pandemic undermine people’s mental well-being. Furthermore, we tested if an intervention, affirmation of these psychological needs, enhances mental well-being. Results of Study 1 ( N = 153) showed that higher levels of satisfaction of BPN were related to higher well-being during the COVID-19 outbreak. In Study 2 ( N = 215), we employed an online intervention enhancing these BPN. We found increased mental well-being through bolstered relatedness in particular. The intervention also decreased perceived stress. Both studies showed that mental well-being during the COVID-19 pandemic is positively related to the ability to work as usual and the number of people contacted via phone or internet but not in person