Epigenetic suppression of hippocampal calbindin-D28k by ΔFosB drives seizure-related cognitive deficits.

The calcium-binding protein calbindin-D28k is critical for hippocampal function and cognition, but its expression is markedly decreased in various neurological disorders associated with epileptiform activity and seizures. In Alzheimer\u27s disease (AD) and epilepsy, both of which are accompanied by recurrent seizures, the severity of cognitive deficits reflects the degree of calbindin reduction in the hippocampal dentate gyrus (DG). However, despite the importance of calbindin in both neuronal physiology and pathology, the regulatory mechanisms that control its expression in the hippocampus are poorly understood. Here we report an epigenetic mechanism through which seizures chronically suppress hippocampal calbindin expression and impair cognition. We demonstrate that ΔFosB, a highly stable transcription factor, is induced in the hippocampus in mouse models of AD and seizures, in which it binds and triggers histone deacetylation at the promoter of the calbindin gene (Calb1) and downregulates Calb1 transcription. Notably, increasing DG calbindin levels, either by direct virus-mediated expression or inhibition of ΔFosB signaling, improves spatial memory in a mouse model of AD. Moreover, levels of ΔFosB and calbindin expression are inversely related in the DG of individuals with temporal lobe epilepsy (TLE) or AD and correlate with performance on the Mini-Mental State Examination (MMSE). We propose that chronic suppression of calbindin by ΔFosB is one mechanism through which intermittent seizures drive persistent cognitive deficits in conditions accompanied by recurrent seizures

Optimization of energy levels by molecular design: evaluation of bis-diketopyrrolopyrrole molecular donor materials for bulk heterojunction solar cells

We report a series of solution-processable, small-molecule, donor materials based on an architecture consisting of two diketopyrrolopyrrole (DPP) cores with different aromatic pi-bridges between the DPP units and different end-capping groups. In general, this architecture leads to desirable light absorption and electronic levels for donor materials. Out of the compounds investigated, a material with a hydrolyzed dithieno(3,2-b;2',3'-d)silole (SDT) core and 2-benzofuran (BFu) end capping groups leads to the most favorable properties for solar cells, capable of generating photocurrent up to 800 nm while producing an open-circuit voltage of over 850 mV, indicating a small loss in electrical potential compared to other bulk heterojunction systems. Device properties can be greatly improved through the use of solvent additives such as 2-chloronaphthalene and initial attempts to optimize device fabrication have resulted in power conversion efficiencies upwards of 4%.close372

A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans

Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. © 2016 Neal et al.1

Spectral and morphological analysis of the remnant of Supernova 1987A with ALMA & ATCA

We present a comprehensive spectral and morphological analysis of the remnant of Supernova (SN) 1987A with the Australia Telescope Compact Array (ATCA) and the Atacama Large Millimeter/submillimeter Array (ALMA). The non-thermal and thermal components of the radio emission are investigated in images from 94 to 672 GHz ($\lambda$ 3.2 mm to 450 $\mu$m), with the assistance of a high-resolution 44 GHz synchrotron template from the ATCA, and a dust template from ALMA observations at 672 GHz. An analysis of the emission distribution over the equatorial ring in images from 44 to 345 GHz highlights a gradual decrease of the east-to-west asymmetry ratio with frequency. We attribute this to the shorter synchrotron lifetime at high frequencies. Across the transition from radio to far infrared, both the synchrotron/dust-subtracted images and the spectral energy distribution (SED) suggest additional emission beside the main synchrotron component ($S_{\nu}\propto\nu^{-0.73}$) and the thermal component originating from dust grains at $T\sim22$ K. This excess could be due to free-free flux or emission from grains of colder dust. However, a second flat-spectrum synchrotron component appears to better fit the SED, implying that the emission could be attributed to a pulsar wind nebula (PWN). The residual emission is mainly localised west of the SN site, as the spectral analysis yields $-0.4\lesssim\alpha\lesssim-0.1$ across the western regions, with $\alpha\sim0$ around the central region. If there is a PWN in the remnant interior, these data suggest that the pulsar may be offset westward from the SN position.Comment: ApJ accepted. 21 pages, emulateapj. References update

Optical Instrument Thermal Control on the Large Ultraviolet/Optical/Infrared Surveyor

The Large Ultraviolet/Optical/Infrared Surveyor (LUVOIR) is a multi-wavelength observatory commissioned by NASA as one of four large mission concept studies for the Astro2020 Decadal Survey. Two concepts are under study which bound a range of cost, risk, and scientific return: an 8-meter diameter unobscured segmented aperture primary mirror and a 15-meter segmented aperture primary mirror. Each concept carries with it an accompanying suite of instruments. The Extreme Coronagraph for Living Planetary Systems (ECLIPS) is a near-ultraviolet (NUV) / optical / near-infrared (NIR) coronagraph; the LUVOIR Ultraviolet Multi-object Spectrograph (LUMOS) provides multi-object imaging spectroscopy in the 100-400 nanometer ultraviolet (UV) range; and the High Definition Imager (HDI) is a wide field-of-view near-UV / optical / near-IR camera that can also perform astrometry. The 15-meter concept also contains an additional instrument, Pollux, which is a high-resolution UV spectro-polarimeter. While the observatory is nominally at a 270 Kelvin operational temperature, the requirements of imaging in both IR and UV require separate detectors operating at different temperature regimes, each with stringent thermal stability requirements. The change in observatory size requires two distinct thermal designs per instrument. In this current work, the thermal architecture is presented for each instrument suite. We describe here the efforts made to achieve the target operational temperatures and stabilities with passive thermal control methods. Additional discussion will focus on how these instrument thermal designs impact the overall system-level architecture of the observatory and indicate the thermal challenges for hardware implementation

Comprehensive analysis of the chromatin landscape in Drosophila melanogaster.

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function

Perceptions of veterinarians and producers concerning Johne’s disease prevalence and control in US beef cow-calf operations

BACKGROUND: Efforts to educate producers and veterinarians in the United States regarding the management, prevention and control of Mycobacterium avium subspecies paratuberculosis (MAP) infection have increased over recent years. While nationwide awareness about MAP infection is improving, current level of awareness among beef producers and veterinarians is largely unknown. This study compares the perceptions of beef producers and veterinarians on the burden of MAP infection in cow-calf herds and on measures to control new infections. Questionnaires were mailed to 989 US beef producers through state Designated Johne’s Coordinators and to 1080 bovine veterinarians belonging to a US nationwide professional association. RESULTS: Twenty-two percent (34/155) of producers reported having infected animals in their herds. The mean (minimum, median, maximum) prevalence reported by producers was 0.8% (0, 0, 10). Twenty-seven percent (27/100) of producers had at least one clinical animal during the previous year. Compared to the small herds (<50 head), the mean test-positive percentages and estimated prevalences were higher in medium (50–149) and highest in large (≥150) herds. Seedstock herds had a lower prevalence and these producers were more likely to enroll in Johne’s disease (JD) control programs and test their herds. Veterinarians reported a mean overall animal level prevalence in their client herds of 5% (0, 2, 60). Similarly, 26% (0, 10, 100) of client herds had at least one infected animal. Mean percentage of infected cows within infected herds was 9% (0.01, 5, 80). Producers generally performed activities to control MAP transmission more frequently than perceived by veterinarians. Compared to veterinarians’ opinions, producers were less likely to cull cows with signs consistent with JD (P < 0.01), but more likely to test purchased additions (P < 0.01). Testing recommendations by veterinarians (n = 277) for beef cow-calf herds were bacterial culture of feces (3%), PCR (14%), ELISA (35%) and a combination of these tests (47%). Seventy-nine percent of veterinarians recommended a 12-month interval between testing. CONCLUSIONS: Seedstock producers who had had JD risk assessments performed on their farms were more supportive of JD control programs and had a correspondingly lower prevalence. It is important to increase educational activities to provide relevant information to veterinarians and producers for better management and control of JD. Educational programs should target larger herds to maximize the impact

Personalized Genetic Risk Counseling to Motivate Diabetes Prevention: A randomized trial

OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week, validated, diabetes prevention program. Middle-risk quartile participants were not studied further. We examined the effect of this genetic counseling intervention on patient self-reported attitudes, program attendance, and weight loss, separately comparing higher-risk and lower-risk result recipients with control participants. RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk, 32 at lower diabetes genetic risk, and 34 untested control subjects. Mean age was 57.9 ± 10.6 years, 61% were men, and average BMI was 34.8 kg/m2, with no differences among randomization groups. Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds, with 33 of 108 (30.6%) losing ≥5% body weight. There were few statistically significant differences in self-reported motivation, program attendance, or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects (P > 0.05 for all but one comparison). CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes