Hippocampal BDNF regulates a shift from flexible, goal-directed to habit memory system function following cocaine abstinence.

The transition from recreational drug use to addiction involves pathological learning processes that support a persistent shift from flexible, goal-directed to habit behavioral control. Here, we examined the molecular mechanisms supporting altered function in hippocampal (HPC) and dorsolateral striatum (DLS) memory systems following abstinence from repeated cocaine. After 3 weeks of cocaine abstinence (experimenter- or self-administered), we tested new behavioral learning in male rats using a dual-solution maze task, which provides an unbiased approach to assess HPC- versus DLS-dependent learning strategies. Dorsal hippocampus (dHPC) and DLS brain tissues were collected after memory testing to identify transcriptional adaptations associated with cocaine-induced shifts in behavioral learning. Our results demonstrate that following prolonged cocaine abstinence rats show a bias toward the use of an inflexible, habit memory system (DLS) in lieu of a more flexible, easily updated memory system involving the HPC. This memory system bias was associated with upregulation and downregulation of brain-derived neurotrophic factor (BDNF) gene expression and transcriptionally permissive histone acetylation (acetylated histone H3, AcH3) in the DLS and dHPC, respectively. Using viral-mediated gene transfer, we overexpressed BDNF in the dHPC during cocaine abstinence and new maze learning. This manipulation restored HPC-dependent behavioral control. These findings provide a system-level understanding of altered plasticity and behavioral learning following cocaine abstinence and inform mechanisms mediating the organization of learning and memory more broadly

Validity of two common asthma-specific quality of life questionnaires: Juniper mini asthma quality of life questionnaire and Sydney asthma quality of life questionnaire

Background This study explored the psychometric properties (internal consistency, construct validity, discriminative ability) of the Juniper Mini Asthma Quality of Life Questionnaire (Mini AQLQ-J) and the Sydney Asthma Quality of Life Questionnaire (AQLQ-S). Methods One hundred fourty-six adults (18-45 years) with asthma requiring regular inhaled corticosteroids were recruited to a trial of written emotional disclosure. Correlational analyses were performed to understand the relationship of the two measures with each other, with symptoms, lung function, asthma control, asthma bother and generic quality of life. Median quality of life scores were compared according to gender, health care usage and levels of asthma severity. Results AQLQ-J and AQLQ-S total scores correlated strongly with each other (rho = -0.80) and moderately with the EuroQol Current Health Status Scale (AQLQ-J: rho = 0.35; AQLQ-S: rho = -0.40). Domain score correlations between AQLQ-J and AQLQ-S were mostly moderate (0.5 < rho < 0.8). Both QoL measures were significantly correlated with symptom score. Correlations with the symptom score asthma module (AQLQ-J: rho = -0.69; AQLQ-S: rho = 0.50) were stronger compared with the total symptom score and the symptom score rhinitis module (AQLQ-J: rho = -0.41; AQLQ-M: rho =0.31). Neither QoL measure was significantly correlated with FEV1 % predicted at the total or the domain level. Total scores of both measures were significantly correlated with subjective asthma control (AQLQ-J: rho = 0.68; AQLQ-S: rho = -0.61) and asthma bother (AQLQ-J: rho = -0.73; AQLQ-M: rho = 0.73). Conclusions This study provides further evidence for the validity of the AQLQ-J and the AQLQ-S in a British population of adult patients with asthma managed in primary care. Correlations with lung function parameters were weak or absent. Correlations with generic quality of life were moderate, those with asthma symptoms, asthma control and asthma bother were strong. Both measures are able to discriminate between levels of asthma severity

Love Don't Need a Reason

"From a stage erected in front of the US Capitol, on April 25, 1993, Michael Callen surveyed the throng: an estimated one million people stretched across the National Mall in the largest public demonstration of queer political solidarity in history. “What a sight,” he told the crowd, his earnest Midwestern twang reverberating through loudspeakers. “You’re a sight for sore eyes. Being gay is the greatest gift I have ever been given, and I don’t care who knows about it.” He then launched into a gorgeous rendition of “Love Don’t Need a Reason,” the AIDS anthem he composed with Marsha Malamet and the late Peter Allen. As Callen finished singing, people stood cheering and flashing the familiar American Sign Language symbol for “I Love You.” For they knew the song’s sentiment rang true for Callen, who had recently announced his retirement from music and activism after a living for more than a decade with what was then called “full-blown AIDS.” After the March on Washington, Callen returned to his recently adopted West Coast home, Los Angeles. In the ensuing months, his health rapidly declined, and on 27 December 1993, Callen died of AIDS-related pulmonary Kaposi’s sarcoma. Love Don’t Need a Reason focuses on Callen’s most important and lasting legacy: his music. A witness to the overlooked last years of Gay Liberation and a major figure in the early years of the AIDS crisis, Michael Callen chronicled these experiences in song. A community organizer, activist, author, and architect of the AIDS self-empowerment movement, he literally changed the way we have sex in an epidemic when he co-authored one of the first safe-sex guides in 1983. A gifted singer, songwriter, and performer, he also made gay music for gay people and used music to educate and empower people with AIDS. Listening again to his music allows us to hear the shifting dynamics of American families, changing notions of masculinity, gay migration to urban areas, the sexual politics of Gay Liberation, and HIV/AIDS activism. Using extensive archival materials and newly-conducted oral history interviews with Callen’s friends, family, and fellow musicians, Matthew J. Jones reintroduces Callen to the history of LGBTQIA+ music and places Callen’s music at the center of his important activist work.

Spin physics with STAR

The STAR collaboration aims to study polarized proton-proton collisions at RHIC. The emphasis of the spin run this year is on transverse single spin asymmetries. Beyond 2001, we aim to determine directly and precisely the gluon polarization, as well as the polarizations of the u, $\bar{u}$, d and $\bar{d}$ quarks in the proton by measuring in addition longitudinal and double spin asymmetries. Furthermore, we aim to measure for the first time the quark transversity distributions. These measurements will improve substantially the knowledge and understanding of the spin structure of the nucleon.Comment: 9 pages, 3 figures. Talk presented at The 3rd Circum-Pan-Pacific Symposium on "High Energy Spin Physics" October 8-13 2001, Beijing, Chin

Short-term Response of Holcus lanatus L. (Common Velvetgrass) to Chemical and Manual Control at Yosemite National Park, USA

One of the highest priority invasive species at both Yosemite and Sequoia and Kings Canyon national parks is Holcus lanatus L. (common velvetgrass), a perennial bunchgrass that invades mid-elevation montane meadows. Despite velvetgrass being a high priority species, there is little information available on control techniques. The goal of this project was to evaluate the short-term response of a single application of common chemical and manual velvetgrass control techniques. The study was conducted at three montane sites in Yosemite National Park. Glyphosate spotspray treatments were applied at 0.5, 1.0, 1.5, and 2.0% concentrations, and compared with hand pulling to evaluate effects on cover of common velvetgrass, cover of other plant species, and community species richness. Posttreatment year 1 cover of common velvetgrass was 12.1% 6 1.6 in control plots, 6.3% 6 1.5 averaged over the four chemical treatments (all chemical treatments performed similarly), and 13.6% 6 1.7 for handpulled plots. This represents an approximately 50% reduction in common velvetgrass cover in chemically- treated plots recoded posttreatment year 1 and no statistically significant reduction in hand pulled plots compared with controls. However, there was no treatment effect in posttreatment year 2, and all herbicide application rates performed similarly. In addition, there were no significant treatment effects on nontarget species or species richness. These results suggest that for this level of infestation and habitat type, (1) one year of hand pulling is not an effective control method and (2) glyphosate provides some level of control in the short-term without impact to nontarget plant species, but the effect is temporary as a single year of glyphosate treatment is ineffective over a twoyear period

Love Don't Need a Reason

"From a stage erected in front of the US Capitol, on April 25, 1993, Michael Callen surveyed the throng: an estimated one million people stretched across the National Mall in the largest public demonstration of queer political solidarity in history. “What a sight,” he told the crowd, his earnest Midwestern twang reverberating through loudspeakers. “You’re a sight for sore eyes. Being gay is the greatest gift I have ever been given, and I don’t care who knows about it.” He then launched into a gorgeous rendition of “Love Don’t Need a Reason,” the AIDS anthem he composed with Marsha Malamet and the late Peter Allen. As Callen finished singing, people stood cheering and flashing the familiar American Sign Language symbol for “I Love You.” For they knew the song’s sentiment rang true for Callen, who had recently announced his retirement from music and activism after a living for more than a decade with what was then called “full-blown AIDS.” After the March on Washington, Callen returned to his recently adopted West Coast home, Los Angeles. In the ensuing months, his health rapidly declined, and on 27 December 1993, Callen died of AIDS-related pulmonary Kaposi’s sarcoma. Love Don’t Need a Reason focuses on Callen’s most important and lasting legacy: his music. A witness to the overlooked last years of Gay Liberation and a major figure in the early years of the AIDS crisis, Michael Callen chronicled these experiences in song. A community organizer, activist, author, and architect of the AIDS self-empowerment movement, he literally changed the way we have sex in an epidemic when he co-authored one of the first safe-sex guides in 1983. A gifted singer, songwriter, and performer, he also made gay music for gay people and used music to educate and empower people with AIDS. Listening again to his music allows us to hear the shifting dynamics of American families, changing notions of masculinity, gay migration to urban areas, the sexual politics of Gay Liberation, and HIV/AIDS activism. Using extensive archival materials and newly-conducted oral history interviews with Callen’s friends, family, and fellow musicians, Matthew J. Jones reintroduces Callen to the history of LGBTQIA+ music and places Callen’s music at the center of his important activist work.

Measuring forces between protein fibers by microscopy

We propose a general scheme for measuring the attraction between mechanically frustrated semiflexible fibers by measuring their thermal fluctuations and shape. We apply this analysis to a system of sickle hemoglobin (HbS) fibers that laterally attract one another. These fibers appear to “zip” together before reaching mechanical equilibrium due to the existence of cross-links into a dilute fiber network. We are also able to estimate the rigidities of the fibers. These rigidities are found to be consistent with sickle hemoglobin “single” fibers 20 nm in diameter, despite recent experiments indicating that fiber bundling sometimes occurs. Our estimate of the magnitude of the interfiber attraction for HbS fibers is in the range 8 ± 7 kBT/μm, or 4 ± 3 kBT/μm if the fibers are assumed, a priori to be single fibers (such an assumption is fully consistent with the data). This value is sufficient to bind the fibers, overcoming entropic effects, although extremely chemically weak. Our results are compared to models for the interfiber attraction that include depletion and van der Waals forces. This technique should also facilitate a similar analysis of other filamentous protein assembles in the future, including β-amyloid, actin, and tubulin

Spectral imaging of thermal damage induced during microwave ablation in the liver

Induction of thermal damage to tissue through delivery of microwave energy is frequently applied in surgery to destroy diseased tissue such as cancer cells. Minimization of unwanted harm to healthy tissue is still achieved subjectively, and the surgeon has few tools at their disposal to monitor the spread of the induced damage. This work describes the use of optical methods to monitor the time course of changes to the tissue during delivery of microwave energy in the porcine liver. Multispectral imaging and diffuse reflectance spectroscopy are used to monitor temporal changes in optical properties in parallel with thermal imaging. The results demonstrate the ability to monitor the spatial extent of thermal damage on a whole organ, including possible secondary effects due to vascular damage. Future applications of this type of imaging may see the multispectral data used as a feedback mechanism to avoid collateral damage to critical healthy structures and to potentially verify sufficient application of energy to the diseased tissue.Comment: 4pg,6fig. Copyright 2018 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other work

Functional interpretation of single cell similarity maps.

We present Vision, a tool for annotating the sources of variation in single cell RNA-seq data in an automated and scalable manner. Vision operates directly on the manifold of cell-cell similarity and employs a flexible annotation approach that can operate either with or without preconceived stratification of the cells into groups or along a continuum. We demonstrate the utility of Vision in several case studies and show that it can derive important sources of cellular variation and link them to experimental meta-data even with relatively homogeneous sets of cells. Vision produces an interactive, low latency and feature rich web-based report that can be easily shared among researchers, thus facilitating data dissemination and collaboration