Self-defining memories predict engagement in structured activity in First Episode Psychosis, independent of neurocognition and metacognition

Background: Self-defining memories (SDM) are vivid personal memories, related to narrative identity. Individuals with schizophrenia report less specific, more negative, and extract less meaning from these memories compared to control groups. Self-defining memories have been shown to be predicted by neurocognition, associated with metacognition, and linked to goal outcomes in healthy controls. As neurocognition and metacognition are known predictors of poor functioning in psychosis, self-defining memories may also be a predictor. No study has assessed the relationship to functioning or pattern of SDMs in First Episode Psychosis. Methods: This was a cross-sectional study involving 71 individuals with First Episode Psychosis (FEP) and 57 healthy controls who completed a self-defining memories questionnaire. FEP participants completed measures of neurocognition, metacognition (Metacognitive Assessment Interview), functional capacity (The UCSD Performance-Based Skills Assessment) and functional outcome (Time-Use Survey). Results: Self-defining memories reported by individuals with FEP were less integrated compared to healthy controls. Within the FEP sample, holding less specific memories was associated with engagement in significantly fewer hours of structured activity per week and specificity of SDMs mediated the relationship between neurocognition and functional outcome, independent of metacognition. Conclusion: This is the first study to assess SDMs in FEP and to explore the important role of SDMs on clinical outcomes, compared to healthy controls. This study suggests that elaborating on specific self-defining memories is a valid therapeutic target and may be considered a tool to improve daily functioning in FEP

Airborne Infectious Agents and Other Pollutants in Automobiles for Domestic Use: Potential Health Impacts and Approaches to Risk Mitigation

Theworld total of passenger cars is expected to go fromthe current one billion to \u3e2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, allergens, endotoxins, particulates, and volatile organics. Such risks may increase in proportion to the unprecedented upsurge in the numbers of family cars globally. Though new technologies may reduce the levels of air pollution from car exhausts and other sources, they are unlikely to impact our in-car exposure to pathogens. Can commercial in-car air decontamination devices reduce the risk from airborne infections and other pollutants?We lack scientifically rigorous protocols to verify the claims of such devices. Here we discuss the essentials of a customized aerobiology facility and test protocols to assess such devices under field-relevant conditions

Morphological and genetic analyses in the Melanoplus packardii group (Orthoptera: Acrididae)

Melanoplus packardii Scudder was described in 1897. Three additional closely-related species were later described and their status as species has been questioned on numerous occasions. We examined morphology from specimens collected in Nebraska which fit descriptions of three of the four forms and specimens that appeared to be hybrids. We found distinct morphological characters suggesting species status for M. foedus and M. packardii, but not for M. foedus fluviatilis. Examination of aedeagi of these three forms suggests that M. foedus and M. packardii are each distinct, but that the aedeagi of M. f. fluviatilis and M. f. foedus cannot be distinguished. Molecular analyses of the three groups did not produce clear separations and suggest gene exchange between these three forms may be ongoing. Together, these data suggest that M. foedus and M. packardii should be recognized as sibling species, but M. foedus fluviatilis is best considered a form of M. foedus, typically found in low lying areas

Morphological and genetic analyses in the Melanoplus packardii group (Orthoptera: Acrididae)

Melanoplus packardii Scudder was described in 1897. Three additional closely-related species were later described and their status as species has been questioned on numerous occasions. We examined morphology from specimens collected in Nebraska which fit descriptions of three of the four forms and specimens that appeared to be hybrids. We found distinct morphological characters suggesting species status for M. foedus and M. packardii, but not for M. foedus fluviatilis. Examination of aedeagi of these three forms suggests that M. foedus and M. packardii are each distinct, but that the aedeagi of M. f. fluviatilis and M. f. foedus cannot be distinguished. Molecular analyses of the three groups did not produce clear separations and suggest gene exchange between these three forms may be ongoing. Together, these data suggest that M. foedus and M. packardii should be recognized as sibling species, but M. foedus fluviatilis is best considered a form of M. foedus, typically found in low lying areas

C1QBP Inhibits DUX4-Dependent Gene Activation and Can Be Targeted with 4MU

FSHD is linked to the misexpression of the DUX4 gene contained within the D4Z4 repeat array on chromosome 4. The gene encodes the DUX4 protein, a cytotoxic transcription factor that presumably causes the symptoms of the disease. However, individuals have been identified who express DUX4 in their muscle biopsies, but who remain asymptomatic, suggesting that there are other factors that modify FSHD penetrance or severity. We hypothesized that an FSHD-modifying factor would physically interact with DUX4, and we took a proteomic approach to identify DUX4-interacting proteins. We identified the multifunctional C1QBP protein as one such factor. C1QBP is known to regulate several processes that DUX4 affects, including gene expression, oxidative stress, apoptosis, and pre-mRNA splicing. We used siC1QBP knockdown assays to determine if C1QBP affects DUX4 activity. While C1QBP had little effect on DUX4 activity in myotubes, we found that it inhibits the kinetics of DUX4-target gene activation during myogenic differentiation. This identifies C1QBP as a regulator of DUX4 activity and a potential target for FSHD therapeutics. Importantly, C1QBP is regulated by binding to the signaling molecule hyaluronic acid (HA). Decreasing HA by treating cells with 4-methylumbelliferone (4MU), an inhibitor of HA synthesis, resulted in a sharp decline in DUX4 activity and also greatly reduced its cytotoxicity. We have found that DUX4-induced cytotoxicity is associated with severe mislocalizaton of C1QBP, which is prevented by 4MU. This defect is not a downstream result of DUX4-induced oxidative stress, as it could not be prevented by treating cells with an antioxidant, nor could it be recapitulated by exposing cells to oxidants. This identifies C1QBP as a target for the treatment of FSHD, and in particular indicates that 4MU, already an approved drug in Europe and currently under investigation for other indications, may be an effective C1QBP-targeting FSHD therapeutic compound

The California Planet Survey. I. Four New Giant Exoplanets

We present precise Doppler measurements of four stars obtained during the past decade at Keck Observatory by the California Planet Survey (CPS). These stars, namely, HD 34445, HD 126614, HD 13931, and Gl 179, all show evidence for a single planet in Keplerian motion. We also present Doppler measurements from the Hobby-Eberly Telescope (HET) for two of the stars, HD 34445 and Gl 179, that confirm the Keck detections and significantly refine the orbital parameters. These planets add to the statistical properties of giant planets orbiting near or beyond the ice line, and merit follow-up by astrometry, imaging, and space-borne spectroscopy. Their orbital parameters span wide ranges of planetary minimum mass (M sin i = 0.38-1.9 M(Jup)), orbital period (P = 2.87-11.5 yr), semimajor axis (a = 2.1-5.2 AU), and eccentricity (e = 0.02-0.41). HD 34445 b (P = 2.87 yr, M sin i = 0.79 MJup, e = 0.27) is a massive planet orbiting an old, G-type star. We announce a planet, HD 126614 Ab, and an M dwarf, HD 126614 B, orbiting the metal-rich star HD 126614 (which we now refer to as HD 126614 A). The planet, HD 126614 Ab, has minimum mass M sin i = 0.38 MJup and orbits the stellar primary with period P = 3.41 yr and orbital separation a = 2.3 AU. The faint M dwarf companion, HD 126614 B, is separated from the stellar primary by 489 mas (33 AU) and was discovered with direct observations using adaptive optics and the PHARO camera at Palomar Observatory. The stellar primary in this new system, HD 126614 A, has the highest measured metallicity ([ Fe/ H] = + 0.56) of any known planet-bearing star. HD 13931 b (P = 11.5 yr, M sin i = 1.88 MJup, e = 0.02) is a Jupiter analog orbiting a near solar twin. Gl 179 b (P = 6.3 yr, M sin i = 0.82 M(Jup), e = 0.21) is a massive planet orbiting a faint M dwarf. The high metallicity of Gl 179 is consistent with the planet-metallicity correlation among M dwarfs, as documented recently by Johnson & Apps.NSF AST-0702821NASA NNX06AH52GMcDonald Observator

Establishment of clonal myogenic cell lines from severely affected dystrophic muscles - CDK4 maintains the myogenic population

<p>Abstract</p> <p>Background</p> <p>A hallmark of muscular dystrophies is the replacement of muscle by connective tissue. Muscle biopsies from patients severely affected with facioscapulohumeral muscular dystrophy (FSHD) may contain few myogenic cells. Because the chromosomal contraction at 4q35 linked to FSHD is thought to cause a defect within myogenic cells, it is important to study this particular cell type, rather than the fibroblasts and adipocytes of the endomysial fibrosis, to understand the mechanism leading to myopathy.</p> <p>Results</p> <p>We present a protocol to establish clonal myogenic cell lines from even severely dystrophic muscle that has been replaced mostly by fat, using overexpression of CDK4 and the catalytic component of telomerase (human telomerase reverse transcriptase; hTERT), and a subsequent cloning step. hTERT is necessary to compensate for telomere loss during <it>in vitro </it>cultivation, while CDK4 prevents a telomere-independent growth arrest affecting CD56+ myogenic cells, but not their CD56- counterpart, <it>in vitro</it>.</p> <p>Conclusions</p> <p>These immortal cell lines are valuable tools to reproducibly study the effect of the FSHD mutation within myoblasts isolated from muscles that have been severely affected by the disease, without the confounding influence of variable amounts of contaminating connective-tissue cells.</p

Understanding Treatment Refusal Among Adults Presenting for HIV-Testing in Soweto, South Africa: A Qualitative Study

HIV treatment initiatives have focused on increasing access to antiretroviral therapy (ART). There is growing evidence, however, that treatment availability alone is insufficient to stop the epidemic. In South Africa, only one third of individuals living with HIV are actually on treatment. Treatment refusal has been identified as a phenomenon among people who are asymptomatic, however, factors driving refusal remain poorly understood. We interviewed 50 purposively sampled participants who presented for voluntary counseling and testing in Soweto to elicit a broad range of detailed perspectives on ART refusal. We then integrated our core findings into an explanatory framework. Participants described feeling “too healthy” to start treatment, despite often having a diagnosis of AIDS. This subjective view of wellness was framed within the context of treatment being reserved for the sick. Taking ART could also lead to unintended disclosure and social isolation. These data provide a novel explanatory model of treatment refusal, recognizing perceived risks and social costs incurred when disclosing one’s status through treatment initiation. Our findings suggest that improving engagement in care for people living with HIV in South Africa will require optimizing social integration and connectivity for those who test positive

Quasiparticle transport in the vortex state of YBa_2Cu_3O_6.9

The effect of vortices on quasiparticle transport in cuprate superconductors was investigated by measuring the low temperature thermal conductivity of YBa_2Cu_3O_6.9 in magnetic fields up to 8 T. The residual linear term (as T \to 0) is found to increase with field, directly reflecting the occupation of extended quasiparticle states. A study for different Zn impurity concentrations reveals a good agreement with recent calculations for a d-wave superconductor, thereby shedding light on the nature of scattering by both impurities and vortices. It also provides a quantitative measure of the gap near the nodes.Comment: 4 pages, 2 included eps figures, significant new analysis wrt other experiments, to appear in Phys Rev Lett 29 March 199

Telomere Position Effect (TPE) Regulates DUX4 in Human Facioscapulohumeral Muscular Dystrophy (FSHD)

Telomeres may regulate human disease by at least two independent mechanisms. 1) Replicative senescence occurs once short telomeres generate DNA damage signals that produce a barrier to tumor progression. 2) Telomere Position Effect (TPE) can change gene expression at intermediate telomere lengths in cultured human cells. We here report a human disease, facioscapulohumeral muscular dystrophy (FSHD) where telomere length may well contribute to its pathogenesis. FSHD is age-related and genetically only 25-60 kb from the end of chromosome 4q. We used a floxable telomerase to generate isogenic clones with different telomere lengths from patients and their unaffected siblings. DUX4, the primary candidate for FSHD pathogenesis, is upregulated >10-fold in FSHD myoblasts-myotubes with short versus long telomeres, and its expression is inversely proportional to telomere length. FSHD may represent a human disease in which TPE contributes to its age-related phenotype