Designing Primary Prevention for People Living with HIV

Today, there are new reasons for a sharper focus on prevention for people living with HIV. Growing numbers of people with the disease are living more healthy, sexual lives. Recent evidence suggests that risk taking among both HIV-positive and negative people is increasing. After nearly two decades of life in the shadow of AIDS, communities are growing weary of traditional prevention messages and many people are openly grappling with difficult questions of intimacy and sex. Increasingly, people living with HIV also face multiple complex economic and substance abuse challenges that complicate prevention efforts.There is an urgent need -- and sufficient expertise -- to move forward with prevention campaigns focused on helping people living with HIV and AIDS avoid passing their infection along to others. Numerous innovative interventions for people with HIV show promise, including:a social marketing campaign for gay men and a five-session group intervention for women living with HIV in Massachusetts,a chat line for positives and a group session program for Latinas/Latinos in Los Angeles,Internet chat room interventions in Atlanta,a group session for gay Asian American-Pacific Islander Americans living with HIV in San Francisco, andPrevention Case Management programs newly funded by the Centers for Disease Control

Age and growth estimates of the winter skate (Leucoraja ocellata) in the western Gulf of Maine

Age and growth estimates for the winter skate (Leucoraja ocellata) were estimated from vertebral band counts on 209 fish ranging in size from 145 to 940 mm total length (TL). An index of average percent error (IAPE) of 5.8% suggests that our aging method represents a precise approach to the age assessment of L. ocellata. Marginal increments were significantly different between months (Kruskal-Wallis P<0.001) and a distinct trend of increasing monthly increment growth began in July. Estimates of von Bertalanffy growth parameters suggest that females attain a slightly larger asymptotic TL (L∞=1374 mm) than males (L∞=1218 mm) and grow more slowly (k=0.059 and 0.074, respectively). The oldest ages obtained for the winter skate were 19 years for males and 18 years for females, which corresponded to total lengths of 932 mm and 940 mm, respectively. The results indicate that the winter skate exhibits the characteristics that have made other elasmobranch populations highly susceptible to exploitation by commercial fisheries

Building genomic infrastructure: Sequencing platinum-standard reference-quality genomes of all cetacean species.

International audienc

Voluntary Exercise Reduces Alzheimer’s-like Pathology After Inflammation in Mice

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has previously shown that 7 consecutive peripheral injections of a bacterial mimetic led to systemic inflammation, increased levels of Ab in the brain, and cognitive dysfunction (Kahn et al., 2012; Weintraub et al., 2013). Currently there are very few effective treatments that diminish AD symptomology. One documented way to decrease inflammation without the use of pharmaceuticals is through regular physical exercise (Cho et al., 2003; Cotman & Berchtold, 2002; Cotman et al., 2007). The present study tested the hypothesis that voluntary exercise would decrease the level of brain Ab following inflammation. Interestingly, we found that two weeks of voluntary wheel running after inflammation led to a reduction of Ab when compared to sedentary recovery. These results indicate that exercise may be an effective modality to reduce AD-like pathology, and that these effects appear to be facilitated by higher versus lower levels of exercise, as measured by total distance run

Interaction of cyclin-dependent kinase 12/CrkRS with cyclin K1 is required for the phosphorylation of the C-terminal domain of RNA polymerase II

CrkRS (Cdc2-related kinase, Arg/Ser), or cyclin-dependent kinase 12 (CKD12), is a serine/threonine kinase believed to coordinate transcription and RNA splicing. While CDK12/CrkRS complexes were known to phosphorylate the C-terminal domain (CTD) of RNA polymerase II (RNA Pol II), the cyclin regulating this activity was not known. Using immunoprecipitation and mass spectrometry, we identified a 65-kDa isoform of cyclin K (cyclin K1) in endogenous CDK12/CrkRS protein complexes. We show that cyclin K1 complexes isolated from mammalian cells contain CDK12/CrkRS but do not contain CDK9, a presumed partner of cyclin K. Analysis of extensive RNA-Seq data shows that the 65-kDa cyclin K1 isoform is the predominantly expressed form across numerous tissue types. We also demonstrate that CDK12/CrkRS is dependent on cyclin K1 for its kinase activity and that small interfering RNA (siRNA) knockdown of CDK12/CrkRS or cyclin K1 has similar effects on the expression of a luciferase reporter gene. Our data suggest that cyclin K1 is the primary cyclin partner for CDK12/CrkRS and that cyclin K1 is required to activate CDK12/CrkRS to phosphorylate the CTD of RNA Pol II. These properties are consistent with a role of CDK12/CrkRS in regulating gene expression through phosphorylation of RNA Pol II

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

Background: Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design: This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion: Previous studies in adults have shown that psychological treatments for insomnia administered by specialist nurses to groups of patients can be effective within a primary care setting. This will be a pilot study to determine whether an educational intervention aimed at primary care teams to deliver problem focused therapy for insomnia can improve sleep management and outcomes for individual adult patients presenting to general practice. The study will also test procedures and collect information in preparation for a larger definitive cluster-randomised trial. The study is funded by The Health Foundation

Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity

The majority of oligodendrogliomas (ODGs) exhibit combined losses of chromosomes 1p and 19q and mutations of isocitrate dehydrogenase (IDH1-R132H or IDH2-R172K). Approximately 70% of ODGs with 1p19q co-deletions harbor somatic mutations in the Capicua Transcriptional Repressor (CIC) gene on chromosome 19q13.2. Here we show that endogenous long (CIC-L) and short (CIC-S) CIC proteins are predominantly localized to the nucleus or cytoplasm, respectively. Cytoplasmic CIC-S is found in close proximity to the mitochondria. To study wild type and mutant CIC function and motivated by the paucity of 1p19q co-deleted ODG lines, we created HEK293 and HOG stable cell lines ectopically co-expressing CIC and IDH1. Non-mutant lines displayed increased clonogenicity, but cells co-expressing the mutant IDH1-R132H with either CIC-S-R201W or -R1515H showed reduced clonogenicity in an additive manner, demonstrating cooperative effects in our assays. Expression of mutant CIC-R1515H increased cellular 2-Hydroxyglutarate (2HG) levels compared to wild type CIC in IDH1-R132H background. Levels of phosphorylated ATP-citrate Lyase (ACLY) were lower in cell lines expressing mutant CIC-S proteins compared to cells expressing wild type CIC-S, supporting a cytosolic citrate metabolism-related mechanism of reduced clonogenicity in our in vitro model systems. ACLY or phospho-ACLY were similarly reduced in CIC-mutant 1p19q co-deleted oligodendroglioma patient samples

Competition between singlet fission and spin-orbit-induced intersystem crossing in anthanthrene and anthanthrone derivatives

Singlet and triplet excited‐state dynamics of anthanthrene and anthanthrone derivatives in solution are studied. Triisopropylsilyl‐ (TIPS) or H‐terminated ethynyl groups are used to tune the singlet and triplet energies to enable their potential applications in singlet fission and triplet fusion processes. Time‐resolved optical and electron paramagnetic resonance (EPR) spectroscopies are used to obtain a mechanistic understanding of triplet formation. The anthanthrene derivatives form triplet states efficiently at a rate (ca. 107 s−1) comparable to radiative singlet fluorescence processes with approximately 30 % triplet yields, despite their large S1‐T1 energy gap (>1 eV) and the lack of carbonyl groups. In contrast, anthanthrone has a higher triplet yield (50±10 %) with a faster intersystem crossing rate (2.7urn:x-wiley:21926506:media:cplu201900410:cplu201900410-math-0001 108 s−1) because of the n‐π* character of the S1←S0 transition. Analysis of time‐resolved spin‐polarized EPR spectra of these compounds reveals that the triplet states are primarily generated by the spin‐orbit‐induced intersystem crossing mechanism. However, at high concentrations, the EPR spectrum of the 4,6,10,14‐tetrakis(TIPS‐ethynyl) anthanthrene triplet state shows a significant contribution from a non‐Boltzmann population of the ms=0 spin sublevel, which is characteristic of triplet formation by singlet fission

LongSAGE profiling of nine human embryonic stem cell lines

Analysis of a 2.6 million longSAGE sequence tag resource generated from nine human embryonic stem cell lines reveals an enrichment of RNA binding proteins and novel ES-specific transcripts