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Insect wings are typically supported by thickened struts called veins. These veins form diverse geometric patterns across insects. For many insect species, even the left and right wings from the same individual have veins with unique topological arrangements, and little is known about how these patterns form. We present a largescale quantitative study of the fingerprint-like "secondary veins." We compile a dataset of wings from 232 species and 17 families from the order Odonata (dragonflies and damselflies), a group with particularly elaborate vein patterns. We characterize the geometric arrangements of veins and develop a simple model of secondary vein patterning. We show that our model is capable of recapitulating the vein geometries of species from other, distantly related winged insect clades. [ABSTRACT FROM AUTHOR]

Recent breakthroughs in generating induced pluripotent stem cells (i PSCs) using four defined factors have revealed the potential utility of stem cells in biological research and clinical applications. However, the low efficiency and slow kinetics of reprogramming related to producing these cells and underlying safety issues, such as viral integration and genetic and epigenetic abnormalities of i PSCs, hamper the further application of i PSCs in laboratory and clinical settings. Previous studies have suggested that reprogramming efficiency can be enhanced and that reprogramming kinetics can be accelerated by manipulating epigenetic status. Herein, we review recent studies on the application of epigenome-modifying small molecules in enhancing reprogramming and functionally replacing some reprogramming factors. We mainly focus on studies that have used small molecules to interfere with epigenome-modifying enzymes, such as DNA methyltransferase, histone acetyltransferase, and histone methyltransferase. The potential use of these small molecules in inducing i PSCs and new ways to identify small molecules of higher potency and fewer side effects are also discussed. [ABSTRACT FROM AUTHOR]

Lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, is a flavin-dependent amine oxidase which specifically demethylates mono- or dimethylated H3K4 and H3K9 via a redox process. It participates in a broad spectrum of biological processes and is of high importance in cell proliferation, adipogenesis, spermatogenesis, chromosome segregation and embryonic development. To date, as a potential drug target for discovering anti-tumor drugs, the medical significance of LSD1 has been greatly appreciated. However, the catalytic mechanism for the rate-limiting reductive halfreaction in demethylation remains controversial. By employing a combined computational approach including molecular modeling, molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, the catalytic mechanism of dimethylated H3K4 demethylation by LSD1 was characterized in details. The three-dimensional (3D) model of the complex was composed of LSD1, CoREST, and histone substrate. A 30-ns MD simulation of the model highlights the pivotal role of the conserved Tyr761 and lysine-water-flavin motif in properly orienting flavin adenine dinucleotide (FAD) with respect to substrate. The synergy of the two factors effectively stabilizes the catalytic environment and facilitated the demethylation reaction. On the basis of the reasonable consistence between simulation results and available mutagenesis data, QM/MM strategy was further employed to probe the catalytic mechanism of the reductive halfreaction in demethylation. The characteristics of the demethylation pathway determined by the potential energy surface and charge distribution analysis indicates that this reaction belongs to the direct hydride transfer mechanism. Our study provides insights into the LSD1 mechanism of reductive half-reaction in demethylation and has important implications for the discovery of regulators against LSD1 enzymes. [ABSTRACT FROM AUTHOR]

Arsenic, a curative agent for acute promyelocytic leukemia, induces cell apoptosis and degradation of BCR-ABL in chronic myelogenous leukemia (CML). We demonstrated that ubiquitination and degradation of BCR-ABL was mediated by c-CBL a RING-type E3 ligase that was also shown to be involved in ubiquitination for many other receptor/protein tyrosine kinases. Our data showed that c-CBL protein was considerably up-regulated by arsenic sulfide (As454). Interestingly, arsenic directly bound the RING finger domain of c-CBL to inhibit its self-ubiquitination/degradation without interfering with the enhancement of ubiquitination and subsequent proteolysis of its substrate BCR-ABL. Degradation of BCR-ABL due to c-CBL induction as a result of arsenic treatment was also observed in vivo in CML mice. These findings provide insight into the molecular mechanisms of arsenic and further support its therapeutic applications in CML in combination with tyrosine kinase inhibitors and potentially also in other malignancies involving aberrant receptor/protein tyrosine kinase signaling. [ABSTRACT FROM AUTHOR]

Consolidation of aversive operant conditioning into long-term memory (LTM) requires CREB-dependent de novo protein synthesis. The newly synthesized proteins are distributed to the synapses in neurons that are involved in memory formation and storage. Accumulating evidence indicates that the presynaptic release mechanisms also play a role in long-term synaptic plasticity. Our understanding of whether the presynaptic proteins undergo de novo synthesis during long-term memory formation is limited. In this study, we investigated the involvement of syntaxin-1, a presynaptic exocytotic protein, and dynamin-1, an endocytotic protein, in the formation of long-term memory. We took advantage of a well-established aversive operant conditioning model of aerial respiratory behavior in the fresh water pond snail Lymnaea stagnalis, and demonstrated that the LTM formation is associated with increased expression of syntaxin-1 and dynamin-1, coincident with elevated levels of CREB1. Partial knockdown of CREB1 gene by double stranded RNA inhibition (dsRNAi) prior to operant conditioning prevented snails from memory consolidation, and reduced the expression of syntaxin-1 and dynamin-1 at both mRNA and protein levels. These findings suggest that CREB1-mediated gene expression is required for the LTM-induced up-regulation of synaptic proteins, syntaxin-1 and dynamin-1, in L. stagnalis. Our study thus offers new insights into the molecular mechanisms that mediate CREB1-dependent long-term memory formation. [ABSTRACT FROM AUTHOR]

To determine whether migration impacted on drug use and HIV-related risk behaviors among injection drug users (IDU), we identified participants in a prospective cohort of IDU (Vancouver Injection Drug User Study) who had reported migrating out of Greater Vancouver between May 1996 and November 2005. We compared risk behaviors before and after a move for individuals who migrated (movers) and for a similar period for non-movers using linear growth curve analyses. In total, 1,122 individuals were included, including 430 (38.3%) women and 331 (29.5%) Aboriginal participants. Among these, 192 (17.1%) individuals reported migrating out of Greater Vancouver between 1996 and 2005 while 930 (82.9%) did not. Movers were significantly younger than non-movers: 32.0 (Interquartile Range [IQR]: 24.3–39.2) and 34.6 (IQR: 26.9–40.8) respectively. A significant decrease in those reporting unstable housing, frequent heroin and cocaine injection occurred only in movers. Our findings suggest that, in this setting, risk-taking among IDU declines following periods of migration out of Greater Vancouver. [ABSTRACT FROM AUTHOR]

Objective: To examine whether there were differential rates of hepatitis C virus (HCV) incidence in injecting drug-using youths who did and did not report involvement in survival sex work. Design: Data were derived from 2 prospective cohort studies of injecting drug users (May 1, 1996, to July 31, 2007). Analyses were restricted to HCV antibody- negative youths who completed baseline and at least 1 follow-up assessment. Setting: Vancouver, British Columbia, Canada. Participants: Of 3074 injecting drug users, 364 (11.8%) were youths (aged 14-24 years) with a median age of 21.3 years and a duration of injecting drug use of 3 years. Main Exposure: Survival sex work involvement. Main Outcome Measure: The Kaplan-Meier method and Cox proportional hazards regression were used to compare HCV incidence among youths who did and did not report survival sex work. Results: Baseline HCV prevalence was 51%, with youths involved in survival sex work significantly more likely to be HCV antibody positive (60% vs 44%; P=.002). In baseline HCV antibody-negative youths, the cumulative HCV incidence at 36 months was significantly higher in those involved in survival sex work (68.4% vs 38.8%; P<.001). The HCV incidence density was 36.8 (95% confidence interval [CI], 24.2-53.5) per 100 person-years in youths reporting survival sex work involvement at baseline compared with 14.1 (9.4-20.3) per 100 person-years in youths not reporting survival sex work. In multivariate Cox proportional hazards analyses, survival sex work was the strongest predictor of elevated HCV incidence (adjusted relative hazard, 2.30; 95% CI, 1.27-4.15). Conclusion: This study calls attention to the critical need for evidence-based social and structural HCV prevention efforts that target youths engaged in survival sex work. [ABSTRACT FROM AUTHOR]

Injection drug users (IDUs) are vulnerable to serious health complications resulting from unsafe injection practices. We examined whether the use of a supervised safer injection facility (SIF) promoted change in injecting practices among a representative sample of 760 IDUs who use a SIF in Vancouver, Canada. Consistent SIF use was compared with inconsistent use on a number of self-reported changes in injecting practice variables. More consistent SIF use is associated with positive changes in injecting practices, including less reuse of syringes, use of sterile water, swabbing injection sites, cooking/filtering drugs, less rushed injections, safe syringe disposal and less public injecting. [ABSTRACT FROM AUTHOR]

Purpose. To examine if there were any gender differences in bone pain and its functional interference among patients referred for palliative radiotherapy. To investigate any gender differences in analgesic consumption and the response to radiation treatmen. Methods and Materials. Patients with bone metastases treated with palliative radiotherapy were interviewed using the Brief Pain Inventory at baseline, 1, 2, and 3 months following the radiation treatment. Patients were asked to rate on a scale of 0-10 their worst, average and current pain as well as how pain interfered with the following: general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. Analgesic consumption in the previous 24 hours and other patient demographics were recorded too. Independent non-parametric Wilcoxon tests were used to evaluate for gender differences in quantitative variables. P value < 0.01 was considered statistically significant. Results. Between May 2003 and April 2005, 199 patients (102 males, 97 females) were accrued. The median Karnofsky Performance Status was 70 and the median age was 66 years. The most common primary cancer sites were prostate, breast and lung. Female reported more severe worst pain (mean 8.3 compared to 7.6 for males, p = 0.0081) even after adjustment of primary cancer sites. There was no gender difference in the functional interference scores, analgesic consumption, and the response to radiation treatment. Conclusion. Our finding of a gender difference in worst pain scores needs to be confirmed in larger studies. [ABSTRACT FROM PUBLISHER]

Many cities are experiencing infectious disease epidemics and substantial community harms as a result of illicit drug use. Although medically supervised smoking facilities (SSFs) remain untested in North America, local health officials in Vancouver are considering to prepare a submission to Health Canada for an exemption to open Canadas first SSF for evaluation. Reluctance of health policymakers to initiate a pilot study of SSFs may be due in part to outstanding questions regarding the potential uptake and community impacts of the intervention. This study was conducted to evaluate the prevalence and correlates of willingness to use an SSF among illicit drug smokers who are enrolled in the Vancouver Injection Drug Users Study. Participants who reported actively smoking cocaine, heroin, or methamphetamine who returned for follow-up between June 2002 and December 2002 were eligible for these analyses. Those who reported willingness to use an SSF were compared with those who were unwilling to use an SSF by using logistic regression analyses. Four hundred and forty-three participants were eligible for this study. Among respondents, 124 (27.99%) expressed willingness to attend an SSF. Variables that were independently associated with willingness to attend an SSF in multivariate analyses included sex-trade work (adjusted odds ratio [AOR] =1.85), crack pipe sharing (AOR =2.24), and residing in the citys HIV epicentre (AOR =1.64). We found that participants who demonstrated a willingness to attend an SSF were more likely to be involved in the sex trade and share crack pipes. Although the impact of SSFs in North America can only be quantified by scientific evaluation, these data indicate a potential for public health and community benefits if SSFs were to become available. [ABSTRACT FROM AUTHOR]

We conducted this study among HIV-infected injection drug users to determine the effect of self-reported alcohol use and prior incarceration at the time of initiating antiretroviral therapy on subsequent HIV-1 RNA suppression. We examined the demographics, recent incarceration history, and drug and alcohol use history from the Vancouver Injection Drug User Study (VIDUS) questionnaire closest to the date of initiating antiretroviral therapy. We linked these data to the HIV/AIDS Drug Treatment Program. There were 234 VIDUS participants who accessed antiretroviral therapy through the Drug Treatment Program from August 1, 1996, to July 31, 2001. In terms of illicit drug use, 196 (84%) reported injecting heroin and cocaine at the time of initiating antiretroviral therapy. Multiple logistic regression revealed that in the 6 months prior to initiating antiretroviral therapy, alcohol use (adjusted odds ratio [AOR] 0.32; 95% CI 0.13-0.81) and incarceration (AOR 0.22; 95% CI 0.09-0.58) were independently associated with lower odds of HIV-1 RNA suppression. Factors positively associated with HIV-1 RNA suppression included: adherence (AOR 1.27; 95% CI 1.06-1.51); lower baseline HIV-1 RNA (AOR 1.30; 95% CI 1.01-1.66); highly active antiretroviral therapy (AOR 4.10; 95% CI 1.56-10.6); months on therapy (AOR 1.1; 95% CI 1.06-1.14). Among HIV-infected injection drug users who were on antiretroviral therapy, any alcohol use and incarceration in the 6 months prior to initiating antiretroviral therapy were negatively associated with achieving HIV-1 RNA suppression. In addition to addiction treatment for active heroin and cocaine use, the identification and treatment of alcohol problems should be supported in this setting. As well, increased outreach to HIV-infected drug users recently released from prison to ensure continuity of care needs to be further developed. [ABSTRACT FROM AUTHOR]

Background Recent policy announcements in Canada and the United States may potentially affect the risk environment for HIV transmission among incarcerated injection drug users (IDU). We sought to evaluate the potential impact of incarceration on HIV risk behaviour among the IDU enrolled in a prospective cohort study. Methods We examined patterns of incarceration among 1247 IDU participants enrolled in a 6-year prospective cohort study in Vancouver, Canada, and tested for potential associations between HIV risk behaviour and incarceration. Correlates of incarceration were identified using generalized estimating equations (GEE). Results At baseline, factors significantly associated with incarceration included daily injection heroin and injection cocaine use and inconsistent condom use with casual sexual partners. In a GEE analysis, factors independently associated with incarceration included: used syringe borrowing (adjusted odds ratio [AOR] = 1.36; [95% CI: 1.16–1.60]), used syringe lending (AOR = 1.31; [95% CI: 1.12–1.55]) and inconsistent condom use with casual sexual partners (AOR = 1.16; [1.02–1.33]). All variables P Conclusion In our study, incarceration was independently associated with HIV transmission and acquisition behaviours. These findings suggest that increased rates of incarceration of IDU may be associated with increased HIV transmission among this group. [ABSTRACT FROM AUTHOR]