Concise Total Synthesis of (+)-Luteoalbusins A and B

The first total synthesis of (+)-luteoalbusins A and B is described. Highly regio- and diastereoselective chemical transformations in our syntheses include a Friedel–Crafts C3-indole addition to a cyclotryptophan-derived diketopiperazine, a late-stage diketopiperazine dihydroxylation, and a C11-sulfidation sequence, in addition to congener-specific polysulfane synthesis and cyclization to the corresponding epipolythiodiketopiperazine. We also report the cytoxicity of both alkaloids, and closely related derivatives, against A549, HeLa, HCT116, and MCF7 human cancer cell lines.National Institute of General Medical Sciences (U.S.) (GM089732

Quantifying the effectiveness of shoreline armoring removal on coastal biota of Puget Sound

Shoreline armoring is prevalent around the world with unprecedented human population growth and urbanization along coastal habitats. Armoring structures, such as riprap and bulkheads, that are built to prevent beach erosion and protect coastal infrastructure from storms and flooding can cause deterioration of habitats for migratory fish species, disrupt aquatic–terrestrial connectivity, and reduce overall coastal ecosystem health. Relative to armored shorelines, natural shorelines retain valuable habitats for macroinvertebrates and other coastal biota. One question is whether the impacts of armoring are reversible, allowing restoration via armoring removal and related actions of sediment nourishment and replanting of native riparian vegetation. Armoring removal is targeted as a viable option for restoring some habitat functions, but few assessments of coastal biota response exist. Here, we use opportunistic sampling of pre- and post-restoration data for five biotic measures (wrack % cover, saltmarsh % cover, number of logs, and macroinvertebrate abundance and richness) from a set of six restored sites in Puget Sound, WA, USA. This broad suite of ecosystem metrics responded strongly and positively to armor removal, and these results were evident after less than one year. Restoration responses remained positive and statistically significant across different shoreline elevations and temporal trajectories. This analysis shows that removing shoreline armoring is effective for restoration projects aimed at improving the health and productivity of coastal ecosystems, and these results may be widely applicable

Molecular Epidemiology of HIV-Associated Tuberculosis in Dar es Salaam, Tanzania: Strain Predominance, Clustering, and Polyclonal Disease

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian “GD” family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common

Avoidant Coping and Self-efficacy Mediate Relationships between Perceived Social Constraints and Symptoms among Long-term Breast Cancer Survivors

Objective Many breast cancer survivors feel constrained in discussing their cancer experience with others. Limited evidence suggests that social constraints (e.g., avoidance and criticism) from loved ones may negatively impact breast cancer survivors' global health, but research has yet to examine relationships between social constraints and common physical symptoms. Informed by social cognitive processing theory, this study examined whether perceived social constraints from partners and healthcare providers (HCPs) were associated with fatigue, sleep disturbance, and attentional functioning among long-term breast cancer survivors (N = 1052). In addition, avoidant coping and self-efficacy for symptom management were examined as potential mediators of these relationships. Methods Long-term breast cancer survivors (mean years since diagnosis = 6) completed questionnaires assessing social constraints from partners and HCPs, avoidant coping, self-efficacy for symptom management, and symptoms (i.e., fatigue, sleep disturbance, and attentional functioning). Structural equation modeling was used to evaluate the hypothesized relationships among variables in two models: one focused on social constraints from partners and one focused on social constraints from HCPs. Results Both models demonstrated good fit. Consistent with theory and prior research, greater social constraints from both partners and HCPs were associated with greater symptom burden (i.e., greater fatigue and sleep disturbance, poorer attentional functioning). In addition, all relationships were mediated by avoidant coping and self-efficacy for symptom management. Conclusions Findings are consistent with social cognitive processing theory and suggest that symptom management interventions may be enhanced by addressing the impact of social constraints from survivors' partners and HCPs on their coping and self-efficacy

Factors associated with depressive symptoms in young long-term breast cancer survivors

Purpose Long-term breast cancer survivors frequently report distress (i.e., depressive symptoms) that impacts their quality of life. Previous studies have found that negative social interactions (“social constraints”) from partners contribute to long-term, unresolved cycling of intrusive thoughts and cognitive avoidance, resulting in psychological distress. However, these relationships have not been tested in long-term breast cancer survivors. Furthermore, the effect of partners’ depressive symptoms on the survivors’ depressive symptoms has not been tested within the context of these relationships. Therefore, the purpose of this study was to test relationships between breast cancer survivors’ depressive symptoms and (1) social constraints, cognitive avoidance, and intrusive thoughts, and (2) partners’ depressive symptoms. Methods Data were from a cross-sectional descriptive study of breast cancer survivors (N = 222) 3–8 years post-diagnosis and their partners, who completed surveys assessing demographic characteristics, social constraints, intrusive thoughts, cognitive avoidance, and depressive symptoms. Structural equation modeling confirmatory path analyses were conducted to determine significant relationships between survivors’ depressive symptoms and all other variables. Results Our model fits the data well. Breast cancer survivors’ depressive symptoms were predicted by social constraints and intrusive thoughts. The relationship between survivors’ depressive symptoms and partners’ depressive symptoms was close but not significant. Conclusions As hypothesized, depressive symptoms were predicted by social constraints and intrusive thoughts. Further research is needed to understand the possible relationship between survivors’ long-term depressive symptoms and cognitive avoidance and partners’ depressive symptoms. Our findings highlight the negative impact of social constraints from partners on psychological outcomes in long-term breast cancer survivors

Long-Term Fear of Recurrence in Young Breast Cancer Survivors and Partners

Background Fear of a breast cancer recurrence is the most prevalent and disruptive source of distress for long-term survivors and their partners. However, few studies have focused on predictors of fear of recurrence. The aim of this study is to test the efficacy of the Social Cognitive Processing Theory (SCPT) in predicting fear of recurrence in long-term breast cancer survivors diagnosed at age 45 years or younger and their partners. Methods In a large cross-sectional study, breast cancer survivors (n = 222) 3–8 years from diagnosis and their partners completed a survey assessing demographic characteristics, fear of recurrence, social constraints, and cognitive processing (intrusive thoughts and cognitive avoidance). Mediation analyses were conducted for survivors and partners separately to determine if cognitive processing would mediate the relationship between social constraints and fear of recurrence. Results Cognitive processing mediated the relationship between social constraints and fear of recurrence both for survivors [F(3,213) = 47.541, R2 = 0.401, p < 0.001] and partners [F(3,215) = 27.917, R2 = 0.280, p < 0.001). Demographic variables were not significant predictors of fear of recurrence. Conclusions As predicted, cognitive processing mediated the relationship between social constraints and fear of recurrence. Results expand the utility of the SCPT in long-term survivors and their partners by supporting its use in intervention design.Acknowledgement: This research was supported by an American Cancer Society grant: RSGPB-04-089-01-PBP. This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service Grants CA189828, CA180795 and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute. Research reported in this publication was supported by the National Institute of Nursing Research of the National Institutes of Health under Award Number F31NR013822. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K05CA175048. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health

The emerging field of venom-microbiomics for exploring venom as a microenvironment, and the corresponding Initiative for Venom Associated Microbes and Parasites (iVAMP)

Venom is a known source of novel antimicrobial natural products. The substantial, increasing number of these discoveries have unintentionally culminated in the misconception that venom and venom-producing glands are largely sterile environments. Culture-dependent and -independent studies on the microbial communities in venom microenvironments reveal the presence of archaea, algae, bacteria, endoparasites, fungi, protozoa, and viruses. Venom-centric microbiome studies are relatively sparse to date and the adaptive advantages that venom-associated microbes might offer to their hosts, or that hosts might provide to venom-associated microbes, remain unknown. We highlight the potential for the discovery of venom-microbiomes within the adaptive landscape of venom systems. The considerable number of known, convergently evolved venomous animals juxtaposed with the comparatively few studies to identify microbial communities in venom provides new possibilities for both biodiversity and therapeutic discoveries. We present an evidence-based argument for integrating microbiology as part of venomics to which we refer to as venom-microbiomics. We also introduce iVAMP, the Initiative for Venom Associated Microbes and Parasites (https://ivamp-consortium.github.io/), as a growing consortium for interested parties to contribute and collaborate within this subdiscipline. Our consortium seeks to support diversity, inclusion and scientific collaboration among all researchers interested in this subdiscipline

Cardiorespiratory fitness and digestive cancer mortality: findings from the Aerobics Center Longitudinal Study (ACLS)

Although higher levels of physical activity are inversely associated with risk of colon cancer, few prospective studies have evaluated overall digestive system cancer mortality in relation to cardiorespiratory fitness (CRF). The authors examined this association among 38,801 men aged 20−88 years and who performed a maximal treadmill exercise test at baseline in the Aerobics Center Longitudinal Study (Dallas, Texas) during 1974−2003. Mortality was assessed over 29 years of follow-up (1974−2003). 283 digestive system cancer deaths occurred during a mean 17-year of observation. Age-adjusted mortality rates per 10,000 person-yrs according to low, moderate, and high CRF groups were 6.8, 4.0, and 3.3 for digestive system cancer (trend p \u3c 0.001). After adjustment for age, examination year, body mass index, smoking, drinking, family history of cancer, personal history of diabetes, hazard ratios for overall digestive cancer deaths (95% confidence interval) for those in the middle and upper 40% of the distribution of CRF relative to those in the lowest 20% were 0.66 (0.49, 0.88) and 0.56 (0.40, 0.80), respectively. Being fit (the upper 80% of CRF) was associated with a lower risk of mortality from colon (0.61 [0.37, 1.00]), colorectal (0.58 [0.37, 0.92]), and liver cancer (0.28 [0.11, 0.72]), compared with being unfit (the lowest 20% of CRF). These findings support a protective role of CRF against total digestive tract, colorectal, and liver cancer deaths in men

The Influence of Cardiorespiratory Fitness on Lung Cancer Mortality

Purpose—Previous studies have suggested that higher levels of physical activity may lower lung cancer risk; however, few prospective studies have evaluated lung cancer mortality in relation to cardiorespiratory fitness (CRF), an objective marker of recent physical activity habits. Methods—Thirty-eight thousand men, aged 20 to 84 years without history of cancer, received a preventive medical examination at the Cooper Clinic in Dallas, TX, between 1974 and 2002. CRF was quantified as maximal treadmill exercise test duration and was grouped for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%). Results—A total of 232 lung cancer deaths occurred during follow-up (mean=17 years). After adjustment for age, examination year, BMI, smoking, drinking, physical activity, and family history of cancer, hazard ratios (95% confidence intervals) for lung cancer deaths across low, moderate and high CRF categories were: 1.0, 0.48 (0.35–0.67), and 0.43 (0.28–0.65) respectively. There was an inverse association between CRF and lung cancer mortality in former (P for trend = 0.005) and current smokers (P for trend \u3c0.001), but not in never smokers (trend P = 0.14). Joint analysis of smoking and fitness status revealed a significant 12-fold higher risk of death in current smokers (HR: 11.9; 95% CI: 6.0–23.6) with low CRF as compared with never smokers who had high CRF. Conclusions—Although the potential for some residual confounding by smoking could not be eliminated, these data suggest that CRF is inversely associated with lung cancer mortality in men. Continued study of CRF in relation to lung cancer, particularly among smokers, may further our understanding of disease etiology and reveal additional strategies for reducing its burden

Kepler-21b: A 1.6REarth Planet Transiting the Bright Oscillating F Subgiant Star HD 179070

We present Kepler observations of the bright (V=8.3), oscillating star HD 179070. The observations show transit-like events which reveal that the star is orbited every 2.8 days by a small, 1.6 R_Earth object. Seismic studies of HD 179070 using short cadence Kepler observations show that HD 179070 has a frequencypower spectrum consistent with solar-like oscillations that are acoustic p-modes. Asteroseismic analysis provides robust values for the mass and radius of HD 179070, 1.34{\pm}0.06 M{\circ} and 1.86{\pm}0.04 R{\circ} respectively, as well as yielding an age of 2.84{\pm}0.34 Gyr for this F5 subgiant. Together with ground-based follow-up observations, analysis of the Kepler light curves and image data, and blend scenario models, we conservatively show at the >99.7% confidence level (3{\sigma}) that the transit event is caused by a 1.64{\pm}0.04 R_Earth exoplanet in a 2.785755{\pm}0.000032 day orbit. The exoplanet is only 0.04 AU away from the star and our spectroscopic observations provide an upper limit to its mass of ~10 M_Earth (2-{\sigma}). HD 179070 is the brightest exoplanet host star yet discovered by Kepler.Comment: Accepted to Ap