bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the Natural Product Rotihibin A as a TOR Kinase Signaling Inhibitor by Unbiased Transcriptional Profiling
Authors: Halder Vivek , Oeljeklaus Julian , Heilmann Geronimo , Krahn Jan H. , Liu Yanlin , Xiong Yan , Schlicht Markus , Schillinger Jasmin , Kracher Barbara , Ehrmann Michael , Kombrink Erich , Kaschani Farnusch , Kaiser Markus 
Published: June 2018

AbstractBioactive natural products are important starting points for developing chemical tools for biological research. For elucidating their bioactivity profile, biological systems with concise complexity such as cell culture systems are frequently used, whereas unbiased investigations in more complex multicellular systems are only rarely explored. Here, we demonstrate with the natural product Rotihibin A and the plant research model system Arabidopsis thaliana that unbiased transcriptional profiling enables a rapid, label‐free, and compound economic evaluation of a natural product′s bioactivity profile in a complex multicellular organism. To this end, we established a chemical synthesis of Rotihibin A as well as that of structural analogues, followed by transcriptional profiling‐guided identification and validation of Rotihibin A as a TOR signaling inhibitor (TOR=target of rapamycin). These findings illustrate that a combined approach of transcriptional profiling and natural product research may represent a technically simple approach to streamline the development of chemical tools from natural products even for biologically complex multicellular biological systems.
Evaluation of 2 breast cancer risk models in a benign breast disease cohort
Authors: Frank Ryan D. , Winham Stacey J. , Vierkant Robert A. , Frost Marlene H. , Radisky Derek C. , Ghosh Karthik , Brandt Kathleen R. , Sherman Mark E. , Visscher Daniel W. , Hartmann Lynn C. , Degnim Amy C. , Vachon Celine M. 
Published: June 2018

BackgroundMore than 1.5 million women per year have a benign breast biopsy resulting in concern about their future breast cancer (BC) risk. This study examined the performance of 2 BC risk models that integrate clinical and histologic findings in this population.MethodsThe BC risk at 5 and 10 years was estimated with the Breast Cancer Surveillance Consortium (BCSC) and Benign Breast Disease to Breast Cancer (BBD‐BC) models for women diagnosed with benign breast disease (BBD) at the Mayo Clinic from 1997 to 2001. Women with BBD were eligible for the BBD‐BC model, but the BCSC model also required a screening mammogram. Calibration and discrimination were assessed.ResultsFifty‐six cases of BC were diagnosed among the 2142 women with BBD (median age, 50 years) within 5 years (118 were diagnosed within 10 years). The BBD‐BC model had slightly better calibration at 5 years (0.89; 95% confidence interval [CI], 0.71‐1.21) versus 10 years (0.81; 95% CI, 0.70‐1.00) but similar discrimination in the 2 time periods: 0.68 (95% CI, 0.60‐0.75) and 0.66 (95% CI, 0.60‐0.71), respectively. In contrast, among the 1089 women with screening mammograms (98 cases of BC within 10 years), the BCSC model had better calibration (0.94; 95% CI, 0.85‐1.43) and discrimination (0.63; 95% CI, 0.56‐0.71) at 10 years versus 5 years (calibration, 1.31; 95% CI, 0.94‐2.25; discrimination, 0.59; 95% CI, 0.46‐0.71) where discrimination was not different from chance.ConclusionsThe BCSC and BBD‐BC models were validated in the Mayo BBD cohort, although their performance differed by 5‐year risk versus 10‐year risk. Further enhancement of these models is needed to provide accurate BC risk estimates for women with BBD.
A home‐based mentored vegetable gardening intervention demonstrates feasibility and improvements in physical activity and performance among breast cancer survivors
Authors: Bail Jennifer R. , Frugé Andrew D. , Cases Mallory G. , De Los Santos Jennifer F. , Locher Julie L. , Smith Kerry P. , Cantor Alan B. , Cohen Harvey J. , Demark‐Wahnefried Wendy 
Published: June 2018

BACKGROUNDThe current study assessed the feasibility of a mentored home‐based vegetable gardening intervention and examined changes in health‐related outcomes among breast cancer survivors (BCS).METHODSBCS were randomized to either a year‐long vegetable gardening intervention to begin immediately or a wait‐list control. Master Gardeners mentored participants in planning, planting, and maintaining 3 seasonal gardens over the course of 1 year. Participant accrual, retention, and satisfaction rates of ≥80% served as feasibility (primary outcome) benchmarks. Secondary outcomes (ie, vegetable consumption, physical activity, performance and function, anthropometrics, biomarkers, and health‐related quality of life) were collected at baseline and post‐intervention (1‐year follow‐up) using subjective and objective measures.RESULTSThe trial surpassed all feasibility benchmarks at 82% of targeted accrual, 95% retention, and 100% satisfaction (ie, experience ratings of “good to excellent” and willingness to “do it again”). Compared with the controls, intervention participants reported significantly greater improvements in moderate physical activity (+14 vs ‐17 minutes/week) and demonstrated improvements in the 2‐Minute Step Test (+22 vs + 10 steps), and Arm Curl (+2.7 vs + 0.1 repetitions) (P values < .05). A trend toward improved vegetable consumption was observed (+0.9 vs + 0.2 servings/day; P = .06). Approximately 86% of participants were continuing to garden at the 2‐year follow‐up.CONCLUSIONSThe results of the current study suggest that a mentored, home‐based vegetable gardening intervention is feasible and offers an integrative and durable approach with which to improve health behaviors and outcomes among BCS. Harvest for Health led to the establishment of a group of trained Master Gardeners and gave rise to local and global community‐based programs. Larger studies are needed to confirm the results presented herein and to define applicability across broader populations of survivors.
Racial and Ethnic Disparities in Travel for Head and Neck Cancer Treatment and the Impact of Travel Distance on Survival
Authors: Graboyes Evan M. , Ellis Mark A. , Li Hong , Kaczmar John M. , Sharma Anand K. , Lentsch Eric J. , Day Terry A. , Hughes Halbert Chanita 
Published: June 2018

BACKGROUNDPatients who travel a long distance (≥50 miles) for cancer care have improved outcomes. However, to the authors' knowledge, the prevalence of long travel distances for treatment by patients with head and neck squamous cell carcinoma (HNSCC), and the effect of travel distance on overall survival (OS), remains unknown.METHODSThe authors used the National Cancer Data base from 2004 through 2013 to identify patients with HNSCC undergoing definitive treatment. Travel distance for treatment was categorized as short (<12.5 miles), intermediate (12.5‐49.9 miles), and long (50‐249.9 miles). The primary outcome, OS, was evaluated using Cox shared‐frailty modeling. A secondary outcome, factors associated with intermediate and long travel distances, was evaluated using multivariable hierarchical logistic regression.RESULTSAmong 118,000 patients with HNSCC, 62,753 (53.2%), 40,644 (34.4%), and 14,603 (12.4%) patients, respectively, traveled short, intermediate, and long distances for treatment. After adjusting for relevant covariates, long travel distance was associated with treatment at academic and high‐volume centers. Patients of black race, of Hispanic ethnicity, with Medicaid insurance, and who were treated with nonsurgical treatment were less likely to travel long distances for treatment (P<.001). Traveling a long distance for treatment was associated with improved OS on multivariable analysis (adjusted hazard ratio, 0.93; 95% confidence interval, 0.89‐0.96) compared with a short distance.CONCLUSIONSTraveling a long distance for HNSCC treatment is associated with improved survival, especially for patients receiving nonsurgical management. Racial and ethnic disparities in travel for HNSCC treatment exist. As regionalization of care continues, future work should identify and address reasons for racial and ethnic disparities in travel that may prevent access to care at high‐volume facilities. Cancer 2018;000:000‐000. © 2018 American Cancer Society.
Asymmetric vasopressin signaling spatially organizes the master circadian clock
Authors: Bedont Joseph L. , Rohr Kayla E. , Bathini Abhijith , Hattar Samer , Blackshaw Seth , Sehgal Amita , Evans Jennifer A. 
Published: June 2018

AbstractThe suprachiasmatic nucleus (SCN) is the neural network that drives daily rhythms in behavior and physiology. The SCN encodes environmental changes through the phasing of cellular rhythms across its anteroposterior axis, but it remains unknown what signaling mechanisms regulate clock function along this axis. Here we demonstrate that arginine vasopressin (AVP) signaling organizes the SCN into distinct anteroposterior domains. Spatial mapping of SCN gene expression using in situ hybridization delineated anterior and posterior domains for AVP signaling components, including complementary patterns of V1a and V1b expression that suggest different roles for these two AVP receptors. Similarly, anteroposterior patterning of transcripts involved in Vasoactive Intestinal Polypeptide‐ and Prokineticin2 signaling was evident across the SCN. Using bioluminescence imaging, we then revealed that inhibiting V1A and V1B signaling alters period and phase differentially along the anteroposterior SCN. V1 antagonism lengthened period the most in the anterior SCN, whereas changes in phase were largest in the posterior SCN. Further, separately antagonizing V1A and V1B signaling modulated SCN function in a manner that mapped onto anteroposterior expression patterns. Lastly, V1 antagonism influenced SCN period and phase along the dorsoventral axis, complementing effects on the anteroposterior axis. Together, these results indicate that AVP signaling modulates SCN period and phase in a spatially specific manner, which is expected to influence how the master clock interacts with downstream tissues and responds to environmental changes. More generally, we reveal anteroposterior asymmetry in neuropeptide signaling as a recurrent organizational motif that likely influences neural computations in the SCN clock network.
Branched‐Chain Polyamine Found in Hyperthermophiles Induces Unique Temperature‐Dependent Structural Changes in Genome‐Size DNA
Authors: Nishio Takashi , Yoshikawa Yuko , Fukuda Wakao , Umezawa Naoki , Higuchi Tsunehiko , Fujiwara Shinsuke , Imanaka Tadayuki , Yoshikawa Kenichi 
Published: June 2018

AbstractA pentavalent branched‐chain polyamine, N4‐bis(aminopropyl)spermidine 3(3)(3)4, is a unique polycation found in the hyperthermophilic archaeon Thermococcus kodakarensis, which grows at temperatures between 60 and 100 °C. We studied the effects of this branched‐chain polyamine on DNA structure at different temperatures up to 80 °C. Atomic force microscopic observation revealed that 3(3)(3)4 induces a mesh‐like structure on a large DNA (166 kbp) at 24 °C. With an increase in temperature, DNA molecules tend to unwind, and multiple nano‐loops with a diameter of 10–50 nm are generated along the DNA strand at 80 °C. These results were compared to those obtained with linear‐chain polyamines, homocaldopentamine 3334 and spermidine, the former of which is a structural isomer of 3(3)(3)4. These specific effects are expected to neatly concern with its role on high‐temperature preference in hyperthermophiles.
Untargeted metabolic profiling reveals geography as the strongest predictor of metabolic phenotypes of a cosmopolitan weed
Authors: Iwanycki Ahlstrand Natalie , Havskov Reghev Nicoline , Markussen Bo , Bruun Hansen Hans Christian , Eiriksson Finnur F. , Thorsteinsdóttir Margrét , Rønsted Nina , Barnes Christopher J. 
Published: June 2018

AbstractPlants produce a multitude of metabolites that contribute to their fitness and survival and play a role in local adaptation to environmental conditions. The effects of environmental variation are particularly well studied within the genus Plantago; however, previous studies have largely focused on targeting specific metabolites. Studies exploring metabolome‐wide changes are lacking, and the effects of natural environmental variation and herbivory on the metabolomes of plants growing in situ remain unknown. An untargeted metabolomic approach using ultra‐high‐performance liquid chromatography–mass spectrometry, coupled with variation partitioning, general linear mixed modeling, and network analysis was used to detect differences in metabolic phenotypes of Plantago major in fifteen natural populations across Denmark. Geographic region, distance, habitat type, phenological stage, soil parameters, light levels, and leaf area were investigated for their relative contributions to explaining differences in foliar metabolomes. Herbivory effects were further investigated by comparing metabolomes from damaged and undamaged leaves from each plant. Geographic region explained the greatest number of significant metabolic differences. Soil pH had the second largest effect, followed by habitat and leaf area, while phenological stage had no effect. No evidence of the induction of metabolic features was found between leaves damaged by herbivores compared to undamaged leaves on the same plant. Differences in metabolic phenotypes explained by geographic factors are attributed to genotypic variation and/or unmeasured environmental factors that differ at the regional level in Denmark. A small number of specialized features in the metabolome may be involved in facilitating the success of a widespread species such as Plantago major into such wide range of environmental conditions, although overall resilience in the metabolome was found in response to environmental parameters tested. Untargeted metabolomic approaches have great potential to improve our understanding of how specialized plant metabolites respond to environmental change and assist in adaptation to local conditions.
Fluctuating thermal environments and time‐dependent effects on fruit fly egg‐hatching performance
Authors: Cavieres Grisel , Bogdanovich José M. , Toledo Paloma , Bozinovic Francisco 
Published: June 2018

AbstractOrganismal performance in a changing environment is dependent on temporal patterns and duration of exposure to thermal variability. We experimentally assessed the time‐dependent effects of thermal variability (i.e., patterns of thermal exposure) on the hatching performance of Drosophila melanogaster. Flies were collected in central Chile and maintained for four generations in laboratory conditions. Fourth generation eggs were acclimated to different thermal fluctuation cycles until hatching occurred. Our results show that the frequency of extreme thermal events has a significant effect on hatching success. Eggs exposed to 24 hr cycles of thermal fluctuation had a higher proportion of eggs that hatched than those acclimated to shorter (6 and 12 hr) and longer cycles (48 hr). Furthermore, eggs subjected to frequent thermal fluctuations hatched earlier than those acclimated to less frequent thermal fluctuations. Overall, we show that, egg‐to‐adult viability is dependent on the pattern of thermal fluctuations experienced during ontogeny; thus, the pattern of thermal fluctuation experienced by flies has a significant and until now unappreciated impact on fitness.
Ecosystem engineering by foxes is mediated by the landscape context—A case study from steppic burial mounds
Authors: Godó Laura , Tóthmérész Béla , Valkó Orsolya , Tóth Katalin , Kiss Réka , Radócz Szilvia , Kelemen András , Török Péter , Švamberková Eva , Deák Balázs 
Published: June 2018

AbstractIn intensively used landscapes, remnant grassland fragments are often restricted to places unsuitable for agricultural cultivation. Such refuges are the ancient burial mounds called “kurgans,” which are typical landscape elements of the Eurasian steppe and forest steppe zone. Due to their hill‐like shape, loose soil structure and undisturbed status kurgans provide proper habitats for burrowing mammals. Accordingly, grassland vegetation on kurgans is often exposed to bioturbation, which can influence the habitat structure and plant species pool. In our study, we explored the effect of fox burrows and landscape context on the habitat properties and vegetation composition of small landscape elements, using kurgans as model habitats. We surveyed the vegetation of fox burrows and that of the surrounding grassland on five kurgans situated in cleared landscapes surrounded by arable lands and five kurgans in complex landscapes surrounded by grazed grasslands. We recorded the percentage cover of vascular plants, the amount of litter, and soil moisture content in twelve 0.5 m × 0.5 m plots per kurgan, in a total of 120 plots. We found that foxes considerably transformed habitat conditions and created microhabitats by changing the soil nutrient availability and reducing total vegetation cover and litter. Several grassland specialist species, mostly grasses (Agropyron cristatum, Elymus hispidus, and Stipa capillata) established in the newly created microhabitats, although the cover of noxious species was also considerable. We found that landscape context influenced the sort of species which could establish on kurgans by affecting the available species pool and soil moisture. Our results revealed that foxes act as ecosystem engineers on kurgans by transforming abiotic and biotic conditions by burrowing. Their engineering activity maintains disturbance‐dependent components of dry grasslands and increases local environmental heterogeneity.
Nuptial gift chemistry reveals convergent evolution correlated with antagonism in mating systems of harvestmen (Arachnida, Opiliones)
Authors: Kahn Penelope C. , Cao Dennis D. , Burns Mercedes , Boyer Sarah L. 
Published: June 2018

AbstractNuptial gifts are material donations given from male to female before or during copulation and are subject to sexual selection in a wide variety of taxa. The harvestman genus Leiobunum has emerged as a model system for understanding the evolution of reproductive morphology and behavior, as transitions between solicitous and antagonistic modes of courtship have occurred multiple times within the lineage and are correlated with convergence in genital morphology. We analyzed the free amino acid content of nuptial gift secretions from five species of Leiobunum using gas chromatography–mass spectrometry. Multivariate analysis of the free amino acid profiles revealed that, rather than clustering based on phylogenetic relationships, nuptial gift chemical composition was better predicted by genital morphology and behavior, suggesting that convergent evolution has acted on the chemical composition of the nuptial gift. In addition, we found that, species with solicitous courtship produce gifts consisting of a 19% larger proportion of essential amino acids as compared to those with more antagonistic courtship interactions. This work represents the first comparative study of nuptial gift chemistry within a phylogenetic framework in any animal group and as such contributes to our understanding of the evolution of reproductive diversity and the participant role of nuptial gift chemistry in mating system transitions.
Acute heart failure management in the USA and Japan: overview of practice patterns and review of evidence
Authors: Tanaka Toshikazu D. , Sawano Mitsuaki , Ramani Ravi , Friedman Mark , Kohsaka Shun 
Published: June 2018

AbstractGlobally, acute heart failure (AHF) remains an ongoing public health issue with its prevalence and mortality increasing in the east and the west. Effective treatment strategies to stabilize AHF are important to alleviate clinical symptoms and to improve clinical outcomes. However, despite the progress in the management of stable and chronic heart failure, no single agent has been proven to play a definitive role in the management of AHF. As a consequence, contemporary treatment strategies for patients with AHF vary greatly by region. This manuscript reviews the medical treatment options for AHF, with an emphasis on the differences between the treatment strategies in the USA and Japan. This information would provide a framework for clinicians to evaluate and manage patients with AHF and highlight the remaining questions to improve clinical outcomes.
A clinically applicable adjuvant for an atherosclerosis vaccine in mice
Authors: Kobiyama Kouji , Vassallo Melanie , Mitzi Jessica , Winkels Holger , Pei Hong , Kimura Takayuki , Miller Jacqueline , Wolf Dennis , Ley Klaus 
Published: June 2018

AbstractVaccination with MHC‐II‐restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen‐specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe‐deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene‐based oil‐in‐water adjuvant similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL‐10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene‐based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine.
Selecting microhaplotypes optimized for different purposes
Authors: Kidd Kenneth K. , Pakstis Andrew J. , Speed William C. , Lagace Robert , Wootton Sharon , Chang Joseph 
Published: June 2018

AbstractMassively parallel sequencing is transforming forensic work by allowing various useful forensic markers, such as STRPs and SNPs, to be multiplexed providing information on ancestry, individual and familial identification, phenotypes for eye/hair/skin pigmentation, and the deconvolution of mixtures. Microhaplotypes also become feasible with massively parallel sequencing, these are DNA segments (smaller than 300 nucleotides) that are selected to contain multiple SNPs unambiguously defining three or more haplotype alleles occurring at common frequencies. The physical extent of a microhaplotype can thus be covered by a single sequence read making these loci phase‐known codominant genetic systems. Such microhaplotypes supply significantly more information than a single SNP can. Our efforts to develop useful sets of microhaplotypes have already identified 182 such loci that we have studied on a large number of human populations from around the world. We present various analyses on 83 populations in our ongoing study for a subset of the best microhaplotypes currently available illustrating their characteristics and potential utility for ancestry, identification, and mixture deconvolution.