bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Weight Gain and Weight Loss on In Vivo Colonocyte Proliferation Rate in People with Obesity
Authors: Magkos Faidon , Sullivan Shelby , Fitch Mark , Smith Gordon , Fabbrini Elisa , Mittendorfer Bettina , Hellerstein Marc , Klein Samuel
Published: October 2017

Objective

To evaluate the effects of diet‐induced changes in energy balance and body weight on in vivo colonocyte fractional proliferation rates (FPR) in people with obesity.

Methods

In vivo colonocyte FPR was assessed in 31 men and women with obesity (BMI: 35.4 ± 4.0 kg/m2, age: 52.6 ± 8.9 years) before and after diet‐induced weight loss, weight gain, or weight maintenance. Subjects ingested aliquots of 2H2O (heavy water) daily for 4 to 7 days, followed by flexible sigmoidoscopy with colon biopsies to assess the incorporation of 2H into the DNA of dividing colonocytes.

Results

Colonocyte FPR averaged 12.7% ± 3.8% per day and correlated directly with intra‐abdominal adipose tissue (IAAT) volume (r = 0.364, P = 0.044). Colonocyte FPR decreased in the weight loss group, did not change in the weight maintenance group, and increased in the weight gain group. The change in colonocyte FPR correlated directly with the percent change in body weight (r = 0.409, P = 0.028) and IAAT volume (r = 0.598, P = 0.001).

Conclusions

A high‐calorie diet and weight gain increase, whereas a low‐calorie diet and weight loss decrease, in vivo colonocyte proliferation rate in people with obesity. These results suggest that changes in energy balance influence the risk of developing colon cancer in people with obesity by regulating colonic mucosal growth rates.
Association Between Weight Loss and the Risk of Cancer after Bariatric Surgery
Authors: Schauer Daniel P. , Feigelson Heather Spencer , Koebnick Corinna , Caan Bette , Weinmann Sheila , Leonard Anthony C. , Powers J. David , Yenumula Panduranga R. , Arterburn David E.
Published: October 2017

Objective

The goal of this study was to determine whether the reduction in cancer risk after bariatric surgery is due to weight loss.

Methods

A retrospective matched cohort study of patients undergoing bariatric surgery was conducted using data from a large integrated health insurance and care delivery system with five sites in four states. The study included 18,355 bariatric surgery subjects and 40,524 nonsurgical subjects matched on age, sex, BMI, site, and Elixhauser comorbidity index. Multivariable Cox proportional hazards models examined the relationship between weight loss at 1 year and incident cancer during up to 10 years of follow‐up.

Results

The study identified 1,196 cases of incident cancer. The average 1‐year postsurgical weight loss was 27% among patients undergoing bariatric surgery versus 1% in matched nonsurgical patients. Percent weight loss at 1 year was significantly associated with a reduced risk of any cancer in adjusted models (HR 0.897, 95% CI: 0.832‐0.968, P = 0.005 for every 10% weight loss) while bariatric surgery was not a significant independent predictor of cancer incidence.

Conclusions

Weight loss after bariatric surgery was associated with a lower risk of incident cancer. There was no apparent independent effect of the bariatric surgery itself on cancer risk that was independent of weight loss.
Inflammation Modifies the Association of Obesity with Circulating 25‐Hydroxyvitamin D Levels in Cancer Survivors
Authors: Yang Lin , Toriola Adetunji T.
Published: October 2017

Objective

Obesity, inflammation, and circulating 25‐hydroxyvitamin D (25‐OHD) have distinct roles in cancer prognosis. The interplay of these factors was investigated by evaluating the associations of body mass index (BMI) with circulating 25‐OHD levels in cancer survivors and determining whether associations were modified by inflammation, defined by C‐reactive protein (CRP) levels.

Methods

Data on cancer survivors were aggregated from the US National Health and Nutrition Examination Survey (2001–2010). Multivariable linear regression models were used to evaluate the associations of BMI with circulating 25‐OHD. Analyses were stratified by CRP levels: low < 1.0 mg/L, moderate 1.0‐3.0 mg/L, and high > 3.0‐9.9 mg/L.

Results

Among 1,305 cancer survivors (mean age = 60.8 years, mean BMI = 28.0 kg/m2), circulating 25‐OHD levels were 8.74 nmol/L lower (95% CI: 4.71 to 12.77) in cancer survivors with BMI ≥ 30.0 kg/m2 compared with those with BMI < 25.0 kg/m2. This association was, however, limited to those with moderate CRP (−9.90 nmol/L, 95% CI: −16.45 to −3.36) and high CRP (−11.61 nmol/L, 95% CI: −18.71 to −5.05), but not among those with low CRP levels (−5.31 nmol/L, 95% CI:−12.66 to 2.04).

Conclusions

A greater understanding of the interplay between 25‐OHD and inflammation in cancer survivors with obesity should allow for targeted secondary prevention and help improve prognosis in these patients.
Simulating the Impact of Crime on African American Women's Physical Activity and Obesity
Authors: Powell‐Wiley Tiffany M. , Wong Michelle S. , Adu‐Brimpong Joel , Brown Shawn T. , Hertenstein Daniel L. , Zenkov Eli , Ferguson Marie C. , Thomas Samantha , Sampson Dana , Ahuja Chaarushi , Rivers Joshua , Lee Bruce Y.
Published: October 2017

Objective

The objective of this study was to quantify the impact of crime on physical activity location accessibility, leisure‐time physical activity (LTPA), and obesity among African American women.

Methods

An agent‐based model was developed in 2016 to represent resource‐limited Washington, DC, communities and their populations to simulate the impact of crime on LTPA and obesity among African American women under different circumstances.

Results

Data analysis conducted between 2016 and 2017 found that in the baseline scenario, African American women had a 25% probability of exercising. Reducing crime so more physical activity locations were accessible (increasing from 10% to 50%) decreased the annual rise in obesity prevalence by 2.69%. Increasing the probability of African American women to exercise to 37.5% further increased the impact of reducing crime on obesity (2.91% annual decrease in obesity prevalence).

Conclusions

These simulations showed that crime may serve as a barrier to LTPA. Reducing crime and increasing propensity to exercise through multilevel interventions (i.e., economic development initiatives to increase time available for physical activity and subsidized health care) may promote greater than linear declines in obesity prevalence. Crime prevention strategies alone can help prevent obesity, but combining such efforts with other ways to encourage physical activity can yield even greater benefits.
Negotiation of subjectivities and intersubjectivities in the classroom
Authors: Morgade Marta , Mendoza Karmele
Published: October 2017

The purpose of this paper is to describe and analyze the presence of intersubjective asymmetries as an ethical, epistemological, and social challenge in a school. We explore various aspects of interaction between teacher, students, and researcher in school during a music room. A workshop of audiovisual narratives that has been made with teenagers in a Spain school with the aim that young people themselves documented their own musical practices through tools and narratives that are common outside of school (audio, photography, video, etc.). We based our work on the principles of participatory research, participants showed those meanings that they had music in their life, all aimed to all the work that serve to modify practices and musical activities at school that were taking place. Some of the obstacles found in workshop are described as barriers that relate to the processes of delegitimization of musical culture of youth reported previously and their knowledge in the school. This project began founding the presence of those intersubjective asymmetries as a challenge to constituting a community of practice and learning, where a pedagogical transformation was waited, new forms of teachers and students participation.
Increasing equitable care for youth through coordinated school health
Authors: Sanetti Lisa M. Hagermoser
Published: October 2017

Nearly a quarter of the students in the U.S. education system have a chronic health condition, disability, or special healthcare need. Students living in poverty and those at risk for or with disabilities have higher rates of health issues and encounter more barriers to accessing appropriate health care than their peers. The reciprocal influences between health and education as critical social determinants for youth are well established and prompted the development of a comprehensive model of school‐based coordinated health, the Whole School, Whole Community, Whole Child (WSCC) model. A brief overview of (a) education‐related health issues experienced by students living in poverty and those at risk for or with disabilities, (b) access to health care, (c) the need for coordinated care, and (d) the WSCC model are provided. The WSCC model represents an unprecedented opportunity to increase equitable care for youth through coordinated school health.
Cross‐species complementation reveals conserved functions for EARLY FLOWERING 3 between monocots and dicots
Authors: Huang He , Gehan Malia A. , Huss Sarah E. , Alvarez Sophie , Lizarraga Cesar , Gruebbling Ellen L. , Gierer John , Naldrett Michael J. , Bindbeutel Rebecca K. , Evans Bradley S. , Mockler Todd C. , Nusinow Dmitri A.
Published: October 2017

Plant responses to the environment are shaped by external stimuli and internal signaling pathways. In both the model plant Arabidopsis thaliana (Arabidopsis) and crop species, circadian clock factors are critical for growth, flowering, and circadian rhythms. Outside of Arabidopsis, however, little is known about the molecular function of clock gene products. Therefore, we sought to compare the function of Brachypodium distachyon (Brachypodium) and Setaria viridis (Setaria) orthologs of EARLY FLOWERING 3, a key clock gene in Arabidopsis. To identify both cycling genes and putative ELF3 functional orthologs in Setaria, a circadian RNA‐seq dataset and online query tool (Diel Explorer) were generated to explore expression profiles of Setaria genes under circadian conditions. The function of ELF3 orthologs from Arabidopsis, Brachypodium, and Setaria was tested for complementation of an elf3 mutation in Arabidopsis. We find that both monocot orthologs were capable of rescuing hypocotyl elongation, flowering time, and arrhythmic clock phenotypes. Using affinity purification and mass spectrometry, our data indicate that BdELF3 and SvELF3 could be integrated into similar complexes in vivo as AtELF3. Thus, we find that, despite 180 million years of separation, BdELF3 and SvELF3 can functionally complement loss of ELF3 at the molecular and physiological level.
Nitrogen Deficiency Induced Alterations in the Root Proteome of a Pair of Potato (Solanum tuberosum L.) Varieties Contrasting for their Response to Low N
Authors: Jozefowicz Anna Maria , Hartmann Anja , Matros Andrea , Schum Annegret , Mock Hans‐Peter
Published: October 2017

Improving crop nitrogen use efficiency is important both from the economic and the environmental viewpoint. Here, the aim is to highlight differences between the proteomic response of the roots of two potato cultivars contrasting in their response to nitrogen (N) deficiency, in an effort to understand which proteins and metabolic pathways contribute to the tolerance of N deprivation. The two cultivars ‘‘Topas’’ (tolerant) and ‘‘Lambada’’ (sensitive) are grown under both an N sufficient and an N deficient regime, using an in vitro‐based cultivation system. Responsive proteins are identified and quantified using label‐free quantitative shotgun proteomics. The contrasting cultivars differed with respect to components of the glutamine synthetase/glutamine oxoglutarate aminotransferase pathway, tricarboxylic acid cycle, the glycolysis/gluconeogenesis pathway as well as protein and amino acid synthesis machinery. Additional differences are associated with protein catabolism and defense mechanisms.
Temperature‐dependent changes in the hydrogen bonded hard segment network and microphase morphology in a model polyurethane: Experimental and simulation studies
Authors: Yildirim Erol , Yurtsever Mine , Yilgör Emel , Yilgör Iskender , Wilkes Garth L.
Published: October 2017

Hydrogen bonding between hard segments has a critical effect on the morphology and properties of polyurethanes. Influence of temperature on hydrogen bonded urethane network and melting behavior of a model semicrystalline segmented polyurethane was investigated by experiments and simulations. Polyurethane was synthesized by the stoichiometric reaction between p‐phenylene diisocyanate and poly(tetramethylene oxide) (PTMO) with a molecular weight of 1000 g/mol. Simulations were carried out using dissipative particle dynamics (DPD) and molecular dynamics (MD) approaches. Experimental melting behavior obtained by various techniques was compared with simulations. DPD simulations showed a room temperature microphase morphology consisting of a three‐dimensional hydrogen‐bonded urethane hard segment network in a continuous and amorphous PTMO matrix. The first‐order melting transitions of crystalline urethane hard segments observed during the continuous isobaric heating in DPD and MD simulations (340–360 K) were in reasonably good agreement with those observed experimentally, such as AFM (320–340 K), WAXS (330–360 K), and FTIR (320–350 K) measurements. Quantitative verification of the melting of urethane hard segments was demonstrated by sharp discontinuities in energy versus temperature plots obtained by MD simulations due to substantial decrease in the number of hydrogen bonds above 340 K. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018, 56, 182–192
Grass cell walls have a role in the inherent tolerance of grasses to the cellulose biosynthesis inhibitor isoxaben
Authors: Brabham Chad , Stork Jozsef , Barrett Michael , DeBolt Seth
Published: October 2017

BACKGROUND

Cellulose biosynthesis inhibitors (CBIs) are pre‐emergence herbicides that inhibit anisotropic cell expansion resulting in a severely swollen and stunted growth phenotype. Resistance to group 21 CBIs, such as isoxaben, is conferred by missense mutations in CELLOSE SYNTHASE A (CesA) genes required for primary cell wall synthesis, concluding that this is their in vivo target.

RESULTS

Herein, we show that grasses exhibit tolerance to group 21 CBIs and explore the mechanism of tolerance to isoxaben in the grass Brachypodium distachyon (L.). Comparative genomics failed to identify synonymous point mutations that have been found to confer isoxaben resistance in the dicot Arabidopsis thaliana (L.). Brachypodium did not metabolize 14C‐isoxaben. We next explored the role of grass‐specific non‐cellulosic cell wall components, specifically the hemicellulose polysaccharide mix linkage glucans (MLG), as a potential tolerance mechanism by compensating for the loss of cellulose during cell elongation. A partial‐transcriptional knockdown T‐DNA insertion was found in a key MLG synthesis gene, Cellulose synthase‐like F6 (CslF6) and this mutant was found to be 2.1 times more sensitive to isoxaben than wild‐type plants.

CONCLUSION

These data suggest that the composition and compensatory response of grass cell walls may be a factor in conferring tolerance to group 21 CBIs. © 2017 Society of Chemical Industry
Slippage estimation and compensation for planetary exploration rovers. State of the art and future challenges
Authors: Gonzalez Ramon , Iagnemma Karl
Published: October 2017

Future lunar/planetary exploration missions will demand mobile robots with the capability of reaching more challenging science targets and driving farther per day than the current Mars rovers. Among other improvements, reliable slippage estimation and compensation strategies will play a key role in enabling a safer and more efficient navigation. This paper reviews and discusses this body of research in the context of planetary exploration rovers. Previously published state‐of‐the‐art methods that have been validated through field testing are included as exemplary results. Limitations of the current techniques and recommendations for future developments and planetary missions close the survey.
Dibutyltin depressed immune functions via NF‐κB, and JAK/STAT signaling pathways in zebrafish (Danio rerio)
Authors: Zhang Chun‐Nuan , Zhang Ji‐Liang , Huang Yong , Ren Hong‐Tao , Guan Su‐Hua , Zeng Qing‐Hui
Published: October 2017

Dibutyltin (DBT) is the degradation products of TBT, which is generally considered higher toxicity than TBT in the immune system. In order to learn more about the mechanisms of immune‐toxic of DBT, we exposed zebrafish (Danio rerio) to 0, 1, 10 and 100 ng/L DBT for 8 weeks. At the end of the experiment, we determined the immune parameters and immune‐related genes. The results showed that with an increase in TBT dose, lysozyme activities and IgM, C3, C4 content in intestine, skin and spleen were all significantly inhibited by the DBT exposure. Fish exposed to 10 ng/L and 100 ng/L showed significantly lower lysozyme activities and IgM, C3, C4 content than those of the control group. Zebrafish exposed to 10 ng/L and 100 ng/L DBT, the mRNA transcript levels of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), tumor necrosis factor‐α (TNF‐α), interferon γ2 (INFγ2), nuclear factor‐κB p65 (NF‐kB p65), inhibitor protein‐κBα (IκBα), IκB kinases β (IKKβ), Janus family of protein tyrosine kinases (JAKs) and the signal transducers and activators of transcription proteins (STATs) all increased with the DBT levels in the intestine and spleen. Those parameters showed significantly higher values in 10 ng/L and 100 ng/L than those of fish in the control group. However, no significant difference was found in IκB kinases α (IKKα) and IκB kinase γ (IKKγ) mRNA levels in the intestine and spleen. These data imply that DBT might be via suppression on IKKβ/IkBa/NF‐kBp65 and JAK/STAT signaling pathways to regulate the immunity of zebrafish.
Experimental Study on the Activities of Al and Ca in Ferrosilicon
Authors: Tomé-Torquemada Silvia , Glaser Björn , Hildal Kjetil , Sichen Du
Published: October 2017

Experiments were carried out to determine the activities of Al and Ca in liquid ferrosilicon (with about 50 wt pct Si) at 1823 K (1550 °C) in their dilution ranges. Liquid FeSi50 and SiO2-Al2O3-CaO slag were stirred mechanically in a graphite crucible to enhance the transfer of Al and Ca between the two phases. The stirring time for the two phases to reach equilibrium was studied. It was found that a time of 45 minutes was long enough to reach the slag–metal equilibrium. The activities of Al and Ca in the ferrosilicon alloy were calculated based on the compositions of the two liquid phases. The activity coefficients obtained for Al and Ca in the liquid FeSi50 at 1823 K (1550 °C) were found to be nearly constant in the composition range studied.
Conserved brain myelination networks are altered in Alzheimer's and other neurodegenerative diseases
Authors: Allen Mariet , Wang Xue , Burgess Jeremy D. , Watzlawik Jens , Serie Daniel J. , Younkin Curtis S. , Nguyen Thuy , Malphrus Kimberly G. , Lincoln Sarah , Carrasquillo Minerva M. , Ho Charlotte , Chakrabarty Paramita , Strickland Samantha , Murray Melissa E. , Swarup Vivek , Geschwind Daniel H. , Seyfried Nicholas T. , Dammer Eric B. , Lah James J. , Levey Allan I. , Golde Todd E. , Funk Cory , Li Hongdong , Price Nathan D. , Petersen Ronald C. , Graff‐Radford Neill R. , Younkin Steven G. , Dickson Dennis W. , Crook Julia R. , Asmann Yan W. , Ertekin‐Taner Nilüfer
Published: October 2017

Introduction

Comparative transcriptome analyses in Alzheimer's disease (AD) and other neurodegenerative proteinopathies can uncover both shared and distinct disease pathways.

Methods

We analyzed 940 brain transcriptomes including patients with AD, progressive supranuclear palsy (PSP; a primary tauopathy), and control subjects.

Results

We identified transcriptional coexpression networks implicated in myelination, which were lower in PSP temporal cortex (TCX) compared with AD. Some of these associations were retained even after adjustments for brain cell population changes. These TCX myelination network structures were preserved in cerebellum but they were not differentially expressed in cerebellum between AD and PSP. Myelination networks were downregulated in both AD and PSP, when compared with control TCX samples.

Discussion

Downregulation of myelination networks may underlie both PSP and AD pathophysiology, but may be more pronounced in PSP. These data also highlight conservation of transcriptional networks across brain regions and the influence of cell type changes on these networks.
A novel volumetric criterion for optimal shape matching of surfaces for protein-protein docking
Authors: Voruganti Hari K. , Dasgupta Bhaskar
Published: October 2017

The problem of molecular docking is to predict whether two given molecules bind together to interact. A shape-based algorithm is proposed for predictive docking by noting that shape complementarity between their outer surfaces is necessary for two molecules to bind. A methodology with five stages has been developed to find the pose in which the shape complementarity is maximum. It involves surface generation, segmentation, parameterization, shape matching, and filtering and scoring. The most significant contribution of this paper is the novel scoring function called ‘Normalized Volume Mismatch’ which evaluates the matching between a pair of surface patches efficiently by measuring the gap or solid volume entrapped between two patches of a pair of proteins when they are placed one against the other at a contact point. After the evaluation, it is found that, with local shape complementarity as the only criterion, the algorithm is able to predict a conformation close to the exact one, in case of known docking conformations, and also rank the same among the top 40 solutions. This is remarkable considering the fact that many existing docking methods fail to rank a near-native conformation among top 50 solutions. The shape-based approaches are used for the initial stage of docking to identify a small set of candidate solutions to be investigated further with exhaustive energy studies etc. The ability of capturing the correct conformation as highly ranked among top few candidate solutions is the most valuable facet of this new predictive docking algorithm.

Highlights A new rigid-body docking algorithm is proposed for protein–protein docking. An approach using techniques of cad/cam for a problem in biology is presented. Unlike many existing ones, a volume based scoring criterion is proposed. The new criteria can capture even multiple possible docking conformation. Entire automatic docking procedures is based on shape complementarity only.
Radiocarbon Measurements of Paper: A Forensic Case Study to Determine the Absolute Age of Paper in Documents and Works of Art
Authors: Huels C Matthias , Pensold Sabine , Pigorsch Enrico
Published: October 2017

In a case study to assess the possibilities and limitations of determining the exact age of paper, we measured radiocarbon (14C) concentrations in bulk-paper cellulose and starch extracts from 20 known-age paper samples of the last 65 yr. As expected, 14C concentrations in single-seasonal grown starch extracts are in reasonably good agreement with post-bomb atmospheric 14C. In contrast, 14C concentrations in bulk-paper cellulose indicate apparent admixtures of tree-ring fibers spanning up to >50 yr. In a forensic investigation, combining 14C results from single-seasonal components like starch with those from long-lived fibers, could potentially enhance the precision of paper production-date estimates for samples made after 1955.
Long-Term versus Short-Term Contingencies in Asset Allocation
Authors: Botshekan Mahmoud , Lucas André
Published: October 2017

We investigate whether long-term and short-term components of typical conditioning variables in asset pricing studies, such as the dividend yield or yield spread, have different implications for optimal asset allocation. We argue that short-term components relate mostly to momentum, and long-term components relate mostly to mean-reversion effects, respectively. Therefore, they may have a different information content for investors with different horizons. We obtain improvements in terms of out-of-sample Sharpe ratios and expected utilities for decomposed state variables that directly reflect information related to the stock market, such as the dividend yield and stock market trend.
Time-Disaggregated Dividend–Price Ratio and Dividend Growth Predictability in Large Equity Markets
Authors: Asimakopoulos Panagiotis , Asimakopoulos Stylianos , Kourogenis Nikolaos , Tsiritakis Emmanuel
Published: October 2017

We consistently show that in large equity markets, the dividend–price ratio is significantly related to the growth of future dividends. To uncover this relation, we use monthly dividends and a mixed data sampling technique, which allows us to address within-year seasonality. Our approach avoids the use of overlapping observations and at the same time reduces the impact of price volatility on the dividend–price ratio. An empirical analysis using market-level data from the United States, United Kingdom, Canada, and Japan strongly supports the dividend growth predictability hypothesis, suggesting that time aggregation of dividends eliminates significant information.
Qualitätssicherung im diagnostischen und interventionellen rheumatologischen Ultraschall
Authors: Tamborrini1 Giorgio , Marx Christian , Ziswiler Hans Rudolf
Published: October 2017

Zusammenfassung. Die Qualitätssicherung zu Gunsten der Patienten ist im Alltag nicht mehr wegzudenken. Diese Arbeit beschreibt wichtige Aspekte bezüglich Sicherstellung von Standards zur Qualitätssicherung und Qualitätsverbesserung im diagnostischen und interventionellen rheumatologischen Ultraschall in der Schweiz durch die Arbeitsgruppe QIR («Quality in Rheumatology»). Qualitätsindikatoren in der Rheumatologie und Qualitätsstandards in der Arthrosonografie werden hervorgehoben und vorgestellt.
Häufige Mundschleimhauterkrankungen
Authors: Mollen Inga
Published: October 2017

Zusammenfassung. Die Beurteilung von Mundschleimhautbefunden ist selbst für das geschulte Auge auf den ersten Blick nicht immer einfach. Viele pathologische Befunde sind selten und werden von niedergelassenen Zahnärzten nur vereinzelt im Verlauf eines Berufslebens gesehen. Innerhalb der stomatologischen Sprechstunde an spezialisierten zahnmedizinischen Zentren können Mundschleimhautveränderungen aus diesem Grund oft schneller und sicherer diagnostiziert und therapiert werden. Dieser Artikel soll einen Überblick über häufige Veränderung der Mundschleimhaut innerhalb unserer stomatologischen Sprechstunde geben.
Invalidisierende Muskelschwäche
Authors: Oestmann Andreas
Published: October 2017

Zusammenfassung. Wir berichten über einen 79-jährigen Patienten mit einer generalisierten Muskelschwäche. Als Ursache fand sich eine bioptisch und durch anti-HMGCR-Antikörper gesicherte Statin-induzierte immunmediierte nekrotisierende Myopathie. Erst die Behandlung mit Rituximab in Kombination mit Steroiden und Azathioprin führte zu einer Besserung der Muskelschwäche.
Lisabeth and Townsend Receive 2017 Mineral and Rock Physics Graduate Research Award
Authors:   AGU
Published: October 2017

Harrison Lisabeth and Joshua Townsend will receive the 2017 Mineral and Rock Physics Graduate Research Award at the 2017 American Geophysical Union Fall Meeting, to be held 11–15 December in New Orleans, La. This award is given annually to “one or more promising young scientists for outstanding contributions achieved during their Ph.D. research.” Recipients of this award are “engaged in experimental and/or theoretical studies of Earth and planetary materials with the purpose of unraveling the physics and chemistry that govern their origin and physical properties.”
Electron carriers in microbial sulfate reduction inferred from experimental and environmental sulfur isotope fractionations
Authors: Wenk Christine B , Wing Boswell A , Halevy Itay
Published: October 2017

Dissimilatory sulfate reduction (DSR) has been a key process influencing the global carbon cycle, atmospheric composition and climate for much of Earth’s history, yet the energy metabolism of sulfate-reducing microbes remains poorly understood. Many organisms, particularly sulfate reducers, live in low-energy environments and metabolize at very low rates, requiring specific physiological adaptations. We identify one such potential adaptation—the electron carriers selected for survival under energy-limited conditions. Employing a quantitative biochemical-isotopic model, we find that the large S isotope fractionations (>55‰) observed in a wide range of natural environments and culture experiments at low respiration rates are only possible when the standard-state Gibbs free energy (ΔG′°) of all steps during DSR is more positive than −10 kJ mol−1. This implies that at low respiration rates, only electron carriers with modestly negative reduction potentials are involved, such as menaquinone, rubredoxin, rubrerythrin or some flavodoxins. Furthermore, the constraints from S isotope fractionation imply that ferredoxins with a strongly negative reduction potential cannot be the direct electron donor to S intermediates at low respiration rates. Although most sulfate reducers have the genetic potential to express a variety of electron carriers, our results suggest that a key physiological adaptation of sulfate reducers to low-energy environments is to use electron carriers with modestly negative reduction potentials.
The impact of elevated CO2 on Prochlorococcus and microbial interactions with ‘helper’ bacterium Alteromonas
Authors: Hennon Gwenn M M , Morris J Jeffrey , Haley Sheean T , Zinser Erik R , Durrant Alexander R , Entwistle Elizabeth , Dokland Terje , Dyhrman Sonya T
Published: October 2017

Prochlorococcus is a globally important marine cyanobacterium that lacks the gene catalase and relies on ‘helper’ bacteria such as Alteromonas to remove reactive oxygen species. Increasing atmospheric CO2 decreases the need for carbon concentrating mechanisms and photorespiration in phytoplankton, potentially altering their metabolism and microbial interactions even when carbon is not limiting growth. Here, Prochlorococcus (VOL4, MIT9312) was co-cultured with Alteromonas (strain EZ55) under ambient (400 p.p.m.) and elevated CO2 (800 p.p.m.). Under elevated CO2, Prochlorococcus had a significantly longer lag phase and greater apparent die-offs after transfers suggesting an increase in oxidative stress. Whole-transcriptome analysis of Prochlorococcus revealed decreased expression of the carbon fixation operon, including carboxysome subunits, corresponding with significantly fewer carboxysome structures observed by electron microscopy. Prochlorococcus co-culture responsive gene 1 had significantly increased expression in elevated CO2, potentially indicating a shift in the microbial interaction. Transcriptome analysis of Alteromonas in co-culture with Prochlorococcus revealed decreased expression of the catalase gene, known to be critical in relieving oxidative stress in Prochlorococcus by removing hydrogen peroxide. The decrease in catalase gene expression was corroborated by a significant ~6-fold decrease in removal rates of hydrogen peroxide from co-cultures. These data suggest Prochlorococcus may be more vulnerable to oxidative stress under elevated CO2 in part from a decrease in ecosystem services provided by heterotrophs like Alteromonas. This work highlights the importance of considering microbial interactions in the context of a changing ocean.
In situ metabolomic- and transcriptomic-profiling of the host-associated cyanobacteria Prochloron and Acaryochloris marina
Authors: Behrendt Lars , Raina Jean-Baptiste , Lutz Adrian , Kot Witold , Albertsen Mads , Halkjær-Nielsen Per , Sørensen Søren J , Larkum Anthony W D , Kühl Michael
Published: October 2017

The tropical ascidian Lissoclinum patella hosts two enigmatic cyanobacteria: (1) the photoendosymbiont Prochloron spp., a producer of valuable bioactive compounds and (2) the chlorophyll-d containing Acaryochloris spp., residing in the near-infrared enriched underside of the animal. Despite numerous efforts, Prochloron remains uncultivable, restricting the investigation of its biochemical potential to cultivation-independent techniques. Likewise, in both cyanobacteria, universally important parameters on light-niche adaptation and in situ photosynthetic regulation are unknown. Here we used genome sequencing, transcriptomics and metabolomics to investigate the symbiotic linkage between host and photoendosymbiont and simultaneously probed the transcriptional response of Acaryochloris in situ. During high light, both cyanobacteria downregulate CO2 fixing pathways, likely a result of O2 photorespiration on the functioning of RuBisCO, and employ a variety of stress-quenching mechanisms, even under less stressful far-red light (Acaryochloris). Metabolomics reveals a distinct biochemical modulation between Prochloron and L. patella, including noon/midnight-dependent signatures of amino acids, nitrogenous waste products and primary photosynthates. Surprisingly, Prochloron constitutively expressed genes coding for patellamides, that is, cyclic peptides of great pharmaceutical value, with yet unknown ecological significance. Together these findings shed further light on far-red-driven photosynthesis in natural consortia, the interplay of Prochloron and its ascidian partner in a model chordate photosymbiosis and the uncultivability of Prochloron.
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Authors: Adalsteinsson Viktor A. , Ha Gavin , Freeman Samuel S. , Choudhury Atish D. , Stover Daniel G. , Parsons Heather A. , Gydush Gregory , Reed Sarah C. , Rotem Denisse , Rhoades Justin , Loginov Denis , Livitz Dimitri , Rosebrock Daniel , Leshchiner Ignaty , Kim Jaegil , Stewart Chip , Rosenberg Mara , Francis Joshua M. , Zhang Cheng-Zhong , Cohen Ofir , Oh Coyin , Ding Huiming , Polak Paz , Lloyd Max , Mahmud Sairah , Helvie Karla , Merrill Margaret S. , Santiago Rebecca A. , O’Connor Edward P. , Jeong Seong H. , Leeson Rachel , Barry Rachel M. , Kramkowski Joseph F. , Zhang Zhenwei , Polacek Laura , Lohr Jens G. , Schleicher Molly , Lipscomb Emily , Saltzman Andrea , Oliver Nelly M. , Marini Lori , Waks Adrienne G. , Harshman Lauren C. , Tolaney Sara M. , Van Allen Eliezer M. , Winer Eric P. , Lin Nancy U. , Nakabayashi Mari , Taplin Mary-Ellen , Johannessen Cory M. , Garraway Levi A. , Golub Todd R. , Boehm Jesse S. , Wagle Nikhil , Getz Gad , Love J. Christopher , Meyerson Matthew
Published: October 2017

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.
Structural basis for receptor recognition of pollen tube attraction peptides
Authors: Zhang Xiaoxiao , Liu Weijia , Nagae Takuya T. , Takeuchi Hidenori , Zhang Heqiao , Han Zhifu , Higashiyama Tetsuya , Chai Jijie
Published: October 2017

Transportation of the immobile sperms directed by pollen tubes to the ovule-enclosed female gametophytes is important for plant sexual reproduction. The defensin-like (DEFL) cysteine-rich peptides (CRPs) LUREs play an essential role in pollen tube attraction to the ovule, though their receptors still remain controversial. Here we provide several lines of biochemical evidence showing that the extracellular domain of the leucine-rich repeat receptor kinase (LRR-RK) PRK6 from Arabidopsis thaliana directly interacts with AtLURE1 peptides. Structural study reveals that a C-terminal loop of the LRR domain (AtPRK6LRR) is responsible for recognition of AtLURE1.2, mediated by a set of residues largely conserved among PRK6 homologs from Arabidopsis lyrata and Capsella rubella, supported by in vitro mutagenesis and semi-in-vivo pollen tube growth assays. Our study provides evidence showing that PRK6 functions as a receptor of the LURE peptides in A. thaliana and reveals a unique ligand recognition mechanism of LRR-RKs.
Depth dependent stress revealed by aftershocks
Authors: Shebalin Peter , Narteau Clément
Published: October 2017

Characterising the state of stress in the brittle upper-crust is essential in mechanics of faulting, industrial production processes, and operational earthquake forecasting. Nevertheless, unresolved questions concern the variation of pore-fluid with depth and the absolute strength on tectonically active faults. Here we show that, along the San Andreas fault system, the time-delay before the onset of the power-law aftershock decay rate (the c-value) varies by three orders of magnitude in the first 20 km below the surface. Despite the influence of the lithostatic stress, there is no continuous change in c-value with depth. Instead, two decay phases are separated by an abrupt increase at an intermediate depth range of 2–5 km. This transitional regime is the only one observed in fluid-injection-induced seismic areas. This provides strong evidence for the role of fluid and a porosity reduction mechanism at depth of few kilometres in active fault zones. Aftershock statistics can then be used to predict changes in differential shear stress with depth until the brittle-ductile transition is reached.
Colour selective control of terahertz radiation using two-dimensional hybrid organic inorganic lead-trihalide perovskites
Authors: Chanana Ashish , Zhai Yaxin , Baniya Sangita , Zhang Chuang , Vardeny Z. Valy , Nahata Ajay
Published: October 2017

Controlling and modulating terahertz signals is of fundamental importance to allow systems level applications. We demonstrate an innovative approach for controlling the propagation properties of terahertz (THz) radiation, through use of both the excitation optical wavelength (colour) and intensity. We accomplish this using two-dimensional (2D) layered hybrid trihalide perovskites that are deposited onto silicon substrates. The absorption properties of these materials in the visible range can be tuned by changing the number of inorganic atomic layers in between the organic cation layers. Optical absorption in 2D perovskites occurs over a broad spectral range above the bandgap, resulting in free carrier generation, as well as over a narrow spectral range near the bandedge due to exciton formation. We find that only the latter contribution gives rise to photo-induced THz absorption. By patterning multiple 2D perovskites with different optical absorption properties onto a single device, we demonstrate both colour selective modulation and focusing of THz radiation. These findings open new directions for creating active THz devices.
Small infrarenal aortic diameter associated with lower-extremity peripheral artery disease in Chinese hypertensive adults
Authors: Liu Jie , Jia Xin , Jia Senhao , Qin Xianhui , Zhang Tao , Liu Lishun , Li Haibo , Rong Dan , Zhou Ziyi , Song Yuxiang , Zuo Shangwei , Duan Chen , Wu Zhongyin , Wei Ren , Ge Yangyang , Wang Xian , Kong Wei , Xu Xiping , Khalil Raouf A. , Huo Yong , Guo Wei
Published: October 2017

Several studies suggest that infrarenal aortic diameter is associated with lower-extremity peripheral artery disease (LE-PAD). However, data regarding the associations between infrarenal aortic diameter and LE-PAD are limited, especially in large sample populations and Asian or Chinese populations. Our analysis included 17279 Chinese hypertensive adults comprising 6590 men and 10689 women with a mean age of 64.74 ± 7.41 years. Participants were selected from 22693 candidates from two large population-based cohort-studies. The primary noninvasive test for diagnosis of LE-PAD is the ankle–brachial index (ABI) at rest and typically an ABI ≤ 0.90 is used to define LE-PAD. The prevalence of LE-PAD was found to significantly decrease as the aortic diameter increased according to the tertile of the aortic diameter. LE-PAD was significantly more prevalent in the lowest tertile (OR = 1.58, 95% CI = 1.29–1.94, p < 0.001) and similarly prevalent in the highest tertile (OR = 0.92, 95% CI = 0.73–1.16, p = 0.49) when compared with the median tertile. No significant interactions between the aortic diameter and any of the stratified variables were found (all p > 0.05). In conclusion, Small aortic diameter (as opposed to large aortic diameter) is significantly associated with LE-PAD in Chinese hypertensive adults.
Two novel diterpenoid heterodimers, Bisebracteolasins A and B, from Euphorbia ebracteolata Hayata, and the cancer chemotherapeutic potential of Bisebracteolasin A
Authors: Yuan Wen-Juan , Ding Xiao , Wang Zhe , Yang Bi-Juan , Li Xiao-Nian , Zhang Yu , Chen Duo-Zhi , Li Shun-Lin , Chen Quan , Di Ying-Tong , Aisa Haji Akber , Hao Xiao-Jiang
Published: October 2017

Rare ent-abietane-rosane diterpenoid heterodimers, Bisebracteolasins A and B (1 and 2, respectively), were isolated from the roots of Euphorbia ebracteolata Hayata. Their structures and absolute configurations were elucidated from spectroscopic data and X-ray diffraction analysis. Compounds 1 and 2 exhibited moderate cytotoxic effects against five cancer cell lines. Compound 1 showed more effective antiproliferative activities against human tumour cells, HL-60 and SMMC-7721, with IC50 values of 2.61 and 4.08 μM, respectively, than 2. Both compounds 1 and 2 inhibit the colorectal cancer stem cell line P6C with IC50 values of 16.48 and 34.76 μM, respectively. Moreover, preliminary biological tests showed compound 1 exhibited inhibitory activity towards tumoursphere formation and migration of the P6C cell line. Overall, we identified two novel diterpenoid heterodimers, and Bisebracteolasin A exhibits therapeutic potential in impeding tumour growth and metastatic ability of cancer stem cells.
Involvement of autophagy in the outcome of mitotic catastrophe
Authors: Sorokina Irina V. , Denisenko Tatiana V. , Imreh Gabriela , Tyurin-Kuzmin Pyotr A. , Kaminskyy Vitaliy O. , Gogvadze Vladimir , Zhivotovsky Boris
Published: October 2017

Evading cell death is a major driving force for tumor progression that is one of the main problems in current cancer research. Mitotic catastrophe (MC) represents attractive platform compromising tumor resistance to current therapeutic modalities. MC appeared as onco-suppressive mechanism and is defined as a stage driving the cell to an irreversible destiny, i.e. cell death via apoptosis or necrosis. Our study highlights that MC induction in colorectal carcinoma cell lines ultimately leads to the autophagy followed by apoptosis. We show that autophagy suppression in Atg 13 knockout non-small cell lung carcinoma cells lead to the dramatic decrease of MC rate. Furthermore, mitochondria-linked anti-apoptotic proteins Mcl-1 and Bcl-xL play a crucial role in the duration of MC and a cross-talk between autophagy and apoptosis. Thus, the suppression of apoptosis by overexpression of Mcl-1 or Bcl-xL affected MC and lead to a significant induction of autophagy in HCT116 wt and HCT116 14-3-3σ−/− cells. Our data demonstrate that MC induction is a critical stage, in which a cell decides how to die, while mitochondria are responsible for the maintaining the balance between MC – autophagy – apoptosis.
Molecular-trapping in Emulsion’s Monolayer: A New Strategy for Production and Purification of Bioactive Saponins
Authors: Obasi Titus C. , Moldovan Radu , Toiu Anca , Braicu Cornelia , Bodoki Ede , Berindan-Neagoe Ioana , Oniga Ilioara , Sandulescu Robert , Oprean Radu
Published: October 2017

Saponins from defatted root-extract of Securidaca longipedunculata were systematically entrapped in emulsion monolayer-barrier and finally recovered in pure form through demulsification. First, their molecules were dispersed in water to engineer a monomolecular film architecture, via self-assembly. Emulsifying with ethyl-ether resulted in swollen micelles and engendered phase-inversion and phase-separation, by disrupting the thermodynamic equilibrium. As positive outcome, a Winsor II system was obtained, having saponin-rich upper phase (ethyl-ether) and impurities bound lower phase (aqueous). Saponin particles underwent transition in insoluble ethyl-ether, precipitated and recovered as solids. The entire process was bioactivity-guided and validated using pooled fractions of securidaca saponins, purified by TLC (RP-C18, F254S). TEM and SEM revealed interesting morphologies and particle sizes between nanometer and micron. At the end, purity output of 90% and total recovery of 94% were achieved. Here we show that “molecular-trapping in emulsion’s monolayer” is an effective method for recovery, production and purification of saponins of plant origin.
N-Myc-Interacting Protein Negatively Regulates TNF-α-Induced NF-κB Transcriptional Activity by Sequestering NF-κB/p65 in the Cytoplasm
Authors: Hou Jingjing , Jiang Shihao , Zhao Jiabao , Zhu Dong , Zhao Xinmeng , Cai Jian-chun , Zhang Si Qing
Published: October 2017

NF-κB is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-κB is not completely understood. Here, we report that the N-Myc and STATs Interactor (NMI), an IFN-inducible protein, is an important negative regulator of NF-κB activity. We found that NMI negatively regulates TNF-α-induced IL-6 and IL-1β production in HeLa cells. Overexpression of NMI inhibits NF-κB transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-κB transcriptional activity. Mechanistically, NMI associates with NF-κB/p65 and inhibits NF-κB/p65 nuclear translocation and thereby negatively regulates NF-κB/p65 transcriptional activity. Taken together, our results demonstrate that NMI modulates the NF-κB signaling pathway by sequestering NF-κB/p65 in the cytoplasm, resulting in reduced IL-6 and IL-1β production after TNF-α stimulation. Treatment with IFNα in the presence of NMI leads to increased apoptosis in tumor cells. These findings reveal a novel mechanism by which NMI regulates NF-κB activity.