bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of child behavior change in parent training: Comment on Weeland et al. (2018)
Authors: Beauchaine Theodore P. , Slep Amy
Published: September 2018

Recently in this journal, Weeland et al. (2018) published a thought-provoking article reporting moderating effects of children's serotonin transporter-linked polymorphisms (5-HTTLPR) on negative parenting during prevention with the Incredible Years series. Participants were parents and young children of 387 families enrolled in the Observational Randomized Control Trial of Childhood Differential Susceptibility study. An equally important finding, which we focus on in this comment, involved null effects for all tests of parenting as a mediator of prevention-induced improvements in children's externalizing behavior. Although such findings may seem surprising, both confirmations of and failures to confirm parenting change as a mediator of child behavior change are common in the prevention and intervention literatures. In this comment, we explore likely reasons for heterogeneity in findings, including both moderators of treatment effect size and methods used to test mediation. Common moderators of prevention and intervention response to Incredible Years include dose, parenting problems at intake, high-risk versus clinical nature of samples, how parenting is measured, and whether child training is included with parent training. All of these moderators affect power to detect mediation. We then discuss conceptual criteria for testing mediation in randomized clinical trials, and problems with interpreting mediating paths in cross-lag panel models. Although the gene effect reported by Weeland et al. is important, their cross-lag panel models do not provide strong tests of parenting as a mediator of child behavior change. We conclude with recommendations for testing mediation in randomized clinical trials.
Nut consumption and metabolic syndrome in US adolescents
Authors: Kim Roy J , Wang Lu , Worley Sarah , Leonard David
Published: September 2018

Objective

To determine whether nut intake is associated with the prevalence of metabolic syndrome in US adolescents.

Design

A cross-sectional analysis of data from the National Health and Nutrition Examination Survey (NHANES) years 2003–2012. Anthropometric measurements, blood tests, 24 h diet recalls and demographic data were retrieved for participating adolescents. Metabolic syndrome was defined according to paediatric-modified Adult Treatment Panel III criteria. The exposure was defined as a nut intake ≥5 g/d.

Setting

USA.

Subjects

Individuals aged 12–19 years (n 2805).

Results

Nut consumption was associated with lower odds for metabolic syndrome (crude OR=0·25; 95 % CI 0·11, 0·55; P≤0·001). This effect was independent of age, sex, race/ethnicity and family income:poverty ratio (adjusted OR=0·27; 95 % CI 0·12, 0·61; P=0·002), and was stable after controlling for nutritional covariates including intake of sugar and total energy consumption (OR=0·36; 95 % CI 0·16, 0·81; P=0·014).

Conclusion

Nut consumption of ≥5 g/d is independently associated with lower odds for metabolic syndrome in US adolescents.
Application of pulsed electric fields for the elimination of highly drug-resistant Candida grown under modelled microgravity conditions
Authors: Lastauskienė Eglė , Novickij Vitalij , Zinkevičienė Auksė , Girkontaitė Irutė , Paškevičius Algimantas , Švedienė Jurgita , Markovskaja Svetlana , Novickij Jurij
Published: September 2018

Candida lusitaniaeandC. guilliermondiiare perfect model organisms for the study ofCandidagenera behaviour in various conditions. Both of them are rare pathogens capable to cause candidiasis in the patients with weakened immune system and can undergo morphology switches related to the increased antifungal drug resistance.Candidagenera yeasts are able to inhabit diverse range of ecological niches including space ships and space stations. During the long-term expeditions, astronauts are affected by various factors that can change the state immune system. In such conditions, the commensal usually non-pathogenic microorganisms can spread through the body of the host and cause infections. Weakened immune system and limited use of drugs in spaceships promote the search of the alternative methods for the biocontrol of microorganisms. Several studies demonstrate that microorganisms are altering their gene expression, physiology, morphology, pathogenicity and evolving resistance to the antifungals under microgravity conditions. Our research indicated that switch to the pseudohyphae morphology leads up 30-fold increased resistance to amphotericin B inC. lusitaniaeandC. guilliermondii. Cultivation of yeasts in rotary cell culture system (RCCS) is related to the altered cell growth and resistance to the antifungal treatment. Our results showed that growth in the RCCS led to the extreme increase in cell resistance to amphotericin B as compared with the standard growth conditions. In our research, we applied electroporation for the biocontrol of twoCandidaspecies.C. lusitaniaeandC. guilliermondiicells grown in RCCS exhibited significantly increased survivability after pulsed electric field (PEF) treatment in comparison with cells grown under routine conditions. We have shown that PEF bursts of 2.5–25 kV cm−1of 100 µs × 8 duration display a dose-dependent permeabilization of both studiedCandidaspecies. Our research indicated that budding cells and pseudohyphae morphology cells, with increased resistance to amphotericin B, can be effectively inactivated after applying PEF higher than 15 kV cm−1.
Modeling CO, CO2and H2O Ice Abundances in the Envelopes of Young Stellar Objects in the Magellanic Clouds
Authors: Pauly Tyler , Garrod Robin T.
Published: September 2018

Massive young stellar objects (MYSOs) in the Magellanic Clouds (MCs) show infrared absorption features corresponding to significant abundances of CO, CO2and H2O ice along the line of sight, with the relative abundances of these ices varying between sources in the Magellanic Clouds and the Milky Way. We use our gas-grain chemical code MAGICKAL, with multiple grain sizes and grain temperatures, and further expand it with a treatment for increased interstellar radiation field intensity to model the elevated dust temperatures observed in the MCs. We also adjust the elemental abundances used in the chemical models, guided by observations of HII regions in these metal-poor satellite galaxies. With a grid of models, we are able to reproduce the relative ice fractions observed in MC MYSOs, indicating that metal depletion and elevated grain temperature are important drivers of the MYSO envelope ice composition. The observed shortfall in CO in the Small Magellanic Cloud can be explained by a combination of reduced carbon abundance and increased grain temperatures. The models indicate that a large variation in radiation field strength is required to match the range of observed LMC abundances.
On the origin of O2 and other volatile species in comets
Authors: Taquet Vianney , Furuya Kenji , Walsh Catherine , van Dishoeck Ewine F.
Published: September 2018

Molecular oxygen, O2, was recently detected in comet 67P by the ROSINA instrument on board the Rosetta spacecraft with a surprisingly high abundance of 4% relative to H2O, making O2 the fourth most abundant in comet 67P. Other volatile species with similar volatility, such as molecular nitrogen N2, were also detected by Rosetta, but with much lower abundances and much weaker correlations with water. Here, we investigate the chemical and physical origin of O2 and other volatile species using the new constraints provided by Rosetta. We follow the chemical evolution during star formation with state-of-the-art astrochemical models applied to dynamical physical models by considering three origins: i) in dark clouds, ii) during forming protostellar disks, and iii) during luminosity outbursts in disks. The models presented here favour a dark cloud (or “primordial”) grain surface chemistry origin for volatile species in comets, albeit for dark clouds which are slightly warmer and denser than those usually considered as solar system progenitors.
Determining the effect of a non-uniform AGB outflow on its chemistry
Authors: Van de Sande M. , Sundqvist J. O. , Millar T. J. , Decin L.
Published: September 2018

The molecular composition of the stellar outflows of AGB stars is determined by the stellar elemental carbon-to-oxygen abundance ratio, together with the physical circumstances in the innermost region of the outflow. Near the stellar surface, thermal equilibrium (TE) can be assumed. This leads to a certain molecular composition with a O- or C-rich signature. However, several molecular species have been detected that are not expected to be present in the inner region under the assumption of TE chemistry. As a solution to explain the presence of these unexpected species, non-equilibrium chemistry in the inner region of the outflow has been proposed. The outflows of AGB stars are generally not spherically symmetric or homogeneous, which influences the penetration of interstellar UV photons throughout the outflow. We investigate the effect of a clumpy, non-homogeneous outflow on the composition of the inner region by introducing a simple porosity formalism in our chemical model.
Processing of astrophysical ices by soft X-rays and swift ions
Authors: Pilling Sergio
Published: September 2018

The employment of soft X-rays and swift ions has been used in laboratory to simulate the physicochemical processing of astrophysical ice analogs by energetic photons and cosmic rays. This processing includes excitation, ionization and molecular dissociation, desorption, as well as triggers the formation of new compounds. Here we present some results from experiments employing infrared spectroscopy in two different laboratories: LNLS/CNPEM in Campinas/Brazil and GANIL/CIRIL/CIMAP in Caen/France. Among the results are the formation of alkenes and aromatic compounds during the irradiation of saturated hydrocarbon-containing ices by cosmic ray analogs, the production of the nucleobase adenine during soft X-ray photolysis of N2:CH4 ice, as well as the formation of peptide bonds during the bombardment of frozen glycine by cosmic ray analogs. The interaction between cosmic ray analogs and ionizing soft X-rays probed in the laboratory allows us to identify reaction routes that lead to chemistry enhancement of astrophysical ices and help us put constrains in prebiotic chemistry.
A role for APP in Wnt signalling links synapse loss with β-amyloid production
Authors: Elliott Christina , Rojo Ana I. , Ribe Elena , Broadstock Martin , Xia Weiming , Morin Peter , Semenov Mikhail , Baillie George , Cuadrado Antonio , Al-Shawi Raya , Ballard Clive G. , Simons Paul , Killick Richard
Published: September 2018

In Alzheimer’s disease (AD), the canonical Wnt inhibitor Dickkopf-1 (Dkk1) is induced by β-amyloid (Aβ) and shifts the balance from canonical towards non-canonical Wnt signalling. Canonical (Wnt-β-catenin) signalling promotes synapse stability, while non-canonical (Wnt-PCP) signalling favours synapse retraction; thus Aβ-driven synapse loss is mediated by Dkk1. Here we show that the Amyloid Precursor Protein (APP) co-activates both arms of Wnt signalling through physical interactions with Wnt co-receptors LRP6 and Vangl2, to bi-directionally modulate synapse stability. Furthermore, activation of non-canonical Wnt signalling enhances Aβ production, while activation of canonical signalling suppresses Aβ production. Together, these findings identify a pathogenic-positive feedback loop in which Aβ induces Dkk1 expression, thereby activating non-canonical Wnt signalling to promote synapse loss and drive further Aβ production. The Swedish familial AD variant of APP (APPSwe) more readily co-activates non-canonical, at the expense of canonical Wnt activity, indicating that its pathogenicity likely involves direct effects on synapses, in addition to increased Aβ production. Finally, we report that pharmacological inhibition of the Aβ-Dkk1-Aβ positive feedback loop with the drug fasudil can restore the balance between Wnt pathways, prevent dendritic spine withdrawal in vitro, and reduce Aβ load in vivo in mice with advanced amyloid pathology. These results clarify a relationship between Aβ accumulation and synapse loss and provide direction for the development of potential disease-modifying treatments.
Hepatic Ago2-mediated RNA silencing controls energy metabolism linked to AMPK activation and obesity-associated pathophysiology
Authors: Zhang Cai , Seo Joonbae , Murakami Kazutoshi , Salem Esam S. B. , Bernhard Elise , Borra Vishnupriya J. , Choi Kwangmin , Yuan Celvie L. , Chan Calvin C. , Chen Xiaoting , Huang Taosheng , Weirauch Matthew T. , Divanovic Senad , Qi Nathan R. , Thomas Hala Einakat , Mercer Carol A. , Siomi Haruhiko , Nakamura Takahisa
Published: September 2018

RNA silencing inhibits mRNA translation. While mRNA translation accounts for the majority of cellular energy expenditure, it is unclear if RNA silencing regulates energy homeostasis. Here, we report that hepatic Argonaute 2 (Ago2)-mediated RNA silencing regulates both intrinsic energy production and consumption and disturbs energy metabolism in the pathogenesis of obesity. Ago2 regulates expression of specific miRNAs including miR-802, miR-103/107, and miR-148a/152, causing metabolic disruption, while simultaneously suppressing the expression of genes regulating glucose and lipid metabolism, including Hnf1β, Cav1, and Ampka1. Liver-specific Ago2-deletion enhances mitochondrial oxidation and ATP consumption associated with mRNA translation, which results in AMPK activation, and improves obesity-associated pathophysiology. Notably, hepatic Ago2-deficiency improves glucose metabolism in conditions of insulin receptor antagonist treatment, high-fat diet challenge, and hepatic AMPKα1-deletion. The regulation of energy metabolism by Ago2 provides a novel paradigm in which RNA silencing plays an integral role in determining basal metabolic activity in obesity-associated sequelae.
Publisher Correction: Strongly-coupled quantum critical point in an all-in-all-out antiferromagnet
Authors: Wang Yishu , Rosenbaum T. F. , Palmer A. , Ren Y. , Kim J.-W. , Mandrus D. , Feng Yejun
Published: September 2018

The original PDF version of the Article contained an error in the last sentence of the author affiliation information, which incorrectly read ‘Correspondence and requests for materials should be addressed to T.$.R. (e-mail: tfr@caltech.edu) or to Y.F. (e-mail: yejun@oist.jp)’. The correct version states ‘T.F.R.’ in place of “T.$.R.’. This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
Deglacial mobilization of pre-aged terrestrial carbon from degrading permafrost
Authors: Winterfeld Maria , Mollenhauer Gesine , Dummann Wolf , Köhler Peter , Lembke-Jene Lester , Meyer Vera D. , Hefter Jens , McIntyre Cameron , Wacker Lukas , Kokfelt Ulla , Tiedemann Ralf
Published: September 2018

The mobilization of glacial permafrost carbon during the last glacial–interglacial transition has been suggested by indirect evidence to be an additional and significant source of greenhouse gases to the atmosphere, especially at times of rapid sea-level rise. Here we present the first direct evidence for the release of ancient carbon from degrading permafrost in East Asia during the last 17 kyrs, using biomarkers and radiocarbon dating of terrigenous material found in two sediment cores from the Okhotsk Sea. Upscaling our results to the whole Arctic shelf area, we show by carbon cycle simulations that deglacial permafrost-carbon release through sea-level rise likely contributed significantly to the changes in atmospheric CO2 around 14.6 and 11.5 kyrs BP.
CXCL12 and MYC control energy metabolism to support adaptive responses after kidney injury
Authors: Yakulov Toma A. , Todkar Abhijeet P. , Slanchev Krasimir , Wiegel Johannes , Bona Alexandra , Groß Martin , Scholz Alexander , Hess Isabell , Wurditsch Anne , Grahammer Florian , Huber Tobias B. , Lecaudey Virginie , Bork Tillmann , Hochrein Jochen , Boerries Melanie , Leenders Justine , de Tullio Pascal , Jouret François , Kramer-Zucker Albrecht , Walz Gerd
Published: September 2018

Kidney injury is a common complication of severe disease. Here, we report that injuries of the zebrafish embryonal kidney are rapidly repaired by a migratory response in 2-, but not in 1-day-old embryos. Gene expression profiles between these two developmental stages identifycxcl12aandmycaas candidates involved in the repair process. Zebrafish embryos withcxcl12a,cxcr4b, ormycadeficiency display repair abnormalities, confirming their role in response to injury. In mice with a kidney-specific knockout,Cxcl12andMycgene deletions suppress mitochondrial metabolism and glycolysis, and delay the recovery after ischemia/reperfusion injury. Probing these observations in zebrafish reveal that inhibition of glycolysis slows fast migrating cells and delays the repair after injury, but does not affect the slow cell movements during kidney development. Our findings demonstrate thatCxcl12andMycfacilitate glycolysis to promote fast migratory responses during development and repair, and potentially also during tumor invasion and metastasis.
Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection
Authors: Zuo Tao , Wong Sunny H. , Cheung Chun Pan , Lam Kelvin , Lui Rashid , Cheung Kitty , Zhang Fen , Tang Whitney , Ching Jessica Y. L. , Wu Justin C. Y. , Chan Paul K. S. , Sung Joseph J. Y. , Yu Jun , Chan Francis K. L. , Ng Siew C.
Published: September 2018

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT (“responders”) display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas “nonresponders” and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.
Contribution of allelic imbalance to colorectal cancer
Authors: Palin Kimmo , Pitkänen Esa , Turunen Mikko , Sahu Biswajyoti , Pihlajamaa Päivi , Kivioja Teemu , Kaasinen Eevi , Välimäki Niko , Hänninen Ulrika A. , Cajuso Tatiana , Aavikko Mervi , Tuupanen Sari , Kilpivaara Outi , van den Berg Linda , Kondelin Johanna , Tanskanen Tomas , Katainen Riku , Grau Marta , Rauanheimo Heli , Plaketti Roosa-Maria , Taira Aurora , Sulo Päivi , Hartonen Tuomo , Dave Kashyap , Schmierer Bernhard , Botla Sandeep , Sokolova Maria , Vähärautio Anna , Gladysz Kornelia , Ongen Halit , Dermitzakis Emmanouil , Bramsen Jesper Bertram , Ørntoft Torben Falck , Andersen Claus Lindbjerg , Ristimäki Ari , Lepistö Anna , Renkonen-Sinisalo Laura , Mecklin Jukka-Pekka , Taipale Jussi , Aaltonen Lauri A.
Published: September 2018

Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point mutations. Importantly, the data reveal several associations between AI target genes, suggesting a role for a network of lineage-determining transcription factors in colorectal tumorigenesis. Overall, the results unravel the contribution of AI in colorectal cancer and provide a plausible explanation why so few genes are commonly affected by point mutations in cancers.
Conserved collateral antibiotic susceptibility networks in diverse clinical strains of Escherichia coli
Authors: Podnecky Nicole L. , Fredheim Elizabeth G. A. , Kloos Julia , Sørum Vidar , Primicerio Raul , Roberts Adam P. , Rozen Daniel E. , Samuelsen Ørjan , Johnsen Pål J.
Published: September 2018

There is urgent need to develop novel treatment strategies to reduce antimicrobial resistance. Collateral sensitivity (CS), where resistance to one antimicrobial increases susceptibility to other drugs, might enable selection against resistance during treatment. However, the success of this approach would depend on the conservation of CS networks across genetically diverse bacterial strains. Here, we examine CS conservation across diverse Escherichia coli strains isolated from urinary tract infections. We determine collateral susceptibilities of mutants resistant to relevant antimicrobials against 16 antibiotics. Multivariate statistical analyses show that resistance mechanisms, in particular efflux-related mutations, as well as the relative fitness of resistant strains, are principal contributors to collateral responses. Moreover, collateral responses shift the mutant selection window, suggesting that CS-informed therapies may affect evolutionary trajectories of antimicrobial resistance. Our data allow optimism for CS-informed therapy and further suggest that rapid detection of resistance mechanisms is important to accurately predict collateral responses.
A considerable fraction of soil-respired CO2 is not emitted directly to the atmosphere
Authors: Sánchez-Cañete Enrique P. , Barron-Gafford Greg A. , Chorover Jon
Published: September 2018

Soil CO2 efflux (Fsoil) is commonly considered equal to soil CO2 production (Rsoil), and both terms are used interchangeably. However, a non-negligible fraction of Rsoil can be consumed in the subsurface due to a host of disparate, yet simultaneous processes. The ratio between CO2 efflux/O2 influx, known as the apparent respiratory quotient (ARQ), enables new insights into CO2 losses from Rsoil not previously captured by Fsoil. We present the first study using continuous ARQ estimates to evaluate annual CO2 losses of carbon produced from Rsoil. We found that up to 1/3 of Rsoil was emitted directly to the atmosphere, whereas 2/3 of Rsoil was removed by subsurface processes. These subsurface losses are attributable to dissolution in water, biological activities and chemical reactions. Having better estimates of Rsoil is key to understanding the true influence of ecosystem production on Rsoil, as well as the role of soil CO2 production in other connected processes within the critical zone.
De novo assembly, characterization, functional annotation and expression patterns of the black tiger shrimp (Penaeus monodon) transcriptome
Authors: Huerlimann Roger , Wade Nicholas M. , Gordon Lavinia , Montenegro Juan D. , Goodall Jake , McWilliam Sean , Tinning Matthew , Siemering Kirby , Giardina Erika , Donovan Dallas , Sellars Melony J. , Cowley Jeff A. , Condon Kelly , Coman Greg J. , Khatkar Mehar S. , Raadsma Herman W. , Maes Gregory E. , Zenger Kyall R. , Jerry Dean R.
Published: September 2018

The black tiger shrimp (Penaeus monodon) remains the second most widely cultured shrimp species globally; however, issues with disease and domestication have seen production levels stagnate over the past two decades. To help identify innovative solutions needed to resolve bottlenecks hampering the culture of this species, it is important to generate genetic and genomic resources. Towards this aim, we have produced the most complete publicly available P. monodon transcriptome database to date based on nine adult tissues and eight early life-history stages (BUSCO - Complete: 98.2% [Duplicated: 51.3%], Fragmented: 0.8%, Missing: 1.0%). The assembly resulted in 236,388 contigs, which were then further segregated into 99,203 adult tissue specific and 58,678 early life-history stage specific clusters. While annotation rates were low (approximately 30%), as is typical for a non-model organisms, annotated transcript clusters were successfully mapped to several hundred functional KEGG pathways. Transcripts were clustered into groups within tissues and early life-history stages, providing initial evidence for their roles in specific tissue functions, or developmental transitions. We expect the transcriptome to provide an essential resource to investigate the molecular basis of commercially relevant-significant traits in P. monodon and other shrimp species.
Transcriptome Analysis of Gossypium hirsutum L. Reveals Different Mechanisms among NaCl, NaOH and Na2CO3 Stress Tolerance
Authors: Zhang Binglei , Chen Xiugui , Lu Xuke , Shu Na , Wang Xiaoge , Yang Xiaomin , Wang Shuai , Wang Junjuan , Guo Lixue , Wang Delong , Ye Wuwei
Published: September 2018

As an important source of fiber and edible oil, cotton has great economic value. In comparison to their individual studies, association and differentiation between salt and alkaline tolerance has not been focused yet by scientists. We have used next-generation RNA-Seq technique to analyze transcriptional changes under salt and alkaline stresses in cotton. Overall, 25,929 and 6,564 differentially expressed genes (DEGs) were identified in roots and leaves, respectively. Gene functional annotation showed that genes involving ionic homeostasis were significantly up-regulated under NaCl stress and Na2CO3 stress, and genes enriched in starch and sucrose metabolism were up-regulated under NaOH stress and Na2CO3 stress. Furthermore, a synergistic enhancing effect between NaCl and NaOH stress was also observed in this study. Likewise, our studies indicate further that genes related with starch and sucrose metabolism were regulated to respond to the high pH under Na2CO3 stress, inducing plant hormone signal transduction and key enzyme reactive oxygen species (ROS) activity to respond to ionic toxicity and intracellular ionic homeostasis. By analyzing the expression profiles of diverse tissues under different salt and alkaline stresses, this study provides valuable ideas for genetic improvements of cotton tolerance to salt-alkaline stress.
The first crystal structure of a DNA-free nuclear receptor DNA binding domain sheds light on DNA-driven allostery in the glucocorticoid receptor
Authors: Frank Filipp , Okafor C. Denise , Ortlund Eric A.
Published: September 2018

The glucocorticoid receptor (GR) is a steroid hormone receptor of the nuclear receptor family that regulates gene expression in response to glucocorticoid hormone signaling. Interaction with specific GR DNA binding sequences causes conformational changes in the GR DNA binding domain (DBD) that result in recruitment of specific sets of co-regulators that determine transcriptional outcomes. We have solved the crystal structure of GR DBD in its DNA-free state, the first such crystal structure from any nuclear receptor. In contrast to previous NMR structures, this crystal structure reveals that free GR DBD adopts a conformation very similar to DNA-bound states. The lever arm region is the most variable element in the free GR DBD. Molecular dynamics of the free GR DBD as well as GR DBD bound to activating and repressive DNA elements confirm lever arm flexibility in all functional states. Cluster analysis of lever arm conformations during simulations shows that DNA binding and dimerization cause a reduction in the number of conformations sampled by the lever arm. These results reveal that DNA binding and dimerization drive conformational selection in the GR DBD lever arm region and show how DNA allosterically controls GR structure and dynamics.
Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa
Authors: Cachet Xavier , Langrand Jerôme , Riffault-Valois Ludivine , Bouzidi Chouaha , Colas Cyril , Dugay Annabelle , Michel Sylvie , Boucaud-Maitre Denis
Published: September 2018

Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.
Cryovolcanism on the Earth: Origin of a Spectacular Crater in the Yamal Peninsula (Russia)
Authors: Buldovicz Sergey N. , Khilimonyuk Vanda Z. , Bychkov Andrey Y. , Ospennikov Evgeny N. , Vorobyev Sergey A. , Gunar Aleksey Y. , Gorshkov Evgeny I. , Chuvilin Evgeny M. , Cherbunina Maria Y. , Kotov Pavel I. , Lubnina Natalia V. , Motenko Rimma G. , Amanzhurov Ruslan M.
Published: September 2018

Geological activity on icy planets and planetoids includes cryovolcanism. Until recently, most research on terrestrial permafrost has been engineering-oriented, and many related phenomena have received too little attention. Although fast processes in the Earth’s cryosphere were known before, they have never been attributed to cryovolcanism. The discovery of a couple of tens of meters wide crater in the Yamal Peninsula aroused numerous hypotheses of its origin, including a meteorite impact or migration of deep gas as a result of global warming. However, the origin of the Yamal crater can be explained in terms of cryospheric processes. Thus, the Yamal crater appears to result from collapse of a large pingo, which formed within a thaw lake when it shoaled and dried out allowing a large talik (that is layer or body of unfrozen ground in a permafrost area) below it to freeze back. The pingo collapsed under cryogenic hydrostatic pressure built up in the closed system of the freezing talik. This happened before the freezing completed, when a core of wet ground remained unfrozen and stored a huge amount of carbon dioxide dissolved in pore water. This eventually reached gas-phase saturation, and the resulting overpressure came to exceed the lithospheric confining stress and the strength of the overlying ice. As the pingo exploded, the demarcation of the crater followed the cylindrical shape of the remnant talik core.
Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips
Authors: Quirós-Solano W. F. , Gaio N. , Stassen O. M. J. A. , Arik Y. B. , Silvestri C. , Van Engeland N. C. A. , Van der Meer A. , Passier R. , Sahlgren C. M. , Bouten C. V. C. , van den Berg A. , Dekker R. , Sarro P. M.
Published: September 2018

We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.
Pharmacological difference between degrader and inhibitor against oncogenic BCR-ABL kinase
Authors: Shibata Norihito , Shimokawa Kenichiro , Nagai Katsunori , Ohoka Nobumichi , Hattori Takayuki , Miyamoto Naoki , Ujikawa Osamu , Sameshima Tomoya , Nara Hiroshi , Cho Nobuo , Naito Mikihiko
Published: September 2018

Chronic myelogenous leukemia (CML) is characterized by the oncogenic fusion protein, BCR-ABL protein kinase, against which clinically useful inhibitors have been developed. An alternative approach to treat CML is to degrade the BCR-ABL protein. Recently, potent degraders against BCR-ABL have been developed by conjugating dasatinib to ligands for E3 ubiquitin ligases. Since the degraders contain the dasatinib moiety, they also inhibit BCR-ABL kinase activity, which complicates our understanding of the impact of BCR-ABL degradation by degraders in CML growth inhibition. To address this issue, we chose DAS-IAP, as a potent BCR-ABL degrader, and developed a structurally related inactive degrader, DAS-meIAP, which inhibits kinase activity but does not degrade the BCR-ABL protein. DAS-IAP showed slightly weaker activity than DAS-meIAP in inhibiting cell growth when CML cells were treated for 48 h. However, DAS-IAP showed sustained growth inhibition even when the drug was removed after short-term treatment, whereas CML cell growth rapidly resumed following removal of DAS-meIAP and dasatinib. Consistently, suppression of BCR-ABL levels and downstream kinase signaling were maintained after DAS-IAP removal, whereas kinase signaling rapidly recovered following removal of DAS-meIAP and dasatinib. These results indicate that BCR-ABL degrader shows more sustained inhibition of CML cell growth than ABL kinase inhibitor.
Effective passivation of Ag nanowire network by transparent tetrahedral amorphous carbon film for flexible and transparent thin film heaters
Authors: Seok Hae-Jun , Kim Jong-Kuk , Kim Han-Ki
Published: September 2018

We developed effective passivation method of flexible Ag nanowire (NW) network electrodes using transparent tetrahedral amorphous carbon (ta-C) film prepared by filtered cathode vacuum arc (FCVA) coating. Even at room temperature process of FCVA, the ta-C passivation layer effectively protect Ag NW network electrode and improved the ambient stability of Ag NW network without change of sheet resistance of Ag NW network. In addition, ta-C coated Ag NW electrode showed identical critical inner and outer bending radius to bare Ag NW due to the thin thickness of ta-C passivation layer. The time-temperature profiles demonstrate that the performance of the transparent and flexible thin film heater (TFH) with the ta-C/Ag NW network is better than that of a TFH with Ag NW electrodes due to thermal stability of FCVA grown ta-C layer. In addition, the transparent and flexible TFHs with ta-C/Ag NW showed robustness against external force due to its high hardness and wear resistance. This indicates that the FCVA coated ta-C is promising passivation and protective layer for chemically weak Ag NW network electrodes against sulfur in ambient.
Sub-wavelength terahertz imaging through optical rectification
Authors: Sanjuan Federico , Gaborit Gwenaël , Coutaz Jean-Louis
Published: September 2018

We record a sub-wavelength terahertz image of a caster sugar grain thanks to optical rectification in the sample excited with a femtosecond laser beam. The lateral spatial resolution of this technique is given by the laser spot size at the sample and here its measured value is 50 μm, i.e. ~λ/12. We give an estimation of the ultimate resolution that could be achieved with this method.
Advanced fabrication of biosensor on detection of Glypican-1 using S-Acetylmercaptosuccinic anhydride (SAMSA) modification of antibody
Authors: Dai Yifan , Abbasi Kevin , DePietro Michael , Butler Samantha , Liu Chung Chiun
Published: September 2018

Glypican-1 (GPC-1) has been recognized as biomarker of pancreatic cancer. Quantification of GPC-1 level is also pivotal to breast cancer and prostate cancer’s patients. We hereby report the first biosensor for GPC-1 detection. Instead of using crosslinking technique and surface immobilization of antibody, we applied a novel method for biosensor fabrication, using S-Acetylmercaptosuccinic anhydride (SAMSA) to modify the Anti-GPC-1 producing a thiol-linked Anti-GPC-1. The thiol-linked Anti-GPC-1 was then directly formed a single-layer antibody layer on the gold biosensor, minimizing the biosensor preparation steps significantly. Time of Flight Secondary Ions Mass Spectroscopy (TOF-SIMS) characterization verified the thiol-linked antibody layer and demonstrated a unique perspective for surface protein characterization. Differential pulse voltammetry (DPV) was applied to quantify GPC-1 antigen in undiluted human serum with a concentration range of 5,000 pg/µL to 100 pg/µL. The performance of this newly designed biosensor was also compared with modified self-assembled monolayer system fabricated biosensor, demonstrating the high-sensitivity and high-reproducibility of the SAMSA modified antibody based biosensor. This simple fabrication method can also expand to detection of other biomolecules. The simplified operation process shows great potential in clinical application development.
Interaction of TBC1D9B with Mammalian ATG8 Homologues Regulates Autophagic Flux
Authors: Liao Yong , Li Min , Chen Xiaoyun , Jiang Yu , Yin Xiao-Ming
Published: September 2018

Autophagosomes are double-membraned vesicles with cytosolic components. Their destination is to fuse with the lysosome to degrade the enclosed cargo. However, autophagosomes may be fused with other membrane compartments and possibly misguided by the RAB molecules from these compartments. The mechanisms ensuring the proper trafficking are not well understood. Yeast ATG8 and its mammalian homologues are critically involved in the autophagosome formation and expansion. We hypothesized that they could be also involved in the regulation of autophagosome trafficking. Using the yeast two-hybrid system, we found that TBC1D9B, a GTPase activating protein for RAB11A, interacted with LC3B. TBC1D9B could also interact with other mammalian ATG8 homologues. This interaction was confirmed with purified proteins in vitro, and by co-immunoprecipitation in vivo. The interacting domain of TBC1D9B with LC3 was further determined, which is unique and different from the known LC3-interacting region previously defined in other LC3-interacting molecules. Functionally, TBC1D9B could be co-localized with LC3B on the autophagosome membranes. Inhibition of TBC1D9B suppressed the turnover of membrane-bound LC3B and the autophagic degradation of long-lived proteins. TBC1D9B can thus positively regulate autophagic flux, possibly through its GTPase activity to inactivate RAB11A, facilitating the proper destination of the autophagosomes to the degradation.
Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells
Authors: Casalino-Matsuda S. Marina , Wang Naizhen , Ruhoff Peder T. , Matsuda Hiroaki , Nlend Marie C. , Nair Aisha , Szleifer Igal , Beitel Greg J. , Sznajder Jacob I. , Sporn Peter H. S.
Published: September 2018

Hypercapnia, the elevation of CO2in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO2for 24 h) vs normocapnia (5% CO2), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO2. These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.
HISDAC-US, historical settlement data compilation for the conterminous United States over 200 years
Authors: Leyk Stefan , Uhl Johannes H.
Published: September 2018

Human settlement plays a key role in understanding social processes such as urbanization and interactions between human and environmental systems but not much is known about the landscape evolution before the era of operational remote sensing technology. In this study, housing and property databases are used to create new gridded settlement layers describing human settlement processes at fine spatial and temporal resolution in the conterminous United States between 1810 and 2015. The main products are a raster composite layer representing the year of first settlement, and a raster time series of built-up intensity representing the sum of building areas in a pixel. Several accompanying uncertainty surfaces are provided to ensure the user is informed about inherent spatial, temporal and thematic uncertainty in the data. A validation study using high quality reference data confirms high levels of accuracy of the resulting data products. These settlement data will be of great interest in disciplines in which the long-term evolution of human settlement represents crucial information to explore novel research questions.
Methods for the detection of reactive oxygen species
Authors: Zhang Yinfeng , Dai Menghong , Yuan Zonghui
Published: September 2018

The combined usage of more than one method is recommended for better detection of reactive oxygen species.
Selectivity reversal of photocatalytic CO2 reduction by Pt loading
Authors: Ma Zhaoyu , Li Penghui , Ye Liqun , Wang Li , Xie Haiquan , Zhou Ying
Published: September 2018

The selectivity of semiconductor photocatalysts for CO2 reduction was effectively reversed from CO to CH4 due to the introduction of Pt.
Proanthocyanidin B2 attenuates postprandial blood glucose and its inhibitory effect on alpha-glucosidase: analysis by kinetics, fluorescence spectroscopy, atomic force microscopy and molecular docking
Authors: Han Lin , Zhang Lingling , Ma Wenfang , Li Ding , Shi Rujie , Wang Min
Published: September 2018

As a dimer of proanthocyanidin, proanthocyanidin B2 (PB2) was found to effectively attenuate postprandial blood glucose in mice after sucrose loading.
A novel sPEEK nanocomposite membrane with well-controlled sPOSS aggregation in tunable nanochannels for fast proton conduction
Authors: Kim Sang-Woo , Choi Seung-Young , Rhee Hee-Woo
Published: September 2018

To greatly increase the proton conductivity of a sPEEK nanocomposite membrane without water swelling problems, sulfonated PEEK (sPEEK) nanocomposite membranes were prepared by regulating the nanocomposite concentration of sulfonated POSS (sPOSS).
Reversible and repeatable phase transition at a negative temperature regime for doped and co-doped spin coated mixed valence vanadium oxide thin films
Authors: Mukherjee Dipta , Dey Arjun , Mary Esther A. Carmel , Sridhara N. , Kumar D. Raghavendra , Rajendra A. , Sharma Anand Kumar , Mukhopadhyay Anoop Kumar
Published: September 2018

Smooth, uniform mixed valance vanadium oxide (VO) thin films are grown on flexible, transparent Kapton and opaque Al6061 substrates by the spin coating technique at a constant rpm of 3000.
Triangular radial Nb2O5nanorod growth onc-plane sapphire for ultraviolet-radiation detection
Authors: Kim Kwan-Woo , Kim Bum Jun , Lee Sang Hoon , Nasir Tuqeer , Lim Hyung-Kyu , Choi Ik Jun , Jeong Byung Joo , Lee Jaeyeong , Yu Hak Ki , Choi Jae-Young
Published: September 2018

The triangular radial Nb2O5nanostructures with excellent crystallinities and 6-fold symmetry were grown epitaxially onc-plane sapphire and employed for ultraviolet-(UV)-radiation detection.
AIE-active polyanetholesulfonic acid sodium salts with room-temperature phosphorescence characteristics for Fe3+ detection
Authors: Qin Xiaojin , Wang Shiqi , Luo Lian , He Gang , Sun Huazhen , Gong Yongyang , Jiang Bingli , Wei Chun
Published: September 2018

Commercialized polyanetholesulfonic acid sodium salts have AIE activity and room temperature phosphorescence characteristics.
Writing and erasing multicolored information in diarylethene-based supramolecular gels
Authors: Hsu Chien-Wei , Sauvée Claire , Sundén Henrik , Andréasson Joakim
Published: September 2018

Diarylethene photoswitches in supramolecular gels constitute a system where the writing and erasing of multicolored fluorescent information is easily achieved.
Assembly modes of hexaphenylalanine variants as function of the charge states of their terminal ends
Authors: Diaferia Carlo , Balasco Nicole , Altamura Davide , Sibillano Teresa , Gallo Enrico , Roviello Valentina , Giannini Cinzia , Morelli Giancarlo , Vitagliano Luigi , Accardo Antonella
Published: September 2018

All F6 variants (charged or uncharged peptides) self-assemble in amyloid-like structures of rich β-sheets.
Double-atom catalysts: transition metal dimer-anchored C2N monolayers as N2 fixation electrocatalysts
Authors: Zhang Xu , Chen An , Zhang Zihe , Zhou Zhen
Published: September 2018

By first-principles computations, we investigated the electrocatalysis of transition metal atom-anchored C2N monolayers (TMx@C2N, x = 1 or 2) for N2 fixation and proposed that Mo2@C2N is a promising electrocatalyst for the reduction of N2 to NH3.
Manipulating the degradation behavior and biocompatibility of Mg alloy through a two-step treatment combining sliding friction treatment and micro-arc oxidation
Authors: Huo Wangtu , Lin Xiao , Lv Lu , Cao Huihui , Yu Sen , Yu Zhentao , Zhang Yusheng
Published: September 2018

The degradation behavior and biocompatibility of Mg alloy could be tailored by a two-step treatment.
Standardized microgel beads as elastic cell mechanical probes
Authors: Girardo S. , Träber N. , Wagner K. , Cojoc G. , Herold C. , Goswami R. , Schlüßler R. , Abuhattum S. , Taubenberger A. , Reichel F. , Mokbel D. , Herbig M. , Schürmann M. , Müller P. , Heida T. , Jacobi A. , Ulbricht E. , Thiele J. , Werner C. , Guck J.
Published: September 2018

Standardized polyacrylamide microgel beads as novel tools to calibrate experiments in biomechanics and to measure stresses in complex tissues.