bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular insights into genome-wide association studies of chronic kidney disease-defining traits
Authors: Xu Xiaoguang , Eales James M. , Akbarov Artur , Guo Hui , Becker Lorenz , Talavera David , Ashraf Fehzan , Nawaz Jabran , Pramanik Sanjeev , Bowes John , Jiang Xiao , Dormer John , Denniff Matthew , Antczak Andrzej , Szulinska Monika , Wise Ingrid , Prestes Priscilla R. , Glyda Maciej , Bogdanski Pawel , Zukowska-Szczechowska Ewa , Berzuini Carlo , Woolf Adrian S. , Samani Nilesh J. , Charchar Fadi J. , Tomaszewski Maciej
Published: November 2018

Genome-wide association studies (GWAS) have identified >100 loci of chronic kidney disease-defining traits (CKD-dt). Molecular mechanisms underlying these associations remain elusive. Using 280 kidney transcriptomes and 9958 gene expression profiles from 44 non-renal tissues we uncover gene expression partners (eGenes) for 88.9% of CKD-dt GWAS loci. Through epigenomic chromatin segmentation analysis and variant effect prediction we annotate functional consequences to 74% of these loci. Our colocalisation analysis and Mendelian randomisation in >130,000 subjects demonstrate causal effects of three eGenes (NAT8B, CASP9 and MUC1) on estimated glomerular filtration rate. We identify a common alternative splice variant in MUC1 (a gene responsible for rare Mendelian form of kidney disease) and observe increased renal expression of a specific MUC1 mRNA isoform as a plausible molecular mechanism of the GWAS association signal. These data highlight the variants and genes underpinning the associations uncovered in GWAS of CKD-dt.
Author Correction: Promoter interactome of human embryonic stem cell-derived cardiomyocytes connects GWAS regions to cardiac gene networks
Authors: Choy Mun-Kit , Javierre Biola M. , Williams Simon G. , Baross Stephanie L. , Liu Yingjuan , Wingett Steven W. , Akbarov Artur , Wallace Chris , Freire-Pritchett Paula , Rugg-Gunn Peter J. , Spivakov Mikhail , Fraser Peter , Keavney Bernard D.
Published: November 2018

In the original version of the Article, the gene symbol for tissue factor pathway inhibitor was inadvertently given as ‘TFP1’ instead of ‘TFPI’. This has now been corrected in both the PDF and HTML versions of the Article.
Demographic stochasticity drives epidemiological patterns in wildlife with implications for diseases and population management
Authors: Lambert Sébastien , Ezanno Pauline , Garel Mathieu , Gilot-Fromont Emmanuelle
Published: November 2018

Infectious diseases raise many concerns for wildlife and new insights must be gained to manage infected populations. Wild ungulates provide opportunities to gain such insights as they host many pathogens. Using modelling and data collected from an intensively monitored population of Pyrenean chamois, we investigated the role of stochastic processes in governing epidemiological patterns of pestivirus spread in both protected and hunted populations. We showed that demographic stochasticity led to three epidemiological outcomes: early infection fade-out, epidemic outbreaks with population collapse, either followed by virus extinction or by endemic situations. Without re-introduction, the virus faded out in >50% of replications within 4 years and did not persist >20 years. Test-and-cull of infected animals and vaccination had limited effects relative to the efforts devoted, especially in hunted populations in which only quota reduction somewhat improve population recovery. Success of these strategies also relied on the maintenance of a high level of surveillance of hunter-harvested animals. Our findings suggested that, while surveillance and maintenance of population levels at intermediate densities to avoid large epidemics are useful at any time, a ‘do nothing’ approach during epidemics could be the ‘least bad’ management strategy in populations of ungulates species facing pestivirus infection.
Marine mammal acoustic detections in the Greenland and Barents Sea, 2013 – 2014 seasons
Authors: De Vreese Steffen , van der Schaar Mike , Weissenberger Jürgen , Erbs Florence , Kosecka Monika , Solé Marta , André Michel
Published: November 2018

While the Greenland and Barents Seas are known habitats for several cetacean and pinniped species there is a lack of long-term monitoring data in this rapidly changing environment. Moreover, little is known of the ambient soundscapes, and increasing off-shore anthropogenic activities can influence the ecosystem and marine life. Baseline acoustic data is needed to better assess current and future soundscape and ecosystem conditions. The analysis of a year of continuous data from three passive acoustic monitoring devices revealed species-dependent seasonal and spatial variation of a large variety of marine mammals in the Greenland and Barents Seas. Sampling rates were 39 and 78 kHz in the respective locations, and all systems were operational at a duty cycle of 2 min on, 30 min off. The research presents a description of cetacean and pinniped acoustic detections along with a variety of unknown low-frequency tonal sounds, and ambient sound level measurements that fall within the scope of the European Marine Strategy Framework (MSFD). The presented data shows the importance of monitoring Arctic underwater biodiversity for assessing the ecological changes under the scope of climate change.
A novel dry-bonding approach to reduce collagen degradation and optimize resin-dentin interfaces
Authors: Stape Thiago Henrique Scarabello , Seseogullari-Dirihan Roda , Tjäderhane Leo , Abuna Gabriel , Martins Luís Roberto Marcondes , Tezvergil-Mutluay Arzu
Published: November 2018

In dentistry, the wet-bonding approach relies on water to maintain demineralized collagen expanded for proper resin infiltration; nevertheless, hydrolytic instability of the resin-dentin interface is inevitable with current bonding techniques. Considering dimethyl sulfoxide’s (DMSO) ability to “biomodify” collagen and precipitate enzymes, the aim was to test whether the use of DMSO would permit adequate resin bonding to H3PO4-etched dehydrated dentin and assess its impact on collagen degradation by host-derived enzymes. Etched dentin surfaces from extracted sound human molars were randomly bonded in wet or dry conditions using aqueous or ethanolic DMSO solutions as pretreatments and bonding resins with or without DMSO. Bonded teeth were sectioned into resin-dentin slabs for confocal in situ zymography and beams for microtensile bond strength test. Demineralized powdered dentin was incubated in the tested DMSO -media and a hydroxyproline assay evaluated dissolution of collagen peptides. Zymography was performed on protein extracts obtained from dry and wet H3PO4-ecthed dentin powder treated with the DMSO- media. The correlative biochemical analysis demonstrated that reduction of water content during dentin hybridization by the innovative dry-bonding approaches with DMSO is effective to inactivate host-derived MMP-2 and MMP-9 and thus reduce collagen degradation while simultaneously optimizing resin-dentin bonding.
Deciphering the evolutionary signatures of pinnipeds using novel genome sequences: The first genomes of Phoca largha, Callorhinus ursinus, and Eumetopias jubatus
Authors: Park Jung Youn , Kim Kwondo , Sohn Hawsun , Kim Hyun Woo , An Yong-Rock , Kang Jung-Ha , Kim Eun-Mi , Kwak Woori , Lee Chul , Yoo DongAhn , Jung Jaehoon , Sung Samsun , Yoon Joon , Kim Heebal
Published: November 2018

The pinnipeds, which comprise seals, sea lions, and walruses, are a remarkable group of marine animals with unique adaptations to semi-aquatic life. However, their genomes are poorly characterized. In this study, we sequenced and characterized the genomes of three pinnipeds (Phoca largha, Callorhinus ursinus, and Eumetopias jubatus), focusing on site-wise sequence changes. We detected rapidly evolving genes in pinniped lineages and substitutions unique to pinnipeds associated with amphibious sound perception. Phenotypic convergence-related sequence convergences are not common in marine mammals. For example, FASN, KCNA5, and IL17RA contain substitutions specific to pinnipeds, yet are potential candidates of phenotypic convergence (blubber, response to hypoxia, and immunity to pathogens) in all marine mammals. The outcomes of this study will provide insight into targets for future studies of convergent evolution or gene function.
Reading ability and phoneme categorization
Authors: O’Brien Gabrielle E. , McCloy Daniel R. , Kubota Emily C. , Yeatman Jason D.
Published: November 2018

Dyslexia is associated with abnormal performance on many auditory psychophysics tasks, particularly those involving the categorization of speech sounds. However, it is debated whether those apparent auditory deficits arise from (a) reduced sensitivity to particular acoustic cues, (b) the difficulty of experimental tasks, or (c) unmodeled lapses of attention. Here we investigate the relationship between phoneme categorization and reading ability, with special attention to the nature of the cue encoding the phoneme contrast (static versus dynamic), differences in task paradigm difficulty, and methodological details of psychometric model fitting. We find a robust relationship between reading ability and categorization performance, show that task difficulty cannot fully explain that relationship, and provide evidence that the deficit is not restricted to dynamic cue contrasts, contrary to prior reports. Finally, we demonstrate that improved modeling of behavioral responses suggests that performance does differ between children with dyslexia and typical readers, but that the difference may be smaller than previously reported.
SEPROGADIC – serum protein-based gastric cancer prediction model for prognosis and selection of proper adjuvant therapy
Authors: Ahn Hee-Sung , Sohn Tae Sung , Kim Mi Jeong , Cho Byoung Kyu , Kim Su Mi , Kim Seung Tae , Yi Eugene C. , Lee Cheolju
Published: November 2018

Gastric cancer (GC) patients usually receive surgical treatment. Postoperative therapeutic options such as anticancer adjuvant therapies (AT) based on prognostic prediction models would provide patient-specific treatment to decrease postsurgical morbidity and mortality rates. Relevant prognostic factors in resected GC patient’s serum may improve therapeutic measures in a non-invasive manner. In order to develop a GC prognostic model, we designed a retrospective study. In this study, serum samples were collected from 227 patients at a 4-week recovery period after D2 lymph node dissection, and 103 cancer-related serum proteins were analyzed by multiple reaction monitoring mass spectrometry. Using the quantitative values of the serum proteins, we developed SEPROGADIC (SErum PROtein-based GAstric cancer preDICtor) prognostic model consisting of 6 to 14 serum proteins depending on detailed purposes of the model, prognosis prediction and proper AT selection. SEPROGADIC could clearly classify patients with good or bad prognosis at each TNM stage (1b, 2, 3 and 4) and identify a patient subgroup who would benefit from CCRT (combined chemoradiation therapy) rather than CTX (chemotherapy), or vice versa. Our study demonstrated that serum proteins could serve as prognostic factors along with clinical stage information in patients with resected gastric cancer, thus allowing patient-tailored postsurgical treatment.
Role of flow of information in the speedup of quantum evolution
Authors: Wang J. , Wu Y. N. , Xie Z. Y.
Published: November 2018

Quantum evolution can be accelerated in a non-Markovian environment. Previous results show that the formation of a system-environment bound state governs the quantum speedup. Although a stronger bound state in the system-environment spectrum may seem like it should cause greater speed of evolution, this seemingly intuitive thinking may not always be correct. We illustrate this by investigating a classical-driven qubit interacting with a photonic crystal waveguide in the presence of a mirror, resulting in non-Markovian dynamics for the system. Within the considered model, we show the influence of the mirror and the classical field on the evolution speed of the system. In particular, we find that the formation of a bound state is not the essential reason for the acceleration of evolution. The quantum speedup is attributed to the flow of information, regardless of the direction in which the information flows. Our conclusion can also be used in other non-Markovian environments.
Clinical performance of an analytically validated assay in comparison to microarray technology to assess PITX2 DNA-methylation in breast cancer
Authors: Schricker Gabriele , Napieralski Rudolf , Noske Aurelia , Piednoir Elodie , Manner Olivia , Schüren Elisabeth , Lauber Jürgen , Perkins Jonathan , Magdolen Viktor , Schmitt Manfred , Ulm Kurt , Weichert Wilko , Kiechle Marion , Martens John W. M. , Wilhelm Olaf G.
Published: November 2018

Significant evidence has accumulated that DNA-methylation of the paired-like homeodomain transcription factor 2 (PITX2) gene can serve as a prognostic and predictive biomarker in breast cancer. PITX2 DNA-methylation data have been obtained so far from microarray and polymerase chain reaction (PCR)-based research tests. The availability of an analytically validated in vitro methylation-specific real-time PCR assay format (therascreen PITX2 RGQ PCR assay) intended for the determination of the percent methylation ratio (PMR) in the (PITX2) promoter 2 prompted us to investigate whether the clinical performance of these different assay systems generate comparable clinical outcome data. Mathematically converted microarray data of a previous breast cancer study (n = 204) into PMR values leads to a PITX2 cut-off value at PMR 14.73. Recalculation of the data to experimentally equivalent PMRs with the PCR PITX2 assay leads to a cut-off value at PMR 12 with the highest statistical significance. This cut-off predicts outcome of high-risk breast cancer patients to adjuvant anthracycline-based chemotherapy (n = 204; Hazard Ratio 2.48; p < 0.001) comparable to microarray generated results (n = 204; Hazard ratio 2.32; p < 0.0001). The therascreen PITX2 RGQ PCR assay is an analytically validated test with high reliability and robustness and predicts outcome of high-risk breast cancer patients to anthracycline-based chemotherapy.
Safe and efficient novel approach for non-invasive gene electrotransfer to skin
Authors: Pasquet Lise , Chabot Sophie , Bellard Elisabeth , Markelc Bostjan , Rols Marie-Pierre , Reynes Jean-Paul , Tiraby Gérard , Couillaud Franck , Teissie Justin , Golzio Muriel
Published: November 2018

Gene transfer into cells or tissue by application of electric pulses (i.e. gene electrotransfer (GET)) is a non-viral gene delivery method that is becoming increasingly attractive for clinical applications. In order to make GET progress to wide clinical usage its efficacy needs to be improved and the safety of the method has to be confirmed. Therefore, the aim of our study was to increase GET efficacy in skin, by optimizing electric pulse parameters and the design of electrodes. We evaluated the safety of our novel approach by assaying the thermal stress effect of GET conditions and the biodistribution of a cytokine expressing plasmid. Transfection efficacy of different pulse parameters was determined using two reporter genes encoding for the green fluorescent protein (GFP) and the tdTomato fluorescent protein, respectively. GET was performed using non-invasive contact electrodes immediately after intradermal injection of plasmid DNA into mouse skin. Fluorescence imaging of transfected skin showed that a sophistication in the pulse parameters could be selected to get greater transfection efficacy in comparison to the standard ones. Delivery of electric pulses only mildly induced expression of the heat shock protein Hsp70 in a luminescent reporting transgenic mouse model, demonstrating that there were no drastic stress effects. The plasmid was not detected in other organs and was found only at the site of treatment for a limited period of time. In conclusion, we set up a novel approach for GET combining new electric field parameters with high voltage short pulses and medium voltage long pulses using contact electrodes, to obtain a high expression of both fluorescent reporter and therapeutic genes while showing full safety in living animals.
Hyperactivated stallion spermatozoa fail to exhibit a rheotaxis-like behaviour, unlike other species
Authors: Romero-Aguirregomezcorta Jon , Sugrue Emer , Martínez-Fresneda Lucía , Newport David , Fair Sean
Published: November 2018

The journey of spermatozoa through the female genital tract is facilitated by rheotaxis, or the cell’s preference to swim against a flow, as well as thigmotaxis, the wall tracking behaviour, which guides them to the site of fertilisation. The aim of this study was to characterise the rheotactic and thigmotactic response of stallion sperm within a microfluidic channel. Stallion sperm rheotaxis was assessed within the microfluidic channel with regard to: (i) A range of flow velocities, (ii) Varying media viscosity and (iii) Sperm hyperactivation. Sperm distribution across the microfluidic channel was also studied and compared to human and ram sperm. Stallion sperm progressed furthest at a velocity range of 10–30 µm/s, with an optimum velocity of 20 µm/s. A flow viscosity of 2.5cP or greater reduced sperm rheotaxis (P < 0.05). Stallion sperm that were hyperactivated were unable to exhibit rheotaxis within the microfluidic channel, whereas, both hyperactivated human and ram sperm did exhibit positive rheotaxis under the same conditions. The number of sperm swimming near the microfluidic channel walls was higher than in the microfluidic channel centre (P < 0.05). This is the first study to illustrate that stallion sperm are rheotactically responsive and increasing viscosity reduces this response. We also demonstrated that sperm are predominantly inclined to swim along a surface and uniquely, hyperactivated stallion sperm are non-progressive and do not exhibit a rheotactic response unlike other species.
Tracing whale myoglobin evolution by resurrecting ancient proteins
Authors: Isogai Yasuhiro , Imamura Hiroshi , Nakae Setsu , Sumi Tomonari , Takahashi Ken-ichi , Nakagawa Taro , Tsuneshige Antonio , Shirai Tsuyoshi
Published: November 2018

Extant cetaceans, such as sperm whale, acquired the great ability to dive into the ocean depths during the evolution from their terrestrial ancestor that lived about 50 million years ago. Myoglobin (Mb) is highly concentrated in the myocytes of diving animals, in comparison with those of land animals, and is thought to play a crucial role in their adaptation as the molecular aqualung. Here, we resurrected ancestral whale Mbs, which are from the common ancestor between toothed and baleen whales (Basilosaurus), and from a further common quadrupedal ancestor between whale and hippopotamus (Pakicetus). The experimental and theoretical analyses demonstrated that whale Mb adopted two distinguished strategies to increase the protein concentration in vivo along the evolutionary history of deep sea adaptation; gaining precipitant tolerance in the early phase of the evolution, and increase of folding stability in the late phase.
Amyloid β toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques
Authors: Kageyama Yusuke , Saito Atsushi , Pletnikova Olga , Rudow Gay L. , Irie Yumi , An Yang , Murakami Kazuma , Irie Kazuhiro , Resnick Susan M. , Fowler David R. , Martin Lee J. , Troncoso Juan C.
Published: November 2018

Amyloid β (Aβ) plays a critical role in the pathogenesis of Alzheimer’s disease. Nevertheless, its distribution and clearance before Aβ plaque formation needs to be elucidated. Using an optimized immunofluorescent staining method, we examined the distribution of Aβ in the post-mortem parietal cortex of 35 subjects, 30 to 65 years of age, APOE ε3/ε3, without AD lesions. We used 11A1, an antibody against an Aβ conformer which forms neurotoxic oligomers. 11A1 immunoreactivity (IR) was present in cortical neurons, pericapillary spaces, astrocytes and the extracellular compartment at 30 years of age. The percentage of neurons with 11A1 IR did not change with age, but the number and percentage of astrocytes with 11A1 IR gradually increased. Notably, the percentage of pericapillary spaces labeled with 11A1 IR declined significantly in the 5th decade of the life, at the same time that 11A1 IR increased in the extracellular space. Our findings indicate that the Aβ toxic conformer is normally present in various cell types and brain parenchyma, and appears to be constitutively produced, degraded, and cleared from the inferior parietal cortex. The decrease in pericapillary Aβ and the concomitant increase of extracellular Aβ may reflect an age-associated impairment in Aβ clearance from the brain.
Rapid and selective recovery of palladium from platinum group metals and base metals using a thioamide-modified calix[4]arene extractant in environmentally friendly hydrocarbon fluids
Authors: Yamada Manabu , Rajiv Gandhi Muniyappan , Shibayama Atsushi
Published: November 2018

A novel macrocyclic calix[4]arene extractant having a long alkyl chain thioamide, 25,26,27,28-tetrakis(N-n-octylthiocarbamoyl)methoxy-5,11,17,23-tetra-tert-butylcalix[4]arene (1), was synthesized from 25,26,27,28-tetrakis(N-n-octylcarbamoyl)methoxy-5,11,17,23-tetra-tert-butylcalix[4]arene (2) using Lawesson’s reagent. Extractant1was characterized using1H NMR,13C NMR, FT-IR spectroscopy, and elemental analysis. The Pd(II) extraction abilities of1and2were studied in high-boiling-point and environmentally friendly hydrocarbon diluents. Pd(II) extraction experiments were conducted using single-metal Pd(II) solutions, simulated mixed palladium group metal (PGM) solutions, and acid-leached automotive catalyst residue solutions. Different experimental conditions, including the shaking time, HCl/HNO3concentration, Pd(II) concentration, extractant concentration, and the organic/aqueous phase ratio, were studied systematically. Extractant1showed very selective (> 99.9%) Pd(II) extraction from the mixed PGM/base metal solutions and the acid-leached automotive catalyst residue solution. Conversely, the Pd(II) extraction ability of extractant2was found to be negligible. Extractant1showed very fast extraction kinetics and a high extraction capacity as compared to those of the commercial extractant di-n-octyl sulfide. Effective stripping of Pd(II) from1was performed using HCI, HNO3, NH3, and HCl-thiourea solutions. Furthermore,1was successfully recycled over five extraction/stripping cycles. The Pd(II) extraction mechanism of1was studied using FT-IR spectroscopy. Extractant1exhibited very selective Pd(II) extraction and high acid stability, demonstrating its industrial applicability for the extraction of Pd(II) from leached automotive catalyst liquors containing PGMs and base metals.
Rapid detection of colistin resistance in Acinetobacter baumannii using MALDI-TOF-based lipidomics on intact bacteria
Authors: Dortet Laurent , Potron Anais , Bonnin Rémy A. , Plesiat Patrick , Naas Thierry , Filloux Alain , Larrouy-Maumus Gerald
Published: November 2018

With the dissemination of extremely drug resistant bacteria, colistin is now considered as the last-resort therapy for the treatment of infection caused by Gram-negative bacilli (including carbapenemase producers). Unfortunately, the increase use of colistin has resulted in the emergence of resistance as well. In A. baumannii, colistin resistance is mostly caused by the addition of phosphoethanolamine to the lipid A through the action of a phosphoethanolamine transferase chromosomally-encoded by the pmrC gene, which is regulated by the two-component system PmrA/PmrB. In A. baumannii clinical isolate the main resistance mechanism to colistin involves mutations in pmrA, pmrB or pmrC genes leading to the overexpression of pmrC. Although, rapid detection of resistance is one of the key issues to improve the treatment of infected patient, detection of colistin resistance in A. baumannii still relies on MIC determination through microdilution, which is time-consuming (16–24 h). Here, we evaluated the performance of a recently described MALDI-TOF-based assay, the MALDIxin test, which allows the rapid detection of colistin resistance-related modifications to lipid A (i.e phosphoethanolamine addition). This test accurately detected all colistin-resistant A. baumannii isolates in less than 15 minutes, directly on intact bacteria with a very limited sample preparation prior MALDI-TOF analysis.
Wide-range tuning of interfacial exchange coupling between ferromagnetic Au/Co and ferrimagnetic Tb/Fe(Co) multilayers
Authors: Frąckowiak Łukasz , Kuświk Piotr , Urbaniak Maciej , Chaves-O’Flynn Gabriel David , Stobiecki Feliks
Published: November 2018

The ability to perform wide-range tuning of the magnetic field required to switch the magnetization of ferromagnetic layers with perpendicular magnetic anisotropy is of great importance for many applications. We show that, for (Au/Co)2(3) multilayers, this field can be changed from minus several kOe to plus several kOe because of changes to the coupling with a ferrimagnetic multilayer [either (Tb/Fe)6 or (Tb/Co)6] across a Au spacer (either homogeneous 1 nm thick or wedge-shaped). The adjustable parameters are the ratio of sublayer thicknesses of the ferrimagnet and the sequence of layers around the Au spacer. The change of the sequence from Co/Au/Co to Tb/Au/Co is accompanied by both the reduction of the interaction energy and the change of the magnetic field sign necessary to switch the magnetization of ferromagnetic multilayers. For a 1 nm thick Au spacer this fields change from positive (negative) to negative (positive) if the ferrimagnet is dominated by the transition metal (rare earth) as a result of its composition. The characteristic oscillatory behavior of RKKY-like coupling is demonstrated using a system with a wedge-shaped Au spacer.
Telomerase gene expression bioassays indicate metabolic activation of genotoxic lower chlorinated polychlorinated biphenyls
Authors: Vasko Theresa , Hoffmann Jenny , Gostek Sonja , Schettgen Thomas , Quinete Natalia , Preisinger Christian , Kraus Thomas , Ziegler Patrick
Published: November 2018

Polychlorinated biphenyls (PCBs) are ubiquitously occurring pollutants with different chemical and toxicological properties. In this study we evaluated blood plasma samples of two PCB-exposed cohorts for their ability to alter telomerase (hTERT) gene expression. Blood plasma from PCB-exposed individuals inhibited hTERT expression depending solely on the concentration of lower chlorinated PCBs, with the lowest observed adverse effect level (LOAEL) at a plasma concentration between 0.5 and 2 µg/L of LC PCBs. Individual OH-metabolites derived from the WHO indicator congeners PCB 28 and PCB 101 mimicked these effects on hTERT expression in vitro with high toxicity, including DNA damage. However, by the combination of different OH-metabolites, the bio effective PCB concentration was reduced and the respective effects on hTERT expression could be increased. At a concentration which showed no toxic activity in MTT assay, hTERT inhibition reflected the interference of OH-PCBs with the mitochondrial respiratory chain, which could lead to the production of reactive oxygen species (ROS). As individual OH-metabolites already showed a much stronger inhibition of hTERT gene expression at a lower concentration than their parental compounds, the hTERT gene expression bioassay described in this study seems to indicate metabolic activation of LC PCBs rather than the mere effect of LC PCBs on their own. In summary, this study provides dose-response linkages between effects of lower chlorinated PCBs and their concentrations in human plasma.
Bayes-Like Integration of a New Sensory Skill with Vision
Authors: Negen James , Wen Lisa , Thaler Lore , Nardini Marko
Published: November 2018

Humans are effective at dealing with noisy, probabilistic information in familiar settings. One hallmark of this is Bayesian Cue Combination: combining multiple noisy estimates to increase precision beyond the best single estimate, taking into account their reliabilities. Here we show that adults also combine a novel audio cue to distance, akin to human echolocation, with a visual cue. Following two hours of training, subjects were more precise given both cues together versus the best single cue. This persisted when we changed the novel cue’s auditory frequency. Reliability changes also led to a re-weighting of cues without feedback, showing that they learned something more flexible than a rote decision rule for specific stimuli. The main findings replicated with a vibrotactile cue. These results show that the mature sensory apparatus can learn to flexibly integrate new sensory skills. The findings are unexpected considering previous empirical results and current models of multisensory learning.
The step-like evolution of Arctic open water
Authors: Goldstein Michael A. , Lynch Amanda H. , Zsom Andras , Arbetter Todd , Chang Andres , Fetterer Florence
Published: November 2018

September open water fraction in the Arctic is analyzed using the satellite era record of ice concentration (1979–2017). Evidence is presented that three breakpoints (shifts in the mean) occurred in the Pacific sector, with higher amounts of open water starting in 1989, 2002, and 2007. Breakpoints in the Atlantic sector record of open water are evident in 1971 in longer records, and around 2000 and 2011. Multiple breakpoints are also evident in the Canadian and Russian halves. Statistical models that use detected breakpoints of the Pacific and Atlantic sectors, as well as models with breakpoints in the Canadian and Russian halves and the Arctic as a whole, outperform linear trend models in fitting the data. From a physical standpoint, the results support the thesis that Arctic sea ice may have critical points beyond which a return to the previous state is less likely. From an analysis standpoint, the findings imply that de-meaning the data using the breakpoint means is less likely to cause spurious signals than employing a linear detrend.
Solid and macroporous Fe3C/N-C nanofibers with enhanced electromagnetic wave absorbability
Authors: Liu Huihui , Li Yajing , Yuan Mengwei , Sun Genban , Liao Qingliang , Zhang Yue
Published: November 2018

A series of solid and macroporous N-doped carbon nanofibers composed of Fe3C nanoparticles (named as solid Fe3C/N-C NFs, solid Fe3C/N-C NFs-1, solid Fe3C/N-C NFs-2, macroporous Fe3C/N-C NFs, macroporous Fe3C/N-C NFs-1 and macroporous Fe3C/N-C NFs-2, respectively) were prepared through carbonization of as-electrospun nanofiber precursors. The results show that the magnetic Fe3C nanoparticles (NPs) dispersed homogeneously on the N-doped carbon fibers; as-prepared six materials exhibit excellent microwave absorption with a lower filler content in comparison with other magnetic carbon hybrid nanocomposites in related literatures. Particularly, the solid Fe3C/N-C NFs have an optimal reflection loss value (RL) of −33.4 dB at 7.6 GHz. For solid Fe3C/N-C NFs-2, the effective absorption bandwidth (EAB) at RL value below −10 dB can be up to 6.2 GHz at 2 mm. The macroporous Fe3C/N-C NFs have a broadband absorption area of 4.8 GHz at 3 mm. The EAB can be obtained in the 3.6–18.0 GHz frequency for the thickness of absorber layer between 2 and 6 mm. These Fe3C–based nanocomposites can be promising as lightweight, effective and low-metal content microwave absorption materials in 1–18 GHz.
Pseudomonas aeruginosa mutants defective in glucose uptake have pleiotropic phenotype and altered virulence in non-mammal infection models
Authors: Raneri Matteo , Pinatel Eva , Peano Clelia , Rampioni Giordano , Leoni Livia , Bianconi Irene , Jousson Olivier , Dalmasio Chiara , Ferrante Palma , Briani Federica
Published: November 2018

Pseudomonasspp. are endowed with a complex pathway for glucose uptake that relies on multiple transporters. In this work we report the construction and characterization ofPseudomonas aeruginosasingle and multiple mutants with unmarked deletions of genes encoding outer membrane (OM) and inner membrane (IM) proteins involved in glucose uptake. We found that a triple ΔgltKGFΔgntPΔkguTmutant lacking all known IM transporters (named GUN for Glucose Uptake Null) is unable to grow on glucose as unique carbon source. More than 500 genes controlling both metabolic functions and virulence traits show differential expression in GUN relative to the parental strain. Consistent with transcriptomic data, the GUN mutant displays a pleiotropic phenotype. Notably, the genome-wide transcriptional profile and most phenotypic traits differ between the GUN mutant and the wild type strain irrespective of the presence of glucose, suggesting that the investigated genes may have additional roles besides glucose transport. Finally, mutants carrying single or multiple deletions in the glucose uptake genes showed attenuated virulence relative to the wild type strain inGalleria mellonella, but not inCaenorhabditis elegansinfection model, supporting the notion that metabolic functions may deeply impactP.aeruginosaadaptation to specific environments found inside the host.
Communal breeding affects offspring behaviours associated with a competitive social environment
Authors: Fischer Stefan , Pujol Neus T. , Bolton Rhiannon , Hurst Jane L. , Stockley Paula
Published: November 2018

Communal breeding is characterised by shared care of offspring produced by more than one female, and can affect the behavioural development of young. The decision to care communally can vary according to local conditions, and has been hypothesised to occur more frequently when social competition is intense. However, it is unknown whether communal rearing of young influences adult behaviours likely to be adaptive under competitive conditions. Here, using a controlled experimental approach, we investigate effects of communal rearing on competitive and exploratory behaviours of adult male house mice. In tests of competitive scent marking, only communally-reared subjects discriminated between related and unrelated rivals, depositing more scent marks in close proximity to unrelated males. Communally-reared subjects also displayed higher exploratory tendencies, with an increased probability of crossing a water barrier, while not exhibiting higher activity levels in an open field test. Since exploration tendencies and discrimination between kin and non-kin are likely to be advantageous when dispersing from the natal territory or in a high density population, our findings suggest that communal rearing prepares male house mice for a competitive social environment. Our results add to growing evidence that the early social environment influences development of important behavioural competences to cope with social challenges later in life.
A Rabbit Corneal Endothelial Dysfunction Model Using Endothelial-Mesenchymal Transformed Cells
Authors: Yamashita Kazuya , Hatou Shin , Inagaki Emi , Higa Kazunari , Tsubota Kazuo , Shimmura Shigeto
Published: November 2018

Unlike humans, rabbit corneal endothelial wounds are known to spontaneously heal. The current study was aimed to develop a new rabbit bullous keratopathy model using corneal endothelial cells that were induced to undergo endothelial-mesenchymal transformation (EMT). EMT was induced in rabbit corneal endothelial cells (RCECs) by culturing with TGFβ and basic FGF Supplemented Medium. The corneal endothelia in recipient rabbits were mechanically scraped from the corneal endothelial surface inside an 8 mm mark. Then, a suspension of EMT-induced RCECs (EMT-RCECs) was injected into the anterior chamber. Eyes injected with freshly isolated RCECs (Fresh RCECs group) and eyes that were scraped without injection of cells (Scrape group) were used as controls. Immediately following operation, subepithelial and stromal edema was observed with increased central corneal thickness and corneal opacity in all groups. In the EMT-RCECs group, bullous keratopathy persisted for 42 days up to the end of the study. In the Fresh-RCECs and Scrape groups, corneal transparency and thickness recovered by 7 days after treatment and was maintained up to 42 days. The activated fibroblast marker, α-SMA, was observed spanning from corneal endothelium to corneal stroma in the EMT-RCECs group. Interestingly, α-SMA was upregulated in the Scrape-group as well. In all groups, there was no damage to other intraocular structures, and intraocular pressure was normal throughout the observation period. Transplanting a fresh donor cornea effectively treated corneal edema due to bullous keratopathy. This model is a promising tool for pre-clinical trials in the development of new therapies against corneal endothelial dysfunction.
Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood
Authors: Knight Anna K. , Park Hea Jin , Hausman Dorothy B. , Fleming Jennifer M. , Bland Victoria L. , Rosa Gisselle , Kennedy Elizabeth M. , Caudill Marie A. , Malysheva Olga , Kauwell Gail P. A. , Sokolow Andrew , Fisher Susan , Smith Alicia K. , Bailey Lynn B.
Published: November 2018

One-carbon metabolism is essential for multiple cellular processes and can be assessed by the concentration of folate metabolites in the blood. One-carbon metabolites serve as methyl donors that are required for epigenetic regulation. Deficiencies in these metabolites are associated with a variety of poor health outcomes, including adverse pregnancy complications. DNA methylation is known to vary with one-carbon metabolite concentration, and therefore may modulate the risk of adverse pregnancy outcomes. This study addresses changes in one-carbon indices over pregnancy and the relationship between maternal and child DNA methylation and metabolite concentrations by leveraging data from 24 mother-infant dyads. Five of the 13 metabolites measured from maternal blood and methylation levels of 993 CpG sites changed over the course of pregnancy. In dyads, maternal and fetal one-carbon concentrations were highly correlated, both early in pregnancy and at delivery. The 993 CpG sites whose methylation levels changed over pregnancy in maternal blood were also investigated for associations with metabolite concentrations in infant blood at delivery, where five CpG sites were associated with the concentration of at least one metabolite. Identification of CpG sites that change over pregnancy may result in better characterization of genes and pathways involved in maintaining a healthy, term pregnancy.
Exploring the Sulfatase 1 Catch Bond Free Energy Landscape using Jarzynski’s Equality
Authors: Walhorn Volker , Möller Ann-Kristin , Bartz Christian , Dierks Thomas , Anselmetti Dario
Published: November 2018

In non-covalent biological adhesion, molecular bonds commonly exhibit a monotonously decreasing life time when subjected to tensile forces (slip bonds). In contrast, catch bonds behave counter intuitively, as they show an increased life time within a certain force interval. To date only a hand full of catch bond displaying systems have been identified. In order to unveil their nature, a number of structural and phenomenological models have been introduced. Regardless of the individual causes for catch bond behavior, it appears evident that the free energy landscapes of these interactions bear more than one binding state. Here, we investigated the catch bond interaction between the hydrophilic domain of the human cell surface sulfatase 1 (Sulf1HD) and its physiological substrate heparan sulfate (HS) by atomic force microscopy based single molecule force spectroscopy (AFM-SMFS). Using Jarzynski’s equality, we estimated the associated Gibbs free energy and provide a comprehensive thermodynamic and kinetic characterization of Sulf1HD/HS interaction. Interestingly, the binding potential landscape exhibits two distinct potential wells which confirms the recently suggested two state binding. Even though structural data of Sulf1HD is lacking, our results allow to draft a detailed picture of the directed and processive desulfation of HS.
Soy-Induced Fecal Metabolome Changes in Ovariectomized and Intact Female Rats: Relationship with Cardiometabolic Health
Authors: Vieira-Potter Victoria J. , Cross Tzu-Wen L. , Swanson Kelly S. , Sarma Saurav J. , Lei Zhentian , Sumner Lloyd W. , Rosenfeld Cheryl S.
Published: November 2018

Phytoestrogens are plant-derived compounds found in a variety of foods, most notably, soy. These compounds have been shown to improve immuno-metabolic health, yet mechanisms remain uncertain. We demonstrated previously that dietary phytoestrogen-rich soy (SOY) rescued metabolic dysfunction/inflammation following ovariectomy (OVX) in female rats; we also noted remarkable shifts in gut microbiota in SOY vs control diet-fed rats. Importantly, specific bacteria that significantly increased in those fed the SOY correlated positively with several favorable host metabolic parameters. One mechanism by which gut microbes might lead to such host effects is through production of bacterial metabolites. To test this possibility, we utilized non-targeted gas chromatography–mass spectrometry (GCMS) to assess the fecal metabolome in those previously studied animals. Partial least square discriminant analysis (PLSDA) revealed clear separation of fecal metabolomes based on diet and ovarian state. In particular, SOY-fed animals had greater fecal concentrations of the beneficial bacterial metabolite, S-equol, which was positively associated with several of the bacteria upregulated in the SOY group. S-equol was inversely correlated with important indicators of metabolic dysfunction and inflammation, suggesting that this metabolite might be a key mediator between SOY and gut microbiome-positive host health outcomes.
Role of filler and its heterostructure on moisture sorption mechanisms in polyimide films
Authors: Sharma Hom N. , Kroonblawd Matthew P. , Sun Yunwei , Glascoe Elizabeth A.
Published: November 2018

Moisture sorption and diffusion exacerbate hygrothermal aging and can significantly alter the chemical and mechanical properties of polymeric-based components over time. In this study, we employ a multi-pronged multi-scale approach to model and understand moisture diffusion and sorption processes in polyimide polymers. A reactive transport model with triple-mode sorption (i.e., Henry’s, Langmuir, and pooling), experiments, and first principles atomistic computations were combined to synergistically explore representative systems of Kapton H and Kapton HN polymers. We find that the CaHPO4 processing aid used in Kapton HN increases the total moisture uptake (~0.5 wt%) relative to Kapton H. Henry’s mode is found to play a major role in moisture uptake for both materials, accounting for >90% contribution to total uptake.However, the pooling mode uptake in Kapton HN was ~5 times higher than in Kapton H. First principles thermodynamics calculations based on density functional theory predict that water molecules chemisorb (with binding energy  ~17–25 kcal/mol) on CaHPO4 crystal surfaces. We identify significant anisotropy in surface binding affinity, suggesting a possible route to tune and mitigate moisture uptake in Kapton-based systems through controlled crystal growth favoring exposure of CaHPO4 (101) surfaces during manufacturing.
Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine
Authors: Tabe Yoko , Saitoh Kaori , Yang Haeun , Sekihara Kazumasa , Yamatani Kotoko , Ruvolo Vivian , Taka Hikari , Kaga Naoko , Kikkawa Mika , Arai Hajime , Miida Takashi , Andreeff Michael , Spagnuolo Paul A. , Konopleva Marina
Published: November 2018

Adipocytes are the prevalent stromal cell type in adult bone marrow (BM), and leukemia cells continuously adapt to deficiency of nutrients acquiring chemoresistant profiles in the BM microenvironment. We have previously shown that fatty acid metabolism is a key energy pathway for survival of acute myeloid leukemia (AML) cells in the adipocyte-abundant BM microenvironment. The novel fatty acid β-oxidation (FAO) inhibitor avocatin B, an odd-numbered carbon lipid derived from the avocado fruit, induced apoptosis and growth inhibition in mono-cultured AML cells. In AML cells co-cultured with BM adipocytes, FAO inhibition with avocatin B caused adaptive stimulation of free fatty acid (FFA) uptake through upregulation of FABP4 mRNA, enhanced glucose uptake and switch to glycolysis. These changes reflect the compensatory response to a shortage of FFA supply to the mitochondria, and facilitate the protection of AML cells from avocatin B–induced apoptosis in the presence of BM adipocytes. However, the combination treatment of avocatin B and conventional anti-AML therapeutic agent cytarabine (AraC) increased reactive oxygen species and demonstrated highly synergistic effects on AML cells under BM adipocyte co-culture condition. These findings highlight the potential for combination regimens of AraC and FAO inhibitors that target bone marrow-resident chemoresistant AML cells.
RNA sequencing-based analysis of the laying hen uterus revealed the novel genes and biological pathways involved in the eggshell biomineralization
Authors: Sah Nirvay , Kuehu Donna Lee , Khadka Vedbar Singh , Deng Youping , Peplowska Karolina , Jha Rajesh , Mishra Birendra
Published: November 2018

Eggshell is the outermost calcified covering of an egg that protects it from microbial invasion and physical damage, and is critical for egg quality. However, understanding of the genes/proteins and the biological pathways regulating the eggshell formation is still obscure. We hypothesized that the transcriptomic analysis of the chicken uteri using RNA-sequencing may reveal novel genes and biological pathways involved in the eggshell biomineralization. RNA-sequence analysis using uteri of laying hens at 15–20 h post-ovulation (layers, n = 3) and non-laying (non-layers, n = 3) hens was carried out. About 229 differentially expressed genes (DEGs) were up-regulated in the layers compared to the non-layers. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Ingenuity Pathway Analysis (IPA) revealed more than ten novel genes and biological pathways related to calcium transport and mineralization in the uterus. Based on the enriched pathways and molecular function analysis, 12 DEGs related to eggshell mineralization were further analyzed in the uteri of layers (3 h and 15–20 h post-ovulation), non-layers and molters using qPCR. Expressions of OC-116 (regulator of mineralization), OTOP2 (modulator of cellular calcium influx), CALCB (intracellular release of Ca-ions), STC2 (increases alkaline phosphatase activity), and ATP2C2 (cellular import of Ca-ions) were significantly higher in the uteri of laying hen at 15–20 h post-ovulation. This study identified the involvement of novel genes and their proposed biological pathways in the regulation of eggshell formation.
Si and Ge based metallic core/shell nanowires for nano-electronic device applications
Authors: Bhuyan Prabal Dev , Kumar Ashok , Sonvane Yogesh , Gajjar P. N. , Magri Rita , Gupta Sanjeev K.
Published: November 2018

One dimensional heterostructure nanowires (NWs) have attracted a large attention due to the possibility of easily tuning their energy gap, a useful property for application to next generation electronic devices. In this work, we propose new core/shell NW systems where Ge and Si shells are built around very thin As and Sb cores. The modification in the electronic properties arises due to the induced compressive strain experienced by the metal core region which is attributed to the lattice-mismatch with the shell region. As/Ge and As/Si nanowires undergo a semiconducting-to-metal transition on increasing the diameter of the shell. The current-voltage (I-V) characteristics of the nanowires show a negative differential conductance (NDC) effect for small diameters that could lead to their application in atomic scale device(s) for fast switching. In addition, an ohmic behavior and upto 300% increment of the current value is achieved on just doubling the shell region. The resistivity of nanowires decreases with the increase in diameter. These characteristics make these NWs suitable candidates for application as electron connectors in nanoelectronic devices.