bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical organization of urban mobility and its connection with city livability
Authors: Bassolas Aleix , Barbosa-Filho Hugo , Dickinson Brian , Dotiwalla Xerxes , Eastham Paul , Gallotti Riccardo , Ghoshal Gourab , Gipson Bryant , Hazarie Surendra A. , Kautz Henry , Kucuktunc Onur , Lieber Allison , Sadilek Adam , Ramasco José J.
Published: October 2019

The recent trend of rapid urbanization makes it imperative to understand urban characteristics such as infrastructure, population distribution, jobs, and services that play a key role in urban livability and sustainability. A healthy debate exists on what constitutes optimal structure regarding livability in cities, interpolating, for instance, between mono- and poly-centric organization. Here anonymous and aggregated flows generated from three hundred million users, opted-in to Location History, are used to extract global Intra-urban trips. We develop a metric that allows us to classify cities and to establish a connection between mobility organization and key urban indicators. We demonstrate that cities with strong hierarchical mobility structure display an extensive use of public transport, higher levels of walkability, lower pollutant emissions per capita and better health indicators. Our framework outperforms previous metrics, is highly scalable and can be deployed with little cost, even in areas without resources for traditional data collection.
Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection
Authors: D’Amato Anthony R. , Puhl Devan L. , Ellman Samuel A. T. , Balouch Bailey , Gilbert Ryan J. , Palermo Edmund F.
Published: October 2019

Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1–10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.
A database for using machine learning and data mining techniques for coronary artery disease diagnosis
Authors: Alizadehsani R. , Roshanzamir M. , Abdar M. , Beykikhoshk A. , Khosravi A. , Panahiazar M. , Koohestani A. , Khozeimeh F. , Nahavandi S. , Sarrafzadegan N.
Published: October 2019

We present the coronary artery disease (CAD) database, a comprehensive resource, comprising 126 papers and 68 datasets relevant to CAD diagnosis, extracted from the scientific literature from 1992 and 2018. These data were collected to help advance research on CAD-related machine learning and data mining algorithms, and hopefully to ultimately advance clinical diagnosis and early treatment. To aid users, we have also built a web application that presents the database through various reports.
Chromosome-level genome assembly of golden pompano (Trachinotus ovatus) in the family Carangidae
Authors: Zhang Dian-Chang , Guo Liang , Guo Hua-Yang , Zhu Ke-Cheng , Li Shang-Qi , Zhang Yan , Zhang Nan , Liu Bao-Suo , Jiang Shi-Gui , Li Jiong-Tang
Published: October 2019

Golden pompano (Trachinotus ovatus), a marine fish in the Carangidae family, has a wide geographical distribution and adapts to severe environmental rigours. It is also an economically valuable aquaculture fish. To understand the genetic mechanism of adaption to environmental rigours and improve the production in aquaculture, we assembled its genome. By combination of Illumina and Pacbio reads, the obtained genome sequence is 647.5 Mb with the contig N50 of 1.80 Mb and the scaffold N50 of 5.05 Mb. The assembly covers 98.9% of the estimated genome size (655 Mb). Based on Hi-C data, 99.4% of the assembled bases are anchored into 24 pseudo-chromosomes. The annotation includes 21,915 protein-coding genes, in which 95.7% of 2,586 BUSCO vertebrate conserved genes are complete. This genome is expected to contribute to the comparative analysis of the Carangidae family.
Multiple-data-based monthly geopotential model set LDCmgm90
Authors: Chen Wei , Luo Jiesi , Ray Jim , Yu Nan , Li Jian Cheng
Published: October 2019

While the GRACE (Gravity Recovery and Climate Experiment) satellite mission is of great significance in understanding various branches of Earth sciences, the quality of GRACE monthly products can be unsatisfactory due to strong longitudinal stripe-pattern errors and other flaws. Based on corrected GRACE Mascon (mass concentration) gridded mass transport time series and updated LDCgam (Least Difference Combination global angular momenta) data, we present a new set of monthly gravity models called LDCmgm90, in the form of Stokes coefficients with order and degree both up to 90. The LDCgam inputs are developed by assimilating degree-2 Stokes coefficients from various versions of GRACE (including Mascon products) and SLR (Satellite Laser Ranging) monthly gravity data into combinations of outputs from various global atmospheric, oceanic, and hydrological circulation models, under the constraints of accurately measured Earth orientation parameters in the Least Difference Combination (LDC) scheme. Taking advantages of the relative strengths of the various input solutions, the LDCmgm90 is free of stripes and some other flaws of classical GRACE products.
Distributed radiomics as a signature validation study using the Personal Health Train infrastructure
Authors: Shi Zhenwei , Zhovannik Ivan , Traverso Alberto , Dankers Frank J. W. M. , Deist Timo M. , Kalendralis Petros , Monshouwer René , Bussink Johan , Fijten Rianne , Aerts Hugo J. W. L. , Dekker Andre , Wee Leonard
Published: October 2019

Prediction modelling with radiomics is a rapidly developing research topic that requires access to vast amounts of imaging data. Methods that work on decentralized data are urgently needed, because of concerns about patient privacy. Previously published computed tomography medical image sets with gross tumour volume (GTV) outlines for non-small cell lung cancer have been updated with extended follow-up. In a previous study, these were referred to as Lung1 (n = 421) and Lung2 (n = 221). The Lung1 dataset is made publicly accessible via The Cancer Imaging Archive (TCIA; https://www.cancerimagingarchive.net). We performed a decentralized multi-centre study to develop a radiomic signature (hereafter “ZS2019”) in one institution and validated the performance in an independent institution, without the need for data exchange and compared this to an analysis where all data was centralized. The performance of ZS2019 for 2-year overall survival validated in distributed radiomics was not statistically different from the centralized validation (AUC 0.61 vs 0.61; p = 0.52). Although slightly different in terms of data and methods, no statistically significant difference in performance was observed between the new signature and previous work (c-index 0.58 vs 0.65; p = 0.37). Our objective was not the development of a new signature with the best performance, but to suggest an approach for distributed radiomics. Therefore, we used a similar method as an earlier study. We foresee that the Lung1 dataset can be further re-used for testing radiomic models and investigating feature reproducibility.
Dynamics of beneficial epidemics
Authors: Berdahl Andrew , Brelsford Christa , Bacco Caterina De , Dumas Marion , Ferdinand Vanessa , Grochow Joshua A. , Hébert-Dufresne Laurent , Kallus Yoav , Kempes Christopher P. , Kolchinsky Artemy , Larremore Daniel B. , Libby Eric , Power Eleanor A. , Stern Caitlin A. , Tracey Brendan D.
Published: October 2019

Pathogens can spread epidemically through populations. Beneficial contagions, such as viruses that enhance host survival or technological innovations that improve quality of life, also have the potential to spread epidemically. How do the dynamics of beneficial biological and social epidemics differ from those of detrimental epidemics? We investigate this question using a breadth-first modeling approach involving three distinct theoretical models. First, in the context of population genetics, we show that a horizontally-transmissible element that increases fitness, such as viral DNA, spreads superexponentially through a population, more quickly than a beneficial mutation. Second, in the context of behavioral epidemiology, we show that infections that cause increased connectivity lead to superexponential fixation in the population. Third, in the context of dynamic social networks, we find that preferences for increased global infection accelerate spread and produce superexponential fixation, but preferences for local assortativity halt epidemics by disconnecting the infected from the susceptible. We conclude that the dynamics of beneficial biological and social epidemics are characterized by the rapid spread of beneficial elements, which is facilitated in biological systems by horizontal transmission and in social systems by active spreading behavior of infected individuals.
Electronic structure of MAPbI3 and MAPbCl3: importance of band alignment
Authors: Caputo Marco , Cefarin Nicola , Radivo Andrea , Demitri Nicola , Gigli Lara , Plaisier Jasper R. , Panighel Mirco , Di Santo Giovanni , Moretti Sacha , Giglia Angelo , Polentarutti Maurizio , De Angelis Filippo , Mosconi Edoardo , Umari Paolo , Tormen Massimo , Goldoni Andrea
Published: October 2019

Since their first appearance, organic-inorganic perovskite absorbers have been capturing the attention of the scientific community. While high efficiency devices highlight the importance of band level alignment, very little is known on the origin of the strong n-doping character observed in the perovskite. Here, by means of a highly accurate photoemission study, we shed light on the energy alignment in perovskite-based devices. Our results suggest that the interaction with the substrate may be the driver for the observed doping in the perovskite samples.
Modeling cancer drug response through drug-specific informative genes
Authors: Parca Luca , Pepe Gerardo , Pietrosanto Marco , Galvan Giulio , Galli Leonardo , Palmeri Antonio , Sciandrone Marco , Ferrè Fabrizio , Ausiello Gabriele , Helmer-Citterich Manuela
Published: October 2019

Recent advances in pharmacogenomics have generated a wealth of data of different types whose analysis have helped in the identification of signatures of different cellular sensitivity/resistance responses to hundreds of chemical compounds. Among the different data types, gene expression has proven to be the more successful for the inference of drug response in cancer cell lines. Although effective, the whole transcriptome can introduce noise in the predictive models, since specific mechanisms are required for different drugs and these realistically involve only part of the proteins encoded in the genome. We analyzed the pharmacogenomics data of 961 cell lines tested with 265 anti-cancer drugs and developed different machine learning approaches for dissecting the genome systematically and predict drug responses using both drug-unspecific and drug-specific genes. These methodologies reach better response predictions for the vast majority of the screened drugs using tens to few hundreds genes specific to each drug instead of the whole genome, thus allowing a better understanding and interpretation of drug-specific response mechanisms which are not necessarily restricted to the drug known targets.
High spatial resolution electrochemical biosensing using reflected light microscopy
Authors: Munteanu Raluca-Elena , Ye Ran , Polonschii Cristina , Ruff Adrian , Gheorghiu Mihaela , Gheorghiu Eugen , Boukherroub Rabah , Schuhmann Wolfgang , Melinte Sorin , Gáspár Szilveszter
Published: October 2019

If the analyte does not only change the electrochemical but also the optical properties of the electrode/solution interface, the spatial resolution of an electrochemical sensor can be substantially enhanced by combining the electrochemical sensor with optical microscopy. In order to demonstrate this, electrochemical biosensors for the detection of hydrogen peroxide and glucose were developed by drop casting enzyme and redox polymer mixtures onto planar, optically transparent electrodes. These biosensors generate current signals proportional to the analyte concentration via a reaction sequence which ultimately changes the oxidation state of the redox polymer. Images of the interface of these biosensors were acquired using bright field reflected light microscopy (BFRLM). Analysis showed that the intensity of these images is higher when the redox polymer is oxidized than when it is reduced. It also revealed that the time needed for the redox polymer to change oxidation state can be assayed optically and is dependent on the concentration of the analyte. By combining the biosensor for hydrogen peroxide detection with BFRLM, it was possible to determine hydrogen peroxide in concentrations as low as 12.5 µM with a spatial resolution of 12 µm × 12 µm, without the need for the fabrication of microelectrodes of these dimensions.
Cardiac Pacemaker Cells Generate Cardiomyocytes from Fibroblasts in Long-Term Cultures
Authors: Kiuchi Shigeki , Usami Akino , Shimoyama Tae , Otsuka Fuminori , Yamaguchi Sachiko , Nakamura Tomonori , Suzuki Shigeto , Ono Kageyoshi
Published: October 2019

Because cardiomyocyte generation is limited, the turnover of cardiomyocytes in adult heart tissues is much debated. We report here that cardiac pacemaker cells can generate cardiomyocytes from fibroblasts in vitro. Sinoatrial node cells (SANCs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. Within a week, a number of fibroblast-like cells were observed to gather around SANCs, and these formed spontaneously beating clusters with cardiomyocyte structures. The clusters expressed genes and proteins that are characteristic of atrial cardiomyocytes. Pharmacological blocking of pacemaker currents inhibited generation of action potentials, and the spontaneous beating were ceased by physically destroying a few central cells. Inhibition of beating during culture also hampered the cluster formation. Moreover, purified guinea pig cardiac fibroblasts (GCFs) expressed cardiac-specific proteins in co-culture with SANCs or in SANC-preconditioned culture medium under electrical stimulation. These results indicate that SANCs can generate cardiomyocytes from cardiac fibroblasts through the influence of humoral factor(s) and electrophysiological activities followed by intracellular Ca2+ oscillations. This potential of SANCs to generate cardiomyocytes indicates a novel mechanism by which cardiomyocytes turns over in the vicinity of pacemaker cells and could be exploited in the development of strategies for cardiac regenerative therapy in adult hearts.
Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems
Authors: Elsana Hassan , Olusanya Temidayo O. B. , Carr-wilkinson Jane , Darby Steven , Faheem Ahmed , Elkordy Amal Ali
Published: October 2019

In gene delivery, non-viral vectors have become the preferred carrier system for DNA delivery. They can overcome major viral issues such as immunogenicity and mutagenicity. Cationic lipid-mediated gene transfer is one of the most commonly used non-viral vectors, which have been shown to be a safe and effective carrier. However, their use in gene delivery often exhibits low transfection efficiency and stability. The aim of this study was to examine the effectiveness of novel non-viral gene delivery systems. This study has investigated the encapsulation and transfection efficiency of cationic liposomes prepared from DOTAP and carboxymethyl-β-cyclodextrin (CD). The encapsulation efficiency of the CD-lipoplex complexes were also studied with and without the addition of Pluronic-F127, using both microfluidic and thin film hydration methods.In vitrotransfection efficiencies of these complexes were determined in COS7 and SH-SY5Y cell lines. Formulation stability was evaluated using liposomes size, zeta potential and polydispersity index. In addition, the external morphology was studied using transmission electron microcopy (TEM). Results revealed that formulations produced by microfluidic method had smaller, more uniform and homogenious size and zeta-potential as well as higher encapsulation efficiency when compared with liposomes manufactured by thin film hydration method. Overall, the results of this study show that carboxymethyl-β-cyclodextrin increased lipoplexes’ encapsulation efficiency using both NanoAssemblr and rotary evaporator manufacturing processes. However, this increase was reduced slightly following the addition of Pluronic-F127. The addition of carboxymethyl-β-cyclodextrin to cationic liposomes resulted in an increase in transfection efficiency in mammalian cell lines. However, this increase appeared to be cell line specific, COS7 showed higher transfection efficiency compared to SH-SY5Y.
Diversity of nectar amino acids in the Fritillaria (Liliaceae) genus: ecological and evolutionary implications
Authors: Roguz Katarzyna , Bajguz Andrzej , Chmur Magdalena , Gołębiewska Agnieszka , Roguz Agata , Zych Marcin
Published: October 2019

Nectar is considered to be a primary food reward for most pollinators. It mostly contains sugars, but also has amino acids. The significance of the concentration and composition of amino acids in nectar is often less understood than that of its volume, sugar concentration and composition. However, there is a trend towards a broader approach in ecological research, which helps to understand nectar properties in an ecological context. The genus Fritillaria, exhibiting great diversity in flower morphology, nectar composition, and dominant pollinators, allows for the possibility to study some of the above. We studied the concentration and composition of amino acids in the nectar of 38 Fritillaria species attracting different groups of pollen vectors (bees, flies, passerines, and hummingbirds). The flowers of fritillaries produced nectar with a varying composition and concentration of amino acids. These differences were mostly associated with the pollinator type. The nectar of passerine bird-pollinated species was rich in amino acids, whereas humming bird-pollinated produced low amino acid nectar. Contrary to previous reports nectar of the insect-pollinated species did not contain a higher amount of proline. Two non-protein amino acids, sarcosine and norvaline, were detected in the floral nectar for the first time.
Metabolic Biomarkers In Midtrimester Maternal Plasma Can Accurately Predict Adverse Pregnancy Outcome in Patients with SLE
Authors: Lee Seung Mi , Lee Eun Mi , Park Jin Kyun , Jeon Hae Sun , Oh Sohee , Hong Subeen , Jung Young Mi , Kim Byoung Jae , Kim Sun Min , Norwitz Errol R. , Lee Eun Bong , Louangsenlath Souphaphone , Park Chan-Wook , Jun Jong Kwan , Park Joong Shin , Lee Do Yup
Published: October 2019

Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcome (APO). Accurate prediction of APO is critical to identify, counsel, and manage these high-risk patients. We undertook this study to identify novel biomarkers in mid-trimester maternal plasma to identify pregnant patients with SLE at increased risk of APOs. The study population consisted of pregnant women whose plasma was taken in mid-trimester and available for metabolic signature: (1) SLE and normal pregnancy outcome (Group 1, n = 21); (2) SLE with APO (Group 2, n = 12); and (3) healthy pregnant controls (Group 3, n = 10). Mid-trimester maternal plasma was analyzed for integrative profiles of primary metabolite and phospholipid using gas chromatography time-of-flight mass spectrometry (GC-TOF MS) and liquid chromatography Orbitrap mass spectrometry (LC-Orbitrap MS). For performance comparison and validation, plasma samples were analyzed for sFlt-1/PlGF ratio. In the study population, APO developed in 12 of 33 women with SLE (36%). Metabolite profiling of mid-trimester maternal plasma samples identified a total of 327 metabolites using GC-TOF MS and LC-Orbitrap MS. Partial least squares discriminant analysis (PLS-DA) showed clear discrimination among the profiles of SLE groups and healthy pregnant controls (Groups 1/2 vs. 3). Moreover, direct comparison between Groups 1 and 2 demonstrated that 4 primary metabolites and 13 lipid molecules were significantly different. Binary logistic regression analysis suggested a potential metabolic biomarker model that could discriminate Groups 1 and 2. Receiver operating characteristic (ROC) analysis revealed the best predictability for APO with the combination model of two metabolites (LysoPC C22:5 and tryptophan) with AUC of 0.944, comparable to the AUC of sFlt-1/PlGF (AUC 0.857). In conclusion, metabolic biomarkers in mid-trimester maternal plasma can accurately predict APO in patients with SLE.
LTA1 is a safe, intranasal enterotoxin-based adjuvant that improves vaccine protection against influenza in young, old and B-cell-depleted (μMT) mice
Authors: Valli E. , Harriett A. J. , Nowakowska M. K. , Baudier R. L. , Provosty W. B. , McSween Z. , Lawson L. B. , Nakanishi Y. , Norton E. B.
Published: October 2019

Enterotoxin-based adjuvants including cholera toxin and heat-labile toxin (LT) are powerful manipulators of mucosal immunity; however, past clinical trials identified unacceptable neurological toxicity when LT or mutant AB5adjuvant proteins were added to intranasal vaccines. Here, we examined the isolated enzymatic A1 domain of LT (LTA1) for intranasal safety and efficacy in combination with influenza (flu) vaccination. LTA1-treated mice exhibited no neurotoxicity, as measured by olfactory system testing and H&E staining of nasal tissue in contrast with cholera toxin. In vaccination studies, intranasal LTA1 enhanced immune responses to inactivated virus antigen and subsequent protection against H1N1 flu challenge in mice (8-week or 24-months). In addition, lung H1N1 viral titers post-challenge correlated to serum antibody responses; however, enhanced protection was also observed in μMT mice lacking B-cells while activation and recruitment of CD4 T-cells into the lung was apparent. Thus, we report that LTA1 protein is a novel, safe and effective enterotoxin adjuvant that improves protection of an intranasal flu vaccination by a mechanism that does not appear to require B-cells.
Cognitive and Behavioural Weaknesses in Children with Reading Disorder and AD(H)D
Authors: Turker Sabrina , Seither-Preisler Annemarie , Reiterer Susanne Maria , Schneider Peter
Published: October 2019

Working memory capacity, an essential prerequisite for language learning and the development of arithmetic skills, has been reported as deficient in children with reading disorder (RD) and attention deficit (hyperactivity) disorder (AD(H)D). However, few studies to date have explored potential associations of working memory impairments and foreign language learning, mathematical skills and school achievement in these groups, in particular in children with a comorbidity of both. In the present study, we assessed working memory, language learning, arithmetic fluency and academic achievement in children (N = 166;Mage = 14.3, range 8–18 y), including typically-developing children (n = 89), subjects with RD (n = 27), AD(H)D (n = 43), and a comorbidity (n = 15). While children with AD(H)D performed similar to typically developing children on all tasks, RD children performed weakly on various language learning and working memory tasks, with major deficits in non-word span, phonetic memory and vocabulary learning. Combining weaknesses of the two groups, children with a comorbidity further performed significantly worse on arithmetic skills, learning of sound-symbol combinations and simple digit span forward. The findings suggest a reconsideration of working memory and learning impairments in AD(H)D, while highlighting the additional weaknesses of comorbid children and pointing out severe foreign language learning difficulties in RD children.
Social context and dominance status contribute to sleep patterns and quality in groups of freely-moving mice
Authors: Karamihalev Stoyo , Flachskamm Cornelia , Eren Noa , Kimura Mayumi , Chen Alon
Published: October 2019

In socially-living species, sleep patterns are often subject to group influences, as individuals adjust to the presence, daily rhythms, and social pressures of cohabitation. However, sleep studies in mice are typically conducted in single-housed individuals. Here, we investigated sleep in a semi-naturalistic environment with freely-moving, group-housed mice using wireless electroencephalographic (EEG) monitoring and video tracking. We found evidence of in-group synchrony of sleep state patterns and effects of social dominance status on sleep quality. These findings highlight the importance of exploring sleep in a social context and are a step toward more informative research on the interplay between social functioning and sleep.
Congruence of morphological and molecular phylogenies of the rove beetle subfamily Staphylininae (Coleoptera: Staphylinidae)
Authors: Cai Chen-Yang , Wang Yong-Li , Liang Lü , Yin Zi-Wei , Thayer Margaret K. , Newton Alfred F. , Zhou Yu-Lingzi
Published: October 2019

Staphylininae is the third largest subfamily of the enormous family Staphylinidae. Monophyly of Staphylininae and its sister relationship to the subfamily Paederinae have been broadly accepted according to both conventional morphology- and molecular-based phylogenies until the last three years. Recent molecular phylogenies rejected monophyly of Staphylininae and regarded Paederinae as a clade within it. This paper re-evaluates the recent molecular work, aiming to clarify the relationship between Staphylininae and Paederinae and resolve intertribal relationships within Staphylininae. Based on a new six-gene data set (5707 bp) for 92 taxa including Oxyporinae (outgroup), representatives of Paederinae, and members of all extant tribes of Staphylininae from published DNA data in GenBank, we generated a well-resolved phylogeny of Staphylininae with all deep nodes (intertribal relationships) strongly supported, and reassert the hypothesis that Staphylininae is monophyletic and indeed the sister group to Paederinae using both Bayesian and maximum likelihood inference. Additionally, our study is a case-study to show that both outgroup selection and completeness of nucleotide data can influence the outcome of a molecular phylogeny. With an increasing number of staphylinid fossils being discovered, the robust phylogeny of Staphylininae inferred by our research will provide a good framework for understanding the early evolution of this group.
Jensen’s force and the statistical mechanics of cortical asynchronous states
Authors: Buendía Victor , Villegas Pablo , di Santo Serena , Vezzani Alessandro , Burioni Raffaella , Muñoz Miguel A.
Published: October 2019

Cortical networks are shaped by the combined action of excitatory and inhibitory interactions. Among other important functions, inhibition solves the problem of the all-or-none type of response that comes about in purely excitatory networks, allowing the network to operate in regimes of moderate or low activity, between quiescent and saturated regimes. Here, we elucidate a noise-induced effect that we call “Jensen’s force” –stemming from the combined effect of excitation/inhibition balance and network sparsity– which is responsible for generating a phase of self-sustained low activity in excitation-inhibition networks. The uncovered phase reproduces the main empirically-observed features of cortical networks in the so-called asynchronous state, characterized by low, un-correlated and highly-irregular activity. The parsimonious model analyzed here allows us to resolve a number of long-standing issues, such as proving that activity can be self-sustained even in the complete absence of external stimuli or driving. The simplicity of our approach allows for a deep understanding of asynchronous states and of the phase transitions to other standard phases it exhibits, opening the door to reconcile, asynchronous-state and critical-state hypotheses, putting them within a unified framework. We argue that Jensen’s forces are measurable experimentally and might be relevant in contexts beyond neuroscience.
Functional characterization of the type I toxin Lpt from Lactobacillus rhamnosus by fluorescence and atomic force microscopy
Authors: Maggi Stefano , Yabre Korotoum , Ferrari Alberto , Lazzi Camilla , Kawano Mitsuoki , Rivetti Claudio , Folli Claudia
Published: October 2019

Lpt is a 29 amino acid long type I toxin identified in the plasmid DNA of wild Lactobacillus rhamnosus strains isolated from food. We previously reported that transcription of the encoding gene was upregulated under nutritional starvation conditions mimicking cheese ripening environment. The heterologous expression of the Lpt peptide in E. coli resulted in cell growth inhibition, nucleoid condensation and compromised integrity of the cell membrane. Fusion of the Lpt peptide with the fluorescent protein mCherry allowed to visualize the accumulation of the peptide into the membrane, while mutagenesis experiments showed that either the insertion of a negatively charged amino acid into the hydrophobic α-helix or deletion of the hydrophilic C-terminal region, leads to a non-toxic peptide. AFM imaging of Lpt expressing E. coli cells has revealed the presence of surface defects that are compatible with the loss of portions of the outer membrane bilayer. This observation provides support for the so-called “carpet” model, by which the Lpt peptide is supposed to destabilize the phospholipid packing through a detergent-like mechanism leading to the removal of small patches of bilayer through micellization.
Transcranial random noise stimulation (tRNS): a wide range of frequencies is needed for increasing cortical excitability
Authors: Moret Beatrice , Donato Rita , Nucci Massimo , Cona Giorgia , Campana Gianluca
Published: October 2019

Transcranial random noise stimulation (tRNS) is a recent neuromodulation protocol. The high-frequency band (hf-tRNS) has shown to be the most effective in enhancing neural excitability. The frequency band of hf-tRNS typically spans from 100 to 640 Hz. Here we asked whether both the lower and the higher half of the high-frequency band are needed for increasing neural excitability. Three frequency ranges (100–400 Hz, 400–700 Hz, 100–700 Hz) and Sham conditions were delivered for 10 minutes at an intensity of 1.5 mA over the primary motor cortex (M1). Single-pulse transcranial magnetic stimulation (TMS) was delivered over the same area at baseline, 0, 10, 20, 30, 45 and 60 minutes after stimulation, while motor evoked potentials (MEPs) were recorded to evaluate changes in cortical excitability. Only the full-band condition (100–700 Hz) was able to modulate excitability by enhancing MEPs at 10 and 20 minutes after stimulation: neither the higher nor the lower sub-range of the high-frequency band significantly modulated cortical excitability. These results show that the efficacy of tRNS is strictly related to the width of the selected frequency range.
Deep Electrical Resistivity Tomography for a 3D picture of the most active sector of Campi Flegrei caldera
Authors: Troiano A. , Isaia R. , Di Giuseppe M. G. , Tramparulo F. D. A. , Vitale S.
Published: October 2019

The central sector of the Campi Flegrei volcano, including the Solfatara maar and Pisciarelli fumarole field, is currently the most active area of the caldera as regards seismicity and gaseous emissions and it plays a significant role in the ongoing unrest. However, a general volcano-tectonic reconstruction of the entire sector is still missing. This work aims to depict, for the first time, the architecture of the area through the application of deep Electrical Resistivity Tomography. We reconstructed a three-dimensional resistivity model for the entire sector. Results provide useful elements to understand the present state of the system and the possible evolution of the volcanic activity and shed solid bases for any attempt to develop physical-mathematical models investigating the ongoing phenomena.
Resistin expression in human monocytes is controlled by two linked promoter SNPs mediating NFKB p50/p50 binding and C-methylation
Authors: Kumar Dilip , Lee Bernett , Puan Kia Joo , Lee Wendy , Luis Boris San , Yusof Nurhashikin , Andiappan Anand Kumar , Del Rosario Ricardo , Poschmann Jeremie , Kumar Pavanish , DeLibero Gennaro , Singhal Amit , Prabhakar Shyam , De Yun Wang , Poidinger Michael , Rötzschke Olaf
Published: October 2019

Resistin is a key cytokine associated with metabolic and inflammatory diseases. Especially in East Asian populations, the expression levels are strongly influenced by genetic polymorphisms. Mechanisms and functional implications of this genetic control are still unknown. By employing reporter assays, EMSA, inhibition studies, bisulphite sequencing, ChIP-Seq and gene-editing we show that the p50/p50 homodimer known to act as repressor for a number of pro-inflammatory genes plays a central role in the genetic regulation of resistin in monocytes along with promoter methylation. In the common RETN haplotype p50/p50 constitutively dampens the expression by binding to the promoter. In an Asian haplotype variant however this interaction is disrupted by the A allele of rs3219175. The SNP is in very close linkage to rs34861192, a CpG SNP, located 280 bp upstream which provides an allele-specific C-methylation site. rs34861192 is located in a 100 bp region found to be methylated in the common but not in the Asian haplotype, resulting in the latter having a higher basal expression, which also associates with elevated histone acetylation (H3K27ac). Genotype associations within cohort data of 200 East Asian individuals revealed significant associations between this haplotype and the plasma levels of factors such as TGF-b, S100B, sRAGE and IL-8 as well as with myeloid DC counts. Thus, the common RETN haplotype is tightly regulated by the epigenetic mechanism linked to p50/p50-binding. This control is lost in the Asian haplotype, which may have evolved to balance the antagonistic RETN effects on pathogen protection vs. metabolic and inflammatory disease induction.
Testing the uniqueness of deep terrestrial life
Authors: Trontelj Peter , Borko Špela , Delić Teo
Published: October 2019

Terrestrial life typically does not occur at depths greater than a few meters. Notable exceptions are massifs of fissured rock with caves and hollow spaces reaching depths of two kilometres and more. Recent biological discoveries from extremely deep caves have been reported as sensations analogous to wondrous deep sea creatures. However, the existence of unique deep terrestrial communities is questionable when caves are understood as integral parts of a bedrock fissure network (BFN) interconnecting all parts of a massif horizontally and vertically. We tested these two opposing hypotheses – unique deep cave fauna vs. BFN – by sampling subterranean communities within the 3D matrix of a typical karst massif. There was no distinction between deep core and shallow upper zone communities. Beta diversity patterns analysed against null models of random distribution were generally congruent with the BFN hypothesis, but suggested gravity-assisted concentration of fauna in deep caves and temperature-dependent horizontal distribution. We propose that the idea of a unique deep terrestrial fauna akin to deep oceanic life is unsupported by data and unwarranted by ecological considerations. Instead, the BFN hypothesis and local ecological and structural factors sufficiently explain the distribution of subterranean terrestrial life even in the deepest karst massifs.
Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment
Authors: Nagtegaal Andries Paul , Broer Linda , Zilhao Nuno R. , Jakobsdottir Johanna , Bishop Charles E. , Brumat Marco , Christiansen Mark W. , Cocca Massimiliano , Gao Yan , Heard-Costa Nancy L. , Evans Daniel S. , Pankratz Nathan , Pratt Sheila R. , Price T. Ryan , Spankovich Christopher , Stimson Mary R. , Valle Karen , Vuckovic Dragana , Wells Helena , Eiriksdottir Gudny , Fransen Erik , Ikram Mohammad Arfan , Li Chuang-Ming , Longstreth W. T. , Steves Claire , Van Camp Guy , Correa Adolfo , Cruickshanks Karen J. , Gasparini Paolo , Girotto Giorgia , Kaplan Robert C. , Nalls Michael , Schweinfurth John M. , Seshadri Sudha , Sotoodehnia Nona , Tranah Gregory J. , Uitterlinden André G. , Wilson James G. , Gudnason Vilmundur , Hoffman Howard J. , Williams Frances M. K. , Goedegebure André
Published: October 2019

Previous research has shown that genes play a substantial role in determining a person’s susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden.
Correlations of C-Reactive Protein and Folate with Smoking, Sport, Hematological Inflammation Biomarkers and Anthropometrics in Syrian University Female Students Cross-Sectional Study
Authors: Rajab Mazen , Jumaa Mohamad , Horaniah Muhammad Yusr , Barakat Ahmad , Bakleh Saied , Zarzour Wafika
Published: October 2019

In Syria, high-Sensitive C-Reactive (hsCRP), folate, and, other health risk data in young women are limited. This cross-sectional study evaluates hsCRP and folate levels along with anthropometric characteristics, lifestyle factors and some biomarkers linked to cardiovascular disease (CVD) risk factors in healthy female students (n = 207, 18–25 years old). Among participants, hsCRP level was at average or high risk of CVD in 20.7% and 2.5% respectively and it was significantly higher in participants who had high body mass index (BMI) (Nonparametric statistical tests, p value < 0.05). Unexpectedly, it did not vary significantly between smokers and nonsmokers. And, it correlated positively with anthropometric and erythrocyte sedimentation rate (ESR) measurements. While folate level was low in 3.4% of participants, no association between hsCRP and folate levels was found. Finally, low hemoglobin level and habit of waterpipe smoking are spreading; and, sport practicing is shrinking. After reviewing similar works, this study suggests that the possible correlation between hsCRP and folate could be displayed in patients older than 30 years. Also, the marked decrease in hemoglobin level needs more attention. Finally, young females in Syria are advised to consider a lifestyle free of smoking and packed with physical activity.
Proteasome activator PA200 regulates myofibroblast differentiation
Authors: Welk Vanessa , Meul Thomas , Lukas Christina , Kammerl Ilona E. , Mulay Shrikant R. , Schamberger Andrea C. , Semren Nora , Fernandez Isis E. , Anders Hans-Joachim , Günther Andreas , Behr Jürgen , Eickelberg Oliver , Korfei Martina , Meiners Silke
Published: October 2019

The proteasome is essential for the selective degradation of most cellular proteins and is fine-tuned according to cellular needs. Proteasome activators serve as building blocks to adjust protein turnover in cell growth and differentiation. Understanding the cellular function of proteasome activation in more detail offers a new strategy for therapeutic targeting of proteasomal protein breakdown in disease. The role of the proteasome activator PA200 in cell function and its regulation in disease is unknown. In this study, we investigated the function of PA200 in myofibroblast differentiation and fibrotic tissue remodeling. PA200 was upregulated in hyperplastic basal cells and myofibroblasts of fibrotic lungs from patients with idiopathic pulmonary fibrosis. Increased expression of PA200 and enhanced formation of PA200-proteasome complexes was also evident in experimental fibrosis of the lung and kidney in vivo and in activated primary human myofibroblasts of the lung in vitro. Transient silencing and overexpression revealed that PA200 functions as a negative regulator of myofibroblast differentiation of human but not mouse cells. Our data thus suggest an unexpected and important role for PA200 in adjusting myofibroblast activation in response to pro-fibrotic stimuli, which fails in idiopathic pulmonary fibrosis.
Annealing induced a well-ordered single crystal δ-MnO2 and its electrochemical performance in zinc-ion battery
Authors: Corpuz Ryan Dula , De Juan Lyn Marie Z. , Praserthdam Supareak , Pornprasertsuk Rojana , Yonezawa Tetsu , Nguyen Mai Thanh , Kheawhom Soorathep
Published: October 2019

Herein, the formation and electrochemical performance of a novel binder-free turbostratic stacked/ well-ordered stacked δ-MnO2-carbon fiber composite cathodes in deep eutectic solvent (DES) based zinc-ion battery (ZIB) is reported. Results of morphological, elemental, and structural analyses revealed directly grown and interconnected δ-MnO2 crumpled nanosheets on a carbon fiber substrate. Moreover, an improvement via a simple annealing strategy in the stacking, surface area and conductivity of the δ-MnO2 sheets was observed. Annealing induces the rearrangement of δ-MnO2 sheets resulting in the transformation from turbostratic stacking to a well-ordered stacking of $${\delta }$$
δ
-MnO2 sheets, as indicated by the selected area electron diffraction (SAED) hexagonal single crystal pattern. Besides, the formation of the well-ordered stacking of $${\delta }$$
δ
-MnO2 sheets exhibited improved electrochemical performance and cyclability, as cathode material for ZIB. The novel strategy described in this study is an essential step for the development of binder-free δ-MnO2-C fiber composite with a well-ordered stacking of δ-MnO2 sheets. This study also demonstrated comparable electrochemical performance between the turbostratic $${\delta }$$
δ
-MnO2 sheets and the well-ordered stacked δ-MnO2 sheets.
Synthesis and investigation of SiO2-MgO coated MWCNTs and their potential application
Authors: Nemeth Krisztian , Varro Nikolett , Reti Balazs , Berki Peter , Adam Balazs , Belina Karoly , Hernadi Klara
Published: October 2019

In the present publication, multiwalled carbon nanotubes (MWCNT) coated with SiO2–MgO nanoparticles were successfully fabricated via sol–gel method to facilitate their incorporation into polymer matrices. Magnesium acetate tetrahydrate and tetraethyl orthosilicate were used as precursors. The coated MWCNTs were characterized by transmission electron microscopy (TEM), X–ray diffraction (XRD) and Raman spectroscopy methods. These investigation techniques verified the presence of the inorganic nanoparticles on the surface of MWCNTs. Surface coated MWCNTs were incorporated into polyamide (PA), polyethylene (PE) and polypropylene (PP) matrices via melt blending. Tensile test and differential scanning calorimetry (DSC) investigations were performed on SiO2–MgO/MWCNT polymer composites to study the reinforcement effect on the mechanical and thermal properties of the products. The obtained results indicate that depending on the type of polymer, the nanoparticles differently influenced the Young’s modulus of polymers. Generally, the results demonstrated that polymers treated with SiO2-MgO/MWCNT nanoparticles have higher modulus than neat polymers. DSC results showed that nanoparticles do not change the melting and crystallization behavior of PP significantly. According to the obtained results, coated MWCNTs are promising fillers to enhance mechanical properties of polymers.
Response Latency Tuning by Retinal Circuits Modulates Signal Efficiency
Authors: Tengölics Ádám Jonatán , Szarka Gergely , Ganczer Alma , Szabó-Meleg Edina , Nyitrai Miklós , Kovács-Öller Tamás , Völgyi Béla
Published: October 2019

In the visual system, retinal ganglion cells (RGCs) of various subtypes encode preprocessed photoreceptor signals into a spike output which is then transmitted towards the brain through parallel feature pathways. Spike timing determines how each feature signal contributes to the output of downstream neurons in visual brain centers, thereby influencing efficiency in visual perception. In this study, we demonstrate a marked population-wide variability in RGC response latency that is independent of trial-to-trial variability and recording approach. RGC response latencies to simple visual stimuli vary considerably in a heterogenous cell population but remain reliable when RGCs of a single subtype are compared. This subtype specificity, however, vanishes when the retinal circuitry is bypassed via direct RGC electrical stimulation. This suggests that latency is primarily determined by the signaling speed through retinal pathways that provide subtype specific inputs to RGCs. In addition, response latency is significantly altered when GABA inhibition or gap junction signaling is disturbed, which further supports the key role of retinal microcircuits in latency tuning. Finally, modulation of stimulus parameters affects individual RGC response delays considerably. Based on these findings, we hypothesize that retinal microcircuits fine-tune RGC response latency, which in turn determines the context-dependent weighing of each signal and its contribution to visual perception.
Fractionated irradiation of right thorax induces abscopal damage on testes leading to decline in fertility
Authors: Zhang Junling , Yao Dan , Song Yimeng , Pan Yan , Zhu Lin , Bai Yang , Xu Yanwu , Zhang Jianghong , Shao Chunlin
Published: October 2019

Radiation-induced abscopal effect (RIAE) may influence radiotherapy efficiency. However, it is unknown whether RIAE triggers abnormal genetic consequence. We present a novel evidence that, when mice were given fractionated irradiation on right thorax, the ultrastructure of blood-testis barrier was damaged in company with apoptosis induction in testes, and the sperm number and vitality were drastically decreased so that both the fertility and the survival of their offspring were reduced. Protein microarray assay and hormone detection showed that some cytokines especially TNF-α, TGF-β and estradiol in the serum of irradiated mice increased to higher levels in consistent with abscopal damage, and this conditioned serum had toxic effect on TM4 cells in vitro. When the mice were fed with cimetidine, the above abscopal responses were significantly attenuated. This study demonstrates in the first time that the thoracic irradiation (Th-IR) induces structural and functional damage in the distal testes and further cause fertility decline of irradiated male mice, which may have important implications in the strategy development of radiotherapy in avoiding abnormal genetic consequence.