bluuebunny/crossref_metadata_2025 huggingface dataset:
A machine-compiled database of genome-wide association studies
Authors: Kuleshov Volodymyr , Ding Jialin , Vo Christopher , Hancock Braden , Ratner Alexander , Li Yang , Ré Christopher , Batzoglou Serafim , Snyder Michael
Published: July 2019

Tens of thousands of genotype-phenotype associations have been discovered to date, yet not all of them are easily accessible to scientists. Here, we describe GWASkb, a machine-compiled knowledge base of genetic associations collected from the scientific literature using automated information extraction algorithms. Our information extraction system helps curators by automatically collecting over 6,000 associations from open-access publications with an estimated recall of 60–80% and with an estimated precision of 78–94% (measured relative to existing manually curated knowledge bases). This system represents a fully automated GWAS curation effort and is made possible by a paradigm for constructing machine learning systems called data programming. Our work represents a step towards making the curation of scientific literature more efficient using automated systems.
Bacterial outer membrane proteins assemble via asymmetric interactions with the BamA β-barrel
Authors: Doyle Matthew T. , Bernstein Harris D.
Published: July 2019

The integration of β-barrel proteins into the bacterial outer membrane (OM) is catalysed by the β-barrel assembly machinery (BAM). The central BAM subunit (BamA) itself contains a β-barrel domain that is essential for OM protein biogenesis, but its mechanism of action is unknown. To elucidate its function, here we develop a method to trap a native Escherichia coli β-barrel protein bound stably to BamA at a late stage of assembly in vivo. Using disulfide-bond crosslinking, we find that the first β-strand of a laterally ‘open’ form of the BamA β-barrel forms a rigid interface with the C-terminal β-strand of the substrate. In contrast, the lipid-facing surface of the last two BamA β-strands forms weaker, conformationally heterogeneous interactions with the first β-strand of the substrate that likely represent intermediate assembly states. Based on our results, we propose that BamA promotes the membrane integration of partially folded β-barrels by a ‘swing’ mechanism.
Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors
Authors: Segal Joe M. , Kent Deniz , Wesche Daniel J. , Ng Soon Seng , Serra Maria , Oulès Bénédicte , Kar Gozde , Emerton Guy , Blackford Samuel J. I. , Darmanis Spyros , Miquel Rosa , Luong Tu Vinh , Yamamoto Ryo , Bonham Andrew , Jassem Wayel , Heaton Nigel , Vigilante Alessandra , King Aileen , Sancho Rocio , Teichmann Sarah , Quake Stephen R. , Nakauchi Hiromitsu , Rashid S. Tamir
Published: July 2019

The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population in human foetal liver using single-cell RNA sequencing. HHyPs are anatomically restricted to the ductal plate of foetal liver and maintain a transcriptional profile distinct from foetal hepatocytes, mature hepatocytes and mature BECs. In addition, molecular heterogeneity within the EpCAM+population of freshly isolated foetal and adult human liver identifies diverse gene expression signatures of hepatic and biliary lineage potential. Finally, we FACS isolate foetal HHyPs and confirm their hybrid progenitor phenotype in vivo. Our study suggests that hepatobiliary progenitor cells previously identified in mice also exist in humans, and can be distinguished from other parenchymal populations, including mature BECs, by distinct gene expression profiles.
Arabidopsis SWR1-associated protein methyl-CpG-binding domain 9 is required for histone H2A.Z deposition
Authors: Potok Magdalena E. , Wang Yafei , Xu Linhao , Zhong Zhenhui , Liu Wanlu , Feng Suhua , Naranbaatar Bilguudei , Rayatpisheh Shima , Wang Zonghua , Wohlschlegel James A. , Ausin Israel , Jacobsen Steven E.
Published: July 2019

Deposition of the histone variant H2A.Z by the SWI2/SNF2-Related 1 chromatin remodeling complex (SWR1-C) is important for gene regulation in eukaryotes, but the composition of the Arabidopsis SWR1-C has not been thoroughly characterized. Here, we aim to identify interacting partners of a conserved Arabidopsis SWR1 subunit ACTIN-RELATED PROTEIN 6 (ARP6). We isolate nine predicted components and identify additional interactors implicated in histone acetylation and chromatin biology. One of the interacting partners, methyl-CpG-binding domain 9 (MBD9), also strongly interacts with the Imitation SWItch (ISWI) chromatin remodeling complex. MBD9 is required for deposition of H2A.Z at a distinct subset of ARP6-dependent loci. MBD9 is preferentially bound to nucleosome-depleted regions at the 5’ ends of genes containing high levels of activating histone marks. These data suggest that MBD9 is a SWR1-C interacting protein required for H2A.Z deposition at a subset of actively transcribing genes.
Computational and experimental demonstrations of one-pot tandem catalysis for electrochemical carbon dioxide reduction to methane
Authors: Zhang Haochen , Chang Xiaoxia , Chen Jingguang G. , Goddard William A. , Xu Bingjun , Cheng Mu-Jeng , Lu Qi
Published: July 2019

Electroreduction of carbon dioxide to hydrocarbons and oxygenates on copper involves reduction to a carbon monoxide adsorbate followed by further transformation to hydrocarbons and oxygenates. Simultaneous improvement of these processes over a single reactive site is challenging due to the linear scaling relationship of the binding strength of key intermediates. Herein, we report improved electroreduction of carbon dioxide by exploiting a one-pot tandem catalysis mechanism based on computational and electrochemical investigations. By constructing a well-defined copper-modified silver surface, adsorbed carbon monoxide generated on the silver sites is proposed to migrate to surface copper sites for the subsequent reduction to methane, which is consistent with insights gained from operando attenuated total reflectance surface enhanced infrared absorption spectroscopic investigations. Our results provide a promising approach for designing carbon dioxide electroreduction catalysts to enable one-pot reduction of products beyond carbon monoxide and formate.
Strong plasmon-molecule coupling at the nanoscale revealed by first-principles modeling
Authors: Rossi Tuomas P. , Shegai Timur , Erhart Paul , Antosiewicz Tomasz J.
Published: July 2019

Strong light-matter interactions in both the single-emitter and collective strong coupling regimes attract significant attention due to emerging applications in quantum and nonlinear optics as well as opportunities for modifying material-related properties. Exploration of these phenomena is theoretically demanding, as polaritons exist at the intersection between quantum optics, solid state physics, and quantum chemistry. Fortunately, nanoscale polaritons can be realized in small plasmon-molecule systems, enabling treatment with ab initio methods. Here, we show that time-dependent density-functional theory calculations access the physics of nanoscale plasmon-molecule hybrids and predict vacuum Rabi splitting. By considering a system comprising a few-hundred-atom aluminum nanoparticle interacting with benzene molecules, we show that cavity quantum electrodynamics holds down to resonators of a few cubic nanometers in size, yielding a single-molecule coupling strength exceeding 200 meV due to a massive vacuum field of 4.5 V · nm−1. In a broader perspective, ab initio methods enable parameter-free in-depth studies of polaritonic systems for emerging applications.
Recent trend reversal for declining European seagrass meadows
Authors: de los Santos Carmen B. , Krause-Jensen Dorte , Alcoverro Teresa , Marbà Núria , Duarte Carlos M. , van Katwijk Marieke M. , Pérez Marta , Romero Javier , Sánchez-Lizaso José L. , Roca Guillem , Jankowska Emilia , Pérez-Lloréns José Lucas , Fournier Jérôme , Montefalcone Monica , Pergent Gérard , Ruiz Juan M. , Cabaço Susana , Cook Kevan , Wilkes Robert J. , Moy Frithjof E. , Trayter Gregori Muñoz-Ramos , Arañó Xavier Seglar , de Jong Dick J. , Fernández-Torquemada Yolanda , Auby Isabelle , Vergara Juan J. , Santos Rui
Published: July 2019

Seagrass meadows, key ecosystems supporting fisheries, carbon sequestration and coastal protection, are globally threatened. In Europe, loss and recovery of seagrasses are reported, but the changes in extent and density at the continental scale remain unclear. Here we collate assessments of changes from 1869 to 2016 and show that 1/3 of European seagrass area was lost due to disease, deteriorated water quality, and coastal development, with losses peaking in the 1970s and 1980s. Since then, loss rates slowed down for most of the species and fast-growing species recovered in some locations, making the net rate of change in seagrass area experience a reversal in the 2000s, while density metrics improved or remained stable in most sites. Our results demonstrate that decline is not the generalised state among seagrasses nowadays in Europe, in contrast with global assessments, and that deceleration and reversal of declining trends is possible, expectingly bringing back the services they provide.
Strong magnetophonon oscillations in extra-large graphene
Authors: Kumaravadivel P. , Greenaway M. T. , Perello D. , Berdyugin A. , Birkbeck J. , Wengraf J. , Liu S. , Edgar J. H. , Geim A. K. , Eaves L. , Krishna Kumar R.
Published: July 2019

Van der Waals materials and their heterostructures offer a versatile platform for studying a variety of quantum transport phenomena due to their unique crystalline properties and the exceptional ability in tuning their electronic spectrum. However, most experiments are limited to devices that have lateral dimensions of only a few micrometres. Here, we perform magnetotransport measurements on graphene/hexagonal boron-nitride Hall bars and show that wider devices reveal additional quantum effects. In devices wider than ten micrometres we observe distinct magnetoresistance oscillations that are caused by resonant scattering of Landau-quantised Dirac electrons by acoustic phonons in graphene. The study allows us to accurately determine graphene’s low energy phonon dispersion curves and shows that transverse acoustic modes cause most of phonon scattering. Our work highlights the crucial importance of device width when probing quantum effects and also demonstrates a precise, spectroscopic method for studying electron-phonon interactions in van der Waals heterostructures.
High-throughput computation and evaluation of raman spectra
Authors: Liang Qiaohao , Dwaraknath Shyam , Persson Kristin A.
Published: July 2019

Raman spectroscopy is used ubiquitously in the characterization of condensed materials, spanning from biomaterials, minerals to polymers, as it provides a unique fingerprint of local bonding and environment. In this work, we design and demonstrate a robust, automatic computational workflow for Raman spectra that employs first-principle calculations based on density functional perturbation theory. A set of computational results are compared to Raman spectra obtained from established experimental databases to estimate the accuracy of the calculated properties across chemical systems and structures. Details regarding the computational methodology and technical validation are presented along with the format of our publicly available data record.
Activity-dependent changes in synaptic protein complex composition are consistent in different detergents despite differential solubility
Authors: Lautz Jonathan D. , Gniffke Edward P. , Brown Emily A. , Immendorf Karen B. , Mendel Ryan D. , Smith Stephen E. P.
Published: July 2019

At the post-synaptic density (PSD), large protein complexes dynamically form and dissociate in response to synaptic activity, comprising the biophysical basis for learning and memory. The use of detergents to isolate the PSD and release its membrane-associated proteins complicates studies of these activity-dependent protein interaction networks, because detergents can simultaneously disrupt the very interactions under study. Despite widespread recognition that different detergents yield different experimental results, the effect of detergent on activity-dependent synaptic protein complexes has not been rigorously examined. Here, we characterize the effect of three detergents commonly used to study synaptic proteins on activity-dependent protein interactions. We first demonstrate that SynGAP-containing interactions are more abundant in 1% Deoxycholate (DOC), while Shank-, Homer- and mGluR5-containing interactions are more abundant in 1% NP-40 or Triton. All interactions were detected preferentially in high molecular weight complexes generated by size exclusion chromatography, although the detergent-specific abundance of proteins in high molecular weight fractions did not correlate with the abundance of detected interactions. Activity-dependent changes in protein complexes were consistent across detergent types, suggesting that detergents do not isolate distinct protein pools with unique behaviors. However, detection of activity-dependent changes is more or less feasible in different detergents due to baseline solubility. Collectively, our results demonstrate that detergents affect the solubility of individual proteins, but activity-dependent changes in protein interactions, when detectable, are consistent across detergent types.
Corridors best facilitate functional connectivity across a protected area network
Authors: Stewart Frances E. C. , Darlington Siobhan , Volpe John P. , McAdie Malcolm , Fisher Jason T.
Published: July 2019

Biologging data allow animal ecologists to directly measure species’ fine-scale spatiotemporal responses to environments, such as movement – critical for our understanding of biodiversity declines in the Anthropocene. Animal movement between resource patches is a behavioral expression of multiple ecological processes that affect individual fitness. Protected area (PA) networks are a tool used to conserve biodiversity by sustaining habitat patches across vast heterogeneous landscapes. However, our ability to design PA networks that conserve biodiversity relies on our accurate understanding of animal movement and functional connectivity; this understanding is rarely tested in real-world situations due to the large geographic expanse of most PA networks. Using a tractable PA network mesocosm, we employ cutting-edge biologging technology to analyze animal movement decisions in response to a highly heterogeneous landscape. We analyze these data to test, in a novel way, three common hypotheses about functional connectivity – structural corridors, least cost paths, and stepping stones. Consistently, animals moved along structurally self-similar corridors. In reference to the Aichi 2020 Biodiversity Targets, relying on species to “stepping stone” across habitat remnants may not achieve protected area network conservation objectives.
Global view of the RAF-MEK-ERK module and its immediate downstream effectors
Authors: Santini Cristina C. , Longden James , Schoof Erwin M. , Simpson Craig D. , Jeschke Grace R. , Creixell Pau , Kim Jinho , Wu Xuewei , Turk Benjamin E. , Rosen Neal , Poulikakos Poulikos I. , Linding Rune
Published: July 2019

Small molecule inhibitors of BRAF and MEK have proven effective at inhibiting tumor growth in melanoma patients, however this efficacy is limited due to the almost universal development of drug resistance. To provide advanced insight into the signaling responses that occur following kinase inhibition we have performed quantitative (phospho)-proteomics of human melanoma cells treated with either dabrafenib, a BRAF inhibitor; trametinib, a MEK inhibitor or SCH772984, an ERK inhibitor. Over nine experiments we identified 7827 class I phosphorylation sites on 4960 proteins. This included 54 phosphorylation sites that were significantly down-modulated after exposure to all three inhibitors, 34 of which have not been previously reported. Functional analysis of these novel ERK targets identified roles for them in GTPase activity and regulation, apoptosis and cell-cell adhesion. Comparison of the results presented here with previously reported phosphorylation sites downstream of ERK showed a limited degree of overlap suggesting that ERK signaling responses may be highly cell line and cue specific. In addition we identified 26 phosphorylation sites that were only responsive to dabrafenib. We provide further orthogonal experimental evidence for 3 of these sites in human embryonic kidney cells over-expressing BRAF as well as further computational insights using KinomeXplorer. The validated phosphorylation sites were found to be involved in actin regulation, which has been proposed as a novel mechanism for inhibiting resistance development. These results would suggest that the linearity of the BRAF-MEK-ERK module is at least context dependent.
BAM8-22 and its receptor MRGPRX1 may attribute to cholestatic pruritus
Authors: Sanjel Babina , Maeng Han-Joo , Shim Won-Sik
Published: July 2019

Pruritus is an unexpected symptom observed in cholestasis and its mechanism is still unclear. Here, we show that bovine adrenal medulla (BAM) 8–22, an endogenous itch-inducing peptide, could be involved in cholestatic pruritus. It was found that bile duct ligation (BDL) mice, an obstructive cholestasis model, showed increased spontaneous scratching behaviour. Importantly, the mRNA level of proenkephalin, a precursor polypeptide of BAM8-22, was significantly increased in the skin of BDL mice. Furthermore, the mRNA level of Mrgprx1, which encodes a receptor for BAM8-22, was significantly increased in the dorsal root ganglia (DRG) of BDL mice. This was further confirmed by elevation of intracellular calcium levels upon BAM8-22 treatment in primarily-cultured DRG neurons. In addition, BDL mice showed augmented scratching behaviour by BAM8-22, indicating enhanced activity of MRGPRX1. Moreover, the skin homogenate of BDL mice induced elevation of intracellular calcium levels through MRGPRX1. Finally, among the various bile acids, chenodeoxycholic acid significantly increased proenkephalin transcription in a human keratinocyte cell line (HaCaT). In conclusion, cholestatic pruritus could be attributed in part to enhanced action of both BAM8-22 in the skin and its receptor MRGPRX1 in sensory neurons.
Heat capacities of thermally manipulated mechanical oscillator at strong coupling
Authors: Kolář Michal , Ryabov Artem , Filip Radim
Published: July 2019

Coherent quantum oscillators are basic physical systems both in quantum statistical physics and quantum thermodynamics. Their realizations in lab often involve solid-state devices sensitive to changes in ambient temperature. We represent states of the solid-state optomechanical oscillator with temperature-dependent frequency by equivalent states of the mechanical oscillator with temperature-dependent energy levels. We interpret the temperature dependence as a consequence of strong coupling between the oscillator and the heat bath. We explore parameter regimes corresponding to anomalous behavior of mechanical and thermodynamic characteristics as a consequence of the strong coupling: (i) The localization and the purification induced by heating, and (ii) the negativity of two generalized heat capacities. The capacities can be used to witness non-linearity in the temperature dependency of the energy levels. Our phenomenological experimentally-oriented approach can stimulate development of new optomechanical and thermomechanical experiments exploring basic concepts of strong coupling thermodynamics.
MICA*049, not MICA*009, is associated with Behçet’s disease in a Chinese population
Authors: Zhu Weifeng , Deng Yan , Wang Jiucun , Guo Xinjian , Ding Weifeng , Chao Jiashuo , Lin Dan , Wang Yuqin , Zhou Xiaodong
Published: July 2019

Behçet’s disease (BD) is a multi-systemic inflammatory disease. Previous reports indicated that MICA*009 confers susceptibility to BD. MICA*049 differs from MICA*009:01, a major MICA*009 subtype, only at codon 335 in exon 6. However, the potential association of MICA*049 with BD  has not been addressed. In this study, we differentiated association among MICA*049, MICA*009 and HLA-B*51 with BD. A Han Chinese cohort consisting of 41 BD patients and 197 ethnically matched controls were examined with sequencing and T-ARMS-PCR for genotyping of MICA, and ARMS-PCR for HLA-B*51. The phenotype frequency of MICA*049 (41.5% versus 8.1%, OR = 8.01, P = 1.91 × 10−8) and HLA-B*51 (46.3% versus 15.7%, OR = 4.62, P = 1.21 × 10−5) were significantly higher in BD patients than those in controls, whereas MICA*009 showed no significant difference between the two groups (17.1% versus 13.2%, OR = 1.35, P = 0.51). After stratification for the effect of HLA-B*51, MICA*049 was still associated with BD in HLA-B*51 negative patients (OR = 40.61, P = 0.02). Our results indicate that MICA*049, not MICA*009, is a risk factor to BD, and that is independent from HLA-B*51 in the Han Chinese cohort.
Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis
Authors: Diani Marco , Casciano Fabio , Marongiu Laura , Longhi Matteo , Altomare Andrea , Pigatto Paolo D. , Secchiero Paola , Gambari Roberto , Banfi Giuseppe , Manfredi Angelo A. , Altomare Gianfranco , Granucci Francesca , Reali Eva
Published: July 2019

The aim of this study is to identify subsets of T cells differentially represented in the circulation of patients with psoriatic arthritis and to evaluate the possibility that they can recirculate between peripheral blood and the inflamed joints. We analyzed the phenotype and cytokine expression in circulating CD8+ and CD4+ T cells in 69 subjects: 28 with cutaneous psoriasis, 15 patients with psoriatic arthritis, and 26 healthy subjects. In the circulation, the percentage of each subset was compared among the groups and correlation was calculated with the serum concentration of C-reactive protein. To investigate the migration of T cells towards the inflamed joints, we performed a transwell migration assay towards patient serum and synovial fluid. In selected patients we analyzed in parallel T cells from peripheral blood and from synovial fluid. In the circulation, we found increased percentage of CD8+ CCR6+ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. CD8+ effector/effector memory T cells showed increased migration towards synovial fluid. Finally, in synovial fluid we found accumulation of CXCR3+ CD8+ T cells and CD69+ cells. CD4+ T cells in the two compartments shared many similarities with CD8+ T cells. The results indicate a role for memory T cell effectors in systemic and joint manifestations of psoriatic arthritis.
Defective hierarchical porous copper-based metal-organic frameworks synthesised via facile acid etching strategy
Authors: Doan Huan V. , Sartbaeva Asel , Eloi Jean-Charles , A. Davis Sean , Ting Valeska P.
Published: July 2019

Introducing hierarchical pore structure to microporous materials such as metal-organic frameworks (MOFs) can be beneficial for reactions where the rate of reaction is limited by low rates of diffusion or high pressure drop. This advantageous pore structure can be obtained by defect formation, mostly via post-synthetic acid etching, which has been studied extensively on water-stable MOFs. Here we show that a water-unstable HKUST-1 MOF can also be modified in a corresponding manner by using phosphoric acid as a size-selective etching agent and a mixture of dimethyl sulfoxide and methanol as a dilute solvent. Interestingly, we demonstrate that the etching process which is time- and acidity- dependent, can result in formation of defective HKUST-1 with extra interconnected hexagonal macropores without compromising on the bulk crystallinity. These findings suggest an intelligent scalable synthetic method for formation of hierarchical porosity in MOFs that are prone to hydrolysis, for improved molecular accessibility and diffusion for catalysis.
Scalable Labeling for Cytoarchitectonic Characterization of Large Optically Cleared Human Neocortex Samples
Authors: Hildebrand Sven , Schueth Anna , Herrler Andreas , Galuske Ralf , Roebroeck Alard
Published: July 2019

Optical clearing techniques and light sheet microscopy have transformed fluorescent imaging of rodent brains, and have provided a crucial alternative to traditional confocal or bright field techniques for thin sections. However, clearing and labeling human brain tissue through all cortical layers and significant portions of a cortical area, has so far remained extremely challenging, especially for formalin fixed adult cortical tissue. Here, we present MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling approach for optically cleared human cortex samples, which can be applied to large (up to 5 mm thick) formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dye protocols in combination with new refractive index matching solutions allows deep volume imaging. This greatly reduces time and cost of imaging cytoarchitecture in thick samples and enables classification of cytoarchitectonic layers over the full cortical depth. We demonstrate application of MASH to large archival samples of human visual areas, characterizing cortical architecture in 3D from the scale of cortical areas to that of single cells. In combination with scalable light sheet imaging and data analysis, MASH could open the door to investigation of large human cortical systems at cellular resolution and in the context of their complex 3-dimensional geometry.
Strong primary care and patients’ survival
Authors: Wensing Michel , Szecsenyi Joachim , Kaufmann-Kolle Petra , Laux Gunter
Published: July 2019

Primary healthcare is the cornerstone of any healthcare system. A major health system reform to strengthen primary care has been implemented in Germany since 2008. Key components include: voluntary participation, intensive management of patients with chronic diseases, coordination of access to medical specialists, continuous quality improvement, and capitation-based reimbursement. The objective of this study was to assess the effect of this reform on survival of enrolled patients. We conducted a comparative cohorts study with 5-year follow-up, starting in the year 2012 in Baden-Wuerttemberg, Germany. Participants were 1,003,336 enrolled patients and 725,310 control patients. A Cox proportional hazards regression model was applied to compare survival of enrolled patients with a composed control cohort of non-enrolled patients, adjusted for a range of patient and physician characteristics. Average age of enrolled patients was 57.3 years and 56.1% were women. Compared to control patients, they had lower mortality (Hazard Ratio: 0.978; 95% CI: 0.968; 0.989). Participation in chronic disease management programs had independent impact on survival rate (Hazard Ratio 0.744, 95% CI: 0.734; 0.753). We concluded that strong primary care is safe and potentially beneficial in terms of patients’ survival.
Antibody responses to flagellin C and Streptococcus gallolyticus pilus proteins in colorectal cancer
Authors: Butt Julia , Fernández de Larrea Nerea , Tjalsma Harold , Roelofs Rian , Kato Ikuko , Martín Vicente , Pérez-Gómez Beatriz , Moreno Victor , Dierssen-Sotos Trinidad , Castilla Jesús , Fernández-Tardón Guillermo , Amiano Pilar , Salas Dolores , Alguacil Juan , Jiménez-Moleón José Juan , Huerta José María , de Sanjosé Silvia , del Campo Rosa , Kogevinas Manolis , Pollán Marina , Pawlita Michael , Waterboer Tim , Boleij Annemarie , Aragonés Nuria
Published: July 2019

Antibodies to Streptococcus gallolyticus subspecies gallolyticus (SGG) have been associated with colorectal cancer (CRC). Because SGG may correlate with impaired gut epithelia, we assessed the association of antibodies to bacterial flagellin C (FliC), a measure potentially related to this impairment, with CRC and the CRC-specific interaction with antibodies to SGG proteins. Antibodies to FliC and SGG pilus proteins Gallo2178 and Gallo2179 were measured in two independent studies, a combined study from Nijmegen and Detroit (93 CRC cases, 74 controls) and a replication data set including 576 cases and 576 controls from the Spanish multicenter multicase-control study (MCC-Spain). Logistic regression was applied to assess whether antibodies to FliC were associated with CRC and modified the association of antibodies to SGG proteins with CRC. Antibodies to FliC were associated with those to SGG Gallo2178 among CRC cases, resulting in an interaction in the association of antibodies to Gallo2178 with CRC (p = 0.007). This association was only present among individuals with high antibody responses to FliC (OR: 2.42, 95% CI: 1.45–4.06). In conclusion, our findings suggest that colorectal tumorigenesis could be accompanied by an impaired integrity of the epithelium that could result in associated increased antibody responses to bacterial proteins.
Plasma-based fast-gelling biohybrid gels for biomedical applications
Authors: Pal Amrita , Tripathi Kunal , Pathak Chandrashekhar , Vernon Brent L.
Published: July 2019

Blood based biomaterials are widely researched and used in different biomedical applications including cell therapy, drug delivery, sealants etc. due to their biocompatibility and biodegradability. Blood derived gels are successfully used in clinical studies due to the presence of fibrinogen and several platelet growth factors. In spite of their wide applications, it is challenging to use blood-based biomaterials due to their low mechanical stability, poor adhesive property and contamination risk. In this study, we used porcine plasma to form gel in presence of biodegradable synthetic crosslinkers. Mechanical strength of this plasma gel could be tailored by altering the amount of crosslinkers for any desired biomedical applications. These plasma gels, formed by the synthetic crosslinkers, were utilized as a drug delivery platform for wound healing due to their low cytotoxicity. A model drug release study with these plasma gels indicated slow and sustained release of the drugs.
Optimal Semiconductors for 3H and 63Ni Betavoltaics
Authors: Maximenko Sergey I. , Moore Jim E. , Affouda Chaffra A. , Jenkins Phillip P.
Published: July 2019

Betavoltaic power sources based on the conversion of radioisotope energy to electrical power are considered an appealing option for remote applications due to extended period of operation and high energy densities. However, to be competitive with other power sources, their efficiency must be increased. This can be done through optimization of the beta source and selection of the semiconductor absorber. This paper evaluates available on the market and developing wideband gap semiconductors as prospective absorbers with 3H and 63Ni sources. Simulation results indicate that among wide band gap materials 4H-SiC and diamond are two optimal semiconductors due to the combination of good coupling efficiencies with isotope sources and good electronic transport properties. Additionally, having good coupling efficiency, an ultra-wide bandgap, and the capability for both n- and p-type doping, c-BN is a promising material for betavoltaic applications.
Impact of local composition on the energetics of E-centres in Si1−xGex alloys
Authors: Christopoulos Stavros-Richard G. , Kuganathan Navaratnarajah , Chroneos Alexander
Published: July 2019

The energetics of the defect chemistry and processes in semiconducting alloys is both technologically and theoretically significant. This is because defects in semiconductors are critical to tune their electronic properties. These processes are less well understood in random semiconductor alloys such as silicon germanium as compared to elementary semiconductors (for example silicon). To model the random silicon germanium alloy we have employed density functional theory calculations in conjunction with the special quasirandom structures model for different compositions. Here we show that, the energetics of substitutional phosphorous-vacancy pairs (E-centres) in Si1−xGex alloys vary greatly with respect to the local Ge concentration and the composition of the alloy. The most energetically favourable E-centres have a Ge atom as a nearest neighbour, whereas the dependence of the binding energy of the E-centres with respect to alloy composition is non-linear.
MC4R and ENPP1 gene polymorphisms and their implication in maternal and neonatal risk for obesity
Authors: Mărginean Claudiu , Mărginean Cristina Oana , Iancu Mihaela , Meliț Lorena Elena , Tripon Florin , Bănescu Claudia
Published: July 2019

The aims of this study were to establish the role of MC4Rrs17782313 and ENPP1rs1044498 gene polymorphisms on pre-pregnancy BMI and the newborn’s status. We performed a cross-sectional study on 185 mothers and their offspring. The groups were divided into: control group- underweight or normal mothers with BMIinitial < 25 kg/m2 (n1 = 134) and study group-overweight/obese mothers with BMIinitial ≥ 25 kg/m2 (n2 = 51). All subjects underwent demographic, anthropometric, paraclinical, bioimpedance and genetic parameters. We found association between initial BMI and gestational weight gain (GWG), and a higher frequency of excessive GWG in overweight/obese women (p = 0.037). Higher values of anthropometric and bioimpedance parameters were observed in overweight/obese versus underweight/normal women. The MC4R rs17782313 and ENPP1 rs1044498 variant genotypes had an increased risk of pre-pregnancy overweight (OR = 1.41; 95% CI:[0.72; 2.78]; OR = 1.34; 95% CI:[0.65; 2.75]). The newborns from mothers with excessive GWG had a higher birth weight (BW) (p = 0.001). Higher MUAC values were noticed in newborns with MC4R rs17782313 wild-type genotype. Also, BW was correlated with GWG status smoking in pregnancy, gestational age and neonatal ENPP1rs1044498 variant genotype (p = 0.026). Our study pointed out the role of MC4R rs17782313 and ENPP1 rs1044498 genotypes in obesity determinisms in mothers and their newborns in correlation with BMI, MUAC, TST and bioimpedance parameters.
Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis
Authors: Lee Sanghee , Nedumaran Balachandar , Hypolite Joseph , Caldwell Brian , Rudolph Michael C. , Malykhina Anna P.
Published: July 2019

Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. In vitro contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.
Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture
Authors: Shichi Yuuki , Sasaki Norihiko , Michishita Masaki , Hasegawa Fumio , Matsuda Yoko , Arai Tomio , Gomi Fujiya , Aida Junko , Takubo Kaiyo , Toyoda Masashi , Yoshimura Hisashi , Takahashi Kimimasa , Ishiwata Toshiyuki
Published: July 2019

Pancreatic cancer, composed of heterogeneous cancer cells, alters epithelial to mesenchymal features during growth and metastasis. In this study, we aimed to characterize pancreatic ductal adenocarcinoma (PDAC) cells showing epithelial or mesenchymal features in 3D culture. In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression and exhibited a round-like appearance encircled by flat cells. PANC-1 cells had high vimentin and low E-cadherin expression and formed grape-like spheres. PK-1 cells had secretary granules and many microvilli, desmosomes, and adherens junctions, while PANC-1 cells had few microvilli, adherens junction, and no desmosomes. Cytokeratin 7, trypsin, CA19-9, and E-cadherin were highly expressed in PK-1 cells but not in PANC-1 cells. Ki-67 was diffusely expressed in PANC-1 spheres but was restricted to the peripheral flat cells of PK-1 spheres. PANC-1 and PK-1 cells were positive for transforming growth factor (TGF) β receptor II and phosphorylated smad2/3, but PK-1 cells were smad4 negative. Taken together, 3D culture enhanced morphofunctional differences of PDAC cells showing epithelial or mesenchymal characteristics, and epithelial phenotype maintenance may be due to the ineffectiveness of the TGF- β pathway. Clarification of heterogeneity using 3D culture may be useful for development of individualized diagnostic and therapeutic methods in patients with PDAC.
Formation and behavior of negative ions in low pressure aniline-containing RF plasmas
Authors: Pattyn Cedric , Kovacevic Eva , Strunskus Thomas , Lecas Thomas , Berndt Johannes
Published: July 2019

This paper is focused on the formation mechanisms and the general behavior of negative ions in low pressure radio-frequency (RF) plasmas operated in a mixture of argon and aniline vapor. This type of plasma is mostly used for the synthesis of polyaniline, one of the most studied conductive polymers. Experiments based on mass spectroscopy measurements reveal the necessity to have a thin layer of plasma synthesized polyaniline on the electrodes to produce negative ions through complex surface reactions. In addition, thin-films deposited using this type of discharge are analyzed by means of Near Edge X-ray Absorption Fine Structure spectroscopy (NEXAFS). The material analysis gives a first indication about the possible contribution of negative ions to polyaniline deposition.
Escherichia coli adaptation and response to exposure to heavy atmospheric pollution
Authors: Zhang Tian , Shi Xiao-Chen , Xia Yangyang , Mai Liqiang , Tremblay Pier-Luc
Published: July 2019

90% of the world population is exposed to heavy atmospheric pollution. This is a major public health issue causing 7 million death each year. Air pollution comprises an array of pollutants such as particulate matters, ozone and carbon monoxide imposing a multifactorial stress on living cells. Here,Escherichia coliwas used as model cell and adapted for 390 generations to atmospheric pollution to assess its long-term effects at the genetic, transcriptomic and physiological levels. Over this period,E.colievolved to grow faster and acquired an adaptive mutation inrpoB, which encodes the RNA polymerase β subunit. Transcriptomic and biochemical characterization showed alteration of the cell membrane composition resulting in lesser permeability after the adaptation process. A second significant change in the cell wall structure of the adapted strain was the greater accumulation of the exopolysaccharides colanic acid and cellulose in the extracellular fraction. Results also indicated that amino acids homeostasis was involved inE.coliresponse to atmospheric pollutants. This study demonstrates that adaptive mutation with transformative physiological impact can be fixed in genome after exposure to atmospheric pollution and also provides a comprehensive portrait of the cellular response mechanisms involved.
Crustal Structure of the Collision-Subduction Zone in South of Iran Using Virtual Seismometers
Authors: Shirzad Taghi , Riahi Mohammad-Ali , Assumpção Marcelo S.
Published: July 2019

Improving the resolution of seismic tomography by adding virtual seismometers is an ambitious aim in regions with poor instrumental coverage. In this study, inter-event empirical Green’s functions (EGFs) were retrieved using cross-correlation of the vertical component of 630 earthquakes with M ≥ 4 which occurred around the collision-subduction transition zone in south Iran. To extract reliable inter-event EGFs and obtain stable tomographic results, we used about 1300 event pairs with good signal-to-noise ratio, each pair well aligned to a seismic station. Our results show that the retrieved inter-event EGFs agree well with those obtained from earthquakes in similar paths. The inverted velocity model presents two main layers including upper crust (up to ~16 km) and middle crust (deeper than ~18 km) in both sides of the Minab-Zendan-Palami transition zone. The upper crust contains two main layers: sedimentary and basement layers with thicknesses ~6 and ~10 km, respectively. Moreover, the main faults cause lateral variations in these main layers. The difference between the average velocities of the middle crust, between the collision and subduction zones, is about 0.5 km/s, delimited by faults. Also, an area with a 30 km width along these faults can be defined as the collision-subduction transition zone.
Cochlear shape reveals that the human organ of hearing is sex-typed from birth
Authors: Braga J. , Samir C. , Risser L. , Dumoncel J. , Descouens D. , Thackeray J. F. , Balaresque P. , Oettlé A. , Loubes J.-M. , Fradi A.
Published: July 2019

Sex differences in behavioral and neural characteristics can be caused by cultural influences but also by sex-based differences in neurophysiological and sensorimotor features. Since signal-response systems influence decision-making, cooperative and collaborative behaviors, the anatomical or physiological bases for any sex-based difference in sensory mechanisms are important to explore. Here, we use uniform scaling and nonparametric representations of the human cochlea, the main organ of hearing that imprints its adult-like morphology within the petrosal bone from birth. We observe a sex-differentiated torsion along the 3D cochlear curve in samples of 94 adults and 22 juvenile skeletons from cross-cultural contexts. The cochlear sexual dimorphism measured in our study allows sex assessment from the human skeleton with a mean accuracy ranging from 0.91 to 0.93 throughout life. We conclude that the human cochlea is sex-typed from an early post-natal age. This, for the first time, allows nondestructive sex determination of juveniles’ skeletal remains in which the biomolecules are too degraded for study but in which the petrosal is preserved, one of the most common bone within archaeological assemblages. Our observed sex-typed cochlear shape from birth is likely associated with complex evolutionary processes in modern humans for reasons not yet fully understood.
Chemical Purification of Terbium-155 from Pseudo-Isobaric Impurities in a Mass Separated Source Produced at CERN
Authors: Webster Ben , Ivanov Peter , Russell Ben , Collins Sean , Stora Thierry , Ramos Joao Pedro , Köster Ulli , Robinson Andrew Paul , Read David
Published: July 2019

Four terbium radioisotopes (149, 152, 155, 161Tb) constitute a potential theranostic quartet for cancer treatment but require any derived radiopharmaceutical to be essentially free of impurities. Terbium-155 prepared by proton irradiation and on-line mass separation at the CERN-ISOLDE and CERN-MEDICIS facilities contains radioactive 139Ce16O and also zinc or gold, depending on the catcher foil used. A method using ion-exchange and extraction chromatography resins in two column separation steps has been developed to isolate 155Tb with a chemical yield of ≥95% and radionuclidic purity ≥99.9%. Conversion of terbium into a form suitable for chelation to targeting molecules in diagnostic nuclear medicine is presented. The resulting 155Tb preparations are suitable for the determination of absolute activity, SPECT phantom imaging studies and pre-clinical trials.
Distance-dependent seed‒seedling transition in the tree Castanopsis sclerophylla is altered by fragment size
Authors: Wang Rong , Shi Yi-Su , Zhang Yu-Xuan , Xu Gao-Fu , Shen Guo-Chun , Chen Xiao-Yong
Published: July 2019

Negative distance-dependence of conspecific seedling mortality (NDisDM) is a crucial stabilizing force that regulates plant diversity, but it remains unclear whether and how fragment size shifts the strength of NDisDM. Here, we surveyed the seed‒seedling transition process for a total of 25,500 seeds of a local dominant tree species on islands of various sizes in a reservoir and on the nearby mainland. We found significant NDisDM on the mainland and large and medium islands, with significantly stronger NDisDM on medium islands. However, positive distance-dependent mortality was detected on small islands. Changes in distance-dependence were critically driven by both rodent attack and pathogen infestation, which were significantly affected by fragment size. Our results emphasize the necessity of incorporating the effects of fragment size on distance-dependent regeneration of dominant plant species into the existing frameworks for better predicting the consequences of habitat fragmentation.
Evolution of Oryza chloroplast genomes promoted adaptation to diverse ecological habitats
Authors: Gao Li-Zhi , Liu Yun-Long , Zhang Dan , Li Wei , Gao Ju , Liu Yuan , Li Kui , Shi Chao , Zhao Yuan , Zhao You-Jie , Jiao Jun-Ying , Mao Shu-Yan , Gao Cheng-Wen , Eichler Evan E.
Published: July 2019

The course, tempo and mode of chloroplast genome evolution remain largely unknown, resulting in limited knowledge about how plant plastome gene and genome evolve during the process of recent plant speciation. Here, we report the complete plastomes of 22 closely relatedOryzaspecies in chronologically ordered stages and generate the first precise map of genomic structural variation, to our knowledge. The occurrence rapidity was estimated on average to be ~7 insertions and ~15 deletions per Myr. Relatively fewer deletions than insertions result in an increased repeat density that causes the observed growth ofOryzachloroplast genome sizes. Genome-wide scanning identified 14 positively selected genes that are relevant to photosynthesis system, eight of which were found independently in shade-tolerant or sun-loving rice species.psaAseemed positively selected in both shade-tolerant and sun-loving rice species. The results show that adaptive evolution of chloroplast genes makes rice species adapt to diverse ecological habitats related to sunlight preferences.
A luminescent biosensor forex vivodetection of HER2-positive breast cancer based on a novel affiprobe
Authors: Nazari Mahboobeh , Emamzadeh Rahman , Minai-Tehrani Arash , Nasir shirazi Mohadeseh , Naimi Azar
Published: July 2019

A novel receptor tyrosine-protein kinase erbB-2 (HER2)-binding affiprobe – named ZHER2:342-RLuc – was designed, produced and assessed in terms of function to detect HER2 positive cells and for preliminary clinical diagnosis.
Polydopamine/puerarin nanoparticle-incorporated hybrid hydrogels for enhanced wound healing
Authors: Zhang Shaohan , Ou Qianmin , Xin Peikun , Yuan Qijuan , Wang Yan , Wu Jun
Published: July 2019

Oxidative damage generated would disrupt the oxidant/antioxidant balance in cells, causing slow wound healing and tissue regeneration. Hydrogel dressing with antioxidant properties can promote wound healing, however, its design is still a challenge.
Cobalt doped β-molybdenum carbide nanoparticles encapsulated within nitrogen-doped carbon for oxygen evolution
Authors: Zhu Xinyang , Zhang Xueping , Huang Liang , Liu Yongqin , Zhang He , Dong Shaojun
Published: July 2019

Herein, we report a novel cobalt doped transitional metal carbide based OER electrocatalyst, cobalt doped β-molybdenum carbide encapsulated by nitrogen doped carbon framework, which shows an overpotential of 262.2 mV at current density of 10 mA cm−2.