bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid
Authors: Watano Ryota , Ohmori Tsukasa , Hishikawa Shuji , Sakata Asuka , Mizukami Hiroaki
Published: February 2020

Adeno-associated virus (AAV) vectors can transduce hepatocytes efficiently in vivo in various animal species, including humans. Few reports, however, have examined the utility of pigs in gene therapy. Pigs are potentially useful in preclinical studies because of their anatomical and physiological similarity to humans. Here, we evaluated the utility of microminipigs for liver-targeted gene therapy. These pigs were intravenously inoculated with an AAV8 vector encoding the luciferase gene, and gene expression was assessed by an in vivo imaging system. Robust transgene expression was observed almost exclusively in the liver, even though the pig showed a low-titer of neutralizing antibody (NAb) against the AAV8 capsid. We assessed the action of NAbs against AAV, which interfere with AAV vector-mediated gene transfer by intravascular delivery. When a standard dose of vector was administered intravenously, transgene expression was observed in both NAb-negative and low-titer (14×)-positive subjects, whereas gene expression was not observed in animals with higher titers (56×). These results are compatible with our previous observations using nonhuman primates, indicating that pigs are useful in gene therapy experiments, and that the role of low-titer NAb in intravenous administration of the AAV vector shows similarities across species.
FOXM1 regulates leukemia stem cell quiescence and survival in MLL-rearranged AML
Authors: Sheng Yue , Yu Chunjie , Liu Yin , Hu Chao , Ma Rui , Lu Xinyan , Ji Peng , Chen Jianjun , Mizukawa Benjamin , Huang Yong , Licht Jonathan D. , Qian Zhijian
Published: February 2020

FOXM1, a known transcription factor, promotes cell proliferation in a variety of cancer cells. Here we show that Foxm1 is required for survival, quiescence and self-renewal of MLL-AF9 (MA9)-transformed leukemia stem cells (LSCs) in vivo. Mechanistically, Foxm1 upregulation activates the Wnt/β-catenin signaling pathways by directly binding to β-catenin and stabilizing β-catenin protein through inhibiting its degradation, thereby preserving LSC quiescence, and promoting LSC self-renewal in MLL-rearranged AML. More importantly, inhibition of FOXM1 markedly suppresses leukemogenic potential and induces apoptosis of primary LSCs from MLL-rearranged AML patients in vitro and in vivo in xenograft mice. Thus, our study shows a critical role and mechanisms of Foxm1 in MA9-LSCs, and indicates that FOXM1 is a potential therapeutic target for selectively eliminating LSCs in MLL-rearranged AML.
Noise-tolerant single photon sensitive three-dimensional imager
Authors: Rehain Patrick , Sua Yong Meng , Zhu Shenyu , Dickson Ivan , Muthuswamy Bharathwaj , Ramanathan Jeevanandha , Shahverdi Amin , Huang Yu-Ping
Published: February 2020

Active imagers capable of reconstructing 3-dimensional (3D) scenes in the presence of strong background noise are highly desirable for many sensing and imaging applications. A key to this capability is the time-resolving photon detection that distinguishes true signal photons from the noise. To this end, quantum parametric mode sorting (QPMS) can achieve signal to noise exceeding by far what is possible with typical linear optics filters, with outstanding performance in isolating temporally and spectrally overlapping noise. Here, we report a QPMS-based 3D imager with exceptional detection sensitivity and noise tolerance. With only 0.0006 detected signal photons per pulse, we reliably reconstruct the 3D profile of an obscured scene, despite 34-fold spectral-temporally overlapping noise photons, within the 6 ps detection window (amounting to 113,000 times noise per 20 ns detection period). Our results highlight a viable approach to suppress background noise and measurement errors of single photon imager operation in high-noise environments.
Prefrontal attentional saccades explore space rhythmically
Authors: Gaillard Corentin , Ben Hadj Hassen Sameh , Di Bello Fabio , Bihan-Poudec Yann , VanRullen Rufin , Ben Hamed Suliann
Published: February 2020

Recent studies suggest that attention samples space rhythmically through oscillatory interactions in the frontoparietal network. How these attentional fluctuations coincide with spatial exploration/displacement and exploitation/selection by a dynamic attentional spotlight under top-down control is unclear. Here, we show a direct contribution of prefrontal attention selection mechanisms to a continuous space exploration. Specifically, we provide a direct high spatio-temporal resolution prefrontal population decoding of the covert attentional spotlight. We show that it continuously explores space at a 7–12 Hz rhythm. Sensory encoding and behavioral reports are increased at a specific optimal phase w/ to this rhythm. We propose that this prefrontal neuronal rhythm reflects an alpha-clocked sampling of the visual environment in the absence of eye movements. These attentional explorations are highly flexible, how they spatially unfold depending both on within-trial and across-task contingencies. These results are discussed in the context of exploration-exploitation strategies and prefrontal top-down attentional control.
A solvent-assisted ligand exchange approach enables metal-organic frameworks with diverse and complex architectures
Authors: Yu Dongbo , Shao Qi , Song Qingjing , Cui Jiewu , Zhang Yongli , Wu Bin , Ge Liang , Wang Yan , Zhang Yong , Qin Yongqiang , Vajtai Robert , Ajayan Pulickel M. , Wang Huanting , Xu Tongwen , Wu Yucheng
Published: February 2020

Unlike inorganic crystals, metal-organic frameworks do not have a well-developed nanostructure library, and establishing their appropriately diverse and complex architectures remains a major challenge. Here, we demonstrate a general route to control metal-organic framework structure by a solvent-assisted ligand exchange approach. Thirteen different types of metal-organic framework structures have been prepared successfully. To demonstrate a proof of concept application, we used the obtained metal-organic framework materials as precursors for synthesizing nanoporous carbons and investigated their electrochemical Na+storage properties. Due to the unique architecture, the one-dimensional nanoporous carbon derived from double-shelled ZnCo bimetallic zeolitic imidazolate framework nanotubes exhibits high specific capacity as well as superior rate capability and cycling stability. Our study offers an avenue for the controllable preparation of well-designed meta-organic framework structures and their derivatives, which would further broaden the application opportunities of metal-organic framework materials.
Author Correction: The ubiquitin ligase UBR5 suppresses proteostasis collapse in pluripotent stem cells from Huntington’s disease patients
Authors: Koyuncu Seda , Saez Isabel , Lee Hyun Ju , Gutierrez-Garcia Ricardo , Pokrzywa Wojciech , Fatima Azra , Hoppe Thorsten , Vilchez David
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The kinase polypharmacology landscape of clinical PARP inhibitors
Authors: Antolin Albert A. , Ameratunga Malaka , Banerji Udai , Clarke Paul A. , Workman Paul , Al-Lazikani Bissan
Published: February 2020

Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein class. Four PARP inhibitors have been approved by the FDA as cancer therapeutics, yet a precise mechanistic rationale to guide clinicians on which to choose for a particular patient is lacking. The four drugs have largely similar PARP family inhibition profiles, but several differences at the molecular and clinical level have been reported that remain poorly understood. Here, we report the first comprehensive characterization of the off-target kinase landscape of four FDA-approved PARP drugs. We demonstrate that all four PARP inhibitors have a unique polypharmacological profile across the kinome. Niraparib and rucaparib inhibit DYRK1s, CDK16 and PIM3 at clinically achievable, submicromolar concentrations. These kinases represent the most potently inhibited off-targets of PARP inhibitors identified to date and should be investigated further to clarify their potential implications for efficacy and safety in the clinic. Moreover, broad kinome profiling is recommended for the development of PARP inhibitors as PARP-kinase polypharmacology could potentially be exploited to modulate efficacy and side-effect profiles.
Rare events in generalized Lévy Walks and the Big Jump principle
Authors: Vezzani Alessandro , Barkai Eli , Burioni Raffaella
Published: February 2020

The prediction and control of rare events is an important task in disciplines that range from physics and biology, to economics and social science. The Big Jump principle deals with a peculiar aspect of the mechanism that drives rare events. According to the principle, in heavy-tailed processes a rare huge fluctuation is caused by a single event and not by the usual coherent accumulation of small deviations. We consider generalized Lévy walks, a class of stochastic processes with power law distributed step durations and with complex microscopic dynamics in the single stretch. We derive the bulk of the probability distribution and using the big jump principle, the exact form of the tails that describes rare events. We show that the tails of the distribution present non-universal and non-analytic behaviors, which depend crucially on the dynamics of the single step. The big jump estimate also provides a physical explanation of the processes driving the rare events, opening new possibilities for their correct prediction.
Experimental observation of drumhead surface states in SrAs3
Authors: Hosen M. Mofazzel , Dhakal Gyanendra , Wang Baokai , Poudel Narayan , Dimitri Klauss , Kabir Firoza , Sims Christopher , Regmi Sabin , Gofryk Krzysztof , Kaczorowski Dariusz , Bansil Arun , Neupane Madhab
Published: February 2020

The topological nodal-line semimetal (TNS) is a unique class of materials with a one dimensional line node accompanied by a nearly dispersionless two-dimensional surface state. However, a direct observation of the so called drumhead surface state within current nodal-line materials is still elusive. Here, using high-resolution angle-resolved photoemission spectroscopy (ARPES) along with first-principles calculations, we report the observation of a topological nodal-loop (TNL) in SrAs3, whereas CaAs3 exhibits a topologically trivial state. Our data reveal that surface projections of the bulk nodal-points are connected by clear drumhead surface states in SrAs3. Furthermore, our magneto-transport and magnetization data clearly suggest the presence (absence) of surface states in SrAs3 (CaAs3). Notably, the observed topological states in SrAs3 are well separated from other bands in the vicinity of the Fermi level. RAs3 where R = Ca, Sr, thus, offers a unique opportunity to realize an archetype nodal-loop semimetal and establish a platform for obtaining a deeper understanding of the quantum phase transitions.
Role of Early PET/CT Imaging with 68Ga-PSMA in Staging and Restaging of Prostate Cancer
Authors: Barakat Andrew , Yacoub Basel , Homsi Maria El , Saad Aldine Amro , El Hajj Albert , Haidar Mohamad B.
Published: February 2020

Ga-68 Prostate-Specific Membrane Antigen PET/CT is a new tool for the assessment of prostate cancer. Standard imaging time is 60 minutes post injection of radiotracer. At 60 minutes, there is physiologic accumulation of radiotracer in the urinary bladder which may cause some lesions in its vicinity to be obscured. Our aim is to determine if early imaging at 3 minutes in addition to standard imaging at 60 minutes can improve the detection of PSMA-avid lesions. A retrospective review of 167 consecutive patients was conducted. Overall, 115 patients (68.9%) were ruled to have prostate cancer based on imaging as seen on early or standard PET/CT images. In 106/115 (64%), the lesions were detected on both early and standard imaging; in 8/115 (6.9%), the lesions were only detected on early imaging; in 1/115 (0.6%) the lesion was detected only on standard imaging. The addition of early imaging significantly improved the overall detection rate of PSMA-avid lesions (p = 0.039). The ratio of patients with lesions detected on early imaging but not on standard imaging in restaging group was 7/88 and was higher than that in staging group 1/79 (p = 0.043). We recommend early imaging in addition to the standard imaging in Ga-68 PSMA PET/CT, particularly in patients presenting for restaging of prostate cancer.
A co-culture nanofibre scaffold model of neural cell degeneration in relevance to Parkinson’s disease
Authors: Chemmarappally Joseph M. , Pegram Henry C. N. , Abeywickrama Neranga , Fornari Enzo , Hargreaves Alan J. , De Girolamo Luigi A. , Stevens Bob
Published: February 2020

Current therapeutic strategies for Parkinson’s disease (PD) aim to delay progression or replace damaged neurons by restoring the original neuronal structures. The poor regenerative capacity of neural tissue highlights the need for the development of cellular environments to model the pathogenesis of PD. In the current work, we have characterised the growth, survival and response to PD mimetics of human SH-SY5Y neuroblastoma and U-87MG glioblastoma cell lines cultured on polyacrylonitrile (PAN) and Jeffamine® doped polyacrylonitrile (PJ) nano-scaffolds. Differentiation induced by a range of agents was evaluated by immunoassays of neural protein biomarkers. PAN and PJ nanofibre scaffolds provided suitable three-dimensional (3D) environment to support the growth, differentiation and network formation of dopaminergic neuron- and astrocyte-like cell populations, respectively. The scaffolds selectively supported the survival and differentiation of both cell populations with prolonged neuronal survival when exposed to PD mimetics in the presence of astrocytes in a co-culture model. Such 3D nanoscaffold-based assays could aid our understanding of the molecular basis of PD mimetic-induced Parkinsonism and the discovery of neuroprotective agents.
Revealing Plasma-Surface Interaction at Atmospheric Pressure: Imaging of Electric Field and Temperature inside the Targeted Material
Authors: Slikboer Elmar , Acharya Kishor , Sobota Ana , Garcia-Caurel Enric , Guaitella Olivier
Published: February 2020

The plasma-surface interaction is studied for a low temperature helium plasma jet generated at atmospheric pressure using Mueller polarimetry on an electro-optic target. The influence of the AC kHz operating frequency is examined by simultaneously obtaining images of the induced electric field and temperature of the target. The technique offers high sensitivity in the determination of the temperature variation on the level of single degrees. Simultaneously, the evolution of the electric field in the target caused by plasma-driven charge accumulation can be measured with the threshold of the order of 105 V/m. Even though a specific electro-optic crystal is used to obtain the results, they are generally applicable to dielectric targets under exposure of a plasma jet when they are of 0.5 mm thickness, have a dielectric constant greater than 4 and are at floating potential. Other techniques to examine the induced electric field in a target do not exist to the best of our knowledge, making this technique unique and necessary. The influence of the AC kHz operating frequency is important because many plasma jet designs used throughout the world operate at different frequency which changes the time between the ionization waves and hence the leftover species densities and stability of the plasma. Results for our jet show a linear operating regime between 20 and 50 kHz where the ionization waves are stable and the temperature increases linearly by 25 K. The charge deposition and induced electric fields do not increase significantly but the surface area does increase due to an extended surface propagation. Additionally, temperature mapping using a 100 μm GaAs probe of the plasma plume area has revealed a mild heat exchange causing a heating of several degrees of the helium core while the surrounding air slightly cools. This peculiarity is also observed without plasma in the gas plume.
Screening of inmates transferred to Spain reveals a Peruvian prison as a reservoir of persistent Mycobacterium tuberculosis MDR strains and mixed infections
Authors: Abascal Estefanía , Herranz Marta , Acosta Fermín , Agapito Juan , Cabibbe Andrea M. , Monteserin Johana , Ruiz Serrano María Jesús , Gijón Paloma , Fernández-González Francisco , Lozano Nuria , Chiner-Oms Álvaro , Cáceres Tatiana , Pintado Pilar Gómez , Acín Enrique , Valencia Eddy , Muñoz Patricia , Comas Iñaki , Cirillo Daniela M. , Ritacco Viviana , Gotuzzo Eduardo , García de Viedma Darío
Published: February 2020

It is relevant to evaluate MDR-tuberculosis in prisons and its impact on the global epidemiology of this disease. However, systematic molecular epidemiology programs in prisons are lacking. A health-screening program performed on arrival for inmates transferred from Peruvian prisons to Spain led to the diagnosis of five MDR-TB cases from one of the biggest prisons in Latin America. They grouped into two MIRU-VNTR–clusters (Callao-1 and Callao-2), suggesting a reservoir of two prevalent MDR strains. A high-rate of overexposure was deduced because one of the five cases was coinfected by a pansusceptible strain. Callao-1 strain was also identified in 2018 in a community case in Spain who had been in the same Peruvian prison in 2002–5. A strain-specific-PCR tailored from WGS data was implemented in Peru, allowing the confirmation that these strains were currently responsible for the majority of the MDR cases in that prison, including a new mixed infection.
Exome Sequencing in Individuals with Isolated Biliary Atresia
Authors: Rajagopalan Ramakrishnan , Tsai Ellen A. , Grochowski Christopher M. , Kelly Susan M. , Loomes Kathleen M. , Spinner Nancy B. , Devoto Marcella
Published: February 2020

Biliary atresia (BA) is a severe pediatric liver disease resulting in necroinflammatory obliteration of the extrahepatic biliary tree. BA presents within the first few months of life as either an isolated finding or with additional syndromic features. The etiology of isolated BA is unknown, with evidence for infectious, environmental, and genetic risk factors described. However, to date, there are no definitive causal genes identified for isolated BA in humans, and the question of whether single gene defects play a major role remains open. We performed exome-sequencing in 101 North American patients of European descent with isolated BA (including 30 parent-child trios) and considered several experimental designs to identify potentially deleterious protein-altering variants that may be involved in the disease. In a case-only analysis, we did not identify genes with variants shared among more than two probands, and burden tests of rare variants using a case-case control design did not yield significant results. In the trio analysis of 30 simplex families (patient and parent trios), we identified 66 de novo variants in 66 genes including potentially deleterious variants in STIP1 and REV1. STIP1 is a co-chaperone for the heat-shock protein, HSP90, and has been shown to have diverse functions in yeast, flies and mammals, including stress-responses. REV1 is known to be a key player in DNA repair pathway and to interact with HSP90. In conclusion, our results do not support the hypothesis that a simple genetic model is responsible for the majority of cases of isolated BA. Our finding of de novo variants in genes linked to evolutionarily conserved stress responses (STIP1 and REV1) suggests that exploration of how genetic susceptibility and environmental exposure may interact to cause BA is warranted.
Elucidating the dual role of grain boundaries as dislocation sources and obstacles and its impact on toughness and brittle-to-ductile transition
Authors: Reiser Jens , Hartmaier Alexander
Published: February 2020

In this paper, we resolve the role of grain boundaries on toughness and the brittle-to-ductile transition. On the one hand, grain boundaries are obstacles for dislocation glide. On the other hand, the intersection points of grain boundaries with the crack front are assumed to be preferred dislocation nucleation sites. Here, we will show that the single contributions of grain boundaries (obstacles vs. source) on toughness and the brittle-to-ductile transition are contradicting, and we will weight the single contributions by performing carefully designed numerical experiments by means of two-dimensional discrete dislocation dynamics modelling. In our parameter studies, we vary the following parameters: (i) the mean free path for dislocation glide, δ, combined with (ii) the (obstacle) force of the grain boundary, ϕ, and (iii) the dislocation source spacing along the crack front, λ. Our results show that for materials or microstructures for which the mean distance of the intersection points of grain boundaries with the crack front is the relevant measure for λ, a decrease of grain size results in an increase of toughness. The positive impact of grain boundaries outweighs the negative consequences of dislocation blocking. Furthermore, our results explain the evolving anisotropy of toughness in cold-worked metals and give further insight into the question of why the grain-size-dependent fracture toughness passes through a minimum (and the brittle-to-ductile transition temperature passes through a maximum) at an intermediate grain size. Finally, a relation of the grain-size-dependence of fracture toughness in the form of K(dδ, dλ) = KIC + kdδ0.5/dλ is deduced.
An objective comparison of detection and segmentation algorithms for artefacts in clinical endoscopy
Authors: Ali Sharib , Zhou Felix , Braden Barbara , Bailey Adam , Yang Suhui , Cheng Guanju , Zhang Pengyi , Li Xiaoqiong , Kayser Maxime , Soberanis-Mukul Roger D. , Albarqouni Shadi , Wang Xiaokang , Wang Chunqing , Watanabe Seiryo , Oksuz Ilkay , Ning Qingtian , Yang Shufan , Khan Mohammad Azam , Gao Xiaohong W. , Realdon Stefano , Loshchenov Maxim , Schnabel Julia A. , East James E. , Wagnieres Georges , Loschenov Victor B. , Grisan Enrico , Daul Christian , Blondel Walter , Rittscher Jens
Published: February 2020

We present a comprehensive analysis of the submissions to the first edition of the Endoscopy Artefact Detection challenge (EAD). Using crowd-sourcing, this initiative is a step towards understanding the limitations of existing state-of-the-art computer vision methods applied to endoscopy and promoting the development of new approaches suitable for clinical translation. Endoscopy is a routine imaging technique for the detection, diagnosis and treatment of diseases in hollow-organs; the esophagus, stomach, colon, uterus and the bladder. However the nature of these organs prevent imaged tissues to be free of imaging artefacts such as bubbles, pixel saturation, organ specularity and debris, all of which pose substantial challenges for any quantitative analysis. Consequently, the potential for improved clinical outcomes through quantitative assessment of abnormal mucosal surface observed in endoscopy videos is presently not realized accurately. The EAD challenge promotes awareness of and addresses this key bottleneck problem by investigating methods that can accurately classify, localize and segment artefacts in endoscopy frames as critical prerequisite tasks. Using a diverse curated multi-institutional, multi-modality, multi-organ dataset of video frames, the accuracy and performance of 23 algorithms were objectively ranked for artefact detection and segmentation. The ability of methods to generalize to unseen datasets was also evaluated. The best performing methods (top 15%) propose deep learning strategies to reconcile variabilities in artefact appearance with respect to size, modality, occurrence and organ type. However, no single method outperformed across all tasks. Detailed analyses reveal the shortcomings of current training strategies and highlight the need for developing new optimal metrics to accurately quantify the clinical applicability of methods.
Coherent control of Optical limiting in atomic systems
Authors: Ghaderi Goran Abad Mohsen , Mahdieh Mahsa , Veisi Mohadeseh , Nadjari Hamid , Mahmoudi Mohammad
Published: February 2020

Generation and control of the reverse saturable absorption (RSA) and optical limiting (OL) are investigated in a four-level Y-type quantum system. It is demonstrated that the applied laser fields induce the RSA and it can be coherently controlled by either intensity or frequency of the applied laser fields. The effect of the static magnetic field on the induced RSA is studied and we obtain that it has a constructive role in determining the intensity range in which the OL is established in the system. In addition, we find that the transmission of the suggested optical limiter can be decreased either by increasing the length of the medium or by getting the atomic system denser. Finally, the Z-scan technique is presented to confirm our theoretical results. The proposed scheme can be used in designing the coherent optical limiters with controllable threshold and intensity range of the OL.
Nitrogen Incorporated Photoactive Brownmillerite Ca2Fe2O5 for Energy and Environmental Applications
Authors: Vavilapalli Durga Sankar , Banik Soma , Peri Raja Gopal , B. Muthuraaman , Miryala Muralidhar , Murakami Masato , Alicja Klimkowicz , K. Asokan , M. S. Ramachandra Rao , Singh Shubra
Published: February 2020

Ca2Fe2O5 (CFO) is a potentially viable material for alternate energy applications. Incorporation of nitrogen in Ca2Fe2O5 (CFO-N) lattice modifies the optical and electronic properties to its advantage. Here, the electronic band structures of CFO and CFO-N were probed using Ultraviolet photoelectron spectroscopy (UPS) and UV-Visible spectroscopy. The optical bandgap of CFO reduces from 2.21 eV to 2.07 eV on post N incorporation along with a clear shift in the valence band of CFO indicating the occupation of N 2p levels over O 2p in the valence band. Similar effect is also observed in the bandgap of CFO, which is tailored upto 1.43 eV by N+ ion implantation. The theoretical bandgaps of CFO and CFO-N were also determined by using the Density functional theory (DFT) calculations. The photoactivity of these CFO and CFO-N was explored by organic effluent degradation under sunlight. The feasibility of utilizing CFO and CFO-N samples for energy storage applications were also investigated through specific capacitance measurements. The specific capacitance of CFO is found to increase to 224.67 Fg−1 upon N incorporation. CFO-N is thus found to exhibit superior optical, catalytic as well as supercapacitor properties over CFO expanding the scope of brownmillerites in energy and environmental applications.
Bioevaluation of superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with dihexadecyl phosphate (DHP)
Authors: Mieloch Adam Aron , Żurawek Magdalena , Giersig Michael , Rozwadowska Natalia , Rybka Jakub Dalibor
Published: February 2020

Superparamagnetic iron oxide nanoparticles (SPIONs) have been investigated for wide variety of applications. Their unique properties render them highly applicable as MRI contrast agents, in magnetic hyperthermia or targeted drug delivery. SPIONs surface properties affect a whole array of parameters such as: solubility, toxicity, stability, biodistribution etc. Therefore, progress in the field of SPIONs surface functionalization is crucial for further development of therapeutic or diagnostic agents. In this study, SPIONs were synthesized by thermal decomposition of iron (III) acetylacetonate Fe(acac)3 and functionalized with dihexadecyl phosphate (DHP) via phase transfer. Bioactivity of the SPION-DHP was assessed on SW1353 and TCam-2 cancer derived cell lines. The following test were conducted: cytotoxicity and proliferation assay, reactive oxygen species (ROS) assay, SPIONs uptake (via Iron Staining and ICP-MS), expression analysis of the following genes: alkaline phosphatase (ALPL); ferritin light chain (FTL); serine/threonine protein phosphatase 2A (PP2A); protein tyrosine phosphatase non-receptor type 11 (PTPN11); transferrin receptor 1 (TFRC) via RT-qPCR. SPION-DHP nanoparticles were successfully obtained and did not reveal significant cytotoxicity in the range of tested concentrations. ROS generation was elevated, however not correlated with the concentrations. Gene expression profile was slightly altered only in SW1353 cells.
Alteration in the potential of sediment phosphorus release along series of rubber dams in a typical urban landscape river
Authors: Bao Linlin , Li Xuyong , Su Jingjun
Published: February 2020

Rubber dams are widely used for landscaping in urban rivers and they retain large amounts of sediments. The sediments are rich in phosphorus (P) which can cause river eutrophication. Little is known about P release in rubber dams. We investigated the potential of sediment P release by isotherm experiment in an urban river with 30 rubber dams of northern China. We found that the potential of sediment P release (percentage saturation of zero equilibrium P concentration, EPCsat) was 76% at natural river part above dams, and then decreased to 67% at the 4th dam because of high deposition of fine sediments within the upper 4 dams. Between the 5th and the 30th dams, EPCsat increased to 90% because of the decrease of fine sediments and water soluble reactive P. EPCsat was also significantly higher (p < 0.05) in April and August than in November. The results suggest that the potential of sediment P release in this dammed river was mainly controlled by sediment grain size and biological effects. Therefore, management strategies for dammed rivers should focus on reducing P inputs and improving the hydraulic conditions.
Variability in estimated gene expression among commonly used RNA-seq pipelines
Authors: Arora Sonali , Pattwell Siobhan S. , Holland Eric C. , Bolouri Hamid
Published: February 2020

RNA-sequencing data is widely used to identify disease biomarkers and therapeutic targets using numerical methods such as clustering, classification, regression, and differential expression analysis. Such approaches rely on the assumption that mRNA abundance estimates from RNA-seq are reliable estimates of true expression levels. Here, using data from five RNA-seq processing pipelines applied to 6,690 human tumor and normal tissues, we show that nearly 88% of protein-coding genes have similar gene expression profiles across all pipelines. However, for >12% of protein-coding genes, current best-in-class RNA-seq processing pipelines differ in their abundance estimates by more than four-fold when applied to exactlythe same samplesandthe same setof RNA-seq reads. Expression fold changes are similarly affected. Many of the impacted genes are widely studied disease-associated genes. We show that impacted genes exhibit diverse patterns of discordance among pipelines, suggesting that many inter-pipeline differences contribute to overall uncertainty in mRNA abundance estimates. A concerted, community-wide effort will be needed to develop gold-standards for estimating the mRNA abundance of the discordant genes reported here. In the meantime, our list of discordantly evaluated genes provides an important resource for robust marker discovery and target selection.
A Microbial Signature Identifies Advanced Fibrosis in Patients with Chronic Liver Disease Mainly Due to NAFLD
Authors: Dong Tien S. , Katzka William , Lagishetty Venu , Luu Kayti , Hauer Meg , Pisegna Joseph , Jacobs Jonathan P.
Published: February 2020

The presence of advanced fibrosis is an important measure of the severity of chronic liver disease. Prior works that have examined the gut microbiome as a novel biomarker for advanced fibrosis have only examined patients with nonalcoholic fatty liver disease. Therefore, our goal was to examine the gut microbiome across varying etiologies of liver disease to create a predictive model for liver fibrosis based upon a microbial signature. Stool samples were obtained from patients with chronic liver disease (n = 50) undergoing FibroScan (ultrasound elastography) at the VA Greater Los Angeles Healthcare System. Healthy control patients (n = 25) were also recruited as a reference population. Fecal samples underwent 16S ribosomal RNA sequencing. Using differentially abundant microbes, a random forest classifier model was created to distinguish advanced fibrosis from mild/moderate fibrosis. The findings were then validated in a separate cohort of chronic liver disease patients (n = 37). Etiologies for liver disease included non-alcoholic liver disease (58.0%), hepatitis C (26.0%), hepatitis B (10.0%), and alcohol (6.0%). Microbiome composition was distinct in liver patients with advanced fibrosis compared to those with minimal fibrosis and healthy controls (p = 0.003). In multivariate negative binomial modeling, 26 bacterial taxa were differentially abundant in patients with advanced fibrosis as compared to those with minimal/moderate fibrosis (q-value < 0.05). A random forests classifier based on these taxa had an AUROC of 0.90 to predict advanced fibrosis. Prevotella copri, which was enriched in patients with advanced fibrosis, was the most strongly predictive microbe in the classifier. The classifier had an AUROC of 0.82 for advanced fibrosis in the validation cohort and Prevotella copri remained the strongest predictive microbe for advanced fibrosis. There is a distinct microbial signature for patients with advanced fibrosis independent of liver disease etiology and other comorbidities. These results suggest that microbial profiles can be used as a non-invasive marker for advanced fibrosis and support the hypothesis that microbes and their metabolites contribute to hepatic fibrosis.
Characteristics of Atrial Fibrillation Patients Suffering Esophageal Injury Caused by Ablation for Atrial Fibrillation
Authors: Zhang Pei , Zhang Yue-Yue , Ye Qian , Jiang Ru-Hong , Liu Qiang , Ye Yang , Wu Jia-Guo , Sheng Xia , Fu Guo-Sheng , Cha Yong-Mei , Jiang Chen-Yang
Published: February 2020

The close proximity of esophagus to the left atrial posterior wall predisposes esophagus to thermal injury during catheter ablation for atrial fibrillation (AF). In this retrospective study, we aimed to investigate risk factors of esophageal injury (EI) caused by catheter ablation for AF. Patients who underwent first-time AF ablation from July 2013 to June 2018 were included. The esophagus was visualized by oral soluble contrast during ablation for all patients and a subset of patients were selected to undergo endoscopic ultrasonography (EUS) to estimate EI post ablation. Degree of EI was categorized as Kansas City classification: type 1: erythema; type 2: ulcers (2a: superficial ulcers; 2b: deep ulcers); type 3: perforation (3a: perforation without communication with the atria; 3b: atrioesophageal fistula [AEF]). Of 3,852 patients, 236 patients (61.5 ± 9.7 years; male, 69%) received EUS (EUS group) and 3616 (63.2 ± 10.9 years; male, 61.1%) without EUS (No-EUS group). In EUS group, EI occurred in 63 patients (type 1 EI in 35 and type 2 EI in 28), and no type 3 EI was observed during follow up. In a multivariable logistic regression analysis, an overlap between the ablation lesion and esophagus was an independent predictor of EI (odds ratio, 21.2; 95% CI: 6.23–72.0; P < 0.001). In No-EUS group, esophagopericardial fistula (EPF; n = 3,0.08%) or AEF (n = 2,0.06%) was diagnosed 4–37 days after ablation. In 3 EPF patients, 2 completely recovered with conservative management and 1 died. Two AEF patients died. Ablation at the vicinity of the esophagus predicts risk of EI. EUS post ablation may prevent the progression of EI and should be considered in management of EI. It remains challenging to identify patients with high risk of EI.
Fabrication of triboelectric nanogenerators based on electrospun polyimide nanofibers membrane
Authors: Kim Yeongjun , Wu Xinwei , Oh Je Hoon
Published: February 2020

Surface modification of polyimides (PIs) using electrospinning would significantly improve the performance of TENGs because of the larger surface area of the electrospun friction layer. However, PIs generally have high solvent resistance, so it is complicated to convert them into nanofibers using electrospinning process. This study aims to fabricate PI nanofibers via simple, one-step electrospinning and utilize them as a friction layer of TENGs for better performance. PI nanofibers were directly electrospun from PI ink made of polyimide powder without any additional process. The effect of PI concentration on spinnability was investigated. Uniform and continuous nanofibrous structures were successfully produced at concentrations of 15 wt% and 20 wt%. Electrospun PI nanofibers were then utilized as a friction layer for TENGs. A TENG with 20 wt% produced an open circuit voltage of 753 V and a short circuit current of 10.79 μA and showed a power density of 2.61 W m−2 at a 100 MΩ load resistance. During tapping experiment of 10,000 cycles, the TENG could stably harvest electrical energy. The harvested energy from the proposed TENG is sufficient to illuminate more than 55 LEDs and drive small electronic devices, and the TENGs exhibit excellent performance as a wearable energy harvester.
Recurrent gene duplication in the angiosperm tribe Delphinieae (Ranunculaceae) inferred from intracellular gene transfer events and heteroplasmic mutations in the plastid matK gene
Authors: Park Seongjun , An Boram , Park SeonJoo
Published: February 2020

The study of intracellular gene transfer may allow for the detection of interesting evolutionary processes such as ancient polyploidization. We compared 24 plastid genomes (plastomes) from tribe Delphinieae, one from tribe Nigelleae and one from tribe Ranunculeae, including five newly sequenced genomes. The functional transfers of the plastids rpl32 and rps16 to the nucleus in tribe Delphinieae were identified. Unexpectedly, we discovered multiple divergent copies of the nuclear-encoded plastid rpl32 in the genus Aconitum. Phylogenetic and synonymous substitution rate analyses revealed that the nuclear-encoded plastid rpl32 underwent two major duplication events. These ancient gene duplication events probably occurred via multiple polyploidization events in Aconitum between 11.9 and 24.7 Mya. Furthermore, our sequence rate analysis indicated that the eight plastid-encoded rpl subunits in Aconitum had a significantly accelerated evolutionary rate compared to those in other genera, suggesting that highly divergent paralogs targeted to the plastid may contribute to an elevated rate of evolution in plastid rpl genes. In addition, heteroplasmy of the plastid matK from two Aconitum species suggested the existence of potentially functional plastid maturases in its plastome. Our results provide insight into the evolutionary history of the tribe Delphinieae.
Publisher Correction: Runx2 stimulates neoangiogenesis through the Runt domain in melanoma
Authors: Cecconi Daniela , Brandi Jessica , Manfredi Marcello , Serena Michela , Dalle Carbonare Luca , Deiana Michela , Cheri Samuele , Parolini Francesca , Gandini Alberto , Marchetto Giulia , Innamorati Giulio , Avanzi Francesco , Antoniazzi Franco , Marengo Emilio , Tiso Natascia , Mottes Monica , Zipeto Donato , Valenti Maria Teresa
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Study of electric conduction mechanisms in bismuth silicate nanofibers
Authors: Batool S. S. , Imran Z. , Rasool Kamran , Ambreen Jaweria , Hassan Safia , Arif Saira , Ahmad Mushtaq , Rafiq M. A.
Published: February 2020

This work represents the nature of conduction mechanism in bismuth silicate (BiSiO) nanofibers as a function of temperature and frequency. Scanning electron micrographs and X-rays diffraction patterns exhibited the formation of cubic phases of Bi4(SiO4)3 and Bi12SiO20 nanofibers respectively with an average diameter of ~200 nm. Temperature dependent (300 K–400 K) electrical characterization of fibers was carried out in frequency range of ~20 Hz–2 MHz. The complex impedance analysis showed contribution from bulk and intergranular parts of nanofibers in conduction. Moreover, analysis of the Cole-Cole plot confirmed the space charge dependent behavior of BiSiO nanofibers. Two types of relaxation phenomena were observed through Modulus analysis. In ac conductivity curve, step like feature of plateau and dispersive regions were described by Maxwell-Wagner effect while the dc part obeyed the Arrhenius law. However, frequency dependent ac conductivity revealed the presence of conduction mechanism in diverse regions that was ascribed to large polaron tunneling model. Detailed analysis of complex Impedance and ac conductivity measurement showed negative temperature coefficient of resistance for the BiSiO nanofibers. Current-voltage (IV) characteristics represented ohmic conduction; followed by space charge limited current conduction at intermediate voltages. Results from both ac and dc measurements were in good agreement with each other.
Identification and validation of reference genes for RT-qPCR normalization in wheat meiosis
Authors: Garrido José , Aguilar Miguel , Prieto Pilar
Published: February 2020

Meiosis is a specialized type of cell division occurring in sexually reproducing organisms to generate haploid cells known as gametes. In flowering plants, male gametes are produced in anthers, being encased in pollen grains. Understanding the genetic regulation of meiosis key events such as chromosome recognition and pairing, synapsis and recombination, is needed to manipulate chromosome associations for breeding purposes, particularly in important cereal crops like wheat. Reverse transcription-quantitative PCR (RT-qPCR) is widely used to analyse gene expression and to validate the results obtained by other transcriptomic analyses, like RNA-seq. Selection and validation of appropriate reference genes for RT-qPCR normalization is essential to obtain reproducible and accurate expression data. In this work, twelve candidate reference genes were evaluated using the mainstream algorithms geNorm, Normfinder, BestKeeper and ΔCt, then ranked from most to least suitable for normalization with RefFinder. Different sets of reference genes were recommended to normalize gene expression data in anther meiosis of bread and durum wheat, their corresponding genotypes in the absence of the Ph1 locus and for comparative studies among wheat genotypes. Comparisons between meiotic (anthers) and somatic (leaves and roots) wheat tissues were also carried out. To the best of our knowledge, our study provides the first comprehensive list of reference genes for robust RT-qPCR normalization to study differentially expressed genes during male meiosis in wheat in a breeding framework.
Temporal-Spatial Analysis of the Warming Effect of Different Cultivated Land Urbanization of Metropolitan Area in China
Authors: Li Jiayang , Zhang Chunxiao , Zheng Xinqi , Chen Youmin
Published: February 2020

The regional warming effect is different when different cultivated land types are converted into urban construction land, while its temporal and spatial changes are unclear. We studied the temporal and spatial changes in the warming effect when dry land was converted to urban land (DL2UBL), and irrigated land to urban land (IL2UBL) in Yangtze River Delta (CSJ), Beijing-Tianjin- Hebei (JJJ) and Chengdu-Chongqing (CY) metropolitan areas from 2000 to 2015. The average warming effect of the three metropolitan areas was more intensive in DL2UBL than in IL2UBL in winter, and opposite occurred in summer. The diurnal warming changes between them were small during the day, but obvious at night, which corresponds to the diurnal change of the latent heat of evaporation. Due to the difference in the spatial distribution of humidity, to the north of 34°N, the warming effect of DL2UBL was stronger than that of IL2UBL, and to the south of 34°N, it was stronger for IL2UBL, while from west to east, the warming trend of DL2UBL and IL2UBL keep pace and decline slightly. The influence in planetary boundary layer was also analyzed. We hope that our findings provide scientific support for future metropolitan land use decisions associated with tradeoffs.
Dietary AGEs involvement in colonic inflammation and cancer: insights from an in vitro enterocyte model
Authors: Geicu Ovidiu I. , Stanca Loredana , Voicu Sorina N. , Dinischiotu Anca , Bilteanu Liviu , Serban Andreea I. , Calu Valentin
Published: February 2020

The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H2O2) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3β phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1β at 6 h; time-dependent increases in IL-8; RAGE and NF-κB p65 upregulation; and IκB inhibition. Co-treatment with anti-RAGE or anti-TNF-α blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.
The role of control region mitochondrial DNA mutations in cardiovascular disease: stroke and myocardial infarction
Authors: Umbria Miriam , Ramos Amanda , Aluja Maria Pilar , Santos Cristina
Published: February 2020

Recent studies associated certain type of cardiovascular disease (CVD) with specific mitochondrial DNA (mtDNA) defects, mainly driven by the central role of mitochondria in cellular metabolism. Considering the importance of the control region (CR) on the regulation of the mtDNA gene expression, the aim of the present study was to investigate the role of mtDNA CR mutations in two CVDs: stroke and myocardial infarction (MI). MtDNA CR mutations (both fixed and in heteroplasmy) were analysed in two demographically-matched case-control samples, using 154 stroke cases, 211 MI cases and their corresponding control individuals. Significant differences were found, reporting mutations m.16145 G > A and m.16311 T > C as potential genetic risk factors for stroke (conditional logistic regression: p = 0.038 and p = 0.018, respectively), whereas the m.72 T > C, m.73 A > G and m.16356 T > C mutations could act as possible beneficial genetic factors for MI (conditional logistic regression: p = 0.001, p = 0.009 and p = 0.016, respectively). Furthermore, our findings also showed a high percentage of point heteroplasmy in MI controls (logistic regression: p = 0.046; OR = 0.209, 95% CI [0.045–0.972]). These results demonstrate the possible role of mtDNA mutations in the CR on the pathogenesis of stroke and MI, and show the importance of including this regulatory region in genetic association studies.