bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Transmission of Optical Lightning Signals Through Complex 3‐D Cloud Scenes
Authors: Peterson Michael
Published: November 2020

Space‐based lightning imagers have shown that complex cloud scenes consisting of multiple tall convective features, anvil clouds, and warm boundary cloud layers are illuminated by lightning in many different ways depending on where the lightning occurs and how energetic it is. Modifications to the optical lightning signals from radiative transfer in the cloud medium can lead to reductions in detection efficiency and location accuracy for these instruments and can also cause some of the optical signals that are detected to have unexpected spatial energy distributions. In this study, we perform Monte Carlo radiative transfer simulations of optical lightning emissions in clouds with complex 3‐D geometries to shed some light on the origins of certain irregular radiance patterns that have been recorded from orbit. We show that diffuse reflections off nearby cloud faces can explain lightning signals in nonelectrified clouds, tall clouds can result in poor optical transmission and suppressed radiances that could lead to missed events and that particularly favorable viewing conditions can cause otherwise normal lightning to produce a superbolt that is orders of magnitude brighter than the same flash seen from a different angle.
The Nature and Origins of Sub‐Neptune Size Planets
Authors: Bean Jacob L. , Raymond Sean N. , Owen James E.
Published: November 2020

Planets intermediate in size between the Earth and Neptune, and orbiting closer to their host stars than Mercury does the Sun, are the most common type of planet revealed by exoplanet surveys over the last quarter century. Results from NASA's Kepler mission have revealed a bimodality in the radius distribution of these objects, with a relative underabundance of planets between 1.5 and 2.0 . This bimodality suggests that sub‐Neptunes are mostly rocky planets that were born with primary atmospheres a few percent by mass accreted from the protoplanetary nebula. Planets above the radius gap were able to retain their atmospheres (“gas‐rich super‐Earths”), while planets below the radius gap lost their atmospheres and are stripped cores (“true super‐Earths”). The mechanism that drives atmospheric loss for these planets remains an outstanding question, with photoevaporation and core‐powered mass loss being the prime candidates. As with the mass‐loss mechanism, there are two contenders for the origins of the solids in sub‐Neptune planets: the migration model involves the growth and migration of embryos from beyond the ice line, while the drift model involves inward‐drifting pebbles that coagulate to form planets close‐in. Atmospheric studies have the potential to break degeneracies in interior structure models and place additional constraints on the origins of these planets. However, most atmospheric characterization efforts have been confounded by aerosols. Observations with upcoming facilities are expected to finally reveal the atmospheric compositions of these worlds, which are arguably the first fundamentally new type of planetary object identified from the study of exoplanets.
Diverse Polygonal Patterned Grounds in the Northern Eridania Basin, Mars: Possible Origins and Implications
Authors: Dang Yanan , Zhang Feng , Zhao Jiannan , Wang Jiang , Xu Yi , Huang Ting , Xiao Long
Published: November 2020

Diverse polygonal patterned grounds are found to occur in the Eridania basin system (a set of connecting irregular‐shaped depressions interpreted as a paleolake basin system) located in the martian highland region between Terra Cimmeria and Sirenum. We here use multiple sets of imagery to document diverse polygonal patterned grounds in the fluvio‐lacustrine deposits of the northern Eridania basin, and interpret their formation mechanisms. The combination of detailed geomorphological mapping, morphometrical analyses, and investigation of the spatial distribution of polygonal patterned grounds with other geologic features leads us to conclude that (1) desiccation process within the clay‐rich materials would primarily contribute to the formation of cracked polygons, while the ridged polygons are best explained by mineral‐filled fractures that have been cemented and variably indurated by fluids; (2) the correlation between polygon size and topography is observed in the northern smooth light‐toned basement units, which can be best explained by the concentration of salt minerals (such as sulfate) in topographic lows so that the growth of fracturing is inhibited; (3) the large polygonal ridges formed in the knobby light‐toned terrains show a spatial distribution and a trend controlled by basin‐scale compressional tectonics and influenced by preexisting topography, for example, impact structures; (4) the linear fracture‐to‐ridge gradation indicates that the polygonal ridges in chlorides might be guided by the subjacent cracks occurring within clay‐rich materials; (5) both features (cracks and ridges) in some places may have formed simultaneously and are spatially distinct due to differences in erosional states; and (6) geologic features show a wealth of information of multiple aqueous events with the evaporation of the last liquid water ponding to form the southern playa where chloride salt precipitates. Crater retention age determination for the chloride‐bearing basement unit places a lower limit for the cessation of the local aqueous events to ∼3.29 Ga, indicating that the open‐system‐style alteration by surface waters on Mars might have continued in the period of the Late Hesperian to Early Amazonian.
An Assessment of xsBa Flux as a Paleoproductivity Indicator and Its Water‐Depth Dependence in the Easternmost Equatorial Pacific Ocean
Authors: Singh Ajay K. , Marcantonio Franco , Lyle Mitchell
Published: November 2020

We present the first regional‐scale records of biogenic Barium (xsBa) fluxes in the Panama basin of the eastern‐equatorial margin of the Pacific Ocean in order to assess xsBa as a paleoproductivity proxy. Measurements of xsBa from 13 cores that range in water depths from about 700 to 3,000 m show an increase in 230Th‐normalized xsBa mass accumulation rates (MARs) with increasing water depth during both marine oxygen isotope stages (MIS) 1 and 2. The correlation of xsBa MARs with depth are strong despite differences in bulk sediment MARs and differing degrees of sediment redistribution. We interpret the increasing xsBa with water depth as likely due to the continued decomposition and remineralization of falling and/or resuspended biogenic particles. xsBa does not seem to be affected by diagenetic sulfate reduction in most of the cores. Calculated estimates of xsBa preservation in the sediment pile are high and fluctuate between 45% and 52% throughout the last 25 kyr. Although xsBa fluxes can be a robust indicator of paleoproductivity, caution is needed if (a) there is evidence of sulfate reduction in sediments being analyzed, and (b) one is trying to quantify differences in paleoproductivity among sites that are located at different depths in the water column.
Quantifying the efficacy of checkpoint inhibitors on CD8+ cytotoxic T cells for immunotherapeutic applications via single-cell interaction
Authors: Sullivan Matthew Ryan , Ugolini Giovanni Stefano , Sarkar Saheli , Kang Wenjing , Smith Evan Carlton , Mckenney Seamus , Konry Tania
Published: November 2020

The inhibition of the PD1/PDL1 pathway has led to remarkable clinical success for cancer treatment in some patients. Many, however, exhibit little to no response to this treatment. To increase the efficacy of PD1 inhibition, additional checkpoint inhibitors are being explored as combination therapy options. TSR-042 and TSR-033 are novel antibodies for the inhibition of the PD1 and LAG3 pathways, respectively, and are intended for combination therapy. Here, we explore the effect on cellular interactions of TSR-042 and TSR-033 alone and in combination at the single-cell level. Utilizing our droplet microfluidic platform, we use time-lapse microscopy to observe the effects of these antibodies on calcium flux in CD8+ T cells upon antigen presentation, as well as their effect on the cytotoxic potential of CD8+ T cells on human breast cancer cells. This platform allowed us to investigate the interactions between these treatments and their impacts on T-cell activity in greater detail than previously applied in vitro tests. The novel parameters we were able to observe included effects on the exact time to target cell killing, contact times, and potential for serial-killing by CD8+ T cells. We found that inhibition of LAG3 with TSR-033 resulted in a significant increase in calcium fluctuations of CD8+ T cells in contact with dendritic cells. We also found that the combination of TSR-042 and TSR-033 appears to synergistically increase tumor cell killing and the single-cell level. This study provides a novel single-cell-based assessment of the impact these checkpoint inhibitors have on cellular interactions with CD8+ T cells.
Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation
Authors: Peng Ling , Wen Li , Shi Qing-Feng , Gao Feng , Huang Bin , Meng Jie , Hu Cheng-Ping , Wang Chang-Ming
Published: November 2020

Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.
Mode-locked short pulses from an 8 μm wavelength semiconductor laser
Authors: Hillbrand Johannes , Opačak Nikola , Piccardo Marco , Schneider Harald , Strasser Gottfried , Capasso Federico , Schwarz Benedikt
Published: November 2020

Quantum cascade lasers (QCL) have revolutionized the generation of mid-infrared light. Yet, the ultrafast carrier transport in mid-infrared QCLs has so far constituted a seemingly insurmountable obstacle for the formation of ultrashort light pulses. Here, we demonstrate that careful quantum design of the gain medium and control over the intermode beat synchronization enable transform-limited picosecond pulses from QCL frequency combs. Both an interferometric radio-frequency technique and second-order autocorrelation shed light on the pulse dynamics and confirm that mode-locked operation is achieved from threshold to rollover current. Furthermore, we show that both anti-phase and in-phase synchronized states exist in QCLs. Being electrically pumped and compact, mode-locked QCLs pave the way towards monolithically integrated non-linear photonics in the molecular fingerprint region beyond 6 μm wavelength.
Molecular estimation of neurodegeneration pseudotime in older brains
Authors: Mukherjee Sumit , Heath Laura , Preuss Christoph , Jayadev Suman , Garden Gwenn A. , Greenwood Anna K. , Sieberts Solveig K. , De Jager Philip L. , Ertekin-Taner Nilüfer , Carter Gregory W. , Mangravite Lara M. , Logsdon Benjamin A.
Published: November 2020

The temporal molecular changes that lead to disease onset and progression in Alzheimer’s disease (AD) are still unknown. Here we develop a temporal model for these unobserved molecular changes with a manifold learning method applied to RNA-Seq data collected from human postmortem brain samples collected within the ROS/MAP and Mayo Clinic RNA-Seq studies. We define an ordering across samples based on their similarity in gene expression and use this ordering to estimate the molecular disease stage–or disease pseudotime-for each sample. Disease pseudotime is strongly concordant with the burden of tau (Braak score, P = 1.0 × 10−5), Aβ (CERAD score, P = 1.8 × 10−5), and cognitive diagnosis (P = 3.5 × 10−7) of late-onset (LO) AD. Early stage disease pseudotime samples are enriched for controls and show changes in basic cellular functions. Late stage disease pseudotime samples are enriched for late stage AD cases and show changes in neuroinflammation and amyloid pathologic processes. We also identify a set of late stage pseudotime samples that are controls and show changes in genes enriched for protein trafficking, splicing, regulation of apoptosis, and prevention of amyloid cleavage pathways. In summary, we present a method for ordering patients along a trajectory of LOAD disease progression from brain transcriptomic data.
Nanoscale-femtosecond dielectric response of Mott insulators captured by two-color near-field ultrafast electron microscopy
Authors: Fu Xuewen , Barantani Francesco , Gargiulo Simone , Madan Ivan , Berruto Gabriele , LaGrange Thomas , Jin Lei , Wu Junqiao , Vanacore Giovanni Maria , Carbone Fabrizio , Zhu Yimei
Published: November 2020

Characterizing and controlling the out-of-equilibrium state of nanostructured Mott insulators hold great promises for emerging quantum technologies while providing an exciting playground for investigating fundamental physics of strongly-correlated systems. Here, we use two-color near-field ultrafast electron microscopy to photo-induce the insulator-to-metal transition in a single VO2 nanowire and probe the ensuing electronic dynamics with combined nanometer-femtosecond resolution (10−21 m ∙ s). We take advantage of a femtosecond temporal gating of the electron pulse mediated by an infrared laser pulse, and exploit the sensitivity of inelastic electron-light scattering to changes in the material dielectric function. By spatially mapping the near-field dynamics of an individual nanowire of VO2, we observe that ultrafast photo-doping drives the system into a metallic state on a timescale of ~150 fs without yet perturbing the crystalline lattice. Due to the high versatility and sensitivity of the electron probe, our method would allow capturing the electronic dynamics of a wide range of nanoscale materials with ultimate spatiotemporal resolution.
The effect of toxic pyridine-alkaloid secondary metabolites on the sunbird gut microbiome
Authors: Gunasekaran Mohanraj , Lalzar Maya , Sharaby Yehonatan , Izhaki Ido , Halpern Malka
Published: November 2020

Sunbirds feed on tobacco tree nectar which contains toxic nicotine and anabasine secondary metabolites. Our aim was to understand the effect of nicotine and anabasine on the gut microbiota composition of sunbirds. Sixteen captive sunbirds were randomly assigned to two diets: artificial nectar either with (treatment) or without (control) added nicotine and anabasine. Excreta were collected at 0, 2, 4 and 7 weeks of treatment and samples were processed for bacterial culture and high-throughput amplicon sequencing of the 16S rRNA gene. The gut microbiome diversity of the treated and control birds changed differently along the seven-week experiment. While the diversity decreased in the control group along the first three samplings (0, 2 and 4 weeks), it increased in the treatment group. The microbiota composition analyses demonstrated that a diet with nicotine and anabasine, significantly changed the birds’ gut microbiota composition compared to the control birds. The abundance of nicotine- and anabasine- degrading bacteria in the excreta of the treated birds, was significantly higher after four and seven weeks compared to the control group. Furthermore, analysis of culturable isolates, including Lactococcus, showed that sunbirds’ gut-associated bacteria were capable of degrading nicotine and anabasine, consistent with their hypothesised role as detoxifying and nutritional symbionts.
The phosphorylated regulator of chemotaxis is crucial throughout biofilm biogenesis in Shewanella oneidensis
Authors: Boyeldieu Anne , Ali Chaouche Amine , Ba Moly , Honoré Flora Ambre , Méjean Vincent , Jourlin-Castelli Cécile
Published: November 2020

The core of the chemotaxis system ofShewanella oneidensisis made of the CheA3 kinase and the CheY3 regulator. When appropriated, CheA3 phosphorylates CheY3, which, in turn, binds to the rotor of the flagellum to modify the swimming direction. In this study, we showed that phosphorylated CheY3 (CheY3-P) also plays an essential role during biogenesis of the solid-surface-associated biofilm (SSA-biofilm). Indeed, in a ΔcheY3 strain, the formation of this biofilm is abolished. Using the phospho-mimetic CheY3D56E mutant, we showed that CheY-P is required throughout the biogenesis of the biofilm but CheY3 phosphorylation is independent of CheA3 during this process. We have recently found that CheY3 interacts with two diguanylate cyclases (DGCs) and with MxdA, the c-di-GMP effector, probably triggering exopolysaccharide synthesis by the Mxd machinery. Here, we discovered two additional DGCs involved in SSA-biofilm development and showed that one of them interacts with CheY3. We therefore propose that CheY3-P acts together with DGCs to control SSA-biofilm formation. Interestingly, two orthologous CheY regulators complement the biofilm defect of a ΔcheY3 strain, supporting the idea that biofilm formation could involve CheY regulators in other bacteria.
Coherent spin transport through helical edge states of topological insulator
Authors: Niyazov R. A. , Aristov D. N. , Kachorovskii V. Yu.
Published: November 2020

We study coherent spin transport through helical edge states of topological insulator tunnel-coupled to metallic leads. We demonstrate that unpolarized incoming electron beam acquires finite polarization after transmission through such a setup provided that edges contain at least one magnetic impurity. The finite polarization appears even in the fully classical regime and is therefore robust to dephasing. There is also a quantum magnetic field-tunable contribution to the polarization, which shows sharp identical Aharonov-Bohm resonances as a function of magnetic flux—with the period hc/2e—and survives at relatively high temperature. We demonstrate that this tunneling interferometer can be described in terms of ensemble of flux-tunable qubits giving equal contributions to conductance and spin polarization. The number of active qubits participating in the charge and spin transport is given by the ratio of the temperature and the level spacing. The interferometer can effectively operate at high temperature and can be used for quantum calculations. In particular, the ensemble of qubits can be described by a single Hadamard operator. The obtained results open wide avenue for applications in the area of quantum computing.
Exosome markers of LRRK2 kinase inhibition
Authors: Wang Shijie , Kelly Kaela , Brotchie Jonathan M. , Koprich James B. , West Andrew B.
Published: November 2020

Hyper-activated LRRK2 is linked to Parkinson’s disease susceptibility and progression. Quantitative measures of LRRK2 inhibition, especially in the brain, maybe critical in the development of successful LRRK2-targeting therapeutics. In this study, two different brain-penetrant and selective LRRK2 small-molecule kinase inhibitors (PFE-360 and MLi2) were orally administered to groups of cynomolgus macaques. Proposed pharmacodynamic markers in exosomes from urine and cerebrospinal fluid (CSF) were compared to established markers in peripheral blood mononuclear cells (PBMCs). LRRK2 kinase inhibition led to reductions in exosome-LRRK2 protein and the LRRK2-substrate pT73-Rab10 in urine, as well as reduced exosome-LRRK2 and autophosphorylated pS1292-LRRK2 protein in CSF. We propose orthogonal markers for LRRK2 inhibition in urine and CSF can be used in combination with blood markers to non-invasively monitor the potency of LRRK2-targeting therapeutics.
Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study
Authors: Cai Lina , Wheeler Eleanor , Kerrison Nicola D. , Luan Jian’an , Deloukas Panos , Franks Paul W. , Amiano Pilar , Ardanaz Eva , Bonet Catalina , Fagherazzi Guy , Groop Leif C. , Kaaks Rudolf , Huerta José María , Masala Giovanna , Nilsson Peter M. , Overvad Kim , Pala Valeria , Panico Salvatore , Rodriguez-Barranco Miguel , Rolandsson Olov , Sacerdote Carlotta , Schulze Matthias B. , Spijkerman Annemieke M. W. , Tjonneland Anne , Tumino Rosario , van der Schouw Yvonne T. , Sharp Stephen J. , Forouhi Nita G. , Riboli Elio , McCarthy Mark I. , Barroso Inês , Langenberg Claudia , Wareham Nicholas J.
Published: November 2020

Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.
Reproducible and stable cycling performance data on secondary zinc oxygen batteries
Authors: Dongmo Saustin , Kreissl Julian Jakob Alexander , Miyazaki Kohei , Abe Takeshi , You Ting-Hsuan , Hu Chi-Chang , Schröder Daniel
Published: November 2020

Electrically rechargeable zinc oxygen batteries are promising energy storage devices. They appeal due to the abundance of zinc metal and their high energy density. Research on zinc oxygen batteries is currently focusing on the development of electrode materials. Since the progress is rapid and no state-of-the-art is agreed upon yet, it is difficult to benchmark their performance. This circumstance also complicates the use of the generated electrochemical data for model-based research – simulating the processes in the battery requires reliable performance data and material properties from experimental investigations. Herein we describe reproducible data on the cycling performance and durability of zinc oxygen batteries. We utilize anodes and gas diffusion electrodes (with the bifunctional catalysts Sr2CoO3Cl, Ru-Sn oxide, and Fe0.1Ni0.9Co2O4 with activated carbon) with low degradation during cycling, and present voltage data of current-dependent discharge and charge. All in all, we stimulate to reuse the data for parameter fitting in model-based work, and also to evaluate novel battery materials by preventing or minimizing side reactions with the testing protocol and setup utilized.
Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis
Authors: Wong Carlos K. H. , Wong Janet Y. H. , Tang Eric H. M. , Au C. H. , Wai Abraham K. C.
Published: November 2020

This systematic review and meta-analysis investigated the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients. Epidemiological studies published in 2020 (from January–March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results, radiological outcomes, and pharmacological and in-patient treatments. 76 studies were included in this meta-analysis, accounting for a total of 11,028 COVID-19 patients in multiple countries. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. The most common comorbidities were hypertension (18.1%, 95% CI 15.4–20.8%). The most frequently identified symptoms were fever (72.4%, 95% CI 67.2–77.7%) and cough (55.5%, 95% CI 50.7–60.3%). For pharmacological treatment, 63.9% (95% CI 52.5–75.3%), 62.4% (95% CI 47.9–76.8%) and 29.7% (95% CI 21.8–37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95% CI 39.9–85.4%) and 20.2% (95% CI 14.6–25.9%) of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.

PROSPERO Registration Number: CRD42020176589
Chronic wasting disease (CWD) prion detection in blood from pre-symptomatic white-tailed deer harboring PRNP polymorphic variants
Authors: Kramm Carlos , Soto Paulina , Nichols Tracy A. , Morales Rodrigo
Published: November 2020

Chronic wasting disease (CWD) is a prionopathy affecting wild and farmed cervids. This disease is endemic in North America and has been recently identified in Europe. Ante-mortem CWD tests of pre-clinical cervids may be an important tool in helping control the spread of this disease. Unfortunately, current CWD diagnostic methods are not suitable for non-tissue type samples. We reported that CWD prions can be detected in blood of pre-clinical CWD-infected white-tailed deer (WTD) with high sensitivity and specificity using the Protein Misfolding Cyclic Amplification (PMCA) assay. However, that report only included animals homozygous for codon 96G, the most common polymorphic version of the prion protein within this animal species. Here, we report CWD prion detection using blood of naturally infected WTD coding one or two copies of the PrP-96S polymorphic variant. Our results, from a blinded screening, show 100% specificity and ~ 58% sensitivity for animals harboring one 96S codon, regardless of their stage within the pre-clinical phase. Detection efficiency for PrP-96S homozygous animals was substantially lower, suggesting that this allele affect peripheral prion replication/tropism. These results provide additional information on the influence of codon 96 polymorphisms and the ability of PMCA to detect CWD in the blood of pre-clinical WTD.
Virulence-determinants and antibiotic-resistance genes of MDR-E. coli isolated from secondary infections following FMD-outbreak in cattle
Authors: Algammal Abdelazeem M. , Hetta Helal F. , Batiha Gaber E. , Hozzein Wael N. , El Kazzaz Waleed M. , Hashem Hany R. , Tawfik Ayat M. , El-Tarabili Reham M.
Published: November 2020

This study aimed to evaluate the prevalence, multidrug-resistance traits, PCR-detection of virulence, and antibiotic-resistance genes of E. coli isolated from secondary infections following FMD-outbreak in cattle. A total of 160 random samples were gathered from private dairy farms in Damietta Province, Egypt. The specimens were subjected to bacteriological examination, serotyping, congo-red binding assay, antibiogram-testing, and PCR-monitoring of virulence-determinant genes (tsh, phoA, hly, eaeA, sta, and lt) as well as the antibiotic-resistance genes (blaTEM, blaKPC, and blaCTX). The prevalence of E. coli was 30% (n = 48) distributed in 8 serogroups (40/48, 83.3%), while 8 isolates (8/48, 16.6%) were untypable. Besides, 83.3% of the examined isolates were positive for CR-binding. The tested strains harbored the virulence genes phoA, hly, tsh, eaeA, sta, and lt with a prevalence of 100% and 50%, 45.8%, 25%, 8.4%, and 6.2%, respectively. Furthermore, 50% of the recovered strains were multidrug-resistant (MDR) to penicillins, cephalosporins, and carbapenems, and are harboring the blaTEM, blaCTX, and blaKPC genes. Moreover, 25% of the examined strains are resistant to penicillins, and cephalosporins, and are harboring the blaTEM and blaCTX genes. To the best of our knowledge, this is the first report concerning the E. coli secondary bacterial infections following the FMD-outbreak. The emergence of MDR strains is considered a public health threat and indicates complicated treatment and bad prognosis of infections caused by such strains. Colistin sulfate and levofloxacin have a promising in vitro activity against MDR-E. coli.
TOXiTAXi: a web resource for toxicity of Bacillus thuringiensis protein compositions towards species of various taxonomic groups
Authors: Baranek Jakub , Pogodziński Bartłomiej , Szipluk Norbert , Zielezinski Andrzej
Published: November 2020

Bioinsecticides consisting of different sets of Bacillus thuringiensis (Bt) Cry, Cyt and Vip toxins are broadly used in pest control. Possible interactions (synergistic, additive or antagonistic) between these proteins can not only influence the overall efficacy of certain Bt-based bioinsecticide, but also raise questions regarding environmental safety. Here, we assemble, summarize and analyze the outcomes of experiments published over 30 years, investigating combinatorial effects among Bt Cry, Cyt and Vip toxins. We collected the results on 118 various two-to-five-component combinations that have been bioassayed against 38 invertebrate species. Synergism, additive effect and antagonism was indicated in 54%, 32% and 14% of experiments, respectively. Synergism was noted most frequently for Cry/Cyt combinations, followed by Cyt/Vip and Cry/Cry. In Cry/Vip combinations, antagonism is more frequent and higher in magnitude compared to other categories. Despite a significant number of tested Bt toxin combinations, most of them have been bioassayed only against one pest species. To aid the research on Bt pesticidal protein activity, we present TOXiTAXi (http://www.combio.pl/toxitaxi/), a universal database and a dedicated web tool to conveniently gather and analyze the existing and future bioassay results on biocidal activity of toxins against various taxonomic groups.
APOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults
Authors: Mole Jilu P. , Fasano Fabrizio , Evans John , Sims Rebecca , Kidd Emma , Aggleton John P. , Metzler-Baddeley Claudia
Published: November 2020

APOE-ε4 is a main genetic risk factor for developing late onset Alzheimer’s disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact ofAPOE-ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterisingAPOE-ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus. Here, we tested the impact ofAPOE-ε4 and two other risk factors, a family history of dementia and obesity, on grey matter macro- and microstructure across the whole brain in 165 asymptomatic individuals (38–71 years). Microstructural properties of apparent neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Orientation Density and Dispersion (NODDI) and quantitative magnetization transfer (qMT) imaging.APOE-ε4 carriers relative to non-carriers had a lower macromolecular proton fraction (MPF) in the left thalamus. No risk effects were present for cortical thickness, subcortical volume, or NODDI indices. Reduced thalamic MPF may reflect inflammation-related tissue swelling and/or myelin loss inAPOE-ε4. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.
Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis
Authors: Kanjana Korawit , Chevaisrakul Parawee , Matangkasombut Ponpan , Paisooksantivatana Karan , Lumjiaktase Putthapoom
Published: November 2020

Immune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value < 0.0001). Also, Treg: CD4+CD25+CD127+ cell ratio demonstrates the similar result (p value < 0.05). Treg inhibitory activity is inversely correlated with the DAS28. Specificity and positive likelihood ratio of inhibitory activity for indicating remission status are 92.31% (95% CI 63.97–99.81) and 11.14 (95% CI 1.67–74.14), respectively. Treg inhibitory activity is a promising prognostic marker and probably represents the immunological remission status in RA.
European landrace diversity for common bean biofortification: a genome-wide association study
Authors: Caproni Leonardo , Raggi Lorenzo , Talsma Elise F. , Wenzl Peter , Negri Valeria
Published: November 2020

Mineral deficiencies represent a global challenge that needs to be urgently addressed. An adequate intake of iron and zinc results in a balanced diet that reduces chances of impairment of many metabolic processes that can lead to clinical consequences. In plants, bioavailability of such nutrients is reduced by presence of compounds such as phytic acid, that can chelate minerals and reduce their absorption. Biofortification of common bean (Phaseolus vulgaris L.) represents an important strategy to reduce mineral deficiencies, especially in areas of the world where this crop plays a key role in the diet. In this study, a panel of diversity encompassing 192 homozygous genotypes, was screened for iron, zinc and phytate seed content. Results indicate a broad variation of these traits and allowed the identification of accessions reasonably carrying favourable trait combinations. A significant association between zinc seed content and some molecular SNP markers co-located on the common bean Pv01 chromosome was detected by means of genome-wide association analysis. The gene Phvul001G233500, encoding for an E3 ubiquitin-protein ligase, is proposed to explain detected associations. This result represents a preliminary evidence that can foster future research aiming at understanding the genetic mechanisms behind zinc accumulation in beans.
Author Correction: Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing
Authors: Begines Belen , Alcudia Ana , Aguilera-Velazquez Raul , Martinez Guillermo , He Yinfeng , Trindade Gustavo F. , Wildman Ricky , Sayagues Maria-Jesus , Jimenez-Ruiz Aila , Prado-Gotor Rafael
Published: November 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preparation of highly wettable coatings on Ti–6Al–4V ELI alloy for traumatological implants using micro-arc oxidation in an alkaline electrolyte
Authors: Gabor Roman , Doubkova Martina , Gorosova Simona , Malanik Karel , Vandrovcova Marta , Cvrcek Ladislav , Drobikova Klara , Mamulova Kutlakova Katerina , Bacakova Lucie
Published: November 2020

Pulsed micro-arc oxidation (MAO) in a strongly alkaline electrolyte (pH > 13), consisting of Na2SiO3⋅9H2O and NaOH, was used to form a thin porous oxide coating consisting of two layers differing in chemical and phase composition. The unique procedure, combining MAO and removal of the outer layer by blasting, enables to prepare a coating suitable for application in temporary traumatological implants. A bilayer formed in an alkaline electrolyte environment during the application of MAO enables the formation of a wear-resistant layer with silicon incorporated in the oxide phase. Following the removal of the outer rutile-containing porous layer, the required coating properties for traumatological applications were determined. The prepared surfaces were characterized by scanning electron microscopy, X-ray diffraction patterns, X-ray photoelectron spectroscopy, atomic force microscopy and contact angle measurements. Cytocompatibility was evaluated using human osteoblast-like Saos-2 cells. The newly-developed surface modifications of Ti–6Al–4V ELI alloy performed satisfactorily in all cellular tests in comparison with MAO-untreated alloy and standard tissue culture plastic. High cell viability was supported, but the modifications allowed only relatively slow cell proliferation, and showed only moderate osseointegration potential without significant support for matrix mineralization. Materials with these properties are promising for utilization in temporary traumatological implants.
Probing local distortion around structural defects in half-Heusler thermoelectric NiZrSn alloy
Authors: Miyazaki Hidetoshi , Ozkendir Osman Murat , Gunaydin Selen , Watanabe Kosuke , Soda Kazuo , Nishino Yoichi
Published: November 2020

The half-Heusler NiZrSn (NZS) alloy is particularly interesting owing to its excellent thermoelectric properties, mechanical strength, and oxidation resistance. However, the experimentally investigated thermal conductivity of half-Heusler NZS alloys shows discrepancies when compared to the theoretical predictions. This study investigates the crystal structure around atomic defects by comparing experimental and theoretical X-ray absorption fine structure (XAFS) spectra of the crystal structure of a half-Heusler NZS alloy. The results of both Zr and Ni K-edge XAFS spectra verified the existence of atomic defects at the vacancy sites distorting the C1b-type crystal structure. We concluded that the distortion of the atoms around the interstitial Ni disorder could be the probable reason for the observed lower thermal conductivity values compared to that predicted theoretically in half-Heusler alloys. Our study makes a significant contribution to the literature because the detailed investigation of the lattice distortion around atomic defects will pave the way to further reduce the thermal conductivity by controlling this distortion.
Beneficial effects of daytime high-intensity light exposure on daily rhythms, metabolic state and affect
Authors: Bilu Carmel , Einat Haim , Zimmet Paul , Vishnevskia-Dai Vicktoria , Kronfeld-Schor Noga
Published: November 2020

While the importance of the circadian system to health and well-being is extensively studied, the role of daylight exposure in these interactions is relatively poorly understood. Here we show, using a diurnal animal model naturally exposed to daylight, that daily morning exposure to 3000 lux, full spectrum electric light has beneficial health effects. Compared with controls, sand rats (Psammomys obesus) subjected to morning light treatment demonstrate daily rhythms with high peak to trough difference in activity, blood glucose levels and per2 gene expression in the suprachiasmatic nucleus, pre-frontal cortex, kidney and liver. The treated animals were also healthier, being normoglycemic, having higher glucose tolerance, lower body and heart weight and lower anxiety- and depression-like behavior. Our results suggest that exposure to high intensity light is important for the proper function of the circadian system and well-being, and are important in face of human's low exposure to daylight and extensive use of artificial light at night.
Chloroplast genomes elucidate diversity, phylogeny, and taxonomy of Pulsatilla (Ranunculaceae)
Authors: Li Qiu-jie , Su Na , Zhang Ling , Tong Ru-chang , Zhang Xiao-hui , Wang Jun-ru , Chang Zhao-yang , Zhao Liang , Potter Daniel
Published: November 2020

Pulsatilla (Ranunculaceae) consists of about 40 species, and many of them have horticultural and/or medicinal value. However, it is difficult to recognize and identify wild Pulsatilla species. Universal molecular markers have been used to identify these species, but insufficient phylogenetic signal was available. Here, we compared the complete chloroplast genomes of seven Pulsatilla species. The chloroplast genomes of Pulsatilla were very similar and their length ranges from 161,501 to 162,669 bp. Eight highly variable regions and potential sources of molecular markers such as simple sequence repeats, large repeat sequences, and single nucleotide polymorphisms were identified, which are valuable for studies of infra- and inter-specific genetic diversity. The SNP number differentiating any two Pulsatilla chloroplast genomes ranged from 112 to 1214, and provided sufficient data for species delimitation. Phylogenetic trees based on different data sets were consistent with one another, with the IR, SSC regions and the barcode combination rbcL + matK + trnH-psbA produced slightly different results. Phylogenetic relationships within Pulsatilla were certainly resolved using the complete cp genome sequences. Overall, this study provides plentiful chloroplast genomic resources, which will be helpful to identify members of this taxonomically challenging group in further investigation.
Stress-induced sleep-like inactivity modulates stress susceptibility in mice
Authors: Nagai Midori , Nagai Hirotaka , Numa Chisato , Furuyashiki Tomoyuki
Published: November 2020

Severe environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.
Discovery of carbon nanotubes in sixth century BC potteries from Keeladi, India
Authors: Kokarneswaran Manivannan , Selvaraj Prakash , Ashokan Thennarasan , Perumal Suresh , Sellappan Pathikumar , Murugan Kandhasamy Durai , Ramalingam Sivanantham , Mohan Nagaboopathy , Chandrasekaran Vijayanand
Published: November 2020

Unique black coatings were observed in the inner wall of pottery shreds excavated from Keeladi, Tamilnadu, India. Raman spectroscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy were used to understand the nature of the coating. The analysis revealed the presence of single, multi-walled carbon nanotubes and layered sheets in the coating. The average diameter of single-walled carbon nanotube found to be about 0.6 ± 0.05 nm. This is the lowest among the single-walled carbon nanotubes reported from artefacts so far and close to the theoretically predicted value (0.4 nm). These nanomaterials were coated in the pottery’s that date backs to sixth century BC, and still retain its stability and adhesion. The findings of nano materials in the pre-historic artifacts, its significance and impact are discussed in this article.
Mutational analysis in familial Alzheimer’s disease of Han Chinese in Taiwan with a predominant mutation PSEN1 p.Met146Ile
Authors: Lin Yung-Shuan , Cheng Chih-Ya , Liao Yi-Chu , Hong Chen-Jee , Fuh Jong-Ling
Published: November 2020

Mutations in PSEN1, PSEN2, or APP genes are known to be causative for autosomal dominant Alzheimer’s disease (ADAD). While more than 400 mutations were reported worldwide, predominantly PSEN1, over 40 mutations have been reported in Han Chinese and were associated with earlier onset and more affected family members. Between 2002 and 2018, 77 patients in the neurological clinic of Taipei Veterans General Hospital with a history suggestive of ADAD were referred for mutational analysis. We retrospectively collected demographics, initial symptoms, neurological features and inheritance. We identified 16 patients with PSEN1 and 1 with APP mutation. Among the mutations identified, PSEN1 p.Pro117Leu, p.Met146Ile, p.Gly206Asp, p.Gly209Glu, p.Glu280Lys and p.Leu286Val and APP p.Asp678His were known pathogenic mutations; PSEN1 p.His131Arg and p.Arg157Ser were classified as likely pathogenic and variance of unknown significance respectively. The mean age at onset was 46.2 ± 6.2 years in patients with mutation found. PSEN1 p.Met146Ile, occurred in 56.2% (9/16) of patients with PSEN1 mutations, was the most frequent mutation in the cohort. The additional neurological features occurring in 9 PSEN1 p.Met146Ile index patients were similar with the literature. We found patients with genetic diagnoses were more likely to have positive family history, younger age at onset and less brain white matter hyperintensity.
Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman
Authors: Awad Hoyam , Gadalla Amal A. H. , Postigo Milagros , Al-Hamidhi Salama , Tageldin Mohammed H. , Skariah Sini , Sultan Ali A. , Johnson Eugene H. , Shiels Brian , Pain Arnab , Thompson Joanne , Babiker Hamza A.
Published: November 2020

Mixed species infections of Theileria spp. are common in nature. Experimental and epidemiological data suggest that mixed species infections elicit cross-immunity that can modulate pathogenicity and disease burden at the population level. The present study examined within-host interactions, over a period of 13 months during natural infections with two Theileria spp., pathogenic (T. lestoquardi) and non-pathogenic (T. ovis), amongst a cohort of naive sheep in Oman. In the first two months after exposure to infection, a high rate of mortality was seen among sheep infected with T. lestoquardi alone. However, subsequently mixed-infections of T. lestoquardi and T. ovis prevailed, and no further death occurred. The overall densities of both parasite species were significantly higher as single infection vs mixed infection and the higher relative density of pathogenic T. lestoquardi indicated a competitive advantage over T. ovis in mixed infection. The density of both species fluctuated significantly over time, with no difference in density between the very hot (May to August) and warm season (September to April). A high degree of genotype multiplicity was seen among T. lestoquardi infections, which increased with rising parasite density. Our results illustrate a potential competitive interaction between the two ovine Theileria spp., and a substantial reduction in the risk of mortality in mixed parasite infections, indicating that T. ovis confers heterologous protection against lethal T. lestoquardi infection.