bluuebunny/crossref_metadata_2025 huggingface dataset:
Dependence of Internal Wave Bolus Transport on Pycnocline Thickness
Authors: Allshouse Michael R. , Swinney Harry L.
Published: June 2020

A bolus is a vortex formed by an internal wave propagating upslope with the shoaling wave. The amount of sediment and biota transported by boluses travelling up the world's continental slopes and onto the continental shelves has not been established but could be vital for maintaining nutrient‐rich coastal ecosystems. Previous laboratory experiments and simulations of shoaling boluses have considered a two‐layer density stratification or a linear density profile. We present experiments on bolus formation and propagation in a stratification with a density profile ρ(z) represented by a tanh‐profile, which describes many ocean pycnoclines. Our laboratory experiments examine pycnoclines with thicknesses varying from nearly zero (a two‐layer system) to large thicknesses where the density varies almost linearly with depth. The bolus volume, displacement upslope, and available potential energy are measured as a function of pycnocline thickness. Maximum upslope displacement is found to be twice that observed for a two‐layer stratification.
Summertime Temperature Variability Increases With Local Warming in Midlatitude Regions
Authors: Chan Duo , Cobb Alison , Zeppetello Lucas R. Vargas , Battisti David S. , Huybers Peter
Published: June 2020

Climate change presents risks both in terms of warming and increased variability that are heightened when compounded. It is thus notable that the simulations in the Coupled Model Intercomparison Project Phase 5 (CMIP5) showing greater Northern midlatitude continental warming also show a greater increase in monthly average temperature variance, particularly in Europe. European variability increases with warming at a rate of 0.40°C2/°C (95% C.I. [0.28, 0.50]), with local warming rates explaining 71% of the intermodel difference in variability changes. Coupling between warming and variance increases the probability of high temperatures compared to a scenario where variance is stable. If warming were to reach 6°C, the risk of monthly average temperature exceeding a 30°C threshold is 4 times greater in the increased‐variance scenario. Despite the simple scaling across models suggesting some common origin, changes in model temperature and variance potentially involve a range of mechanisms whose contributions remain unclear.
Ice Breakup Controls Dissipation of Wind Waves Across Southern Ocean Sea Ice
Authors: Ardhuin Fabrice , Otero Mark , Merrifield Sophia , Grouazel Antoine , Terrill Eric
Published: June 2020

Sea ice inhibits the development of wind‐generated surface gravity waves which are the dominant factor in upper ocean mixing and air‐sea fluxes. In turn, sea ice properties are modified by wave action. Understanding the interaction of ice and waves is important for characterizing both air‐sea interactions and sea ice dynamics. Current leading theory attributes wave attenuation primarily to scattering by ice floes. Here we use new in situ wave measurements to show that attenuation is dominated by dissipation with negligible effect by scattering. Time series of wave height in ice exhibit an “on/off” behavior that is consistent with switching between two states of sea ice: a relatively unbroken state associated with strong damping (off), possibly caused by ice flexure, and very weak attenuation (on) across sea ice that has been broken up by wave action.
Atlantic‐Pacific Gradients Drive Last Millennium Hydroclimate Variability in Mesoamerica
Authors: Bhattacharya Tripti , Coats Sloan
Published: June 2020

The paleoclimatic record from Mexico and Central America, or Mesoamerica, documents dramatic swings in hydroclimate over the past few millennia. However, the dynamics underlying these past changes remain obscure. We use proxy indicators of hydroclimate to show that last millennium hydroclimate variability was dominated by opposite‐signed moisture anomalies in northern and southern Mesoamerica. This pattern results from changes in moisture convergence driven by Atlantic‐Pacific interbasin temperature gradients. While this pattern is reproduced by several models and multiple experiments with a single model, models appear to disagree about the underlying dynamics of this interbasin gradient. Moreover, disagreement about the interbasin gradient, and associated hydroclimate pattern, dominates spread in 21st century regional hydroclimate projections. These results emphasize the role of interbasin asymmetries in governing past and future regional climate change. They also demonstrate that paleoclimate studies can elucidate mechanisms directly relevant to projecting future hydroclimate in climate change hot spots like Mesoamerica.
Regional Pattern of the Ocean's Biological Pump Based on Geochemical Observations
Authors: Quay Paul , Emerson Steven , Palevsky Hilary
Published: June 2020

Despite the impact of the ocean's biological pump on future atmospheric CO2 and deep ocean O2 concentrations, organic matter export rates are poorly known because observations are scarce and mostly short term. Thus, we rely on satellite data and models to yield export rates, yet neither approach is sufficiently validated. We present multiyear export estimates based mainly on observed O2 and CO2 surface layer budgets across the Pacific and North Atlantic Oceans and compare to satellite‐ and model‐based estimates. We find that regional variability in observed export is modest (threefold) and lower than model‐ and satellite‐based estimates (threefold to sevenfold). Neither model‐ nor satellite‐based export reproduces the regional export trends in the Pacific. We find that winter mixed layer depth is critical in determining annual export rates in the subpolar N. Atlantic.
Photochemistry of Methane and Ethane in the Martian Atmosphere
Authors: Taysum Benjamin M. , Palmer Paul I.
Published: June 2020

We develop an existing 1‐D photochemistry model to include a comprehensive description of organic chemistry on Mars that includes the oxidation products of methane (CH4) and ethane (C2H6),a longer‐chain hydrocarbon that can be used to differentiate between abiotic and biotic surface releases of CH4. We find that CH4 is most volatile between 20 and 50 km during Mars' northern summer, where the local atmospheric CH4 lifetime lowers to 25–60 years. We study atmospheric formaldehyde (HCHO) and formic acid (HCOOH), as the two common oxidation products of CH4 and C2H6, and acetaldehyde (CH3CHO) and acetic acid (CH3COOH) as unique products of C2H6. We focus our analysis of these gases at Mars' aphelion and perihelion at latitudes between ‐30° and 30°, altitudes from the surface to 70 km, and from a homogeonous initial condition of 50 pptv of CH4 and C2H6. From this initial condition, CH4 produces HCHO in a latitude‐independent layered structure centered at 20–30 km at aphelion with column‐averaged mixing ratios of 10−4 pptv, and oxidation of C2H6 produces HCHO at 10−2 pptv. Formic acid has an atmospheric lifetime spanning 1–10 sols below 10 km that shows little temporal or zonal variability and is produced in comparable abundances (10−5 pptv) by the oxidation of C2H6 and CH4. We also find that oxidation of 50 pptv of C2H6 results in 10−3 pptv of CH3CHO and 10−4 pptv of CH3COOH. Subsequent UV photolysis of this CH3CHO results in 10−4 pptv of atmospheric CH4, potentially representing a new atmospheric source of Martian CH4.
Myotubularin-related protein 7 activates peroxisome proliferator-activated receptor-gamma
Authors: Weidner Philip , Söhn Michaela , Schroeder Torsten , Helm Laura , Hauber Veronika , Gutting Tobias , Betge Johannes , Röcken Christoph , Rohrbacher Florian N. , Pattabiraman Vijaya R. , Bode Jeffrey W. , Seger Rony , Saar Daniel , Nunes-Alves Ariane , Wade Rebecca C. , Ebert Matthias P. A. , Burgermeister Elke
Published: June 2020

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor drugable by agonists approved for treatment of type 2 diabetes, but also inhibits carcinogenesis and cell proliferation in vivo. Activating mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mitigate these beneficial effects by promoting a negative feedback-loop comprising extracellular signal-regulated kinase 1/2 (ERK1/2) and mitogen-activated kinase kinase 1/2 (MEK1/2)-dependent inactivation of PPARγ. To overcome this inhibitory mechanism, we searched for novel post-translational regulators of PPARγ. Phosphoinositide phosphatase Myotubularin-Related-Protein-7 (MTMR7) was identified as cytosolic interaction partner of PPARγ. Synthetic peptides were designed resembling the regulatory coiled-coil (CC) domain of MTMR7, and their activities studied in human cancer cell lines and C57BL6/J mice. MTMR7 formed a complex with PPARγ and increased its transcriptional activity by inhibiting ERK1/2-dependent phosphorylation of PPARγ. MTMR7-CC peptides mimicked PPARγ-activation in vitro and in vivo due to LXXLL motifs in the CC domain. Molecular dynamics simulations and docking predicted that peptides interact with the steroid receptor coactivator 1 (SRC1)-binding site of PPARγ. Thus, MTMR7 is a positive regulator of PPARγ, and its mimicry by synthetic peptides overcomes inhibitory mechanisms active in cancer cells possibly contributing to the failure of clinical studies targeting PPARγ.
Discovery and quality analysis of a comprehensive set of structural variants and short tandem repeats
Authors: Jakubosky David , Smith Erin N. , D’Antonio Matteo , Jan Bonder Marc , Young Greenwald William W. , D’Antonio-Chronowska Agnieszka , Matsui Hiroko ,   i2QTL Consortium, Bonder Marc J. , Cai Na , Carcamo-Orive Ivan , D’Antonio Matteo , Frazer Kelly A. , Young Greenwald William W. , Jakubosky David , Knowles Joshua W. , Matsui Hiroko , McCarthy Davis J. , Mirauta Bogdan A. , Montgomery Stephen B. , Quertermous Thomas , Seaton Daniel D. , Smail Craig , Smith Erin N. , Stegle Oliver , Stegle Oliver , Montgomery Stephen B. , DeBoever Christopher , Frazer Kelly A.
Published: June 2020

Structural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but are not routinely analyzed in genetic studies because they are difficult to accurately identify and genotype. Because SVs and STRs range in size and type, it is necessary to apply multiple algorithms that incorporate different types of evidence from sequencing data and employ complex filtering strategies to discover a comprehensive set of high-quality and reproducible variants. Here we assemble a set of 719 deep whole genome sequencing (WGS) samples (mean 42×) from 477 distinct individuals which we use to discover and genotype a wide spectrum of SV and STR variants using five algorithms. We use 177 unique pairs of genetic replicates to identify factors that affect variant call reproducibility and develop a systematic filtering strategy to create of one of the most complete and well characterized maps of SVs and STRs to date.
Single molecule secondary structure determination of proteins through infrared absorption nanospectroscopy
Authors: Ruggeri Francesco Simone , Mannini Benedetta , Schmid Roman , Vendruscolo Michele , Knowles Tuomas P. J.
Published: June 2020

The chemical and structural properties of biomolecules determine their interactions, and thus their functions, in a wide variety of biochemical processes. Innovative imaging methods have been developed to characterise biomolecular structures down to the angstrom level. However, acquiring vibrational absorption spectra at the single molecule level, a benchmark for bulk sample characterization, has remained elusive. Here, we introduce off-resonance, low power and short pulse infrared nanospectroscopy (ORS-nanoIR) to allow the acquisition of infrared absorption spectra and chemical maps at the single molecule level, at high throughput on a second timescale and with a high signal-to-noise ratio (~10–20). This high sensitivity enables the accurate determination of the secondary structure of single protein molecules with over a million-fold lower mass than conventional bulk vibrational spectroscopy. These results pave the way to probe directly the chemical and structural properties of individual biomolecules, as well as their interactions, in a broad range of chemical and biological systems.
A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities
Authors: Narayan Ravi S. , Molenaar Piet , Teng Jian , Cornelissen Fleur M. G. , Roelofs Irene , Menezes Renee , Dik Rogier , Lagerweij Tonny , Broersma Yoran , Petersen Naomi , Marin Soto Jhon Alexander , Brands Eelke , van Kuiken Philip , Lecca Maria C. , Lenos Kristiaan J. , In ‘t Veld Sjors G. J. G. , van Wieringen Wessel , Lang Frederick F. , Sulman Erik , Verhaak Roel , Baumert Brigitta G. , Stalpers Lucas J. A. , Vermeulen Louis , Watts Colin , Bailey David , Slotman Ben J. , Versteeg Rogier , Noske David , Sminia Peter , Tannous Bakhos A. , Wurdinger Tom , Koster Jan , Westerman Bart A.
Published: June 2020

Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value.
Simultaneous EEG-fMRI during a neurofeedback task, a brain imaging dataset for multimodal data integration
Authors: Lioi Giulia , Cury Claire , Perronnet Lorraine , Mano Marsel , Bannier Elise , Lécuyer Anatole , Barillot Christian
Published: June 2020

Combining EEG and fMRI allows for integration of fine spatial and accurate temporal resolution yet presents numerous challenges, noticeably if performed in real-time to implement a Neurofeedback (NF) loop. Here we describe a multimodal dataset of EEG and fMRI acquired simultaneously during a motor imagery NF task, supplemented with MRI structural data. The study involved 30 healthy volunteers undergoing five training sessions. We showed the potential and merit of simultaneous EEG-fMRI NF in previous work. Here we illustrate the type of information that can be extracted from this dataset and show its potential use. This represents one of the first simultaneous recording of EEG and fMRI for NF and here we present the first open access bi-modal NF dataset integrating EEG and fMRI. We believe that it will be a valuable tool to (1) advance and test methodologies for multi-modal data integration, (2) improve the quality of NF provided, (3) improve methodologies for de-noising EEG acquired under MRI and (4) investigate the neuromarkers of motor-imagery using multi-modal information.
Aerial surveys of waterbirds in Australia
Authors: Kingsford Richard T. , Porter John L. , Brandis Kate J. , Ryall Sharon
Published: June 2020

Tracking long-term environmental change is important, particularly for freshwater ecosystems, often with high rates of decline. Waterbirds are key indicators of freshwater ecosystem change, with groups reflecting food availability (e.g. piscivores and fish). We store waterbird (species abundance, numbers of nests and broods) and wetland area data from aerial surveys of waterbirds across Australia, mostly at the species’ level (∼100 species) from three aerial survey programs: Eastern Australian Waterbird Survey, National Survey and Murray-Darling Basin wetlands. Across eastern Australia, we survey up to 2,000 wetlands annually (October, since 1983), along 10 survey bands (30 km wide), east to west across about one third of Australia. In 2008, we surveyed 4,858 wetlands across Australia and each year (since 2010) we survey the major wetlands in the Murray-Darling Basin. These data inform regulation of hunting seasons in Victoria and South Australia, Game bird culling in NSW, State of the Environment Reporting, environmental assessments, river and wetland management, the status of individual species and identification of high conservation sites.
Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice
Authors: Pérez-Matute Patricia , Íñiguez María , de Toro María , Recio-Fernández Emma , Oteo José A.
Published: June 2020

Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 & 18), and FT-A (administration of their own feces before developing obesity at weeks 17 & 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.
Focussing Protons from a Kilojoule Laser for Intense Beam Heating using Proximal Target Structures
Authors: McGuffey C. , Kim J. , Wei M. S. , Nilson P. M. , Chen S. N. , Fuchs J. , Fitzsimmons P. , Foord M. E. , Mariscal D. , McLean H. S. , Patel P. K. , Stephens R. B. , Beg F. N.
Published: June 2020

Proton beams driven by chirped pulse amplified lasers have multi-picosecond duration and can isochorically and volumetrically heat material samples, potentially providing an approach for creating samples of warm dense matter with conditions not present on Earth. Envisioned on a larger scale, they could heat fusion fuel to achieve ignition. We have shown in an experiment that a kilojoule-class, multi-picosecond short pulse laser is particularly effective for heating materials. The proton beam can be focussed via target design to achieve exceptionally high flux, important for the applications mentioned. The laser irradiated spherically curved diamond-like-carbon targets with intensity 4 × 1018 W/cm2, producing proton beams with 3 MeV slope temperature. A Cu witness foil was positioned behind the curved target, and the gap between was either empty or spanned with a structure. With a structured target, the total emission of Cu Kα fluorescence was increased 18 fold and the emission profile was consistent with a tightly focussed beam. Transverse proton radiography probed the target with ps order temporal and 10 μm spatial resolution, revealing the fast-acting focussing electric field. Complementary particle-in-cell simulations show how the structures funnel protons to the tight focus. The beam of protons and neutralizing electrons induce the bright Kα emission observed and heat the Cu to 100 eV.
Shedding of Brucella melitensis happens through milk macrophages in the murine model of infection
Authors: Jansen Wiebke , Demars Aurore , Nicaise Charles , Godfroid Jacques , de Bolle Xavier , Reboul Angéline , Al Dahouk Sascha
Published: June 2020

Although shedding of zoonotic brucellae in milk has been demonstrated in natural hosts, these data are still missing for the standard murine infection model. We therefore analysed shedding kinetics and the niche of B. melitensis in murine milk. Pregnant Balb/cByJ mice were intraperitoneally infected with 105 CFU of the 16 M reference strain, a 16 M mCherry mutant or a human isolate. Milk was collected over the course of lactation, and subjected to culture and immunofluorescence assays. Bacteria were also quantified in spleen and mammary glands of maternal mice and in spleen of the litter. The shedding of the three strains did not differ significantly (p = 0.301), ranging from log10 1.5 to 4.04 CFU/ml. A total of 73% of the mice excreted B. melitensis into the milk with peak values at mid-lactation; up to 30 bacteria/cell were found in macrophages and neutrophils. While the bacterial counts in the spleen of lactating females confirmed a well-established infection, only 50% of the pups harboured brucellae in their spleen, including the spleen of an uninfected pup fed by an infected foster mother. In conclusion, the murine model of infection may contribute to a better understanding of the zoonotic transmission of brucellosis.
Learned Representation of Implied Serial Order in Posterior Parietal Cortex
Authors: Munoz Fabian , Jensen Greg , Kennedy Benjamin C. , Alkan Yelda , Terrace Herbert S. , Ferrera Vincent P.
Published: June 2020

Monkeys can learn the implied ranking of pairs of images drawn from an ordered set, despite never seeing all of the images simultaneously and without explicit spatial or temporal cues. We recorded the activity of posterior parietal cortex (including lateral intraparietal area LIP) neurons while monkeys learned 7-item transitive inference (TI) lists with 2 items presented on each trial. Behavior and neuronal activity were significantly influenced by the ordinal relationship of the stimulus pairs, specifically symbolic distance (the difference in rank) and joint rank (the sum of the ranks). Symbolic distance strongly predicted decision accuracy and learning rate. An effect of joint rank on performance was found nested within the symbolic distance effect. Across the population of neurons, there was significant modulation of firing correlated with the relative ranks of the two stimuli presented on each trial. Neurons exhibited selectivity for stimulus rank during learning, but not before or after. The observed behavior is poorly explained by associative or reward mechanisms, and appears more consistent with a mental workspace model in which implied serial order is mapped within a spatial framework. The neural data suggest that posterior parietal cortex supports serial learning by representing information about the ordinal relationship of the stimuli presented during a given trial.
Sex differences in dendritic spine density and morphology in auditory and visual cortices in adolescence and adulthood
Authors: Parker Emily M. , Kindja Nathan L. , Cheetham Claire E. J. , Sweet Robert A.
Published: June 2020

Dendritic spines are small protrusions on dendrites that endow neurons with the ability to receive and transform synaptic input. Dendritic spine number and morphology are altered as a consequence of synaptic plasticity and circuit refinement during adolescence. Dendritic spine density (DSD) is significantly different based on sex in subcortical brain regions associated with the generation of sex-specific behaviors. It is largely unknown if sex differences in DSD exist in auditory and visual brain regions and if there are sex-specific changes in DSD in these regions that occur during adolescent development. We analyzed dendritic spines in 4-week-old (P28) and 12-week-old (P84) male and female mice and found that DSD is lower in female mice due in part to fewer short stubby, long stubby and short mushroom spines. We found striking layer-specific patterns including a significant age by layer interaction and significantly decreased DSD in layer 4 from P28 to P84. Together these data support the possibility of developmental sex differences in DSD in visual and auditory regions and provide evidence of layer-specific refinement of DSD over adolescent brain development.
Structural characterization of SnO nanoparticles synthesized by the hydrothermal and microwave routes
Authors: Dias J. S. , Batista F. R. M. , Bacani R. , Triboni E. R.
Published: June 2020

SnO particles were synthesized by an alkali-assisted hydrothermal and microwave methods. The aqueous-based reactions were carried out at pH ~ 8, under inert atmosphere (Ar). The reactions were taken under different times, and a full XRD structural analysis was made to evaluate the conversion from the Sn6O4(OH)4 intermediate to SnO particles. Williamson-Hall analysis showed that the size and strain of the SnO particles were time and route treatment dependent. Microwave heating yielded a single tetragonal SnO phase after 1 h of thermal treatment, and TEM images revealed spherical-shaped SnO nanoparticles with an average size of 9(1) nm. While by the hydrothermal treatment single SnO phase was obtained only after 4 hours, yielding non-uniform and elongated particles with sub-micrometric size. A dissolution-recrystallization process was taken into account as the mechanism for SnO particles formation, in which hydroxylated complexes, Sn2(OH)6−2, then condense to form the oxide. The time-shorting reaction provided by the microwave-assisted synthesis may be attributed to better heat distribution.
Clinical analysis in immunocompetent and immunocompromised patients with pulmonary cryptococcosis in western China
Authors: Qu Junyan , Zhang Xiaoli , Lu Yang , Liu Xijiao , Lv Xiaoju
Published: June 2020

Cryptococcosis is a systemic infection and it may occur in immunocompromised and immunocompetent hosts. In order to better understand the clinical characteristics of patients with PC in different immune status, we retrospectively investigated the clinical, radiological, and treatment profiles of immunocompetent and immunocompromised patients with PC during a 10-year period (2008–2017). As a result, out of 136 patients, 94 (69.1%) were immunocompromised hosts. For the PC patients without CNS involvement, higher percentage of immunocompetent patients (39.5%, 15/38) had asymptomatic presentation than immunocompromised patients (6.3%, 3/48) (P < 0.05). Multiple pulmonary nodules (72.7%, 56/77), ground-glass attenuation/interstitial changes (94.4%, 17/18) and cavitation (88.6%, 31/35) were significantly frequent in immunocompromised patients (P < 0.05). A total of 47 patients were misdiagnosed as tuberculosis or tumors based on CT signs. PC was likely to be misdiagnosed as tuberculosis in immunocompromised patients (88.2%, 15/17), and tumor was more likely to be considered in immunocompetent patients (43.3%, 13/30). Immunocompetent patients accounted for 80% (24/30) of patients with definite diagnosis on surgical lung biopsy. Fluconazole monotherapy can achieve good clinical outcome in most PC patients without central nervous system (CNS) involvement (91.5%, 54/59). After 3 months of treatment, 92.7% (38/41) patients have improved imaging findings. In conclusion, PC has diverse imaging manifestations and it is easily misdiagnosed. Lobectomy should be carefully selected in immunocompetent patients with a single lung lesion. Fluconazole monotherapy is preferred for PC patients without CNS involvement.
Patterns and Rates of Plastid rps12 Gene Evolution Inferred in a Phylogenetic Context using Plastomic Data of Ferns
Authors: Liu Shanshan , Wang Zhen , Wang Hui , Su Yingjuan , Wang Ting
Published: June 2020

The trans-splicing rps12 gene of fern plastomes (plastid genomes) exhibits a unique structure owing to its variations in intragenic exon location and intron content, and thus, it provides an excellent model system for examining the effect of plastid gene structure on rates and patterns of molecular evolution. In this study, 16 complete fern plastome sequences were newly generated via the Illumina HiSeq sequencing platform. We reconstructed the phylogeny of ferns and inferred the patterns and rates of plastid rps12 gene evolution in a phylogenetic context by combining these plastome data with those of previously published fern species. We uncovered the diversity of fern plastome evolution by characterizing the structures of these genomes and obtained a highly supported phylogenetic framework for ferns. Furthermore, our results revealed molecular evolutionary patterns that were completely different from the patterns revealed in previous studies. There were significant differences in the patterns and rates of nucleotide substitutions in both intron-containing and intron-less rps12 alleles. Rate heterogeneity between single-copy (SC) and inverted repeat (IR) exons was evident. Unexpectedly, however, IR exons exhibited significantly higher synonymous substitution rates (dS) than SC exons, a pattern that contrasts the regional effect responsible for decreased rates of nucleotide substitutions in IRs. Our results reveal that structural changes in plastid genes have important effects on evolutionary rates, and we propose possible mechanisms to explain the variations in the nucleotide substitution rates of this unusual gene.
Prediction of advanced fibrosis in non-alcoholic fatty liver disease using gut microbiota-based approaches compared with simple non-invasive tools
Authors: Lang Sonja , Farowski Fedja , Martin Anna , Wisplinghoff Hilmar , Vehreschild Maria J. G. T. , Krawczyk Marcin , Nowag Angela , Kretzschmar Anne , Scholz Claus , Kasper Philipp , Roderburg Christoph , Lammert Frank , Goeser Tobias , Steffen Hans-Michael , Demir Münevver
Published: June 2020

Liver fibrosis is the major determinant of liver related complications in patients with non-alcoholic fatty liver disease (NAFLD). A gut microbiota signature has been explored to predict advanced fibrosis in NAFLD patients. The aim of this study was to validate and compare the diagnostic performance of gut microbiota-based approaches to simple non-invasive tools for the prediction of advanced fibrosis in NAFLD. 16S rRNA gene sequencing was performed in a cohort of 83 biopsy-proven NAFLD patients and 13 patients with non-invasively diagnosed NAFLD-cirrhosis. Random Forest models based on clinical data and sequencing results were compared with transient elastography, the NAFLD fibrosis score (NFS) and FIB-4 index. A Random Forest model containing clinical features and bacterial taxa achieved an area under the curve (AUC) of 0.87 which was only marginally superior to a model without microbiota features (AUC 0.85). The model that aimed to validate a published algorithm achieved an AUC of 0.71. AUC’s for NFS and FIB-4 index were 0.86 and 0.85. Transient elastography performed best with an AUC of 0.93. Gut microbiota signatures might help to predict advanced fibrosis in NAFLD. However, transient elastography achieved the best diagnostic performance for the detection of NAFLD patients at risk for disease progression.
Reduced Graphene Oxide-Silver Nanoparticles for Optical Pulse Generation in Ytterbium- and Erbium-Doped Fiber Lasers
Authors: Ahmad Harith , Albaqawi Hissah Saedoon , Yusoff Norazriena , Reduan Siti Aisyah , Yi Chong Wu
Published: June 2020

This work has demonstrated the potential of a reduced graphene oxide silver/polyvinyl alcohol (rGO-Ag/PVA) film as a saturable absorber (SA) in ytterbium and erbium based Q-switched optical fiber lasers. The facile hydrothermal method was used to synthesize the nanocomposite between rGO and Ag nanoparticles. This was followed by a simple solution method to form the rGO-Ag film using PVA as the host polymer. From nonlinear absorption characterization, the rGO-Ag/PVA SA was determined to have a modulation depth of 30%, a nonsaturable loss of 70%, and a saturable intensity of 0.63 kW/cm2. Stable self-starting Q-switched pulses were obtained at the threshold pump power of 72.76 mW and 18.63 mW in the ytterbium-doped (YDFL) and erbium-doped fiber laser (EDFL) cavities respectively. The center operating wavelengths were observed at 1044.4 nm and 1560 nm for the two cavities. The shortest pulse width and maximum repetition rate of the YDFL and EDFL were 1.10 µs and 62.10 kHz and 1.38 µs and 76.63 kHz respectively. This work has demonstrated that the rGO-Ag/PVA film is suitable as an SA for pulse generation in the 1.0 and 1.5 μm regions and would have many potential photonics applications.
Active control on topological immunity of elastic wave metamaterials
Authors: Li Guan-Hua , Ma Tian-Xue , Wang Yi-Ze , Wang Yue-Sheng
Published: June 2020

The topology concept in the condensed physics and acoustics is introduced into the elastic wave metamaterial plate, which can show the topological property of the flexural wave. The elastic wave metamaterial plate consists of the hexagonal array which is connected by the piezoelectric shunting circuits. The Dirac point is found by adjusting the size of the unit cell and numerical simulations are illustrated to show the topological immunity. Then the closing and breaking of the Dirac point can be generated by the negative capacitance circuits. These investigations denote that the topological immunity can be achieved for flexural wave in mechanical metamaterial plate. The experiments with the active control action are finally carried out to support the numerical design.
Whole-genome sequencing provides new insights into genetic mechanisms of tropical adaptation in Nellore (Bos primigenius indicus)
Authors: Fernandes Júnior Gerardo Alves , de Oliveira Henrique Nunes , Carvalheiro Roberto , Cardoso Diercles Francisco , Fonseca Larissa Fernanda Simielli , Ventura Ricardo Vieira , de Albuquerque Lucia Galvão
Published: June 2020

Most of the knowledge about genetic variants at the sequence level in cattle is for Bos primigenius taurus populations. Here, we presented a complete genomic characterization of 52 Nellore (Bos primigenius indicus) bulls, revealing specific zebu DNA variants with putative impact in tropical adaptation and productive traits. Single nucleotide polymorphisms (SNPs) and insertion/deletion (INDELs) mutations were identified using the newest bovine reference genome ARS_UCD1.2, and variant functional consequences were predicted using the Ensembl VEP software. A total of 35,753,707 SNPs and 4,492,636 INDELs were detected and annotated to their functional effects. We identified 400 genes that comprised both, a SNP and an INDEL, of high functional impact on proteins (i.e. variants that cause protein truncation, loss of function or triggering nonsense-mediated decay). Among these, we highlight the following genes: BoLA, associated with cattle immune response to infections and reproduction aspects; HSPA8, DNAJC27, and DNAJC28, involved with thermoregulatory protective mechanisms in mammals; and many olfactory signaling pathway related genes that are important genetic factors in the evolution of mammalian species. All these functional aspects are directly related to cattle adaptability to tropical environments.
Characterization of different alginate lyases for dissolving Pseudomonas aeruginosa biofilms
Authors: Blanco-Cabra Núria , Paetzold Bernhard , Ferrar Tony , Mazzolini Rocco , Torrents Eduard , Serrano Luis , LLuch-Senar Maria
Published: June 2020

Aggregates of Pseudomonas aeruginosa form a protective barrier against antibiotics and the immune system. These barriers, known as biofilms, are associated with several infectious diseases. One of the main components of these biofilms is alginate, a homo- and hetero-polysaccharide that consists of β-D-mannuronate (M) and α-L-guluronate (G) units. Alginate lyases degrade this sugar and have been proposed as biotherapeutic agents to dissolve P. aeruginosa biofilms. However, there are contradictory reports in the literature regarding the efficacy of alginate lyases against biofilms and their synergistic effect with antibiotics. We found that most positive reports used a commercial crude extract from Flavobacterium multivorum as the alginate lyase source. By using anion exchange chromatography coupled to nano LC MS/MS, we identified two distinct enzymes in this extract, one has both polyM and polyG (polyM/G) degradation activities and it is similar in sequence to a broad-spectrum alginate lyase from Flavobacterium sp. S20 (Alg2A). The other enzyme has only polyG activity and it is similar in sequence to AlyA1 from Zobellia galactanivorans. By characterizing both of these enzymes together with three recombinant alginate lyases (a polyM, a polyG and a polyM/G), we showed that only enzymes with polyM/G activity such as Alg2A and A1-II’ (alginate lyase from Sphingomonas sp.) are effective in dissolving biofilms. Furthermore, both activities are required to have a synergistic effect with antibiotics.
Reference Genes for Expression Studies in Human CD8+ Naïve and Effector Memory T Cells under Resting and Activating Conditions
Authors: Geigges Marco , Gubser Patrick M. , Unterstab Gunhild , Lecoultre Yannic , Paro Renato , Hess Christoph
Published: June 2020

Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) is widely used for mRNA quantification. To accurately measure changing gene transcript levels under different experimental conditions, the use of appropriate reference gene transcripts is instrumental. In T cell immunology, suitable reference genes have been reported for bulk CD4+ and CD8+ T cells. However, many CD4+ and CD8+ T cell subsets have been described in the past. Although they respond differently to given activation stimuli, proper validation of suitable reference genes in these subsets is lacking. In this study, we evaluated twelve commonly used reference gene products in human naïve (NV) and effector memory (EM) CD8+ T cells under non-activated and activated (2 h, 10 h and 20 h) conditions. We used five different statistical approaches for data analysis. Our results show that a number of widely used reference transcripts become differentially expressed under activating conditions. Using them as references markedly alters results as exemplified with IFNG mRNA expression. The only candidate reference gene products that remained stable during the activation process were 18S rRNA and SDHA mRNA, encouraging their usage as reference gene products for RT-qPCR experiments, when quantifying mRNA levels in human NV and EM CD8+ T cells.
Clinical Validation of Targeted and Untargeted Metabolomics Testing for Genetic Disorders: A 3 Year Comparative Study
Authors: Almontashiri Naif A. M. , Zha Li , Young Kim , Law Terence , Kellogg Mark D. , Bodamer Olaf A. , Peake Roy W. A.
Published: June 2020

Global untargeted metabolomics (GUM) has entered clinical diagnostics for genetic disorders. We compared the clinical utility of GUM with traditional targeted metabolomics (TM) as a screening tool in patients with established genetic disorders and determined the scope of GUM as a discovery tool in patients with no diagnosis under investigation. We compared TM and GUM data in 226 patients. The first cohort (n = 87) included patients with confirmed inborn errors of metabolism (IEM) and genetic syndromes; the second cohort (n = 139) included patients without diagnosis who were undergoing evaluation for a genetic disorder. In patients with known disorders (n = 87), GUM performed with a sensitivity of 86% (95% CI: 78–91) compared with TM for the detection of 51 diagnostic metabolites. The diagnostic yield of GUM in patients under evaluation with no established diagnosis (n = 139) was 0.7%. GUM successfully detected the majority of diagnostic compounds associated with known IEMs. The diagnostic yield of both targeted and untargeted metabolomics studies is low when assessing patients with non-specific, neurological phenotypes. GUM shows promise as a validation tool for variants of unknown significance in candidate genes in patients with non-specific phenotypes.
Nano-engineering the material structure of preferentially oriented nano-graphitic carbon for making high-performance electrochemical micro-sensors
Authors: Cuniberto Edoardo , Alharbi Abdullah , Wu Ting , Huang Zhujun , Sardashti Kasra , You Kae-Dyi , Kisslinger Kim , Taniguchi Takashi , Watanabe Kenji , Kiani Roozbeh , Shahrjerdi Davood
Published: June 2020

Direct synthesis of thin-film carbon nanomaterials on oxide-coated silicon substrates provides a viable pathway for building a dense array of miniaturized (micron-scale) electrochemical sensors with high performance. However, material synthesis generally involves many parameters, making material engineering based on trial and error highly inefficient. Here, we report a two-pronged strategy for producing engineered thin-film carbon nanomaterials that have a nano-graphitic structure. First, we introduce a variant of the metal-induced graphitization technique that generates micron-scale islands of nano-graphitic carbon materials directly on oxide-coated silicon substrates. A novel feature of our material synthesis is that, through substrate engineering, the orientation of graphitic planes within the film aligns preferentially with the silicon substrate. This feature allows us to use the Raman spectroscopy for quantifying structural properties of the sensor surface, where the electrochemical processes occur. Second, we find phenomenological models for predicting the amplitudes of the redox current and the sensor capacitance from the material structure, quantified by Raman. Our results indicate that the key to achieving high-performance micro-sensors from nano-graphitic carbon is to increase both the density of point defects and the size of the graphitic crystallites. Our study offers a viable strategy for building planar electrochemical micro-sensors with high-performance.
Activation of GPR35 protects against cerebral ischemia by recruiting monocyte-derived macrophages
Authors: Sharmin Ozayra , Abir Ariful Haque , Potol Abdullah , Alam Mahabub , Banik Jewel , Rahman A.F.M. Towheedur , Tarannum Nuzhat , Wadud Rasiqh , Habib Zaki Farhad , Rahman Mahbubur
Published: June 2020

Pamoic acid is a potent ligand for G protein Coupled Receptor 35 (GPR35) and exhibits antinociceptive property. GPR35 activation leads to increased energy utilization and the expression of anti-inflammatory genes. However, its role in brain disorders, especially in stroke, remains unexplored. Here we show in a mouse model of stroke that GPR35 activation by pamoic acid is neuroprotective. Pharmacological inhibition of GPR35 reveals that pamoic acid reduces infarcts size in a GPR35 dependent manner. The flowcytometric analysis shows the expression of GPR35 on the infiltrating monocytes/macrophages and neutrophils in the ischemic brain. Pamoic acid treatment results in a preferential increment of noninflammatory Ly-6CLo monocytes/macrophages in the ischemic brain along with the reduced neutrophil counts. The neuroprotective effect of GPR35 activation depends on protein kinase B (Akt) and p38 MAPK. Together we conclude that GPR35 activation by pamoic acid reprograms Ly-6CLo monocytes/macrophages to relay a neuroprotective signal into the ischemic brain.
Involvement of GLWamide neuropeptides in polyp contraction of the adult stony coral Euphyllia ancora
Authors: Shikina Shinya , Chiu Yi-Ling , Zhang Yan , Yi-ChenYao  , Liu Tai-Yu , Tsai Pin-Hsuan , Zatylny-Gaudin Céline , Chang Ching-Fong
Published: June 2020

The existence and function of neurons remain largely unexplored in scleractinian corals. To gain a better understanding of neuronal functions in coral physiology, this study focused on Glycine-Leucine-Tryptophan-amide family neuropeptides (GLWamides), which have been shown to induce muscle contraction and larval metamorphosis in other cnidarians. Molecular identification and functional characterization of GLWamides in the adult stony coral Euphyllia ancora were performed. We successfully elucidated the full-length cDNA of GLWamide preprohormone in E. ancora (named EaGLW preprohormone). The deduced amino acid sequence was predicted to contain six potential GLWamide peptides. Tissue distribution analysis demonstrated that transcripts of EaGLW preprohormone were mainly expressed in the mouth (including the pharynx) and tentacles of the polyps. Immunodetection with an anti-GLWamide monoclonal antibody revealed that GLWamide neurons were mainly distributed in the epidermis of the mouth region and tentacle, in agreement with the distribution patterns of the transcripts. Treatment of the isolated mouth and tentacles with synthetic GLWamide peptides induced the contraction of these isolated tissues. Treatment of polyps with synthetic GLWamide peptides induced the contraction of polyps. These results suggest that GLWamides are involved in polyp contraction (myoactivity) in adult scleractinians. Our data provide new information on the physiological function of neuropeptides in scleractinians.
Predictive Factors for Outcomes of Selective Laser Trabeculoplasty
Authors: Hirabayashi Matthew , Ponnusamy Vikram , An Jella
Published: June 2020

We sought to  determine predictive factors for selective laser trabeculoplasty (SLT) outcome. 252 eyes from 198 adult patients with open-angle glaucoma who underwent SLT between July 2016 and February 2018 with a minimum 6 month follow up were reviewed. We defined success as ≥20% IOP reduction or ≥1 medication reduction without an IOP lowering procedure. We also evaluated the relationship of these factors to postoperative IOP elevation >5 mmHg (IOP spikes). Our primary outcome measure was association between age, type and severity of glaucoma, pigmentation of the trabecular meshwork (PTM), total energy delivered, and baseline intraocular pressure (IOP) with success. At 2 and 6 months, 33.6% (76/226) and 38.5% (97/252) of eyes met success criteria respectively. Baseline IOP > 18 mmHg was significantly associated with success both at 2 and 6 months, reducing IOP by 5.4 ± 5.3 mmHg (23.7% reduction), whereas those with lower baseline remained at −0.7 ± 4.6 mmHg (4.9% increase) at 6 months (P < 0.001). No other baseline characteristics significantly predicted success or IOP spikes. Patients with higher baseline IOPs had greater success rates and mean IOP reduction at both 2 and 6 months following SLT. Age, type and severity of glaucoma, PTM, or total energy delivery had no association with procedural success or IOP spikes. Patients with higher baseline IOP may experience greater lowering of IOP after SLT. However, SLT may be equally successful for patients with a variety of other characteristics.
The surface plasmonic welding of silver nanowiresviaintense pulsed light irradiation combined with NIR for flexible transparent conductive films
Authors: Chung Wan-Ho , Jang Yong-Rae , Hwang Yeon-Taek , Kim Sang-Ho , Kim Hak-Sung
Published: June 2020

The surface plasmon welding of AgNWsviacombined intense pulsed light (IPL) irradiation was shown.
The effects of silk layer-by-layer surface modification on the mechanical and structural retention of extracellular matrix scaffolds
Authors: Bi Xuewei , Li Linhao , Mao Zhinan , Liu Bo , Yang Lingbing , He Wei , Fan Yubo , Li Xiaoming
Published: June 2020

The SF layer-by-layer surface functionalized SIS membrane exhibits tunable mechanical properties and degradation rate, satisfactory biocompatibility and good bioactivity.
Customized hydrogel substrates for serum-free expansion of functional hMSCs
Authors: Le Ngoc Nhi T. , Liu Tianran Leona , Johnston James , Krutty John D. , Templeton Kayla Marie , Harms Victoria , Dias Andrew , Le Hau , Gopalan Padma , Murphy William L.
Published: June 2020

Synthetic hydrogel arrays combined with a design of experiments approach identified hydrogel compositions for media-agnostic human mesenchymal stromal cell culture.
Novel ferrocenyl functionalised phosphinecarboxamides: synthesis, characterisation and coordination
Authors: Navrátil Michal , Faria Erica N. , Panahy Geve , Císařová Ivana , Goicoechea Jose M. , Štěpnička Petr
Published: June 2020

Ru(ii) and Rh(iii) complexes of the primary phosphinecarboxamide FcNHC(O)PH2 undergo facile dehydrohalogenation to produce phosphide-bridged dimers as syn and anti isomers.