bluuebunny/crossref_metadata_2025 huggingface dataset:
A mixed vertebrate eggshell assemblage from the Transylvanian Late Cretaceous
Authors: Fernández Mariela Soledad , Wang Xia , Vremir Mátyás , Laurent Chris , Naish Darren , Kaiser Gary , Dyke Gareth
Published: February 2019

A Late Cretaceous-aged multi-taxon nesting site from Romania preserved in three dimensions reveals the earliest example of nest site sharing yet known from the vertebrate fossil record. Eggshell and osteological evidence combined in this single accumulation demonstrate that at least four vertebrate taxa including enantiornithine birds and another avian of indeterminate affinities as well as crocodylomorphs and gekkotan squamates nested together in the same place. Colonial nesting in enantiornithines was previously described from this site; here, we present the first fossil evidence that other vertebrates also nested in the same place, perhaps exploiting the presence of the large bird colony. We describe four distinct eggshell morphotypes that have been collected from this site and draw palaeoecological inferences based on this unique multi-taxon nesting association.
Photo-polymerization as a new approach to fabricate the active layer of forward osmosis membrane
Authors: Pardeshi Pankaj M. , Mungray Alka A.
Published: February 2019

A novel approach is employed to prepare the active layer of the forward osmosis membrane by the photo-polymerization method. The poly (ethylene glycol) phenyl ether acrylate (PPEA) and methacrylic acid (MAA) are used as monomers. The emphasis is given to analysing the effect of monomer concentration on chemical functional groups of active layer, thermal stability, surface morphology, roughness, interfacial free energy, organic fouling tendency and osmotic flux performance. The functional groups of the active layer are characterized by ATR-FTIR. Furthermore, thermal analysis (TGA/DTG) is performed to calculate grafting density and thermal stability of prepared FO membranes. Surface morphology and roughness are characterized by atomic force microscopy (AFM). Unlike control polyamide active layer membrane that suffered from organic fouling (28.14 ± 3.70% flux decline and 95% flux recovery), the photo-polymerized 75/25 active layer FO membrane demonstrated the low fouling propensity (2.77 ± 0.62% flux decline) and high flux recovery (nearly ~100%). The interfacial free energy and low fouling property of 75/25 FO membrane is also reflected in improved osmotic flux performance with 11.20 ± 0.79 L/g (AL-FS) and 8.41 ± 0.22 L/g (AL-DS) reverse solute flux selectivity (RSFS) (Jw/Js) than control polyamide FO membrane (7.94 ± 0.22 L/g (AL-FS) and 7.64 ± 0.54 L/g (AL-DS)).
Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3′,5′-adenosine monophosphate (Epac) in murine skeletal muscle
Authors: Matthews Hugh R. , Tan Sapphire R. X. , Shoesmith Jonathan A. , Ahmad Shiraz , Valli Haseeb , Jeevaratnam Kamalan , Huang Christopher L.-H.
Published: February 2019

We investigated effects of pharmacological triggering of exchange protein directly activated by cyclic-3′,5′-adenosine monophosphate (Epac) on Nav1.4 currents from intact murine (C67BL6) skeletal muscle fibres for the first time. This employed a loose patch clamp technique which examined ionic currents in response to superimposed 10-ms V1 steps to varying degrees of depolarisation, followed by V2 steps to a fixed, +100 mV depolarisation relative to resting membrane potential following 40 mV hyperpolarising prepulses of 50 ms duration. The activation and inactivation properties of the resulting Na+ membrane current densities revealed reduced maximum currents and steepnesses in their voltage dependences after addition of the Epac activator 8-(4-chlorophenylthio)adenosine-3′,5′-cyclic monophosphate (1 µM) to the bathing Krebs-Henseleit solutions. Contrastingly, voltages at half-maximal current and timecourses of currents obtained in response to the V1 depolarising steps were unchanged. These effects were abolished by further addition of the RyR-inhibitor dantrolene (10 µM). In contrast, challenge by dantrolene alone left both currents and their parameters intact. These effects of Epac activation in inhibiting skeletal muscle, Nav1.4, currents, complement similar effects previously reported in the homologous Nav1.5 in murine cardiomyocytes. They are discussed in terms of a hypothesis implicating Epac actions in increasing RyR-mediated SR Ca2+ release resulting in a Ca2+-mediated inhibition of Nav1.4. The latter effect may form the basis for Ca2+-dependent Na+ channel dysregulation in SCN4A channelopathies associated with cold- and K+-aggravated myotonias.
Sex Difference in the Association between High-sensitivity C-reactive Protein and Depression: The 2016 Korea National Health and Nutrition Examination Survey
Authors: Lee San , Oh Sarah Soyeon , Jang Sung-In , Park Eun-Cheol
Published: February 2019

Elevated levels of circulating high-sensitivity C-reactive protein (hs-CRP) have been observed in depression, with the body mass index (BMI) being a major mediator of this association. However, the sex difference in the association between hs-CRP and depression remains unclear. This study aimed to investigate the sex difference in the association between hs-CRP and depression. Data from the 2016 Korea National Health and Nutritional Examination Survey were used for our study. High hs-CRP was defined as >3.0 mg/L, while depression was determined using a cut-off score of 10 in the Patient Health Questionnaire-9. The study population comprised 5,483 Korean adults. Men with high hs-CRP levels showed statistically higher prevalence of depression than those with low hs-CRP levels (8.90% vs. 3.65%, P < 0.0001). The high hs-CRP group was 1.86 times more likely to have depression after adjusting for BMI and other covariates in men (adjusted odds ratio: 1.86; 95% confidence interval: 1.07–3.25; P = 0.029). Meanwhile, no statistically significant association between hs-CRP and depression was found among women. Depression was considerably associated with hs-CRP only in men, indicating a biological difference between men and women that can independently modify the relationship between hs-CRP and depression.
Clinical Potential of a New Approach to MRI Acceleration
Authors: Dispenza Nadine L. , Littin Sebastian , Zaitsev Maxim , Constable R. Todd , Galiana Gigi
Published: February 2019

Fast ROtary Nonlinear Spatial ACquisition (FRONSAC) was recently introduced as a new strategy that applies nonlinear gradients as a small perturbation to improve image quality in highly undersampled MRI. In addition to experimentally showing the previously simulated improvement to image quality, this work introduces the insight that Cartesian-FRONSAC retains many desirable features of Cartesian imaging. Cartesian-FRONSAC preserves the existing linear gradient waveforms of the Cartesian sequence while adding oscillating nonlinear gradient waveforms. Experiments show that performance is essentially identical to Cartesian imaging in terms of (1) resilience to experimental imperfections, like timing errors or off-resonance spins, (2) accommodating scan geometry changes without the need for recalibration or additional field mapping, (3) contrast generation, as in turbo spin echo. Despite these similarities to Cartesian imaging, which provides poor parallel imaging performance, Cartesian-FRONSAC consistently shows reduced undersampling artifacts and better response to advanced reconstruction techniques. A final experiment shows that hardware requirements are also flexible. Cartesian-FRONSAC improves accelerated imaging while retaining the robustness and flexibility critical to real clinical use.
The Spatial Patterns of Red Beds and Danxia Landforms: Implication for the formation factors–China
Authors: Yan Luobin , Peng Hua , Zhang Shaoyun , Zhang Ruoxi , Kašanin-Grubin Milica , Lin Kairong , Tu Xinjun
Published: February 2019

This research examined the distribution features of red beds and 1,100 Danxia landform sites across China, while probing the relationship between these spatial patterns and geological elements. This study is based on geological and tectonic maps of China. ArcGIS software was used to process the adjacent index, then perform a spatial analysis of Danxia landforms and red beds, and a coupling analysis of Danxia landforms and red beds with tectonics. Based on a point pattern analysis of Danxia landforms, the adjacent index is 0.31, and the coefficient of variation verified by Thiessen polygon reaches 449%. These figures reflect the clustered distribution pattern of the Danxia landforms. Across the country, Danxia landforms are concentrated into three areas, namely, the Southeast China region, the Sichuan Basin region and the Qilian-Liupan region. The exposure of red beds covers 9.16 × 105 km2, which accounts for 9.5% of the total land area of China. With this research background, the geological elements of tectonics and their effects on the distribution, number, and spatial pattern of Danxia landforms and red beds were analyzed.
DRUGPATH – a novel bioinformatic approach identifies DNA-damage pathway as a regulator of size maintenance in human ESCs and iPSCs
Authors: Kovacic Boris , Rosner Margit , Schlangen Karin , Kramer Nina , Hengstschläger Markus
Published: February 2019

Genetic and biochemical screening approaches often fail to identify functionally relevant pathway networks because many signaling proteins contribute to multiple gene ontology pathways. We developed a DRUGPATH-approach to predict pathway-interactomes from high-content drug screen data. DRUGPATH is based upon combining z-scores of effective inhibitors with their corresponding and validated targets. We test DRUGPATH by comparing homeostatic pathways in human embryonic stem cells (hESCs), human induced pluripotent stem cells (hiPSCs) and human amniotic fluid stem cells (hAFSCs). We show that hAFSCs utilize distinct interactomes compared to hESCs/hiPSCs and that pathways orchestrating cell cycle and apoptosis are strongly interconnected, while pathways regulating survival and size are not. Interestingly, hESCs/hiPSCs regulate their size by growing exact additional sizes during each cell cycle. Chemical and genetic perturbation studies show that this “adder-model” is dependent on the DNA-damage pathway. In the future, the DRUGPATH-approach may help to predict novel pathway interactomes from high-content drug screens.
Biosynthetic investigation of γ-lactones in Sextonia rubra wood using in situ TOF-SIMS MS/MS imaging to localize and characterize biosynthetic intermediates
Authors: Fu Tingting , Houël Emeline , Amusant Nadine , Touboul David , Genta-Jouve Grégory , Della-Negra Serge , Fisher Gregory L. , Brunelle Alain , Duplais Christophe
Published: February 2019

Molecular analysis by parallel tandem mass spectrometry (MS/MS) imaging contributes to the in situ characterization of biosynthetic intermediates which is crucial for deciphering the metabolic pathways in living organisms. We report the first use of TOF-SIMS MS/MS imaging for the cellular localization and characterization of biosynthetic intermediates of bioactive γ-lactones rubrynolide and rubrenolide in the Amazonian tree Sextonia rubra (Lauraceae). Five γ-lactones, including previously reported rubrynolide and rubrenolide, were isolated using a conventional approach and their structural characterization and localization at a lateral resolution of ~400 nm was later achieved using TOF-SIMS MS/MS imaging analysis. 2D/3D MS imaging at subcellular level reveals that putative biosynthetic γ-lactones intermediates are localized in the same cell types (ray parenchyma cells and oil cells) as rubrynolide and rubrenolide. Consequently, a revised metabolic pathway of rubrynolide was proposed, which involves the reaction between 2-hydroxysuccinic acid and 3-oxotetradecanoic acid, contrary to previous studies suggesting a single polyketide precursor. Our results provide insights into plant metabolite production in wood tissues and, overall, demonstrate that combining high spatial resolution TOF-SIMS imaging and MS/MS structural characterization offers new opportunities for studying molecular and cellular biochemistry in plants.
Chronic sleep restriction in the rotenone Parkinson’s disease model in rats reveals peripheral early-phase biomarkers
Authors: Fagotti Juliane , Targa Adriano D. S. , Rodrigues Lais S. , Noseda Ana Carolina D. , Dorieux Flávia W. C. , Scarante Franciele F. , Ilkiw Jessica L. , Louzada Fernando M. , Chowdhury Namrata R. , van der Veen Daan R. , Middleton Benita , Pennings Jeroen L. A. , Swann Jonathan R. , Skene Debra J. , Lima Marcelo M. S.
Published: February 2019

Parkinson’s disease (PD) is a chronic disorder that presents a range of premotor signs, such as sleep disturbances and cognitive decline, which are key non-motor features of the disease. Increasing evidence of a possible association between sleep disruption and the neurodegenerative process suggests that sleep impairment could produce a detectable metabolic signature on the disease. In order to integrate neurocognitive and metabolic parameters, we performed untargeted and targeted metabolic profiling of the rotenone PD model in a chronic sleep restriction (SR) (6 h/day for 21 days) condition. We found that SR combined with PD altered several behavioural (reversal of locomotor activity impairment; cognitive impairment; delay of rest-activity rhythm) and metabolic parameters (branched-chain amino acids, tryptophan pathway, phenylalanine, and lipoproteins, pointing to mitochondrial impairment). If combined, our results bring a plethora of parameters that represents reliable early-phase PD biomarkers which can easily be measured and could be translated to human studies.
Fungal spore involvement in the resuspension of radiocaesium in summer
Authors: Igarashi Yasuhito , Kita Kazuyuki , Maki Teruya , Kinase Takeshi , Hayashi Naho , Hosaka Kentaro , Adachi Kouji , Kajino Mizuo , Ishizuka Masahide , Sekiyama Tsuyoshi Thomas , Zaizen Yuji , Takenaka Chisato , Ninomiya Kazuhiko , Okochi Hiroshi , Sorimachi Atsuyuki
Published: February 2019

We observed the atmospheric resuspension of radiocaesium, derived from the Fukushima Dai-ichi Nuclear Power Plant accident, at Namie, a heavily contaminated area of Fukushima, since 2012. During the survey periods from 2012 to 2015, the activity concentrations of radiocaesium in air ranged from approximately 10−5 to 10−2 Bq per m3 and were higher in the warm season than in the cold season. Electron microscopy showed that the particles collected on filters in summer were predominantly of biological origin (bioaerosols), with which the observed radiocaesium activity concentration varied. We conducted an additional aerosol analysis based on fluorescent optical microscopic observation and high-throughput DNA sequencing technique to identify bioaerosols at Namie in 2015 summer. The concentrations of bioaerosols fluctuated the order of 106 particles per m3, and the phyla Basidiomycota and Ascomycota (true Fungi) accounted for approximately two-thirds of the bioaerosols. Moreover, the fungal spore concentration in air was positively correlated with the radiocaesium concentration at Namie in summer 2016. The bioaerosol emissions from Japanese mixed forests in the temperate zone predominately included fungal cells, which are known to accumulate radiocaesium, and should be considered an important scientific issue that must be addressed.
Belief of agency changes dynamics in sensorimotor networks
Authors: Buchholz Verena N. , David Nicole , Sengelmann Malte , Engel Andreas K.
Published: February 2019

Controlling an event through one’s own action usually induces a sense of agency, a feeling that arises when an expected outcome matches the intention. The neural correlates of this feeling remain controversial however, as experimental manipulation of the action-outcome chain often introduces mismatch or prediction errors that strongly correlate with the sense of agency. Here, we took a different approach and manipulated the causal belief (self-attribution vs. computer-attribution) by external cues during matched visuo-motor tapping conditions. With magneto-encephalography, we studied the sense of agency from a network perspective, investigating in source space the modulation of local population activity and changes in functional connectivity with motor cortex. Our results show that during the belief of agency primary motor cortex (M1) shows stronger functional connectivity (mediated by the beta band) to inferior parietal lobe and right middle temporal gyrus (MTG). Furthermore, the local feed-forward activity (gamma band power) in extrastriate body area and MTG disappears with that belief. After changes in action context, left M1 shows stronger connectivity in the alpha band with right premotor cortex and left insular-temporal cortex a network that might support active inference in social action context. Finally, a better tapping performance in this rhythmic task was related to alpha power modulations in the bilateral cerebellum and bilateral fusiform body-area, with power suppression during a more precise performance. These findings highlight the role of multiple networks supporting the sense of agency by changing their relative contribution for different causal beliefs.
Antitumor potential of new low molecular weight antioxidative preparations from the white rot fungus Cerrena unicolor against human colon cancer cells
Authors: Matuszewska Anna , Stefaniuk Dawid , Jaszek Magdalena , Pięt Mateusz , Zając Adrian , Matuszewski Łukasz , Cios Iga , Grąz Marcin , Paduch Roman , Bancerz Renata
Published: February 2019

The aim of this study was to investigate the anticancer and antioxidant activities of low molecular weight subfractions isolated from secondary metabolites produced by the wood degrading fungus Cerrena unicolor. Human colon cancer cells (stage I) HT-29 and human normal colon epithelial cells CCD 841 CoTr were used in the research. The present study demonstrated that the low molecular weight subfractions exhibited inhibitory activity towards human colon cancer cells HT-29 at a concentration range of 25–200 μg/mL. All 6 subfractions inhibited proliferation of cells down to 47.5–9.2% at the highest concentrations in a dose-dependent manner. The most desired activity was exhibited by subfractions S, 3, 4, and 5, as the proliferation of HT-29 cells was inhibited to the greatest extent (16.5, 47.5, 42.7, and 26.1% of the control, respectively), while the effect on CCD 841 CoTr cells was the mildest (inhibition to 54.4, 71.4, 79.4, and 53.4%, compared to the control, respectively). The microscopic observation revealed that all extracts induced programmed cell death, i.e. apoptosis (up to 44.4% (subfraction 6) towards HT-29 and less than 20% (most fractions) towards CCD 841 CoTr), with no or a significantly low level of necrosis in both cell lines at the same time.
Spin-momentum locked spin manipulation in a two-dimensional Rashba system
Authors: Kohda Makoto , Okayasu Takanori , Nitta Junsaku
Published: February 2019

Spin-momentum locking, which constrains spin orientation perpendicular to electron momentum, is attracting considerable interest for exploring various spin functionalities in semiconductors and topological materials. Efficient spin generation and spin detection have been demonstrated using the induced helical spin texture. Nevertheless, spin manipulation by spin-momentum locking remains a missing piece because, once bias voltage is applied to induce the current flow, the spin orientation must be locked by the electron momentum direction, thereby rendering spin phase control difficult. Herein, we demonstrate the spin-momentum locking-induced spin manipulation for ballistic electrons in a strong Rashba two-dimensional system. Electron spin rotates in a circular orbital motion for ballistically moving electrons, although spin orientation is locked towards the spin-orbit field because of the helical spin texture. This fact demonstrates spin manipulation by control of the electron orbital motion and reveals potential effects of the orbital degree of freedom on the spin phase for future spintronic and topological devices and for the processing of quantum information.
Preparation of Glass-ceramics Using Chromium-containing Stainless Steel Slag: Crystal Structure and Solidification of Heavy Metal Chromium
Authors: OuYang ShunLi , Zhang YuXuan , Chen YuXin , Zhao ZengWu , Wen Ming , Li BaoWei , Shi Yu , Zhang MingZhe , Liu ShiLiang
Published: February 2019

It is a useful way to stabilize the elements of heavy metal in the glass-ceramics with the form of ions due to the environmental pollution of heavy metal, such as Cr. The glass-ceramics of excellent combination properties were prepared, and the effect of stabilizing Cr-containing stainless steel slag with different concentrations of nitric acid leaching test were investigated. It was found that the major crystalline phase was diopside or anorthite with or without the amount stainless steel slag. Moreover, the continuous refinement of grains exhibited with the increase of amount of stainless steel slag. The results indicated that the excellent physical and mechanical properties, including density (2.9 g/cm3), hardness (729.27HV0.3), bending strength (222.9 MPa), and the solid solution of Cr in excess of 0.00057% for the glass-ceramics were related to the change of microstructure and phase structure. There showed the potential for reusing and detoxifying stainless steel slag.
Field-Tunable 0-π-Transitions in SnTe Topological Crystalline Insulator SQUIDs
Authors: Schönle Joachim , Borisov Kiril , Klett Robin , Dyck Denis , Balestro Franck , Reiss Günter , Wernsdorfer Wolfgang
Published: February 2019

The manifestation of spin-orbit interactions, long known to dramatically affect the band structure of heavy-element compounds, governs the physics in the surging class of topological matter. A particular example is found in the new family of topological crystalline insulators. In this systems transport occurs at the surfaces and spin-momentum locking yields crystal-symmetry protected spin-polarized transport. We investigated the current-phase relation of SnTe thin films connected to superconducting electrodes to form SQUID devices. Our results demonstrate that an assisting in-plane magnetic field component can induce 0-π-transitions. We attribute these findings to giant g-factors and large spin-orbit coupling of SnTe topological crystalline insulator, which provides a new platform for investigation of the interplay between spin-orbit physics and topological transport.
Effects of green seaweed extract on Arabidopsis early development suggest roles for hormone signalling in plant responses to algal fertilisers
Authors: Ghaderiardakani Fatemeh , Collas Ellen , Damiano Deborah Kohn , Tagg Katherine , Graham Neil S. , Coates Juliet C.
Published: February 2019

The growing population requires sustainable, environmentally-friendly crops. The plant growth-enhancing properties of algal extracts have suggested their use as biofertilisers. The mechanism(s) by which algal extracts affect plant growth are unknown. We examined the effects of extracts from the common green seaweed Ulva intestinalis on germination and root development in the model land plant Arabidopsis thaliana. Ulva extract concentrations above 0.1% inhibited Arabidopsis germination and root growth. Ulva extract <0.1% stimulated root growth. All concentrations of Ulva extract inhibited lateral root formation. An abscisic-acid-insensitive mutant, abi1, showed altered sensitivity to germination- and root growth-inhibition. Ethylene- and cytokinin-insensitive mutants were partly insensitive to germination-inhibition. This suggests that different mechanisms mediate each effect of Ulva extract on early Arabidopsis development and that multiple hormones contribute to germination-inhibition. Elemental analysis showed that Ulva contains high levels of Aluminium ions (Al3+). Ethylene and cytokinin have been suggested to function in Al3+-mediated root growth inhibition: our data suggest that if Ulva Al3+ levels inhibit root growth, this is via a novel mechanism. We suggest algal extracts should be used cautiously as fertilisers, as the inhibitory effects on early development may outweigh any benefits if the concentration of extract is too high.
New microhylid frog genus from Peninsular India with Southeast Asian affinity suggests multiple Cenozoic biotic exchanges between India and Eurasia
Authors: Garg Sonali , Biju S. D.
Published: February 2019

Anurans in Peninsular India exhibit close biogeographical links with Gondwana as well as Laurasia, often explainable by the geological history of the Indian subcontinent; its breakup from Gondwanan landmasses followed by long isolation that resulted in diversification of endemic lineages, and subsequent land connections with Asia that enabled dispersal of widespread groups. Although widely distributed, the frog subfamily Microhylinae mostly comprises of geographically restricted genera found either in Southeast and East Asia or Peninsular India and Sri Lanka. Here we report a previously unknown microhylid from the Western Ghats in Peninsular India with closest relatives found over 2,000 km away in Southeast Asia. Based on integrated evidence from mitochondrial and nuclear DNA, adult and tadpole morphology, hand musculature, male advertisement call, and geographical distance, we recognize this enigmatic frog as a distinct new species and genus endemic to the Western Ghats. The discovery ofMysticellus frankigen. et sp. nov. and its close evolutionary relationship with the Southeast Asian genusMicrylettaalso provide insights on the biogeography of Microhylinae. Genus-level divergences within the subfamily suggest multiple Cenozoic biotic exchange events between India and Eurasia, particularly through postulated Eocene land bridges via Southeast Asia prior to accretion of the two landmasses.
Effect of Age, High-Fat Diet, and Rat Strain on Serum Biomarkers and Telomere Length and Global DNA Methylation in Peripheral Blood Mononuclear Cells
Authors: Antonini James M. , Kodali Vamsi , Meighan Terence G. , Roach Katherine A. , Roberts Jenny R. , Salmen Rebecca , Boyce Greg R. , Zeidler-Erdely Patti C. , Kashon Michael , Erdely Aaron , Shoeb Mohammad
Published: February 2019

The objective of the current study was to determine if age, diet, and genetic disposition (animal strain) in an animal model had early effects on specific molecular markers in circulating peripheral blood mononuclear cells (PBMCs). Three strains [Sprague-Dawley (SD), Fischer 344 (F344), and Brown-Norway (BN)] of male rats were maintained on a high-fat (HF) or regular diet. Blood was collected at 4, 12, and 24 wk to assess chemistry and to recover PBMCs. Triglycerides and body weight gain increased at all time points in the HF diet group for each strain. Telomere length in PBMCs decreased in the HF diet group compared to the regular diet group up to 24 wk in all strains. Telomere length decreased in PBMCs at 24 wk compared to baseline in all strains, indicating an age-related effect. These findings highlight that diet and age cause changes in PBMCs recovered from different strains of rats. The next tier of studies will examine the contribution of an occupational exposure (e.g., welding fume inhalation) in combination with diet, age, and strain, to assess changes in the molecular responses of isolated PBMCs. In addition, studies involving lifestyle exposure (e.g., tobacco smoke) are in the planning stages and will assess the long-term effects of exposure in our animal model.
Immunofluorescence Tomography: High-resolution 3-D reconstruction by serial-sectioning of methacrylate embedded tissues and alignment of 2-D immunofluorescence images
Authors: Parfitt Geraint J.
Published: February 2019

Immunofluorescence tomography is a high-resolution 3-D reconstruction method based on methacrylate embedding and serial-sectioning, where 2-D images of immuno-stained serial-sections are computationally aligned into image stacks, and the 3-D volume rendered. Butyl-Methyl Methacrylate (BMMA) plastic was adopted as it preserves excellent tissue morphology and can be de-plasticized easily using an organic solvent, which enables immuno-staining of serial-sections without antibody penetration issues over millimeters of 3-D reconstructed tissue (Z-depth). High axial Z-resolution over a large volume was achieved by cutting serial-sections at 2 µm thickness. Stained sections were imaged by multiple modalities, including immunofluorescence, electron microscopy and second harmonic generation (SHG), and there are advantages over confocal microscopy as the tissue does not need to be cleared, while antibody penetration or light scattering issues are minimized. The plastic serial-sections can be re-probed, without a loss in tissue structure, using low pH glycine hydrochloride antibody elution. It is a cost-effective approach as the microscopes needed are significantly cheaper than confocal microscopes and sections can be kept indefinitely. Therefore, immunofluorescence tomography is a powerful new tool to quantify sub-populations of cells in high-resolution 3-D using antibody fluorescence. This article describes the immunofluorescence tomography method for 3-D reconstruction of epithelial tissues such as mammary gland, cornea and the hair follicle.
A novel luciferase-based assay for the detection of Chimeric Antigen Receptors
Authors: Gopalakrishnan Ramakrishnan , Matta Hittu , Choi Sunju , Natarajan Venkatesh , Prins Ruben , Gong Songjie , Zenunovic Arta , Narasappa Nell , Patel Fatima , Prakash Rekha , Chaudhary Vishan , Sikri Varun , Chitnis Saurabh Deepak , Kochegarov Andrei , Wang Dan , Falat Magdalena , Kahn Michael , Keerthipati Pooja Smruthi , Sharma Naman , Lenka Jyotirmayee , Stieben Tomas Meza , Braun Jason , Batra Ankita , Purvis Katelyn , Ito Kenta , Lee Jae Han , Jeronimo Alberto , Zamora Hannalei Mae , Membreno Allen , Qiu Queenie , Peshin Supriya , Namburu Lalith , Chaudhary Preet M.
Published: February 2019

Chimeric Antigen Receptor-T (CAR-T) cell immunotherapy has produced dramatic responses in hematologic malignancies. One of the challenges in the field is the lack of a simple assay for the detection of CARs on the surface of immune effector cells. In this study, we describe a novel luciferase-based assay, termed Topanga Assay, for the detection of CAR expression. The assay utilizes a recombinant fusion protein, called Topanga reagent, generated by joining the extra-cellular domain of a CAR-target in frame with one of the marine luciferases or their engineered derivatives. The assay involves incubation of CAR expressing cells with the Topanga reagent, a few washes and measurement of luminescence. The assay can detect CARs comprising either immunoglobulin- or non-immunoglobulin-based antigen binding domains. We further demonstrate that addition of epitope tags to the Topanga reagent not only allows its convenient one step purification but also extends its use for detection of CAR cells using flow cytometry. However, crude supernatant containing the secreted Topanga reagent can be directly used in both luminescence and flow-cytometry based assays without prior protein purification. Our results demonstrate that the Topanga assay is a highly sensitive, specific, convenient, economical and versatile assay for the detection of CARs.
Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation
Authors: Suleiman Said , Klassen Sergej , Katz Ira , Balakirski Galina , Krabbe Julia , von Stillfried Saskia , Kintsler Svetlana , Braunschweig Till , Babendreyer Aaron , Spillner Jan , Kalverkamp Sebastian , Schröder Thomas , Moeller Manfred , Coburn Mark , Uhlig Stefan , Martin Christian , Rieg Annette D.
Published: February 2019

Argon exerts neuroprotection. Thus, it might improve patients’ neurological outcome after cerebral disorders or cardiopulmonary resuscitation. However, limited data are available concerning its effect on pulmonary vessel and airways. We used rat isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of rats and humans to assess this topic. IPL: Airway and perfusion parameters, oedema formation and the pulmonary capillary pressure (Pcap) were measured and the precapillary and postcapillary resistance (Rpost) was calculated. In IPLs and PCLS, the pulmonary vessel tone was enhanced with ET-1 or remained unchanged. IPLs were ventilated and PCLS were gassed with argon-mixture or room-air. IPL: Argon reduced the ET-1-induced increase of Pcap, Rpost and oedema formation (p < 0.05). PCLS (rat): Argon relaxed naïve pulmonary arteries (PAs) (p < 0.05). PCLS (rat/human): Argon attenuated the ET-1-induced contraction in PAs (p < 0.05). Inhibition of GABAB-receptors abolished argon-induced relaxation (p < 0.05) in naïve or ET-1-pre-contracted PAs; whereas inhibition of GABAA-receptors only affected ET-1-pre-contracted PAs (p < 0.01). GABAA/B-receptor agonists attenuated ET-1-induced contraction in PAs and baclofen (GABAB-agonist) even in pulmonary veins (p < 0.001). PLCS (rat): Argon did not affect the airways. Finally, argon decreases the pulmonary vessel tone by activation of GABA-receptors. Hence, argon might be applicable in patients with pulmonary hypertension and right ventricular failure.
The potential role of temperate Japanese regions as refugia for the coral Acropora hyacinthus in the face of climate change
Authors: Nakabayashi Aki , Yamakita Takehisa , Nakamura Takashi , Aizawa Hiroaki , Kitano Yuko F , Iguchi Akira , Yamano Hiroya , Nagai Satoshi , Agostini Sylvain , Teshima Kosuke M. , Yasuda Nina
Published: February 2019

As corals in tropical regions are threatened by increasing water temperatures, poleward range expansion of reef-building corals has been observed, and temperate regions are expected to serve as refugia in the face of climate change. To elucidate the important indicators of the sustainability of coral populations, we examined the genetic diversity and connectivity of the common reef-building coral Acropora hyacinthus along the Kuroshio Current, including recently expanded (<50 years) populations. Among the three cryptic lineages found, only one was distributed in temperate regions, which could indicate the presence of Kuroshio-associated larval dispersal barriers between temperate and subtropical regions, as shown by oceanographic simulations as well as differences in environmental factors. The level of genetic diversity gradually decreased towards the edge of the species distribution. This study provides an example of the reduced genetic diversity in recently expanded marginal populations, thus indicating the possible vulnerability of these populations to environmental changes. This finding underpins the importance of assessing the genetic diversity of newly colonized populations associated with climate change for conservation purposes. In addition, this study highlights the importance of pre-existing temperate regions as coral refugia, which has been rather underappreciated in local coastal management.
Tuning carrier concentration in a superacid treated MoS2 monolayer
Authors: Molas Maciej R. , Gołasa Katarzyna , Bala Łukasz , Nogajewski Karol , Bartos Miroslav , Potemski Marek , Babiński Adam
Published: February 2019

The effect of bis(trifluoromethane) sulfonimide (TFSI, superacid) treatment on the optical properties of MoS2 monolayers is investigated by means of photoluminescence, reflectance contrast and Raman scattering spectroscopy employed in a broad temperature range. It is shown that when applied multiple times, the treatment results in progressive quenching of the trion emission/absorption and in the redshift of the neutral exciton emission/absorption associated with both the A and B excitonic resonances. Based on this evolution, a trion complex related to the B exciton in monolayer MoS2 is unambiguously identified. A defect-related emission observed at low temperatures also disappears from the spectrum as a result of the treatment. Our observations are attributed to effective passivation of defects on the MoS2 monolayer surface. The passivation reduces the carrier density, which in turn affects the out-of-plane electric field in the sample. The observed tuning of the carrier concentration strongly influences also the Raman scattering in the MoS2 monolayer. An enhancement of Raman scattering at resonant excitation in the vicinity of the A neutral exciton is clearly seen for both the out-of-plane A′1 and in-plane E′ modes. On the contrary, when the excitation is in resonance with a corresponding trion, the Raman scattering features become hardly visible. These results confirm the role of the excitonic charge state plays in the resonance effect of the excitation energy on the Raman scattering in transition metal dichalcogenides.
Oman coral δ18O seawater record suggests that Western Indian Ocean upwelling uncouples from the Indian Ocean Dipole during the global-warming hiatus
Authors: Watanabe Takaaki K. , Watanabe Tsuyoshi , Yamazaki Atsuko , Pfeiffer Miriam , Claereboudt Michel R.
Published: February 2019

The Indian Ocean Dipole (IOD) is an interannual mode of climate variability in the Indian Ocean that has intensified with 20th century global-warming. However, instrumental data shows a global-warming hiatus between the late-1990s and 2015. It is presently not clear how the global-warming hiatus affects modes of climate variability such as the IOD, and their basin-wide ocean-atmosphere teleconnections. Here, we present a 26-year long, biweekly record of Sr/Ca and δ18O from a Porites coral drilled in the Gulf of Oman. Sea surface temperature (SSTanom) is calculated from Sr/Ca ratios, and seawater δ18O (δ18Osw-anom) is estimated by subtracting the temperature component from coral δ18O. Our δ18Osw-anom record reveals a significant regime shift in 1999, towards lower mean δ18Osw values, reflecting intensified upwelling in the western Indian Ocean. Prior to the 1999 regime shift, our SSTanom and δ18Osw-anom show a clear IOD signature, with higher values in the summer of positive-IOD years due to weakened upwelling. The IOD signature in SSTanom and δ18Osw-anom disappears with the overall intensification of upwelling after the 1999 regime shift. The inferred increase in upwelling is likely driven by an intensified Walker circulation during the global-warming hiatus. Upwelling in the Western Indian Ocean uncouples from the IOD.
Label-free and Non-destruction Determination of Single- and Double-Strand DNA based on Quantum Weak Measurement
Authors: Guan Tian , Yang Yuxuan , Zhang Qianwen , He Yonghong , Xu Naihan , Li Dongmei , Shi Lixuan , Xu Yang , Wang Xiangnan
Published: February 2019

The process of unwinding and renaturation of DNA has been widely used in studies of nucleotide sequence organization. Compared with traditional methods for DNA unwinding and renaturation, the label-free and non-destruction detection technology is significant and desiderated. We realized an optical system based on optical rotation via weak measurement for detection of single- and double-strand state of DNA. The optical rotation, which was induced by the status change of single and double DNA strands, was exploited to modulate the preselected polarization of a weak measurement system. With this modulation, the optical rotation caused by the separation of DNA strands can be determined through the center wavelength shift of the output spectrum. By monitoring the wavelength shift in real time, the separation processes of the DNAs with different base ratio (25% and 70%) and length (4nt and 40nt), and DNAs with three terminally modified cholesterol molecules were experimentally explored in varied pH and temperature conditions. In addition, the detection limit of the DNA concentration was obtained to be 5 × 10−6 mol/L. Our work based on optical rotation detection of single- and double-strand DNA exhibits the unique advantages of real-time monitoring, label-free, non-destruction and simplicity.
Shallow magma pre-charge during repeated Plinian eruptions at Sakurajima volcano
Authors: Araya Naoki , Nakamura Michihiko , Yasuda Atsushi , Okumura Satoshi , Sato Tomoki , Iguchi Masato , Miki Daisuke , Geshi Nobuo
Published: February 2019

Vigorous explosive eruptions that produce continuous high eruption plumes (Plinian eruptions) are generally assumed to tap a magma reservoir. The 1914 Plinian eruption at the Sakurajima volcano located on the Aira caldera rim is one such case, where the main magma reservoir was assumed to be located approximately 10 km beneath the caldera. However, we report that estimated magma storage depths immediately prior to the eruption were much shallower (0.9–3.2 km) on the basis of pressure at which volatiles within the phenocryst melt inclusions and plagioclase rims were finally equilibrated. The same is observed for two historic Plinian eruptions in 1471 and 1779. This depth is even shallower than the shallowest magma reservoir estimated from the pressure source for geodetic deformation during recent Vulcanian explosions (4 km beneath the crater). We propose that the magmas were fed from a thick conduit pre-charged from deeper reservoirs. The ground subsidence observed after 1914 within the Aira caldera may have been caused by conduit recharge following the eruption. Voluminous conduit recharge could be key to forecasting the next possible large eruption at the Sakurajima volcano.
Diattenuation Imaging reveals different brain tissue properties
Authors: Menzel Miriam , Axer Markus , Amunts Katrin , De Raedt Hans , Michielsen Kristel
Published: February 2019

When transmitting polarised light through histological brain sections, different types of diattenuation (polarisation-dependent attenuation of light) can be observed: In some brain regions, the light is minimally attenuated when it is polarised parallel to the nerve fibres (referred to as D+), in others, it is maximally attenuated (referred to as D−). The underlying mechanisms of these effects and their relationship to tissue properties were so far unknown. Here, we demonstrate in experimental studies that diattenuation of both types D+ and D− can be observed in brain tissue samples from different species (rodent, monkey, and human) and that the strength and type of diattenuation depend on the nerve fibre orientations. By combining finite-difference time-domain simulations and analytical modelling, we explain the observed diattenuation effects and show that they are caused both by anisotropic absorption (dichroism) and by anisotropic light scattering. Our studies demonstrate that the diattenuation signal depends not only on the nerve fibre orientations but also on other brain tissue properties like tissue homogeneity, fibre size, and myelin sheath thickness. This allows to use the diattenuation signal to distinguish between brain regions with different tissue properties and establishes Diattenuation Imaging as a valuable imaging technique.
Cassowary casques act as thermal windows
Authors: Eastick Danielle L. , Tattersall Glenn J. , Watson Simon J. , Lesku John A. , Robert Kylie A.
Published: February 2019

Many ideas have been put forward for the adaptive value of the cassowary casque; and yet, its purpose remains speculative. Homeothermic animals elevate body temperature through metabolic heat production. Heat gain must be offset by heat loss to maintain internal temperatures within a range for optimal performance. Living in a tropical climate, cassowaries, being large bodied, dark feathered birds, are under thermal pressure to offload heat. We tested the original hypothesis that the casque acts as a thermal window. With infrared thermographic analyses of living cassowaries over an expansive range of ambient temperatures, we provide evidence that the casque acts as a thermal radiator, offloading heat at high temperatures and restricting heat loss at low temperatures. Interestingly, at intermediate temperatures, the casque appears thermally heterogeneous, with the posterior of the casque heating up before the front half. These findings might have implications for the function of similar structures in avian and non-avian dinosaurs.
Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development
Authors: Cullen Harriet , Krishnan Michelle L. , Selzam Saskia , Ball Gareth , Visconti Alessia , Saxena Alka , Counsell Serena J. , Hajnal Jo , Breen Gerome , Plomin Robert , Edwards A. David
Published: February 2019

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (β = −0.24, p = 8 × 10−4) and a European subsample (β = −0.24, p = 8 × 10−3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.
Conservation implications of turtle declines in Australia’s Murray River system
Authors: Van Dyke J. U. , Spencer R. –J. , Thompson M. B. , Chessman B. , Howard K. , Georges A.
Published: February 2019

Conservation requires rapid action to be effective, which is often difficult because of funding limitations, political constraints, and limited data. Turtles are among the world’s most endangered vertebrate taxa, with almost half of 356 species threatened with extinction. In Australia’s Murray River, nest predation by invasive foxes (Vulpes vulpes) was predicted to drive turtle declines in the 1980s. We assessed populations of the broad-shelled turtle (Chelodina expansa), eastern long-necked turtle (C. longicollis), and Murray River turtle (Emydura macquarii) in the Murray River and some of its associated waterways. Our results suggest that the predicted decline is occurring. All three species are rare in the lower Murray River region, and were undetected in many locations in South Australia. Moreover,E. macquariihad considerable population aging almost everywhere, possibly due to comprehensive nest destruction by foxes.Chelodina longicollisalso had population aging at some sites. Sustained low recruitment has potential to lead to collapses as turtles age, which is particularly worrying because it was predicted over 30 years ago and may have already occurred in South Australia. Our results show that turtle declines were not mitigated since that prediction. If the crash continues, a vertebrate guild responsible for considerable nutrient cycling in the aquatic ecosystem will disappear. Our results highlight a worst-case outcome when species declines are predicted, but insufficiently mitigated.
Tuning octahedral tilts and the polar nature ofA-site deficient perovskites
Authors: Beqiri Dashnor , Cascos Vanessa , Roberts-Watts Jennie , Clark Ewan R. , Bousquet Eric , Bristowe Nicholas C. , McCabe Emma E.
Published: February 2019

This work explores the possibility of tuning the structural chemistry ofA-site deficient perovskite materialsLn1/3NbO3, and the balance between proper and hybrid-improper mechanisms for polar behaviour in these systems.
Interconversion of hydrated protons at the interface between liquid water and platinum
Authors: Rice Peter S. , Mao Yu , Guo Chenxi , Hu P.
Published: February 2019

The free energy barriers for hydrogen transfer at the H2O/Pt(111) interface calculated usingab initiomolecular dynamics and umbrella sampling.