bluuebunny/crossref_metadata_2025 huggingface dataset:
Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors
Authors: Ralvenius William T. , Neumann Elena , Pagani Martina , Acuña Mario A. , Wildner Hendrik , Benke Dietmar , Fischer Nina , Rostaher Ana , Schwager Simon , Detmar Michael , Frauenknecht Katrin , Aguzzi Adriano , Hubbs Jed Lee , Rudolph Uwe , Favrot Claude , Zeilhofer Hanns Ulrich
Published: August 2018

Chronic itch is a highly debilitating condition affecting about 10% of the general population. The relay of itch signals is under tight control by inhibitory circuits of the spinal dorsal horn, which may offer a hitherto unexploited therapeutic opportunity. Here, we found that specific pharmacological targeting of inhibitory α2 and α3GABAA receptors reduces acute histaminergic and non-histaminergic itch in mice. Systemic treatment with an α2/α3GABAA receptor selective modulator alleviates also chronic itch in a mouse model of atopic dermatitis and in dogs sensitized to house dust mites, without inducing sedation, motor dysfunction, or loss of antipruritic activity after prolonged treatment. Transsynaptic circuit tracing, immunofluorescence, and electrophysiological experiments identify spinal α2 and α3GABAA receptors as likely molecular targets underlying the antipruritic effect. Our results indicate that drugs targeting α2 and α3GABAA receptors are well-suited to alleviate itch, including non-histaminergic chronic itch for which currently no approved treatment exists.
Freeze-on limits bed strength beneath sliding glaciers
Authors: Meyer Colin R. , Downey Anthony S. , Rempel Alan W.
Published: August 2018

Discharge from sliding outlet glaciers controls uncertainty in projections for future sea level. Remarkably, over 90% of glacial area is subject to gravitational driving stresses below 150 kPa (median ∼70 kPa). Longstanding explanations that appeal to the shear-thinning rheology of ice tend to overpredict driving stresses and are restricted to areas where ice sheets only deform (roughly 50%). Over the more dynamic portions that slide, driving stresses must be balanced by thermo-mechanical interactions that control basal strength. Here we show that median bed strength is comparable to a threshold effective stress set by ice–liquid surface energy and till pore size. Above this threshold, ice infiltrates sediment to produce basal layers of debris-rich ice, even where net melting takes place. We demonstrate that the narrow range of inferred bed strengths can be explained by the mechanical resistance to sliding where roughness is enhanced by heterogeneous freeze-on.
Investigation of the mechanism of chromium removal in (3-aminopropyl)trimethoxysilane functionalized mesoporous silica
Authors: Lee JinHyeong , Kim Jae-Hyun , Choi Keunsu , Kim Hee-Gon , Park Jeong-Ann , Cho So-Hye , Hong Seok Won , Lee Jung-Hyun , Lee Jun Hee , Lee Soonjae , Lee Seung Yong , Choi Jae-Woo
Published: August 2018

We are proposed that a possible mechanism for Cr(VI) removal by functionalized mesoporous silica. Mesoporous silica was functionalized with (3-aminopropyl)trimethoxysilane (APTMS) using the post-synthesis grafting method. The synthesized materials were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), N2 adsorption-desorption analysis, Fourier-transform infrared (FT-IR), thermogravimetric analyses (TGA), and X-ray photoelectron spectroscopy (XPS) to confirm the pore structure and functionalization of amine groups, and were subsequently used as adsorbents for the removal of Cr(VI) from aqueous solution. As the concentration of APTMS increases from 0.01 M to 0.25 M, the surface area of mesoporous silica decreases from 857.9 m2/g to 402.6 m2/g. In contrast, Cr(VI) uptake increases from 36.95 mg/g to 83.50 mg/g. This indicates that the enhanced Cr(VI) removal was primarily due to the activity of functional groups. It is thought that the optimum concentration of APTMS for functionalization is approximately 0.05 M. According to XPS data, NH3+ and protonated NH2 from APTMS adsorbed anionic Cr(VI) by electrostatic interaction and changed the solution pH. Equilibrium data are well fitted by Temkin and Sips isotherms. This research shows promising results for the application of amino functionalized mesoporous silica as an adsorbent to removal Cr(VI) from aqueous solution.
Length-scale dependency of biomimetic hard-soft composites
Authors: Mirzaali M. J. , Edens M. E. , de la Nava A. Herranz , Janbaz S. , Vena P. , Doubrovski E. L. , Zadpoor A. A.
Published: August 2018

Biomimetic composites are usually made by combining hard and soft phases using, for example, multi-material additive manufacturing (AM). Like other fabrication methods, AM techniques are limited by the resolution of the device, hence, setting a minimum length scale. The effects of this length scale on the performance of hard-soft composites are not well understood. Here, we studied how this length scale affects the fracture toughness behavior of single-edge notched specimens made using random, semi-random, and ordered arrangements of the hard and soft phases with five different ratios of hard to soft phases. Increase in the length scale (40 to 960 μm) was found to cause a four-fold drop in the fracture toughness. The effects of the length scale were also modulated by the arrangement and volumetric ratio of both phases. A decreased size of the crack tip plastic zone, a crack path going through the soft phase, and highly strained areas far from the crack tip were the main mechanisms explaining the drop of the fracture toughness with the length scale.
Late Palaeolithic cave art and permafrost in the Southern Ural
Authors: Dublyansky Yuri , Moseley Gina E. , Lyakhnitsky Yuri , Cheng Hai , Edwards Lawrence R. , Scholz Denis , Koltai Gabriella , Spötl Christoph
Published: August 2018

Shulgan-Tash (also known as Kapova) cave located on the western slope of the Ural Mountains (Russia) is the easternmost European cave art monument of late Palaeolithic age. Radiocarbon dates from cultural layers in the cave suggest an age of about 16.3 to 19.6 ka (cal BP), but dates directly on the paintings were not obtained. In order to constrain the age of this art using an independent method, we performed detailed 230Th-U dating of calcite flowstone underlying and overgrowing the paintings at 22 sites in three halls of the cave. The youngest age for the underlying calcite (i.e., the maximum age of the cave art) is 36.4 ± 0.1 ka, and the oldest overlying calcite (constraining the minimum age of the cave art) is 14.5 ± 0.04 ka. The ca. 21.9 ka-long hiatus in calcite deposition during which the paintings were made is attributed to regional permafrost conditions and sub-zero temperatures inside the cave during Marine Isotope Stage (MIS) 2. This is supported by samples of cryogenic cave calcite, which document seven episodes of freezing and thawing of permafrost associated with stadials and interstadials of MIS 3, respectively.
i-GONAD (improved genome-editing via oviductal nucleic acids delivery), a convenient in vivo tool to produce genome-edited rats
Authors: Takabayashi Shuji , Aoshima Takuya , Kabashima Katsuya , Aoto Kazushi , Ohtsuka Masato , Sato Masahiro
Published: August 2018

Zygote-microinjection or in vitro electroporation of isolated zygotes are now widely used methods to produce genome-edited mice. However, these technologies require laborious and time-consuming ex vivo handling of fertilized eggs, including zygote isolation, gene delivery into zygotes and embryo transfer into recipients. We recently developed an alternative method called improved genome-editing via oviductal nucleic acids delivery (i-GONAD), which does not require the above-mentioned ex vivo handing of zygotes, but instead involves intraoviductal instillation of genome-editing components, Cas9 protein and synthetic gRNAs, into the oviducts of pregnant females at the late 1-cell embryo stage under a dissecting microscope and subsequent electroporation. With this method, we succeeded in generating genome-edited mice at relatively high efficiencies (for example, knockout alleles were produced at ~97% efficiency). Here, we extended this improved technology to rats, and found that i-GONAD can create genome-edited rats in various strains, including Sprague Dawley and Lewis, and F1 hybrids (between Sprague Dawley and Brown Norway), with efficiencies of ~62% for indel mutations and ~9% for knock-ins. Thus, i-GONAD will be especially useful for the production of genome-edited rats in small laboratories where expensive micromanipulator systems and highly skilled personnel for embryo manipulation are unavailable.
Extensive genomic diversity among Mycobacterium marinum strains revealed by whole genome sequencing
Authors: Das Sarbashis , Pettersson B. M. Fredrik , Behra Phani Rama Krishna , Mallick Amrita , Cheramie Martin , Ramesh Malavika , Shirreff Lisa , DuCote Tanner , Dasgupta Santanu , Ennis Don G. , Kirsebom Leif. A.
Published: August 2018

Mycobacterium marinum is the causative agent for the tuberculosis-like disease mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its geographical distribution, M. marinum is known to occupy diverse fish as hosts. However, information about its genomic diversity is limited. Here, we provide the genome sequences for 15 M. marinum strains isolated from infected humans and fish. Comparative genomic analysis of these and four available genomes of the M. marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the strains, leading to the conclusion that M. marinum should be divided into two different clusters, the “M”- and the “Aronson”-type. We suggest that these two clusters should be considered to represent two M. marinum subspecies. Our data also show that the M. marinum pan-genome for both groups is open and expanding and we provide data showing high number of mutational hotspots in M. marinum relative to other mycobacteria such as Mycobacterium tuberculosis. This high genomic diversity might be related to the ability of M. marinum to occupy different ecological niches.
The role of Chinese Milk Vetch as cover crop in complex soil nitrogen dynamics in rice rotation system of South China
Authors: Xie Zhijian , Zhou Chunhuo , Shah Farooq , Iqbal Amjad , Ni GuoRong
Published: August 2018

The effect of Chinese Milk Vetch (CMV) residues as a cover crop on the performance of rice plants and nitrogen mobilization and mineralization in paddy soil was evaluated in a pot-culture experiment. Three treatments were included in the trial, i.e. without exogenous-N (Control or CK), urea fertilizer as the sole N-source (N) and urea plus CMV (NM). The results revealed higher amounts of total-N, inorganic-N, acid hydrolysable-N and non-acid hydrolysable-N in the soil under NM, followed by N and CK treatments at tillering, booting and maturity stages of rice. A similar trend was observed for various soil ammonia oxidizing bacteria, aerobic and anaerobic bacteria. Correlation coefficients exhibited a negative correlation of residual exogenous-15N with only amino acid nitrogen (P < 0.01). Moreover, low abundance of the key functional gene amoA in rice was found in CK treatment. From the results it can be concluded that the nitrogen from organic source can improve the availability of total-N, inorganic-N and NH4 in the soil, especially at the later stages of rice growth.
Groundwater depletion causing reduction of baseflow triggering Ganges river summer drying
Authors: Mukherjee Abhijit , Bhanja Soumendra Nath , Wada Yoshihide
Published: August 2018

In summer (pre-monsoon) of recent years, low water level among the last few decades, has been observed in several lower Indian reaches of the Ganges (or Ganga) river (with estimated river water level depletion rates at the range of −0.5 to −38.1 cm/year between summers of 1999 and 2013 in the studied reaches). Here, we show this Ganges river depletion is related to groundwater baseflow reduction caused by ongoing observed groundwater storage depletion in the adjoining Gangetic aquifers (Ganges basin, −0.30 ± 0.07 cm/year or −2.39 ± 0.56 km3/year). Our estimates show, 2016-baseflow amount (~1.0 × 106 m3/d) has reduced by ~59%, from the beginning of the irrigation-pumping age of 1970s (2.4 × 106 m3/d) in some of the lower reaches. The net Ganges river water reduction could jeopardize domestic water supply, irrigation water requirements, river transport, ecology etc. of densely populated northern Indian plains. River water reduction has direct impact on food production indicating vulnerability to more than 100 million of the population residing in the region. The results of this study could be used to decipher the groundwater-linked river water depletion as well as the regional water security in other densely populated parts of the globe.
Fragile aspects of topological transition in lossy and parity-time symmetric quantum walks
Authors: Harter Andrew K. , Saxena Avadh , Joglekar Yogesh N.
Published: August 2018

Quantum walks often provide telling insights about the structure of the system on which they are performed. In $${\mathscr{P}}{\mathscr{T}}$$
P
T
-symmetric and lossy dimer lattices, the topological properties of the band structure manifest themselves in the quantization of the mean displacement of such a walker. We investigate the fragile aspects of a topological transition in these two dimer models. We find that the transition is sensitive to the initial state of the walker on the Bloch sphere, and the resultant mean displacement has a robust topological component and a quasiclassical component. In $${\mathscr{P}}{\mathscr{T}}$$
P
T
symmetric dimer lattices, we also show that the transition is smeared by nonlinear effects that become important in the $${\mathscr{P}}{\mathscr{T}}$$
P
T
-symmetry broken region. By carrying out consistency checks via analytical calculations, tight-binding results, and beam-propagation-method simulations, we show that our predictions are easily testable in today’s experimental systems.
Quantitative phase imaging unravels new insight into dynamics of mesenchymal and amoeboid cancer cell invasion
Authors: Tolde Ondřej , Gandalovičová Aneta , Křížová Aneta , Veselý Pavel , Chmelík Radim , Rosel Daniel , Brábek Jan
Published: August 2018

Observation and analysis of cancer cell behaviour in 3D environment is essential for full understanding of the mechanisms of cancer cell invasion. However, label-free imaging of live cells in 3D conditions is optically more challenging than in 2D. Quantitative phase imaging provided by coherence controlled holographic microscopy produces images with enhanced information compared to ordinary light microscopy and, due to inherent coherence gate effect, enables observation of live cancer cells’ activity even in scattering milieu such as the 3D collagen matrix. Exploiting the dynamic phase differences method, we for the first time describe dynamics of differences in cell mass distribution in 3D migrating mesenchymal and amoeboid cancer cells, and also demonstrate that certain features are shared by both invasion modes. We found that amoeboid fibrosarcoma cells’ membrane blebbing is enhanced upon constriction and is also occasionally present in mesenchymally invading cells around constricted nuclei. Further, we demonstrate that both leading protrusions and leading pseudopods of invading fibrosarcoma cells are defined by higher cell mass density. In addition, we directly document bundling of collagen fibres by protrusions of mesenchymal fibrosarcoma cells. Thus, such a non-invasive microscopy offers a novel insight into cellular events during 3D invasion.
Fire-induced structural changes and long-term stability of burned historical rag papers
Authors: Ahn Kyujin , Schedl Andreas , Zweckmair Thomas , Rosenau Thomas , Potthast Antje
Published: August 2018

When a fire strikes libraries or archives, physical deterioration of the paper is so severe that its chemical properties are often regarded as less important. However, knowledge of the chemical changes of the papers upon nearly burning is necessary to design a subsequent conservation treatment. In the present study, we have examined a rag paper object, which partially survived a fire, and analysed its chemical properties by various methods. The polymeric state of cellulose, as well as its low-molar mass degradation products, were assessed. Comparison to an identical, unharmed duplicate provided a more profound understanding of the changes caused by the fire. Light scattering analysis revealed conformational changes of the cellulose molecule after high-temperature impact, and a chemical cross-linking was observed. In our study, we found the integrity of cellulose to depend on the temperature profile induced by the fire. The low thermal conductivity of cellulose protects the material even in close proximity to the burned edges.
Effect of dual task on gait asymmetry in patients after anterior cruciate ligament reconstruction
Authors: Shi Huijuan , Huang Hongshi , Yu Yuanyuan , Liang Zixuan , Zhang Si , Yu Bing , Liu Hui , Ao Yingfang
Published: August 2018

Individuals who received anterior cruciate ligament (ACL) reconstruction surgeries demonstrated lower extremity movement asymmetries. The purpose of this study was to determine if psychological impairment was a contributor to lower extremity movement asymmetries in walking for individuals who received ACL reconstruction surgeries. Three-dimensional videographic and force plate data were collected for 25 males after unilateral ACL reconstruction performing walking without (single-task condition) and with the concurrent cognitive task (dual-task condition). Both uninjured and injured legs had significantly smaller peak knee flexion angle and peak knee extension moment during loading response and mid-stance phases in dual-task condition compared to single task condition (P ≤ 0.012). Walking condition and leg had significant interaction effects on peak hip adduction angle during mid-stance phase (P = 0.042) and peak hip abduction moment during loading response phase (P = 0.048). The inter-leg difference of peak hip adduction angle during mid-stance (P = 0.038) and terminal stance (P = 0.036) phases, and peak hip abduction moment during loading response phase (P = 0.024) were significantly decreased in dual-task condition compared to single-task condition. Psychological factors have significant effects on post-operative movements of both injured and uninjured knees of individuals who received ACL reconstruction surgery. Although physical factors may be primary contributors to the post-operative lower extremity movement asymmetries, psychological factors also contribute to the post-operative hip movement asymmetries.
A multi-state model of chemoresistance to characterize phenotypic dynamics in breast cancer
Authors: Howard Grant R. , Johnson Kaitlyn E. , Rodriguez Ayala Areli , Yankeelov Thomas E. , Brock Amy
Published: August 2018

The development of resistance to chemotherapy is a major cause of treatment failure in breast cancer. While mathematical models describing the dynamics of resistant cancer cell subpopulations have been proposed, experimental validation has been difficult due to the complex nature of resistance that limits the ability of a single phenotypic marker to sufficiently identify the drug resistant subpopulations. We address this problem with a coupled experimental/modeling approach to reveal the composition of drug resistant subpopulations changing in time following drug exposure. We calibrate time-resolved drug sensitivity assays to three mathematical models to interrogate the models’ ability to capture drug response dynamics. The Akaike information criterion was employed to evaluate the three models, and it identified a multi-state model incorporating the role of population heterogeneity and cellular plasticity as the optimal model. To validate the model’s ability to identify subpopulation composition, we mixed different proportions of wild-type MCF-7 and MCF-7/ADR resistant cells and evaluated the corresponding model output. Our blinded two-state model was able to estimate the proportions of cell types with an R-squared value of 0.857. To the best of our knowledge, this is the first work to combine experimental time-resolved drug sensitivity data with a mathematical model of resistance development.
Effective soil erosion control represents a significant net carbon sequestration
Authors: Ran Lishan , Lu Xixi , Fang Nufang , Yang Xiankun
Published: August 2018

The debate over whether soil erosion is a carbon (C) sink or atmospheric CO2 source remains highly controversial. For the first time, we report the magnitude of C stabilization associated with soil erosion control for an entire large river basin. The soil erosion of the Yellow River basin in northern China is among the most severe worldwide. Progressive soil conservation has been implemented by the Chinese government since the 1970s, including the largest ever revegetation programme, the Grain-for-Green Project, which began in 1999. Based on compiled hydrological records and organic carbon (OC) data, together with primary production estimates, we evaluated the sequestered OC resulting from soil conservation. Compared with that at baseline in 1950–1970, in which significant soil conservation did not occur, the fate of erosion-induced OC was substantially altered in the period from 2000–2015. Approximately 20.6 Tg of OC were effectively controlled per year by soil conservation efforts. Simultaneously, the decomposition of erosion-induced soil organic carbon (SOC) declined from 8 Tg C yr−1 to current 5.3 Tg C yr−1. The reduced C emissions (2.7 Tg C yr−1) within the Yellow River basin alone account for 12.7% of the mean C accumulation acquired via forest expansion throughout all of China previously assessed. If the accumulated C in restored plants and soils was included, then 9.7 Tg C yr−1 was reduced from the atmospheric C pool during this period, which represents a tremendous C-capturing benefit. Thus, the increased C storage obtained via soil conservation should be considered in future C inventories.
Highly efficient capture of cancer cells expressing EGFR by microfluidic methods based on antigen-antibody association
Authors: Ohnaga Takashi , Takei Yoshinori , Nagata Takuya , Shimada Yutaka
Published: August 2018

Epidermal growth factor receptor (EGFR) was evaluated as a target antigen for cancer cell capture by microfluidic methods based on antigen-antibody association. A polymer CTC-chip microfluidic device was surface-functionalized with three different anti-EGFR antibodies and used to capture EGFR-expressing cancer cells. Capture efficacy depended on the type of antibody used, and cetuximab efficiently captured cancer cell lines that had a wide range of EGFR expression. Capture efficiency was analyzed from the viewpoint of antigen-antibody association in a kinetic process, i.e., cell rolling well-known in leukocyte adhesion, and antibodies with a smaller dissociation constant were shown to result in more efficient capture. Moreover, a lower limit of cellular EGFR expression level for the capture was estimated and methods to decrease the limit were discussed based on densities of anti-EGFR antibody on the device surface.
Optimising complementary soft tissue synchrotron X-ray microtomography for reversibly-stained central nervous system samples
Authors: Strotton Merrick C. , Bodey Andrew J. , Wanelik Kazimir , Darrow Michele C. , Medina Esau , Hobbs Carl , Rau Christoph , Bradbury Elizabeth J.
Published: August 2018

Synchrotron radiation microtomography (SRμCT) is a nominally non-destructive 3D imaging technique which can visualise the internal structures of whole soft tissues. As a multi-stage technique, the cumulative benefits of optimising sample preparation, scanning parameters and signal processing can improve SRμCT imaging efficiency, image quality, accuracy and ultimately, data utility. By evaluating different sample preparations (embedding media, tissue stains), imaging (projection number, propagation distance) and reconstruction (artefact correction, phase retrieval) parameters, a novel methodology (combining reversible iodine stain, wax embedding and inline phase contrast) was optimised for fast (~12 minutes), high-resolution (3.2–4.8 μm diameter capillaries resolved) imaging of the full diameter of a 3.5 mm length of rat spinal cord. White-grey matter macro-features and micro-features such as motoneurons and capillary-level vasculature could then be completely segmented from the imaged volume for analysis through the shallow machine learning SuRVoS Workbench. Imaged spinal cord tissue was preserved for subsequent histology, establishing a complementary SRμCT methodology that can be applied to study spinal cord pathologies or other nervous system tissues such as ganglia, nerves and brain. Further, our ‘single-scan iterative downsampling’ approach and side-by-side comparisons of mounting options, sample stains and phase contrast parameters should inform efficient, effective future soft tissue SRμCT experiment design.
Social support rescues acute stress-induced cognitive impairments by modulating ERK1/2 phosphorylation in adolescent mice
Authors: Kim Ji-Woon , Ko Mee Jung , Gonzales Edson Luck , Kang Ri Jin , Kim Do Gyeong , Kim Yujeong , Seung Hana , Oh Hyun A , Eun Pyeong Hwa , Shin Chan Young
Published: August 2018

Social support can relieve stress-induced behavioural outcomes, although its underlying molecular mechanisms are not fully understood. Here, we evaluated whether social interactions can prevent the restraint stress (RS)-induced cognitive impairments in male adolescent mice by utilizing molecular, cellular, and behavioural approaches. Acute RS in adolescent ICR mice impaired the working memory in the Y-maze test and memory consolidation and retrieval in the novel-object-recognition test (NORT). In addition, RS increased the extracellular signal-regulated kinases 1/2 phosphorylation (p-ERK1/2) in the prefrontal cortex (PFC) and corticosterone levels in the plasma. Interestingly, these outcomes were normalized by the presence of a conspecific animal (social support) during RS. RS also significantly upregulated the expression levels of known stress-relevant genes such as Egr1, Crh, and Crhr1, which were normalized by social support. Systemic injection of SL327 (an inhibitor of MEK1/2 that also blocks its downstream signal ERK1/2) prior to RS rescued the working memory impairments and the increased p-ERK1/2 while normalizing the expression of Egr1. Our results suggest that social support can alleviate the RS-induced cognitive impairments partly by modulating ERK1/2 phosphorylation and gene transcription in the PFC, and provide novel insights into the molecular mechanisms of the stress-buffering effects of social support.
Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer
Authors: Szaryńska Magdalena , Olejniczak Agata , Kobiela Jarosław , Łaski Dariusz , Śledziński Zbigniew , Kmieć Zbigniew
Published: August 2018

The therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines. We found that the detailed configuration of CSC-like markers significantly influenced the maturation and activation of DCs after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented the opposite impact on treated DCs as showed by many significant correlations. The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in tumor sample the lower number of activated DCs evidenced after stimulation. Moreover, our results showed superiority of the spherical culture model over the adherent one since spherical HCT116 and HT29 cells presented similar influence on DCs properties as CRC patients cancer cells. We concluded that the DCs features may depend directly on the properties of CSCs affected by progression status of tumor.
Automated Gleason grading of prostate cancer tissue microarrays via deep learning
Authors: Arvaniti Eirini , Fricker Kim S. , Moret Michael , Rupp Niels , Hermanns Thomas , Fankhauser Christian , Wey Norbert , Wild Peter J. , Rüschoff Jan H. , Claassen Manfred
Published: August 2018

The Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations. In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa = 0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort. Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Cardiomyocytes Derived from Human CardiopoieticAmniotic Fluids
Authors: Di Baldassarre Angela , D’Amico Maria A , Izzicupo Pascal , Gaggi Giulia , Guarnieri Simone , Mariggiò Maria A , Antonucci Ivana , Corneo Barbara , Sirabella Dario , Stuppia Liborio , Ghinassi Barbara
Published: August 2018

Human amniotic fluid (hAF) cells share characteristics of both embryonic and adult stem cells. They proliferate rapidly and can differentiate into cells of all embryonic germ layers but do not form teratomas. Embryoid-bodies obtained from hAF have cardiac differentiation potential, but terminal differentiation to cardiomyocytes (CMs) has not yet been described. Our purpose was to promote cardiac differentiation in hAFcells. Cells were exposed to inducing factors for up to 15 days. Only the subset of hAF cells expressing the multipotency markers SSEA4, OCT4 and CD90 (CardiopoieticAF cells) responded to the differentiation process by increasing the expression of the cardiac transcription factors Nkx2.5 and GATA4, sarcomeric proteins (cTnT, α-MHC, α-SA), Connexin43 and atrial and ventricular markers. Furthermore, differentiated cells were positive for the calcium pumps CACNA1C and SERCA2a, with approximately 30% of CardiopoieticAF-derived CM-like cells responding to caffeine or adrenergic stimulation. Some spontaneous rare beating foci were also observed. In conclusion, we demonstrated that CardiopoieticAF cells might differentiate toward the cardiac lineage giving rise to CM-like cells characterized by several cardiac-specific molecular, structural, and functional properties.
Highly-stable write-once-read-many-times switching behaviors of 1D–1R memristive devices based on graphene quantum dot nanocomposites
Authors: Sung Sihyun , Wu Chaoxing , Jung Hyun Soo , Kim Tae Whan
Published: August 2018

One diode and one resistor (1D–1R) memristive devices based on inorganic Schottky diodes and poly(methylsilsesquioxane) (PMSSQ):graphene quantum dot (GQD) hybrid nanocomposites were fabricated to achieve stable memory characteristics. Current-voltage (I-V) curves for the Al/PMSSQ:GQDs/Al/p-Si/Al devices at room temperature exhibited write-once, read-many-times memory (WORM) characteristics with an ON/OFF ratio of as large as 104 resulting from the formation of a 1D–1R structure. I-V characteristics of the WORM 1D–1R device demonstrated that the memory and the diode behaviors of the 1D–1R device functioned simultaneously. The retention time of the WORM 1D–1R devices could be maintained at a value larger than 104 s under ambient conditions. The operating mechanisms of the devices were analyzed on the basis of the I–V results and with the aid of the energy band diagram.
Distribution of oxidized DJ-1 in Parkinson’s disease-related sites in the brain and in the peripheral tissues: effects of aging and a neurotoxin
Authors: Mita Yuichiro , Kataoka Yuto , Saito Yoshiro , Kashi Takuma , Hayashi Kojiro , Iwasaki Asa , Imanishi Takanori , Miyasaka Tomohiro , Noguchi Noriko
Published: August 2018

DJ-1 plays an important role in antioxidant defenses, and a reactive cysteine at position 106 (Cys106) of DJ-1, a critical residue of its biological function, is oxidized under oxidative stress. DJ-1 oxidation has been reported in patients with Parkinson’s disease (PD), but the relationship between DJ-1 oxidation and PD is still unclear. In the present study using specific antibody for Cys106-oxidized DJ-1 (oxDJ-1), we analyzed oxDJ-1 levels in the brain and peripheral tissues in young and aged mice and in a mouse model of PD induced using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). OxDJ-1 levels in the brain, heart, and skeletal muscle were high compared with other tissues. In the brain, oxDJ-1 was detected in PD-related brain sites such as the substantia nigra (SN) of the midbrain, olfactory bulb (OB), and striatum. In aged wild-type mice, oxDJ-1 levels in the OB, striatum, and heart tended to decrease, while those in the skeletal muscle increased significantly. Expression of dopamine-metabolizing enzymes significantly increased in the SN and OB of aged DJ-1−/− mice, accompanied by a complementary increase in glutathione peroxidase 1. MPTP treatment concordantly changed oxDJ-1 levels in PD-related brain sites and heart. These results indicate that the effects of physiological metabolism, aging, and neurotoxin change oxDJ-1 levels in PD-related brain sites, heart, and skeletal muscle where mitochondrial load is high, suggesting a substantial role of DJ-1 in antioxidant defenses and/or dopamine metabolism in these tissues.
Delay-Induced Multistability and Loop Formation in Neuronal Networks with Spike-Timing-Dependent Plasticity
Authors: Madadi Asl Mojtaba , Valizadeh Alireza , Tass Peter A.
Published: August 2018

Spike-timing-dependent plasticity (STDP) adjusts synaptic strengths according to the precise timing of pre- and postsynaptic spike pairs. Theoretical and computational studies have revealed that STDP may contribute to the emergence of a variety of structural and dynamical states in plastic neuronal populations. In this manuscript, we show that by incorporating dendritic and axonal propagation delays in recurrent networks of oscillatory neurons, the asymptotic connectivity displays multistability, where different structures emerge depending on the initial distribution of the synaptic strengths. In particular, we show that the standard deviation of the initial distribution of synaptic weights, besides its mean, determines the main properties of the emergent structural connectivity such as the mean final synaptic weight, the number of two-neuron loops and the symmetry of the final structure. We also show that the firing rates of the neurons affect the evolution of the network, and a more symmetric configuration of the synapses emerges at higher firing rates. We justify the network results based on a two-neuron framework and show how the results translate to large recurrent networks.
DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function
Authors: Somogyvári Milán , Gecse Eszter , Sőti Csaba
Published: August 2018

The FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity.
Assessment of physical inactivity and locomotor dysfunction in adults with visual impairment
Authors: Inoue Sachiko , Kawashima Motoko , Hiratsuka Yoshimune , Nakano Tadashi , Tamura Hiroshi , Ono Koichi , Murakami Akira , Tsubota Kazuo , Yamada Masakazu
Published: August 2018

To evaluate the association between vision-related quality of life (QoL), physical inactivity, and locomotor dysfunction in subjects with visual impairment.This cross-sectional study included 215 visually impaired subjects recruited from six ophthalmology departments in Japan. The physical inactivity and locomotor dysfunction associated with their visual impairment was investigated. The physical activity level was assessed using the short form of the International Physical Activity Questionnaire and classified as high, moderate, or low. Locomotor function was evaluated with the Geriatric Locomotive Function Scale. Vision-related QoL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire. Background data, including for age, sex, best-corrected visual acuity for each eye, causative eye diseases, systemic comorbidities, and body mass index, were also collected.The average patient age was 69.6 (range, 20–93 years; standard deviation, 14.5 years) and 118 patients (54.9%) were men. Multivariate analysis showed that vision-related QoL and best-corrected visual acuity in the worse eye were significantly associated with physical inactivity and that vision-related QoL, female sex, age, and presence of systemic comorbidity were significantly associated with locomotor dysfunction. Vision-related quality of life is associated with physical inactivity and locomotor dysfunction.
Floral evolution by simplification in Monanthotaxis (Annonaceae) and hypotheses for pollination system shifts
Authors: Hoekstra Paul H. , Wieringa Jan J. , Smets Erik , Chatrou Lars W.
Published: August 2018

Simplification by reduction has occurred many times independently in the floral evolution of angiosperms. These reductions have often been attributed to changes in reproductive biology. In the angiosperm plant family Annonaceae, most species have flowers with six petals, and many stamens and carpels. In the genus Monanthotaxis several deviations from this pattern have been observed, including flowers that contain three petals and three stamens only. New DNA sequences were generated for 42 specimens of Monanthotaxis. Five chloroplast markers and two nuclear markers for 72 out of 94 species of Monanthotaxis were used to reconstruct a phylogeny of the genus, which revealed several well-supported, morphologically distinct clades. The evolution of four quantitative and two qualitative floral characters was mapped onto this phylogeny, demonstrating a reduction in flower size and number of flower parts in Monanthotaxis. A large variation in stamen forms and numbers, strong correlations between petal size, stamen and carpel number, combined with a non-gradual mode of evolution and the sympatric co-occurrence of Monanthotaxis species from different clades suggest that the high diversity in the African rainforest of this genus is caused by switches in pollination systems.
Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
Authors: Umbarawan Yogi , Syamsunarno Mas Rizky A. A. , Koitabashi Norimichi , Obinata Hideru , Yamaguchi Aiko , Hanaoka Hirofumi , Hishiki Takako , Hayakawa Noriyo , Sano Motoaki , Sunaga Hiroaki , Matsui Hiroki , Tsushima Yoshito , Suematsu Makoto , Kurabayashi Masahiko , Iso Tatsuya
Published: August 2018

The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy.
High Sensitivity and Selectivity of AsP Sensor in Detecting SF6 Decomposition Gases
Authors: Jin Wang , Guofeng Yang , Junjun Xue , Jianming Lei , Qing Cai , Dunjun Chen , Hai Lu , Rong Zhang , Youdou Zheng
Published: August 2018

The sensing properties of monolayer arsenic phosphorus (AsP) for the adsorption of SF6, H2O, O2, and SF6 decomposition gases (SO2 and H2S) are theoretically investigated by the first-principle calculations. We calculate the adsorption energy, equilibrium distance, Mulliken charge transfer, and electron localization function (ELF) to explore whether AsP is suitable for detecting SF6 decomposition gases. By comparing the adsorption performance of SF6, H2O, O2, and H2S gases, we have revealed that the SO2 gas molecules could form stable chemisorption with AsP monolayer. The results demonstrate that AsP is highly sensitive and selective to SO2 gas molecules with robust adsorption energy and apparent charge transfer. Furthermore, the current-voltage (I–V) curves reveal that only the adsorption of SO2 can largely modify the resistance of AsP. Our results show that gas sensors based on AsP monolayer could be better than that of black phosphorene (BP) to diagnose the state of online gas-insulated switchgear (GIS).
Visible-light driven catalase-like activity of blackberry-shaped {Mo72Fe30} nanovesicles: combined kinetic and mechanistic studies
Authors: Mokhtari Rezvan , Rezaeifard Abdolreza , Jafarpour Maasoumeh , Farrokhi Alireza
Published: August 2018

Catalase-like activity of blackberry-shaped {Mo72Fe30} nanovesicles was exploited in aqueous solution under visible-light irradiation.
Synthesis of vanadium phosphorus oxide catalysts promoted by iron-based ionic liquids and their catalytic performance in selective oxidation ofn-butane
Authors: Dai Fei , Li Zihang , Chen Xuejing , He Bin , Liu Ruixia , Zhang Suojiang
Published: August 2018

Catalytic performance of undoped and Fe-doped VPO catalysts.
The chameleonic reactivity of dilithio bis(alkylamido)cyclodiphosph(iii)azanes with chlorophosphines
Authors: Otang Mathew E. , Josephson David , Duppong Todd , Stahl Lothar
Published: August 2018

Analogous reactions do not necessarily give analogous products.
Ligand and solvent control of selectivity in the C–H activation of a pyridylimine-substituted 1-naphthalene; a combined synthetic and computational study
Authors: Simayi Rena , Gillbard Simone M. , Cross Warren B. , Hope Eric G. , Singh Kuldip , Solan Gregory A.
Published: August 2018

The site-selectivity of C–H activation in a 1-substituted naphthalene is explored using palladium(ii) chloride salts; the experimental findings are fully supported by DFT calculations.
Single gold bipyramids on a silanized substrate as robust plasmonic sensors for liquid environments
Authors: Rye Jan-Michael , Bonnet Christophe , Lerouge Frédéric , Pellarin Michel , Lermé Jean , Parola Stéphane , Cottancin Emmanuel
Published: August 2018

Samples of silanized bipyramids are investigated as single scale plasmonic sensors in various liquid environments and during several months.
Anomalous isoelectronic chalcogen rejection in 2D anisotropic vdW TiS3(1−x)Se3x trichalcogenides
Authors: Agarwal Ashutosh , Qin Ying , Chen Bin , Blei Mark , Wu Kedi , Liu Lei , Shen Yuxia , Wright David , Green Matthew D. , Zhuang Houlong , Tongay Sefaattin
Published: August 2018

Alloying in 2D trichalcogenide TiSSe shows unusual isoelectronic doping rejection.
High temperature thermally conductive nanocomposite textile by “green” electrospinning
Authors: Wang Jiemin , Li Quanxiang , Liu Dan , Chen Cheng , Chen Zhiqiang , Hao Jian , Li Yinwei , Zhang Jin , Naebe Minoo , Lei Weiwei
Published: August 2018

Recently, thermally regulating textiles have attracted wide interest owing to their ability to realize personal cooling and provide thermal comfort.
Sandwich type polyoxometalates encapsulated into the mesoporous material: synthesis, characterization and catalytic application in the selective oxidation of sulfides
Authors: Naseri Elham , Khoshnavazi Roushan
Published: August 2018

The A-type sandwich POMs of [(HOSnIVOH)3(PW9O34)2]12–(P2W18Sn3) and [(OCeIVO)3(PW9O34)2]12–(P2W18Ce3) were immobilized for the first time into the porous MIL-101 MOF. Their catalytic activities were examined in the oxidation of sulfides to sulfones at room temperature.
Bioinspired hybrid eumelanin–TiO2antimicrobial nanostructures: the key role of organo–inorganic frameworks in tuning eumelanin's biocide action mechanism through membrane interaction
Authors: Vitiello Giuseppe , Zanfardino Anna , Tammaro Olimpia , Di Napoli Michela , Caso Maria Federica , Pezzella Alessandro , Varcamonti Mario , Silvestri Brigida , D'Errico Gerardino , Costantini Aniello , Luciani Giuseppina
Published: August 2018

Hybrid TiO2/eumelanin nanostructures showed a peculiar biocide mechanism against Gram(−) bacteria, based on the ROS action, produced by eumelanin degradation under visible light irradiation, and the interactions with external bacterial membranes.
The ameliorating effect of the combined extract from GreekThymus vulgarisand bee's honey on the hydrocortisone-induced osteoporosis in rat bone cellsviamodulating the bone turnover, oxidative stress, and inflammation
Authors: Abu-Serie Marwa M. , Habashy Noha H.
Published: August 2018

Many of the functional foods are designed to decrease the risk of chronic diseases like osteoporosis (OP) which is the most common bone disorder affecting millions of people.
Characterization of single-stranded DNA-binding protein SsbB fromStaphylococcus aureus: SsbB cannot stimulate PriA helicase
Authors: Chen Kuan-Lin , Cheng Jen-Hao , Lin Chih-Yang , Huang Yen-Hua , Huang Cheng-Yang
Published: August 2018

Single-stranded DNA-binding proteins (SSBs) are essential to cells as they participate in DNA metabolic processes, such as DNA replication, repair, and recombination.