bluuebunny/crossref_metadata_2025 huggingface dataset:
pyPhotometry: Open source Python based hardware and software for fiber photometry data acquisition
Authors: Akam Thomas , Walton Mark E.
Published: March 2019

Fiber photometry is the process of recording bulk neural activity by measuring fluorescence changes in activity sensitive indicators such as GCaMP through an optical fiber. We present a system of open source hardware and software for fiber photometry data acquisition consisting of a compact, low cost, data acquisition board built around the Micropython microcontroller, and a cross platform graphical user interface (GUI) for controlling acquisition and visualising signals. The system can acquire two analog and two digital signals, and control two external LEDs via built in LED drivers. Time-division multiplexed illumination allows independent readout of fluorescence evoked by different excitation wavelengths from a single photoreceiver signal. Validation experiments indicate this approach offers better signal to noise for a given average excitation light intensity than sinusoidally-modulated illumination. pyPhotometry is substantially cheaper than commercial hardware filling the same role, and we anticipate, as an open source and comparatively simple tool, it will be easily adaptable and therefore of broad interest to a wide range of users.
Acute kidney injury in cancer patients: A nationwide survey in China
Authors: Jin Juan , Wang Yafang , Shen Quanquan , Gong Jianguang , Zhao Li , He Qiang
Published: March 2019

Cancer patients have a high risk for acute kidney injury (AKI); however, the incidence, severity, and risk factors of malignancy-related AKI (MR-AKI) are unclear. This study aimed to assess MR-AKI risk factors and provide reliable data for AKI prevention, diagnosis, and management in China. This cross-sectional study analysed data from 44 academic and local hospitals in China. AKI patients were identified based on 2 screening criteria: the 2012 Kidney Disease: Improving Global Outcomes-AKI definition and the expanded screening criteria for patients with no repeated serum creatinine (SCr) test within 7 days and those who recovered from AKI. Patients whose SCr level increased or decreased by 50% during hospitalization, compared with that at admission, were considered to have AKI according to the expanded criteria. A total of 7,604 AKI patients were enrolled (1,418 with MR-AKI). Patient characteristics were compared between the MR-AKI and non-MR-AKI groups. Multivariate logistic models were used to statistically assess risk factors. The proportions of MR-AKI patients in academic and local hospitals were 20.2% and 14.1%, respectively. The incidence of MR-AKI was higher in mid-China (the affluent region), elderly patients, and groups with higher per capita gross domestic product. Among MR-AKI cases, gastrointestinal cancer (50.1%) was the most common malignancy, followed by cancers of the reproductive (15.3%), haematological (13.1%), respiratory (11.8%), and other systems (8.3%), and cancers of unknown classification (1.4%). Of 268 hospital deaths, respiratory, haematological, gastrointestinal, reproductive, other system, and unknown classification cancers accounted for 29.3%, 18.8%, 18.6%, 12.9%, 16.9%, and 20.0%, respectively. Increased age, advanced AKI stage at peak, level of per capita gross domestic product, geographic region, and renal replacement therapy indication were risk factors for hospital mortality in patients with gastrointestinal MR-AKI, whereas cardiovascular disease history, AKI stage at peak, and geographic region were risk factors for mortality in patients with reproductive MR-AKI. The incidence and mortality of MR-AKI vary by hospital, economic level, age, geographic region, and malignancy type. High MR-AKI incidence was associated with gastrointestinal cancers and higher level of medical care provided by academic hospitals in affluent regions such as Beijing, Shanghai, and other provincial-level cities. Elderly patients with advanced gastrointestinal cancer in mid-China showed the highest incidence of MR-AKI and in-hospital mortality, and thus require special attention.
Naturally available wild pollination services have economic value for nature dependent smallholder crop farms in Tanzania
Authors: Tibesigwa Byela , Siikamäki Juha , Lokina Razack , Alvsilver Jessica
Published: March 2019

Despite the importance of naturally available wild pollination ecosystem services in enhancing sub-Saharan African smallholder farms’ productivity, their values to actual farming systems remain unknown. We develop a nationally representative empirical assessment by integrating nationally representative plot level panel data with spatially and temporally matched land cover maps to identify the contribution of wild pollinators to crop revenue. Our estimation results reveal distinct and robust contributions by natural habitats of wild pollinators - forests - to plot-level crop revenue, where habitats in near proximity to plots contribute much more value than those farther away. When contrasting between pollinator-dependent and pollinator-independent crops, we find that the positive effects emerge only for pollinator-dependent crops, while pollinator-independent crops show no benefits. We conclude the empirical assessment by using our estimates to evaluate changes in crop revenue associated with the actual habitat reduction during 2008–2013. We find that this change in the natural habitats of wild pollinators has reduced crop revenue possibly by as much as 29% (mean) and 4% (median). To our knowledge, this is the first empirical assessment to use nationally representative smallholder farms to assess the value of naturally available wild pollination ecosystem services. Our results magnify the documented benefits of forest conservation, as this preserves pollinators’ natural habitats, and by extension its inhabitants, who play an important role in boosting crop yields of nature dependent smallholder farms.
Distinguishing Lipid Subtypes by Amplifying Contrast from J-Coupling
Authors: Uche Ifeanyi K. , Galiana Gigi
Published: March 2019

Previous work has highlighted the complicated and distinctive dynamics that set signal evolution during a train of spin echoes, especially with nonuniform echo spacing applied to complex molecules like fats. The work presented here regards those signal patterns as codes that can be used as a contrast mechanism, capable of distinguishing mixtures of molecules with an imaging sequence, sidestepping many challenges of spectroscopy. For particular arrays of echo spacings, non-monotonic and distinctive signal evolution can be enhanced to improve contrast between target species. This work presents simulations that show how contrast between two molecules: (a) depends on the specific sequence of echo spacing, (b) is directly linked to the presence of J-coupling, and (c) can be relatively insensitive to variations in B0, T2 and B1. Imaging studies with oils demonstrate this phenomenon experimentally and also show that spin echo codes can be used for quantification. Finally, preliminary experiments apply the method to human liver in vivo, verifying that the presence of fat can lead to nonmonotonic codes like those seen in vitro. In summary, nonuniformly spaced echo trains introduce a new approach to molecular imaging of J-coupled species, such as lipids, which may have implications diagnosing metabolic diseases.
Volcaniclastic tide-modulated tempestite in a coastal tuff ring, Jeju Island, Korea
Authors: Sohn Chanwoo , Sohn Young Kwan
Published: March 2019

The need for more accurate and extensive records of storm activity is increasing because of growing population and infrastructure in coastal areas. Records of past storm activity have consequently been sought from diverse sedimentary proxies in marginal marine environments, as well as historical documents. In this paper, we introduce a unique record of a 3.7 ka BP storm event preserved in a coastal tuff ring on Jeju Island, Korea. The tuff ring formed mostly above high tide level by primary volcanic processes, but contains three interbeds of horizontally laminated to hummocky/swaly cross-stratified deposits with intervening mud drapes up to an altitude of ~4.6 m above high tide level. These interbeds were formed by wave activity in a swash to surf zone when the sea level rose several meters above normal high-tide level during a storm event, and the triple intercalation of the wave-worked deposits reflects three tidal cycles during a storm event that lasted 1.5 day. Jeju Island contains the most complete record of an ancient storm event ever reported in the tuff ring, and highlights the significance of coastal volcanoes in the study of extreme depositional events in coastal areas, such as storms and tsunamis.
Nuclear FGFR2 negatively regulates hypoxia-induced cell invasion in prostate cancer by interacting with HIF-1 and HIF-2
Authors: Lee Jae Eun , Shin Seung-Hyun , Shin Hyun-Woo , Chun Yang-Sook , Park Jong-Wan
Published: March 2019

The fibroblast growth factor receptor 2 (FGFR2) is a membrane receptor that promotes cell proliferation and differentiation. FGFR2 is also present in the nucleus, which raises a question on a new role of FGFR2 in regulating gene expression. Hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2) are nuclear proteins that transactivate many genes essential for cancer survival and metastasis under hypoxic conditions. Here, we investigated if nuclear FGFR2 modulates the HIF-driven hypoxic response. Using the TCGA database, we found that FGFR2 downregulation is associated with poor prognosis in prostate cancer. A gene-set enrichment analysis showed that metastasis- and hypoxia-related genes are associated with a low expression of FGFR2 in prostate cancer. Thus, we tested the possibility that FGFR2 negatively regulates the hypoxia-triggered metastasis of prostate cancer. FGFR2 controls migration and invasion of prostate cancer cells under hypoxia by inhibiting the HIF-driven gene expression. FGFR2 and HIF proteins co-localize and associate in the nucleus under hypoxia. FGFR2 interacts with the transactivation domain of HIF-1α and blocks the recruitment of coactivator p300, resulting in repression of HIF target genes. Based on these results, we propose a novel function of FGFR2 as a metastasis suppressor by controlling HIF-mediated hypoxic responses.
Host Taxon Predictor - A Tool for Predicting Taxon of the Host of a Newly Discovered Virus
Authors: Gałan Wojciech , Bąk Maciej , Jakubowska Małgorzata
Published: March 2019

Recent advances in metagenomics provided a valuable alternative to culture-based approaches for better sampling viral diversity. However, some of newly identified viruses lack sequence similarity to any of previously sequenced ones, and cannot be easily assigned to their hosts. Here we present a bioinformatic approach to this problem. We developed classifiers capable of distinguishing eukaryotic viruses from the phages achieving almost 95% prediction accuracy. The classifiers are wrapped in Host Taxon Predictor (HTP) software written in Python which is freely available at https://github.com/wojciech-galan/viruses_classifier. HTP’s performance was later demonstrated on a collection of newly identified viral genomes and genome fragments. In summary, HTP is a culture- and alignment-free approach for distinction between phages and eukaryotic viruses. We have also shown that it is possible to further extend our method to go up the evolutionary tree and predict whether a virus can infect narrower taxa.
Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function
Authors: van der Merwe Yolandi , Faust Anne E. , Sakalli Ecem T. , Westrick Caroline C. , Hussey George , Chan Kevin C. , Conner Ian P. , Fu Valeria L. N. , Badylak Stephen F. , Steketee Michael B.
Published: March 2019

Injury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.
High individual variability in the transcriptomic response of Mediterranean mussels to Vibrio reveals the involvement of myticins in tissue injury
Authors: Rey-Campos Magalí , Moreira Rebeca , Valenzuela-Muñoz Valentina , Gallardo-Escárate Cristian , Novoa Beatriz , Figueras Antonio
Published: March 2019

Mediterranean mussels (Mytilus galloprovincialis) are sessile filter feeders that live in close contact with numerous marine microorganisms. As all invertebrates, they lack an adaptive immune response and how these animals are able to respond to a bacterial infection and discriminate it from their normal microbiome is difficult to understand. In this work, we conducted Illumina sequencing of the transcriptome of individual mussels before and after being infected with Vibrio splendidus. The control mussels were injected with filtered seawater. We demonstrate that a great variability exists among individual transcriptomes and that each animal showed an exclusive repertoire of genes not shared with other individuals. The regulated genes in both the control and infected mussels were also analyzed and, unexpectedly, the sampling before the injection was considered a stress stimulus strong enough to trigger and modulate the response in hemocytes, promoting cell migration and proliferation. We found a clear response against the injection of filtered seawater, suggesting a reaction against a tissue injury in which the myticins, the most expressed antimicrobial peptides in mussel, appeared significantly up regulated. Functional experiments with flow cytometry confirmed the transcriptomic results since a significant alteration of hemocyte structures and a decrease in the number of hemocytes positive for myticin C were found only after a Vibrio infection and not observed when mussels were bled before, generating a tissue injury. Therefore, we report the involvement of myticins in the response to a danger signal such as a simple injection in the adductor muscle.
Regional perturbation of gene transcription is associated with intrachromosomal rearrangements and gene fusion transcripts in high grade ovarian cancer
Authors: Krzyzanowski Paul M. , Sircoulomb Fabrice , Yousif Fouad , Normand Josee , La Rose Jose , E. Francis Kyle , Suarez Fernando , Beck Tim , McPherson John D. , Stein Lincoln D. , Rottapel Robert K.
Published: March 2019

Genomic rearrangements are a hallmark of cancer biology and progression, allowing cells to rapidly transform through alterations in regulatory structures, changes in expression patterns, reprogramming of signaling pathways, and creation of novel transcripts via gene fusion events. Though functional gene fusions encoding oncogenic proteins are the most dramatic outcomes of genomic rearrangements, we investigated the relationship between rearrangements evidenced by fusion transcripts and local expression changes in cancer using transcriptome data alone. 9,953 gene fusion predictions from 418 primary serious ovarian cancer tumors were analyzed, identifying depletions of gene fusion breakpoints within coding regions of fused genes as well as an N-terminal enrichment of breakpoints within fused genes. We identified 48 genes with significant fusion-associated upregulation and furthermore demonstrate that significant regional overexpression of intact genes in patient transcriptomes occurs within 1 megabase of 78 novel gene fusions that function as central markers of these regions. We reveal that cancer transcriptomes select for gene fusions that preserve protein and protein domain coding potential. The association of gene fusion transcripts with neighboring gene overexpression supports rearrangements as mechanism through which cancer cells remodel their transcriptomes and identifies a new way to utilize gene fusions as indicators of regional expression changes in diseased cells with only transcriptomic data.
Keratoconic eyes with stable corneal tomography could benefit more from custom intraocular lens design than normal eyes
Authors: Schröder Simon , Eppig Timo , Liu Weidi , Schrecker Jens , Langenbucher Achim
Published: March 2019

We investigated whether eyes with keratoconic corneal tomography pattern could benefit more from aberration correction with custom intraocular lenses (IOLs) than normal cataractous eyes despite the effect of misalignment on the correction of aberrations. Custom IOLs (cIOLs) were calculated for twelve normal and twelve keratoconic eyes using personalized numerical ray tracing models. The Stiles-Crawford weighted root-mean-square spot-size (wRMS) at the virtual fovea was evaluated for cIOLs and aberration-neutral IOLs (nIOLs) in a simulated clinical study with 500 virtual IOL implantations per eye and per IOL. IOL misalignment (decentration, tilt, rotation) and pupillary ectopia (4.5 mm iris aperture) were varied upon each virtual implantation. The nIOLs achieved average wRMS of 16.4 ± 4.3 μm for normal, and 92.7 ± 34.4 μm for keratoconic eyes (mean ± standard deviation). The cIOLs reduced the average wRMS to 10.3 ± 5.8 μm for normal, and 28.5 ± 18.6 μm for keratoconic eyes. The cIOLs produced smaller wRMS than nIOLs in most virtual implantations (86.7% for normal and 99.4% for keratoconic eyes). IOL misalignment resulted in larger wRMS variations in the keratoconus group than in the normal group. Custom freeform IOL-optics-design may become a promising option for the correction of advanced aberrations in eyes with non-progressive keratoconic corneal tomography pattern.
Experimental demonstration of broadband light trapping by exciting surface modes of an all-dielectric taper
Authors: Huang Tsung-Yu , Yen Ta-Jen
Published: March 2019

We design an all-dielectric taper and then excite its surface modes by illuminating a plane wave upon the taper to achieve broadband light trapping spanning from 20 to 100 GHz. Via Lewin’s theory, such excitation of surface modes could be analogous to “trapped rainbow”, i.e., activation of negative Goos-Hänchen effect within a negative refractive waveguide. To further reinforce this statement, the corresponding power flow distributions within the all-dielectric taper are recorded in finite-integration time domain simulation and suggest that a chromatic incident pulse is indeed trapped at different critical thicknesses of the taper, a character of the negative refractive waveguide. Finally, the transmittance is measured and compared to the simulated ones. The two followed the similar trend.
Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model
Authors: van der Merwe Johannes , van der Veeken Lennart , Ferraris Sebastiano , Gsell Willy , Himmelreich Uwe , Toelen Jaan , Ourselin Sebastien , Melbourne Andrew , Vercauteren Tom , Deprest Jan
Published: March 2019

Preterm birth is the most significant problem in contemporary obstetrics accounting for 5–18% of worldwide deliveries. Encephalopathy of prematurity encompasses the multifaceted diffuse brain injury resulting from preterm birth. Current animal models exploring the underlying pathophysiology of encephalopathy of prematurity employ significant insults to generate gross central nervous system abnormalities. To date the exclusive effect of prematurity was only studied in a non-human primate model. Therefore, we aimed to develop a representative encephalopathy of prematurity small animal model only dependent on preterm birth. Time mated New-Zealand white rabbit does were either delivered on 28 (pre-term) or 31 (term) postconceptional days by caesarean section. Neonatal rabbits underwent neurobehavioral evaluation on 32 days post conception and then were transcardially perfuse fixed. Neuropathological assessments for neuron and oligodendrocyte quantification, astrogliosis, apoptosis and cellular proliferation were performed. Lastly,ex-vivohigh-resolution Magnetic Resonance Imaging was used to calculate T1 volumetric and Diffusion Tensor Imaging derived fractional anisotropy and mean diffusivity. Preterm birth was associated with a motoric (posture instability, abnormal gait and decreased locomotion) and partial sensory (less pain responsiveness and failing righting reflex) deficits that coincided with global lower neuron densities, less oligodendrocyte precursors, increased apoptosis and less proliferation. These region-specific histological changes corresponded with Magnetic Resonance Diffusion Tensor Imaging differences. The most significant differences were seen in the hippocampus, caudate nucleus and thalamus of the preterm rabbits. In conclusion this model of preterm birth, in the absence of any other contributory events, resulted in measurable neurobehavioral deficits with associated brain structural and Magnetic Resonance Diffusion Tensor Imaging findings.
Hierarchical supercrystalline nanocomposites through the self-assembly of organically-modified ceramic nanoparticles
Authors: Domènech Berta , Kampferbeck Michael , Larsson Emanuel , Krekeler Tobias , Bor Büsra , Giuntini Diletta , Blankenburg Malte , Ritter Martin , Müller Martin , Vossmeyer Tobias , Weller Horst , Schneider Gerold A.
Published: March 2019

Biomaterials often display outstanding combinations of mechanical properties thanks to their hierarchical structuring, which occurs through a dynamically and biologically controlled growth and self-assembly of their main constituents, typically mineral and protein. However, it is still challenging to obtain this ordered multiscale structural organization in synthetic 3D-nanocomposite materials. Herein, we report a new bottom-up approach for the synthesis of macroscale hierarchical nanocomposite materials in a single step. By controlling the content of organic phase during the self-assembly of monodisperse organically-modified nanoparticles (iron oxide with oleyl phosphate), either purely supercrystalline or hierarchically structured supercrystalline nanocomposite materials are obtained. Beyond a critical concentration of organic phase, a hierarchical material is consistently formed. In such a hierarchical material, individual organically-modified ceramic nanoparticles (Level 0) self-assemble into supercrystals in face-centered cubic superlattices (Level 1), which in turn form granules of up to hundreds of micrometers (Level 2). These micrometric granules are the constituents of the final mm-sized material. This approach demonstrates that the local concentration of organic phase and nano-building blocks during self-assembly controls the final material’s microstructure, and thus enables the fine-tuning of inorganic-organic nanocomposites’ mechanical behavior, paving the way towards the design of novel high-performance structural materials.
Event-to-event intensification of the hydrologic cycle from 1.5 °C to a 2 °C warmer world
Authors: Madakumbura Gavin D. , Kim Hyungjun , Utsumi Nobuyuki , Shiogama Hideo , Fischer Erich M. , Seland Øyvind , Scinocca John F. , Mitchell Daniel M. , Hirabayashi Yukiko , Oki Taikan
Published: March 2019

The Paris agreement was adopted to hold the global average temperature increase to well below 2 °C and pursue efforts to limit it to 1.5 °C. Here, we investigate the event-to-event hydroclimatic intensity, where an event is a pair of adjacent wet and dry spells, under future warming scenarios. According to a set of targeted multi-model large ensemble experiments, event-wise intensification will significantly increase globally for an additional 0.5 °C warming beyond 1.5 °C. In high latitudinal regions of the North American continent and Eurasia, this intensification is likely to involve overwhelming increases in wet spell intensity. Western and Eastern North America will likely experience more intense wet spells with negligible changes of dry spells. For the Mediterranean region, enhancement of dry spells seems to be dominating compared to the decrease in wet spell strength, and this will lead to an overall event-wise intensification. Furthermore, the extreme intensification could be 10 times stronger than the mean intensification. The high damage potential of such drastic changes between flood and drought conditions poses a major challenge to adaptation, and the findings suggest that risks could be substantially reduced by achieving a 1.5 °C target.
On the resilience of magic number theory for conductance ratios of aromatic molecules
Authors: Ulčakar Lara , Rejec Tomaž , Kokalj Jure , Sangtarash Sara , Sadeghi Hatef , Ramšak Anton , Jefferson John H. , Lambert Colin J.
Published: March 2019

If simple guidelines could be established for understanding how quantum interference (QI) can be exploited to control the flow of electricity through single molecules, then new functional molecules, which exploit room-temperature QI could be rapidly identified and subsequently screened. Recently it was demonstrated that conductance ratios of molecules with aromatic cores, with different connectivities to electrodes, can be predicted using a simple and easy-to-use “magic number theory.” In contrast with counting rules and “curly-arrow” descriptions of destructive QI, magic number theory captures the many forms of constructive QI, which can occur in molecular cores. Here we address the question of how conductance ratios are affected by electron-electron interactions. We find that due to cancellations of opposing trends, when Coulomb interactions and screening due to electrodes are switched on, conductance ratios are rather resilient. Consequently, qualitative trends in conductance ratios of molecules with extended pi systems can be predicted using simple ‘non-interacting’ magic number tables, without the need for large-scale computations. On the other hand, for certain connectivities, deviations from non-interacting conductance ratios can be significant and therefore such connectivities are of interest for probing the interplay between Coulomb interactions, connectivity and QI in single-molecule electron transport.
Comparison of pattern electroretinograms of glaucoma patients with parafoveal scotoma versus peripheral nasal step
Authors: Jung Kyoung In , Jeon Sooji , Kim Yong Chan , Park Chan Kee
Published: March 2019

Retinal ganglion cells are distributed disproportionately with retinal eccentricity. Pattern electroretinogram (PERG) stimuli resulted in reduced responses with more eccentric stimuli. Therefore, we investigated whether PERG amplitude is associated with the location of visual field (VF) defect in primary open-angle glaucoma. Data from Twenty-nine glaucoma patients with a parafoveal scotoma (PFS) within the central 10° of fixation, 23 glaucoma patients with a peripheral nasal step (PNS), and 27 normal control subjects were analyzed in this study. Electroretinograms (ERGs) were obtained using a commercial ERG stimulator (Neuro-ERG). The thickness of the ganglion cell-inner plexiform layer (GCIPL) was measured using spectral-domain optical coherence tomography. A lower N95 amplitude was observed in both PFS and PNS compared to the normal control (Both P < 0.001). The N95 amplitude of the PFS group was significantly lower than that of the PNS group (P = 0.034). Average GCIPL thickness correlated positively with N95 amplitude (r = 0.368, P = 0.002), but did not correlate significantly with global mean sensitivity (r = 0.228, P = 0.073) or mean deviation on 24-2 standard automated perimetry (r = 0.173, P = 0.176). In conclusion, parafoveal VF defects were associated with the lower PERG amplitude. Therefore, it is necessary to take into account the location of VF defects in evaluating PERGs of glaucoma patients.
The traumatic brain injury mitigation effects of a new viscoelastic add-on liner
Authors: Siegkas Petros , Sharp David J. , Ghajari Mazdak
Published: March 2019

Traumatic brain injury (TBI) affects millions of people worldwide with significant personal and social consequences. New materials and methods offer opportunities for improving designs of TBI prevention systems, such as helmets. We combined empirical impact tests and computational modelling to test the effectiveness of new viscoelastic add-on components in decreasing biomechanical forces within the brain during helmeted head impacts. Motorcycle helmets with and without the viscoelastic components were fitted on a head/neck assembly and were tested under oblique impact to replicate realistic accident conditions. Translational and rotational accelerations were measured during the tests. The inclusion of components reduced peak accelerations, with a significant effect for frontal impacts and a marginal effect for side and rear impacts. The head accelerations were then applied on a computational model of TBI to predict strain and strain-rate across the brain. The presence of viscoelastic components in the helmet decreased strain and strain-rate for frontal impacts at low impact speeds. The effect was less pronounced for front impact at high speeds and for side and rear impacts. This work shows the potential of the viscoelastic add-on components as lightweight and cost-effective solutions for enhancing helmet protection and decreasing strain and strain-rate across the brain during head impacts.
Deformation Twinning in Polycrystalline Mg Microstructures at High Strain Rates at the Atomic Scales
Authors: Agarwal Garvit , Dongare Avinash M.
Published: March 2019

Large scale molecular dynamics (MD) simulations are carried out to investigate the twinning behavior as well as the atomic scale micromechanisms of growth of tension and compression twins in polycrystalline Mg microstructures at high strain rates. A new defect characterization algorithm (extended-common neighbor analysis (E-CNA)) is developed that allows for an efficient identification of various types of twins in HCP microstructures. Unlike other local orientation analysis methods, the E-CNA method allows for atomic scale characterization of the structure of different types of twin boundaries in HCP microstructures. The MD simulations suggest that the local orientation of individual grains with the loading axis plays a critical role in determining the ability of grains to nucleate either compression twins or tension twins. The twinning behavior is observed through nucleation of a pair of planar faults and lateral growth of the twins occurs through nucleation of steps along the planar faults. The kinetics of migration of steps that determine the rate of growth of twins are investigated at the atomic scales. The twin tip velocity computed at high strain rates compares well with the experimentally reported values in the literature.
The role of the polymeric network in the water sensitivity of modern oil paints
Authors: La Nasa Jacopo , Lee Judith , Degano Ilaria , Burnstock Aviva , van den Berg Klaas Jan , Ormsby Bronwyn , Bonaduce Ilaria
Published: March 2019

Spectroscopic and mass spectrometric analytical techniques were used to characterise two naturally aged Winsor & Newton (W&N) Winsor Green (phthalocyanine green, PG7) artists’ oil colour paint swatches dating to 1993 and 2003. Infrared and Energy Dispersive X-ray (EDX) analysis indicated that the swatches were of closely similar composition, yet the swatch from 2003 was water-sensitive whilst the swatch from 1993 was not. Water-sensitivity is a conservation challenge associated with significant numbers of modern oil paintings and this study aimed to further develop our understanding of the molecular causes of water sensitivity. SEM elemental mapping of samples taken from both swatches provided no indication for the formation of epsomite – a known cause of water sensitivity in some modern oil paintings. Liquid chromatography coupled with mass spectrometry (HPLC-MS) and gas chromatography coupled with mass spectrometry (GC-MS) also revealed very similar qualitative-quantitative composition in terms of unbound and esterified medium fractions. The polymeric network was investigated using analytical pyrolysis. A combination of flash pyrolysis coupled with gas chromatography mass spectrometry (Py-GC-MS) together with evolved gas analysis mass spectrometry (EGA-MS) revealed that the polymeric material was relatively more abundant in the non-water-sensitive paint. This is the first multi-analytical study that has demonstrated a correlation between water-sensitivity and the degree of polymerisation of the oil medium; independent of other known causes of water-sensitivity.
A genome-wide map of circular RNAs in adult zebrafish
Authors: Sharma Disha , Sehgal Paras , Mathew Samatha , Vellarikkal Shamsudheen Karuthedath , Singh Angom Ramcharan , Kapoor Shruti , Jayarajan Rijith , Scaria Vinod , Sivasubbu Sridhar
Published: March 2019

Circular RNAs (circRNAs) are transcript isoforms generated by back-splicing of exons and circularisation of the transcript. Recent genome-wide maps created for circular RNAs in humans and other model organisms have motivated us to explore the repertoire of circular RNAs in zebrafish, a popular model organism. We generated RNA-seq data for five major zebrafish tissues - Blood, Brain, Heart, Gills and Muscle. The repertoire RNA sequence reads left over after reference mapping to linear transcripts were used to identify unique back-spliced exons utilizing a split-mapping algorithm. Our analysis revealed 3,428 novel circRNAs in zebrafish. Further in-depth analysis suggested that majority of the circRNAs were derived from previously well-annotated protein-coding and long noncoding RNA gene loci. In addition, many of the circular RNAs showed extensive tissue specificity. We independently validated a subset of circRNAs using polymerase chain reaction (PCR) and divergent set of primers. Expression analysis using quantitative real time PCR recapitulate selected tissue specificity in the candidates studied. This study provides a comprehensive genome-wide map of circular RNAs in zebrafish tissues.
Hydrogen peroxide-based products alter inflammatory and tissue damage-related proteins in the gingival crevicular fluid of healthy volunteers: a randomized trial
Authors: Colares Valderlane L. P. , Lima Suellen N. L. , Sousa Nágila C. F. , Araújo Mizael C. , Pereira Domingos M. S. , Mendes Saulo J. F. , Teixeira Simone A. , Monteiro Cristina de A. , Bandeca Matheus C. , Siqueira Walter L. , Moffa Eduardo B. , Muscará Marcelo N. , Fernandes Elizabeth S.
Published: March 2019

Hydrogen peroxide (H2O2)-based products are effective in tooth whitening; however, their safety is controversial as they may harm patient tissues/cells. These effects are suggested to be concentration-dependent; nonetheless, to date, there are no reports on H2O2-mediated oxidative damage in the gingival tissue, and neither whether this can be detected in gingival crevicular fluid (GCF) samples. We hypothesize that H2O2 whitening products may cause collateral oxidative tissue damage following in office application. Therefore, H2O2 and nitric oxide (NO) levels were investigated in GCF samples obtained from patients undergoing dental bleaching with H2O2 at different concentrations, in a randomized, double-blind, split-mouth clinical trial. A proteomic analysis of these samples was also performed. H2O2-based whitening products promoted inflammation which was detected in GCF samples and lasted for longer following 35% H2O2 bleaching. This included time-dependent changes in NO levels and in the abundance of proteins associated with NO synthesis, oxidative stress, neutrophil regulation, nucleic acid damage, cell survival and/or tissue regeneration. Overall, H2O2-based products used in office promote inflammation irrespective of their concentration. As the inflammation caused by 35% H2O2 is longer, patients may benefit better from using lower concentrations of this bleaching product, as they may result in less tissue damage.
Microarray assessment of N-glycan-specific IgE and IgG profiles associated with Schistosoma mansoni infection in rural and urban Uganda
Authors: Nkurunungi Gyaviira , van Diepen Angela , Nassuuna Jacent , Sanya Richard E. , Nampijja Margaret , Nambuya Irene , Kabagenyi Joyce , Serna Sonia , Reichardt Niels-Christian , van Ree Ronald , Webb Emily L. , Elliott Alison M. , Yazdanbakhsh Maria , Hokke Cornelis H.
Published: March 2019

Core β-1,2-xylose and α-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of schistosome infection with responses to these motifs, we assessed plasma IgE and IgG reactivity using microarray technology among Ugandans from ruralSchistosoma mansoni(Sm)-endemic islands (n = 209), and from proximate urban communities with lowerSmexposure (n = 62). IgE and IgG responses to core β-1,2-xylose and α-1,3-fucose modified N-glycans were higher in rural versus urban participants. Among rural participants, IgE and IgG to core β-1,2-xylose were positively associated withSminfection and concentration peaks coincided with the infection intensity peak in early adolescence. Responses to core α-1,3-fucose were elevated regardless ofSminfection status and peaked before the infection peak. Among urban participants,Sminfection intensity was predominantly light and positively associated with responses to both motifs. Principal component and hierarchical cluster analysis reduced the data to a set of variables that captured core β-1,2-xylose- and α-1,3-fucose-specific responses, and confirmed associations withSmand the rural environment. Responses to core β-1,2-xylose and α-1,3-fucose have distinctive relationships withSminfection and intensity that should further be explored for associations with protective immunity, and cross-reactivity with other exposures.
Impact of next-generation vehicles on tropospheric ozone estimated by chemical transport model in the Kanto region of Japan
Authors: Hata Hiroo , Tonokura Kenichi
Published: March 2019

The plans to introduce next-generation hybrid and zero-emission vehicles in the market are now enacted by governments in many countries to manage both global warming and air pollution problems. There are only a few studies evaluating the effects of the next-generation vehicles on the changes in concentrations of ozone generated by the photochemical reactions between volatile organic compounds and nitrogen oxides (NOx). To evaluate these changes, we performed chemical transport modeling in the Kanto region, Japan in the summer of 2013. The results show that if the vehicles are substituted by hybrid vehicles, average ozone concentrations increase in urban areas and decrease in suburban areas due to NOx titration. Substitution with zero-emission passenger vehicles decreases the concentrations in both urban and suburban areas. Substitution with both hybrid and zero-emission passenger and heavy-duty vehicles highly increases the concentrations in urban areas. Using the model results, we also discuss the effect of ozone concentration changes on premature mortality of humans in summer. The results suggest that, in some cases the introduction of next-generation vehicles might exasperate ozone concentrations, even leading to 5 to 10 times higher premature mortality during the summer compared to that of influenza and heat stroke in Japan.
Whole transcriptome targeted gene quantification provides new insights on pulmonary sarcomatoid carcinomas
Authors: Alì Greta , Bruno Rossella , Poma Anello Marcello , Affinito Ornella , Monticelli Antonella , Piaggi Paolo , Ricciardi Sara , Lucchi Marco , Melfi Franca , Chella Antonio , Cocozza Sergio , Fontanini Gabriella
Published: March 2019

Pulmonary sarcomatoid carcinomas (PSC) are a rare group of lung cancer with a median overall survival of 9–12 months. PSC are divided into five histotypes, challenging to diagnose and treat. The identification of PSC biomarkers is warranted, but PSC molecular profile remains to be defined. Herein, a targeted whole transcriptome analysis was performed on 14 PSC samples, evaluated also for the presence of the main oncogene mutations and rearrangements. PSC expression data were compared with transcriptome data of lung adenocarcinomas (LUAD) and squamous cell carcinomas (LUSC) from The Cancer Genome Atlas. Deregulated genes were used for pathway enrichment analysis; the most representative genes were tested by immunohistochemistry (IHC) in an independent cohort (30 PSC, 31 LUAD, 31 LUSC). All PSC cases were investigated for PD-L1 expression. Thirty-eight genes deregulated in PSC were identified, among these IGJ and SLMAP were confirmed by IHC. Moreover, Forkhead box signaling and Fanconi anemia pathways were specifically enriched in PSC. Finally, some PSC harboured alterations in genes targetable by tyrosine kinase inhibitors, as EGFR and MET. We provide a deep molecular characterization of PSC; the identification of specific molecular profiles, besides increasing our knowledge on PSC biology, might suggest new strategies to improve patients management.
4-Hexylresorcinol and silk sericin increase the expression of vascular endothelial growth factor via different pathways
Authors: Jo You-Young , Kim Dae-Won , Choi Je-Yong , Kim Seong-Gon
Published: March 2019

Angiogenesis plays an important role in active inflammation and wound healing. Our results showed that silk sericin and 4-hexylresorcinol (4HR) increased vascular endothelial growth factor (VEGF) expression in a dose-dependent manner in RAW264.7 cells. Unlike 4HR, silk sericin increased the expression of hypoxia inducible factor-1α (HIF-1α) and HIF-2α. Pretreatment with an HIF inhibitor decreased the sericin-induced increase in VEGF expression. However, the HIF inhibitor did not affect the 4HR-induced increase in VEGF expression. An inhibitor of matrix metalloproteinase (MMP) declined the 4HR-induced increase in VEGF expression. Silk sericin increased production of reactive oxygen species (ROS), whereas 4HR decreased ROS. M1 markers were increased by silk sericin treatment, and M2 markers were increased by 4HR treatment. VEGF and angiogenin expression were higher in rats treated with a 4HR-incorporated silk mat than in rats treated with a silk mat alone. In conclusion, silk sericin and 4HR increased VEGF expression in RAW264.7 cells via HIF-mediated and MMP-mediated pathways, respectively. Silk sericin exerted like pro-oxidant effects and 4HR exerted anti-oxidant effects. Rats treated with a 4HR-incorporated silk mat showed higher levels of VEGF and angiogenin than those treated with a silk mat alone.
Isolation and characterization of myogenic precursor cells from human cremaster muscle
Authors: Naldaiz-Gastesi Neia , Goicoechea María , Aragón Isabel M-ª , Pérez-López Virginia , Fuertes-Alvarez Sandra , Herrera-Imbroda Bernardo , López de Munain Adolfo , de Luna-Diaz Resi , Baptista Pedro M. , Fernández M. Alejandro , Lara María Fernanda , Izeta Ander
Published: March 2019

Human myogenic precursor cells have been isolated and expanded from a number of skeletal muscles, but alternative donor biopsy sites must be sought after in diseases where muscle damage is widespread. Biopsy sites must be relatively accessible, and the biopsied muscle dispensable. Here, we aimed to histologically characterize the cremaster muscle with regard number of satellite cells and regenerative fibres, and to isolate and characterize human cremaster muscle-derived stem/precursor cells in adult male donors with the objective of characterizing this muscle as a novel source of myogenic precursor cells. Cremaster muscle biopsies (or adjacent non-muscle tissue for negative controls; N = 19) were taken from male patients undergoing routine surgery for urogenital pathology. Myosphere cultures were derived and tested for their in vitro and in vivo myogenic differentiation and muscle regeneration capacities. Cremaster-derived myogenic precursor cells were maintained by myosphere culture and efficiently differentiated to myotubes in adhesion culture. Upon transplantation to an immunocompromised mouse model of cardiotoxin-induced acute muscle damage, human cremaster-derived myogenic precursor cells survived to the transplants and contributed to muscle regeneration. These precursors are a good candidate for cell therapy approaches of skeletal muscle. Due to their location and developmental origin, we propose that they might be best suited for regeneration of the rhabdosphincter in patients undergoing stress urinary incontinence after radical prostatectomy.
Ocean acidification increases the accumulation of titanium dioxide nanoparticles (nTiO2) in edible bivalve mollusks and poses a potential threat to seafood safety
Authors: Shi Wei , Han Yu , Guo Cheng , Su Wenhao , Zhao Xinguo , Zha Shanjie , Wang Yichen , Liu Guangxu
Published: March 2019

Large amounts of anthropogenic CO2 in the atmosphere are taken up by the ocean, which leads to ‘ocean acidification’ (OA). In addition, the increasing application of nanoparticles inevitably leads to their increased release into the aquatic environment. However, the impact of OA on the bioaccumulation of nanoparticles in marine organisms still remains unknown. This study investigated the effects of OA on the bioaccumulation of a model nanoparticle, titanium dioxide nanoparticles (nTiO2), in three edible bivalves. All species tested accumulated significantly greater amount of nTiO2 in pCO2-acidified seawater. Furthermore, the potential health threats of realistic nTiO2 quantities accumulated in bivalves under future OA scenarios were evaluated with a mouse assay, which revealed evident organ edema and alterations in hematologic indices and blood chemistry values under future OA scenario (pH at 7.4). Overall, this study suggests that OA would enhance the accumulation of nTiO2 in edible bivalves and may therefore increase the health risk for seafood consumers.
Ripening of bananas using Bowdichia virgilioides Kunth leaves
Authors: da Costa Nascimento Rivaildo , de Oliveira Freire Oliveiros , Ribeiro Lylian Souto , Araújo Mikael Bolke , Finger Fernando Luiz , Soares Marcus Alvarenga , Wilcken Carlos Frederico , Zanuncio José Cola , Souto Ribeiro Wellington
Published: March 2019

Bananas are usually ripened with calcium carbide (CaC2), a dangerous substance that can cause food poisoning. The objective was to test the empirical ripening banana method using Bowdichia virgilioides leaves compared to carbide. Ripening tests were carried out using ‘Pacovan’ banana fruits with B. virgilioides leaves and carbide following the empirical method used by Borborema farmers, Paraíba, Brazil. Bowdichia virgilioides leaves induced increased respiration and ascorbic acid production and reduced acidity, chlorophyll and pH in banana fruits like CaC2. Leaves of B. virgilioides induce ripening of ‘Pacovan’ banana with safer and same results than with CaC2.