bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating Antecedent Moisture Conditions and Intraevent Variability of Rainfall on Flood Frequency Analysis in Poorly Gauged Basins
Authors: Cea L. , Fraga I.
Published: October 2018

Rainfall‐runoff models are frequently used for the prediction of flood discharges from extreme rainfall data in poorly gauged basins. However, the conventional methods used to estimate the frequency of flood discharges from precipitation data do not incorporate a realistic representation of the spatial and temporal structure of rainfall at the study site nor of the antecedent soil moisture content. Temporally and spatially idealized rainfall patterns that do not represent properly the intraevent variability of rainfall are in general assumed. In this paper, we propose a methodology for flood frequency analysis based on the hydrological simulation of potentially hazardous real storm events. The aim of the proposed method is to incorporate the impact of the spatial and temporal intraevent variability of rainfall on flood discharge estimates without making strong assumptions about the spatial and temporal patterns of storms. It also includes a calibrated relation between the antecedent rainfall depth and the soil infiltration capacity, in order to consider the combined effect of antecedent soil moisture content and rainfall intensity. The flood frequency estimates obtained with the proposed methodology are compared to those estimated with a conventional method based on the definition of synthetic design hyetographs from local intensity‐duration‐frequency curves. The analysis is presented in two watersheds of 84 and 353 km2 located in the NW of Spain. Results highlight the role of the antecedent soil moisture in flood frequency analysis and show that the conventional methodology tends to overestimate the flood discharges when compared to the proposed approach.
Experimental and Numerical Study of Evaporation From Wavy Surfaces by Coupling Free Flow and Porous Media Flow
Authors: Gao Bo , Davarzani Hossein , Helmig Rainer , Smits Kathleen M.
Published: October 2018

The macroscale roughness of the soil surface has significant influences on the mass/energy interactions between the subsurface and the atmosphere during evaporation. However, most previous works only consider evaporation behavior from flat surfaces. Based on experimental and numerical approaches, the goal of this work is to provide a framework for the understanding of the mechanisms of evaporation from irregular soil surfaces at representative elementary volume scale. A coupling free flow‐porous media flow model was developed to describe evaporation under nonisothermal conditions. For simplicity, sinusoidal‐type wavy surfaces were considered. To validate this modeling approach, an experiment using an open‐ended wind tunnel and soil tank was conducted. The experimental system was instrumented with various environmental sensors to continuously collect atmospheric and subsurface data. Results demonstrate that the surface roughness directly affects both atmospheric and diffusion‐dominated stages I and II evaporation behavior, respectively. The atmospheric conditions directly affect the boundary layer during stage I. The evaporation rate is determined by the diffusion in the boundary layer, but not that in the porous media. The soil properties exert intrinsic influence on the capillary flow and determine the evaporation amount. The complex interaction between capillarity and the boundary layer leads to a heterogeneous distribution of evaporative flux with undulation (i.e., location along the soil surface) and time. Additionally, more and steeper waves indicate more influence from capillary flow, enhancing evaporation compared to a single wave system with the same wave amplitude, while steeper waves also result in a thicker boundary layer and weaken evaporation.
The Impact of Rainfall Space‐Time Structure in Flood Frequency Analysis
Authors: Zhu Zhihua , Wright Daniel B. , Yu Guo
Published: October 2018

Flood hydrologic response is influenced by rainfall structure (i.e., variability in space and time). How this structure shapes flood frequency is unknown, and flood frequency analyses typically neglect or simplify potentially important aspects of rainfall variability. This study seeks to understand how rainfall structure impacts flood frequency. We use stochastic storm transposition combined with a 15‐year record of hourly, 4‐km2 radar rainfall to generate 10,000 synthetic extreme rain events. These events are resampled into four “scenarios” with differing spatial and temporal resolutions, which are used as input to a distributed hydrologic model. Analysis of variance is used to identify the proportions of total flood peak variability attributable to spatial and to temporal rainfall variability under two antecedent soil moisture conditions. We simulate peak discharges for recurrence intervals of 2 to 500 years for 1,343 subwatersheds ranging in size from 16 to 4,400 km2 in Turkey River in the Midwestern United States, which is situated in a typically humid continental climactic region. Antecedent soil moisture modulates the role of rainfall structure in simulated flood response, particularly for more frequent events and large watershed scales. Rainfall spatial structure is more important than temporal structure for drainage areas larger than approximately 2,000 km2 (approximately 200 km2) for wet (dry) initial soil conditions, especially when soils are dry, while the reverse is true for smaller subwatersheds. The results appear to be related to the differing propensities for surface and subsurface runoff production as a function of basin scale, event magnitude, and soil saturation. Our results suggest that hydrologic model‐based flood frequency analyses, and particularly efforts attempting to spanning a range of scales, must carefully consider rainfall structure.
Towards smart self-clearing glaucoma drainage device
Authors: Park Hyunsu , Raffiee Amir Hossein , John Simon W. M. , Ardekani Arezoo M. , Lee Hyowon
Published: October 2018

For patients who are unresponsive to pharmacological treatments of glaucoma, an implantable glaucoma drainage devices (GDD) are often used to manage the intraocular pressure. However, the microscale channel that removes excess aqueous humor from the anterior chamber often gets obstructed due to biofouling, which necessitates additional surgical intervention. Here we demonstrate the proof-of-concept for smart self-clearing GDD by integrating magnetic microactuators inside the drainage tube of GDD. The magnetic microactuators can be controlled using externally applied magnetic fields to mechanically clear biofouling-based obstruction, thereby eliminating the need for surgical intervention. In this work, our prototype magnetic microactuators were fabricated using low-cost maskless photolithography to expedite design iteration. The fabricated devices were evaluated for their static and dynamic mechanical responses. Using transient numerical analysis, the fluid–structure interaction of our microactuator inside a microtube was characterized to better understand the amount of shear force generated by the device motion. Finally, the anti-biofouling performance of our device was evaluated using fluorescein isothiocyanate labeled bovine serum albumin. The microactuators were effective in removing proteinaceous film deposited on device surface as well as on the inner surface of the microchannel, which supports our hypothesis that a smart self-clearing GDD may be possible by integrating microfabricated magnetic actuators in chronically implanted microtubes.
Mediterranean diet adherence and rate of cerebral Aβ-amyloid accumulation: Data from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing
Authors: Rainey-Smith Stephanie R. , Gu Yian , Gardener Samantha L. , Doecke James D. , Villemagne Victor L. , Brown Belinda M. , Taddei Kevin , Laws Simon M. , Sohrabi Hamid R. , Weinborn Michael , Ames David , Fowler Christopher , Macaulay S. Lance , Maruff Paul , Masters Colin L. , Salvado Olivier , Rowe Christopher C. , Scarmeas Nikolaos , Martins Ralph N.
Published: October 2018

Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer’s disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ; a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0–9; higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission tomography at baseline, 18 and 36 months: Only individuals categorised as “Aβ accumulators”, and thus considered to be on the AD pathway, were included in the analysis (N = 77). The relationship between MeDi adherence, MeDi components, and change in cerebral Aβ load (baseline to 36 months) was evaluated using Generalised Linear Modelling, accounting for age, gender, education, Apolipoprotein E ε4 allele status, body mass index and total energy intake. Higher MeDi score was associated with less Aβ accumulation in our cohort (β = −0.01 ± 0.004, p = 0.0070). Of the individual MeDi score components, a high intake of fruit was associated with less accumulation of Aβ (β = −0.04 ± 0.01, p = 0.00036). Our results suggest MeDi adherence is associated with reduced cerebral AD pathology accumulation over time. When our results are considered collectively with previous data linking the MeDi to slower cognitive decline, it is apparent that MeDi adherence warrants further investigation in the quest to delay AD onset.
Patterns of schizophrenia symptoms: hidden structure in the PANSS questionnaire
Authors: Lefort-Besnard Jérémy , Varoquaux Gaël , Derntl Birgit , Gruber Oliver , Aleman Andre , Jardri Renaud , Sommer Iris , Thirion Bertrand , Bzdok Danilo
Published: October 2018

The clinical presentation of patients with schizophrenia has long been described to be very heterogeneous. Coherent symptom profiles can probably be directly derived from behavioral manifestations quantified in medical questionnaires. The combination of machine learning algorithms and an international multi-site dataset (n = 218 patients) identified distinctive patterns underlying schizophrenia from the widespread PANSS questionnaire. Our clustering approach revealed a negative symptom patient group as well as a moderate and a severe group, giving further support for the existence of schizophrenia subtypes. Additionally, emerging regression analyses uncovered the most clinically predictive questionnaire items. Small subsets of PANSS items showed convincing forecasting performance in single patients. These item subsets encompassed the entire symptom spectrum confirming that the different facets of schizophrenia can be shown to enable improved clinical diagnosis and medical action in patients. Finally, we did not find evidence for complicated relationships among the PANSS items in our sample. Our collective results suggest that identifying best treatment for a given individual may be grounded in subtle item combinations that transcend the long-trusted positive, negative, and cognitive categories.
Sialyltransferase ST3GAL1 promotes cell migration, invasion, and TGF-β1-induced EMT and confers paclitaxel resistance in ovarian cancer
Authors: Wu Xin , Zhao Junda , Ruan Yuanyuan , Sun Li , Xu Congjian , Jiang Hua
Published: October 2018

Sialyltransferases transfer sialic acid to nascent oligosaccharides and are upregulated in cancer. The inhibition of sialyltransferases is emerging as a potential strategy to prevent metastasis in several cancers, including ovarian cancer. ST3GAL1 is a sialyltransferase that catalyzes the transfer of sialic acid from cytidine monophosphate-sialic acid to galactose-containing substrates and is associated with cancer progression and chemoresistance. However, the function of ST3GAL1 in ovarian cancer is uncertain. Herein, we use qRT-PCR, western blotting, and immunohistochemistry to assess the expression of ST3GAL1 in ovarian cancer tissue and cell lines and investigate whether it influences resistance to paclitaxel in vitro and in a mouse xenograft model. We found that ST3GAL1 is upregulated in ovarian cancer tissues and in the ovarian cancer cell lines SKOV-3 and OVCAR3 but downregulated in A2780 ovarian cancer cells. Overexpression of ST3GAL1 in A2780 cells increases cell growth, migration, and invasion whereas ST3GAL1 knockdown in SKOV-3 cells decreases cell growth, migration, and invasion. Furthermore, overexpression of ST3GAL1 increases resistance to paclitaxel while downregulation of ST3GAL1 decreases resistance to paclitaxel in vitro, and overexpression of ST3GAL1 increases tumorigenicity and resistance to paclitaxel in vivo. Transforming growth factor-β1 can increase ST3GAL1 expression and induce ovarian cell epithelial–mesenchymal transition (EMT). However, knockdown of ST3GAL1 inhibits EMT expression. Taken together, our findings have identified a regulatory mechanism involving ST3GAL1 in ovarian cancer. ST3GAL1 may be a promising target for overcoming paclitaxel resistance in ovarian carcinoma.
The cisplatin-induced lncRNA PANDAR dictates the chemoresistance of ovarian cancer via regulating SFRS2-mediated p53 phosphorylation
Authors: Wang Hao , Fang Lei , Jiang Jing , Kuang Ye , Wang Beidi , Shang Xiumin , Han Peilin , Li Yue , Liu Meimei , Zhang Zongfeng , Li Peiling
Published: October 2018

As a component of p53-dependent lncRNA (long non-coding RNA), PANDAR (the promoter of CDKN1A antisense DNA damage activated RNA) participates in the epigenetic regulation in human cancer. However, the involvement of PANDAR in cancer chemoresistance is unknown. In this study, we report that PANDAR serves as a negative regulator of cisplatin sensitivity in human ovarian cancer via PANDAR-SRFS2-p53 feedback regulation in nuclear. Our data showed that among the drugs commonly used in ovarian cancer therapy, cisplatin induces higher levels of PANDAR compared with doxorubicin and paclitaxel. We also proved that PANDAR exhibited higher expression in cisplatin-resistant ovarian cancer tissues and cells, compared with cisplatin-sensitive ones, and this expression pattern depends on wild-type p53 (wt-p53), not mutant-p53 (mt-p53). In vitro and in vivo, PANDAR overexpression improved cell survival rate and tumor growth in response to cisplatin, while depletion of PANDAR leads to a reduced tumor growth. Further investigation revealed that PANDAR-reduced cisplatin sensitivity was likely or partly due to the PANDAR-binding protein SFRS2 (arginine/serine-rich 2), a splicing factor with the ability to negative regulate p53 and its phosphorylation at Serine 15 (Ser15). This feedback regulation of PANDAR–SFRS2–p53 leads to a reduced transactivation of p53-related pro-apoptotic genes, such as PUMA (p53-upregulated modulator of apoptosis). In addition, in platinum-treated patients with relapsed ovarian cancer, resistant period was positively correlated with the expression of PANDAR and SFRS2, and inversely associated with expression of p53-Ser15 and PUMA in these clinical tissues. Last but not least, the role of PANDAR in chemoresistance was confirmed in patients with ovarian cancer. These findings reveal a novel regulatory maneuver of cancer cells in response to chemostress, and might shed light on overcoming cisplatin resistance in ovarian cancer.
Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus
Authors: Espinoza Claudia , Guzman Segundo Jose , Zhang Xiaomin , Jonas Peter
Published: October 2018

Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations.
Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis
Authors: Cambré Isabelle , Gaublomme Djoere , Burssens Arne , Jacques Peggy , Schryvers Nadia , De Muynck Amélie , Meuris Leander , Lambrecht Stijn , Carter Shea , de Bleser Pieter , Saeys Yvan , Van Hoorebeke Luc , Kollias George , Mack Matthias , Simoens Paul , Lories Rik , Callewaert Nico , Schett Georg , Elewaut Dirk
Published: October 2018

Many pro-inflammatory pathways leading to arthritis have global effects on the immune system rather than only acting locally in joints. The reason behind the regional and patchy distribution of arthritis represents a longstanding paradox. Here we show that biomechanical loading acts as a decisive factor in the transition from systemic autoimmunity to joint inflammation. Distribution of inflammation and erosive disease is confined to mechano-sensitive regions with a unique microanatomy. Curiously, this pathway relies on stromal cells but not adaptive immunity. Mechano-stimulation of mesenchymal cells induces CXCL1 and CCL2 for the recruitment of classical monocytes, which can differentiate into bone-resorbing osteoclasts. Genetic ablation ofCCL2or pharmacologic targeting of its receptor CCR2 abates mechanically-induced exacerbation of arthritis, indicating that stress-induced chemokine release by mesenchymal cells and chemo-attraction of monocytes determines preferential homing of arthritis to certain hot spots. Thus, mechanical strain controls the site-specific localisation of inflammation and tissue damage in arthritis.
Neomorphic PDGFRA extracellular domain driver mutations are resistant to PDGFRA targeted therapies
Authors: Ip Carman K. M. , Ng Patrick K. S. , Jeong Kang Jin , Shao S. H. , Ju Zhenlin , Leonard P. G. , Hua Xu , Vellano Christopher P. , Woessner Richard , Sahni Nidhi , Scott Kenneth L. , Mills Gordon B.
Published: October 2018

Activation of platelet-derived growth factor receptor alpha (PDGFRA) by genomic aberrations contributes to tumor progression in several tumor types. In this study, we characterize 16 novel PDGFRA mutations identified from different tumor types and identify three previously uncharacterized activating mutations that promote cell survival and proliferation. PDGFRA Y288C, an extracellular domain mutation, is primarily high mannose glycosylated consistent with trapping in the endoplasmic reticulum (ER). Strikingly, PDGFRA Y288C is constitutively dimerized and phosphorylated in the absence of ligand suggesting that trapping in the ER or aberrant glycosylation is sufficient for receptor activation. Importantly, PDGFRA Y288C induces constitutive phosphorylation of Akt, ERK1/2, and STAT3. PDGFRA Y288C is resistant to PDGFR inhibitors but sensitive to PI3K/mTOR and MEK inhibitors consistent with pathway activation results. Our findings further highlight the importance of characterizing functional consequences of individual mutations for precision medicine.
Progressive divisions of multipotent neural progenitors generate late-born chandelier cells in the neocortex
Authors: Sultan Khadeejah T. , Liu Wenying Angela , Li Zhao-Lu , Shen Zhongfu , Li Zhizhong , Zhang Xin-Jun , Dean Owen , Ma Jian , Shi Song-Hai
Published: October 2018

Diverse γ-aminobutyric acid (GABA)-ergic interneurons provide different modes of inhibition to support circuit operation in the neocortex. However, the cellular and molecular mechanisms underlying the systematic generation of assorted neocortical interneurons remain largely unclear. Here we show that NKX2.1-expressing radial glial progenitors (RGPs) in the mouse embryonic ventral telencephalon divide progressively to generate distinct groups of interneurons, which occupy the neocortex in a time-dependent, early inside-out and late outside-in, manner. Notably, the late-born chandelier cells, one of the morphologically and physiologically highly distinguishable GABAergic interneurons, arise reliably from continuously dividing RGPs that produce non-chandelier cells initially. Selective removal of Partition defective 3, an evolutionarily conserved cell polarity protein, impairs RGP asymmetric cell division, resulting in premature depletion of RGPs towards the late embryonic stages and a consequent loss of chandelier cells. These results suggest that consecutive asymmetric divisions of multipotent RGPs generate diverse neocortical interneurons in a progressive manner.
An information-theoretic framework for deciphering pleiotropic and noisy biochemical signaling
Authors: Jetka Tomasz , Nienałtowski Karol , Filippi Sarah , Stumpf Michael P. H. , Komorowski Michał
Published: October 2018

Many components of signaling pathways are functionally pleiotropic, and signaling responses are marked with substantial cell-to-cell heterogeneity. Therefore, biochemical descriptions of signaling require quantitative support to explain how complex stimuli (inputs) are encoded in distinct activities of pathways effectors (outputs). A unique perspective of information theory cannot be fully utilized due to lack of modeling tools that account for the complexity of biochemical signaling, specifically for multiple inputs and outputs. Here, we develop a modeling framework of information theory that allows for efficient analysis of models with multiple inputs and outputs; accounts for temporal dynamics of signaling; enables analysis of how signals flow through shared network components; and is not restricted by limited variability of responses. The framework allows us to explain how identity and quantity of type I and type III interferon variants could be recognized by cells despite activating the same signaling effectors.
Magnetic field compatible circuit quantum electrodynamics with graphene Josephson junctions
Authors: Kroll J. G. , Uilhoorn W. , van der Enden K. L. , de Jong D. , Watanabe K. , Taniguchi T. , Goswami S. , Cassidy M. C. , Kouwenhoven L. P.
Published: October 2018

Circuit quantum electrodynamics has proven to be a powerful tool to probe mesoscopic effects in hybrid systems and is used in several quantum computing (QC) proposals that require a transmon qubit able to operate in strong magnetic fields. To address this we integrate monolayer graphene Josephson junctions into microwave frequency superconducting circuits to create graphene based transmons. Using dispersive microwave spectroscopy we resolve graphene’s characteristic band dispersion and observe coherent electronic interference effects confirming the ballistic nature of our graphene Josephson junctions. We show that the monoatomic thickness of graphene renders the device insensitive to an applied magnetic field, allowing us to perform energy level spectroscopy of the circuit in a parallel magnetic field of 1 T, an order of magnitude higher than previous studies. These results establish graphene based superconducting circuits as a promising platform for QC and the study of mesoscopic quantum effects that appear in strong magnetic fields.
Publisher Correction: Inference of RNA decay rate from transcriptional profiling highlights the regulatory programs of Alzheimer’s disease
Authors: Alkallas Rached , Fish Lisa , Goodarzi Hani , Najafabadi Hamed S.
Published: October 2018

The original version of this Article contained an error in Figure 3, where panel d was inadvertently replaced with a duplicate of panel c during typesetting. Also, the legend of Figure 5f incorrectly read ‘310 AD patients (blue dots, r = –0.4) and 157 non-demented individuals (green dots, r = –0.1)’, and should have read ‘310 AD patients (blue dots, r = –0.1) and 157 non-demented individuals (green dots, r = –0.4)’. Both of these errors have now been corrected in both the PDF and HTML versions of the Article.
Nanoembryonic thermoelastic equilibrium and enhanced properties of defected pretransitional materials
Authors: Xu Ye-Chuan , Rao Wei-Feng , Morris John W. , Khachaturyan Armen G.
Published: October 2018

Behaviors of displacive phase-transforming materials above the temperature of transformation, where abnormal thermal, elastic, magnetic properties are often observed, are mostly explained by intrinsic peculiarities in electronic/atomic structure. Here, we show these properties may also be attributed to extrinsic effects caused by a thermoelastic equilibrium in highly defected pretransitional materials. We demonstrate that the stress concentration near stress-generating defects such as dislocations and coherent precipitates could result in the stress-induced transformation within nanoscale regions, producing equilibrium embryos of the product phase. These nanoembryos in thermoelastic equilibrium could anhysteretically change their equilibrium size in response to changes in applied stress or magnetic fields leading to superelasticity or supermagnetostriction. Similar response to cooling may explain the observed diffuse phase transformation, changes in the coefficient of thermal expansion and effective elastic modulus, which, in turn, may explain the invar and elinvar behaviors.
Early heme oxygenase 1 induction delays tumour initiation and enhances DNA damage repair in liver macrophages of Mdr2−/− mice
Authors: Barikbin Roja , Berkhout Laura , Bolik Julia , Schmidt-Arras Dirk , Ernst Thomas , Ittrich Harald , Adam Gerhard , Parplys Ann , Casar Christian , Krech Till , Karimi Khalil , Sass Gabriele , Tiegs Gisa
Published: October 2018

Multi drug resistance protein 2 knockout mice (Mdr2−/−) are a mouse model of chronic liver inflammation and inflammation-induced tumour development. Here we investigated the kinetics of early heme oxygenase 1 (HO-1) induction on inflammation, tumour development, and DNA damage in Mdr2−/− mice. HO-1 was induced by intraperitoneal injection of cobalt protoporphyrin IX (CoPP) twice weekly for 9 consecutive weeks. Immediately after HO-1 induction, liver function improved and infiltration of CD4+ and CD8+ T cells was reduced. Furthermore, we observed increased p38 activation with concomitant reduction of Cyclin D1 expression in aged Mdr2−/− mice. Long-term effects of HO-1 induction included increased CD8+ T cell infiltration as well as delayed and reduced tumour growth in one-year-old animals. Unexpectedly, DNA double-strand breaks were detected predominantly in macrophages of 65-week-old Mdr2−/− mice, while DNA damage was reduced in response to early HO-1 induction in vivo and in vitro. Overall, early induction of HO-1 in Mdr2−/− mice had a beneficial short-term effect on liver function and reduced hepatic T cell accumulation. Long-term effects of early HO-1 induction were increased CD8+ T cell numbers, decreased proliferation as wells as reduced DNA damage in liver macrophages of aged animals, accompanied by delayed and reduced tumour growth.
Development of a 3D Collagen Model for the In Vitro Evaluation of Magnetic-assisted Osteogenesis
Authors: Yuan Zhiyu , Memarzadeh Kaveh , Stephen Abish S. , Allaker Robert P. , Brown Robert A. , Huang Jie
Published: October 2018

Magnetic stimulation has been applied to bone regeneration, however, the cellular and molecular mechanisms of repair still require a better understanding. A three-dimensional (3D) collagen model was developed using plastic compression, which produces dense, cellular, mechanically strong native collagen structures. Osteoblast cells (MG-63) and magnetic iron oxide nanoparticles (IONPs) were incorporated into collagen gels to produce a range of cell-laden models. A magnetic bio-reactor to support cell growth under static magnetic fields (SMFs) was designed and fabricated by 3D printing. The influences of SMFs on cell proliferation, differentiation, extracellular matrix production, mineralisation and gene expression were evaluated. Polymerase chain reaction (PCR) further determined the effects of SMFs on the expression of runt-related transcription factor 2 (Runx2), osteonectin (ON), and bone morphogenic proteins 2 and 4 (BMP-2 and BMP-4). Results demonstrate that SMFs, IONPs and the collagen matrix can stimulate the proliferation, alkaline phosphatase production and mineralisation of MG-63 cells, by influencing matrix/cell interactions and encouraging the expression of Runx2, ON, BMP-2 and BMP-4. Therefore, the collagen model developed here not only offers a novel 3D bone model to better understand the effect of magnetic stimulation on osteogenesis, but also paves the way for further applications in tissue engineering and regenerative medicine.
Self-structuring in Zr1−xAlxN films as a function of composition and growth temperature
Authors: Ghafoor N. , Petrov I. , Holec D. , Greczynski G. , Palisaitis J. , Persson P. O. A. , Hultman L. , Birch J.
Published: October 2018

Nanostructure formation via surface-diffusion-mediated segregation of ZrN and AlN in Zr1−xAlxN films during high mobility growth conditions is investigated for 0 ≤ × ≤ 1. The large immiscibility combined with interfacial surface and strain energy balance resulted in a hard nanolabyrinthine lamellar structure with well-defined (semi) coherent c-ZrN and w-AlN domains of sub-nm to ~4 nm in 0.2 ≤ × ≤ 0.4 films, as controlled by atom mobility. For high AlN contents (x > 0.49) Al-rich ZrN domains attain wurtzite structure within fine equiaxed nanocomposite wurtzite lattice. Slow diffusion in wurtzite films points towards crystal structure dependent driving force for decomposition. The findings of unlikelihood of iso-structural decomposition in c-Zr1−xAlxN, and stability of w-Zr1−xAlxN (in large × films) is complemented with first principles calculations.
Impact of DNA extraction method and targeted 16S-rRNA hypervariable region on oral microbiota profiling
Authors: Teng Fei , Darveekaran Nair Sree Sankar , Zhu Pengfei , Li Shanshan , Huang Shi , Li Xiaolan , Xu Jian , Yang Fang
Published: October 2018

Amplification and sequencing of 16S amplicons are widely used for profiling the structure of oral microbiota. However, it remains not clear whether and to what degree DNA extraction and targeted 16S rRNA hypervariable regions influence the analysis. Based on a mock community consisting of five oral bacterial species in equal abundance, we compared the 16S amplicon sequencing results on the Illumina MiSeq platform from six frequently employed DNA extraction procedures and three pairs of widely used 16S rRNA hypervariable primers targeting different 16S rRNA regions. Technical reproducibility of selected 16S regions was also assessed. DNA extraction method exerted considerable influence on the observed bacterial diversity while hypervariable regions had a relatively minor effect. Protocols with beads added to the enzyme-mediated DNA extraction reaction produced more accurate bacterial community structure than those without either beads or enzymes. Hypervariable regions targeting V3-V4 and V4-V5 seemed to produce more reproducible results than V1-V3. Neither sequencing batch nor change of operator affected the reproducibility of bacterial diversity profiles. Therefore, DNA extraction strategy and 16S rDNA hypervariable regions both influenced the results of oral microbiota biodiversity profiling, thus should be carefully considered in study design and data interpretation.
Differential recognition of Haemophilus influenzae whole bacterial cells and isolated lipooligosaccharides by galactose-specific lectins
Authors: Kalograiaki Ioanna , Euba Begoña , Fernández-Alonso María del Carmen , Proverbio Davide , St. Geme Joseph W. , Aastrup Teodor , Garmendia Junkal , Cañada F. Javier , Solís Dolores
Published: October 2018

Bacterial surfaces are decorated with carbohydrate structures that may serve as ligands for host receptors. Based on their ability to recognize specific sugar epitopes, plant lectins are extensively used for bacteria typing. We previously observed that the galactose-specific agglutinins from Ricinus communis (RCA) and Viscum album (VAA) exhibited differential binding to nontypeable Haemophilus influenzae (NTHi) clinical isolates, their binding being distinctly affected by truncation of the lipooligosaccharide (LOS). Here, we examined their binding to the structurally similar LOS molecules isolated from strains NTHi375 and RdKW20, using microarray binding assays, saturation transfer difference NMR, and molecular dynamics simulations. RCA bound the LOSRdKW20 glycoform displaying terminal Galβ(1,4)Glcβ, whereas VAA recognized the Galα(1,4)Galβ(1,4)Glcβ epitope in LOSNTHi375 but not in LOSRdKW20, unveiling a different presentation. Binding assays to whole bacterial cells were consistent with LOSNTHi375 serving as ligand for VAA, and also suggested recognition of the glycoprotein HMW1. Regarding RCA, comparable binding to NTHi375 and RdKW20 cells was observed. Interestingly, an increase in LOSNTHi375 abundance or expression of HMW1 in RdKW20 impaired RCA binding. Overall, the results revealed that, besides the LOS, other carbohydrate structures on the bacterial surface serve as lectin ligands, and highlighted the impact of the specific display of cell surface components on lectin binding.
Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice
Authors: Reale Carla , Porreca Immacolata , Russo Filomena , Marotta Maria , Roberto Luca , Russo Nicola Antonino , Carchia Emanuele , Mallardo Massimo , De Felice Mario , Ambrosino Concetta
Published: October 2018

Genetic and environmental factors contribute to thyroid diseases. Although still debated, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is thought to induce thyroid dysfunction in humans and rodents. The data here reported point out the contribution of the exposure window and genetic background in mediating the low-dose TCDD effects on thyroid. Indeed, early (from E0.5 to PND30) and low-dose (0,001 μg/kg/day) TCDD exposure reduced the circulating fT4 and altered the expression of thyroid specific transcripts. The role of genetic components was estimated monitoring the same markers in Pax8+/− and Nkx2-1+/− mice, susceptible to thyroid dysfunction, exposed to 0, 1 μg/kg/day TCDD from E15.5 to PND60. Haploinsufficiency of either Pax8 or Nkx2-1 genes exacerbated the effects of the exposure impairing the thyroid enriched mRNAs in sex dependent manner. Such effect was mediated by mechanisms involving the Nkx2-1/p53/p65/IĸBα pathway in vitro and in vivo. Foetal exposure to TCDD impaired both thyroid function and genes expression while thyroid development and differentiation did not appear significantly affected. In mouse, stronger effects were related to earlier exposure or specific genetic background such as either Pax8 or Nkx2-1 haploinsufficiency, both associated to hypothyroidism in humans. Furthermore, our data underline that long exposure time are needed to model in vitro and in vivo results.
Genome-wide Identification, Classification, and Expression Pattern of Homeobox Gene Family in Brassica rapa under Various Stresses
Authors: Khan Nadeem , Hu Chun-mei , Khan Waleed Amjad , Wang Wenli , Ke Han , Huijie Dong , Zhishuo Zhang , Hou Xilin
Published: October 2018

Homeobox (HB) genes are crucial for plant growth and development processes. They encode transcription factors and responses to various stresses, as reported by recent emerging evidence. In this study, a total of 113 BraHB genes were identified in Brassica rapa. On the basis of domain organization and phylogenetic analysis, the BraHBs were grouped into nine subclasses, in which homeobox leucine-zipper (HB LZP-III) showed the highest number of genes (28) compared to other subclasses. The BraHBs exhibited similarities in exon–intron organization and motif composition among the members of the same subclasses. The analysis revealed that HB-Knotted was more preferentially retained than any other subclass of BraHB. Furthermore, we evaluated the impact of whole-genome triplication on the evolution of BraHBs. In order to analyze the subgenomes of B. rapa, we identified 39 paralogous pairs for which synonymous substitution values were lower than 1.00 for further purifying selection. Finally, the expression patterns of BraHBs across six tissues expressed dynamic variations combined with their responses against multiple stresses. The current study provides brief information on the homeobox gene family in B. rapa. Our findings can serve as a reference for further functional analysis of BraHBs.
Rational design, synthesis, characterization and catalytic properties of high-quality low-silica hierarchical FAU- and LTA-type zeolites
Authors: Parsapur Rajesh K. , Selvam Parasuraman
Published: October 2018

Despite the development of several synthetic strategies employing various templates as (pore) structure directing agents, the preparation of high-quality aluminum-rich hierarchical zeolites (designated as ZH) with Si/Al < 5 from its molecular precursors is still a challenge to the scientific community. For the first time, we report here, a successful synthesis methodology for the preparation of hierarchical zeolites, having FAU and LTA topologies with uniform micropores and mesopores by a rationally designed method. Here, a stable supramolecular self-assembly was achieved under the challenging synthesis conditions by tailoring the zeolitization process, viz., by a homogeneous nucleation and a multi-step crystallization. This has resulted in regular mesoporosity in FAU-type zeolites and a unique mesoporosity in LTA-type zeolites, hitherto not reported so far.
Comparative Transcriptional Profiling and Physiological Responses of Two Contrasting Oat Genotypes under Salt Stress
Authors: Wu Bin , Munkhtuya Yarvaan , Li Jianjiang , Hu Yani , Zhang Qian , Zhang Zongwen
Published: October 2018

Salinity is one of the major abiotic factors that affect productivity in oat. Here, we report a comparison of the transcriptomes of two hexaploid oat cultivars, ‘Hanyou-5’ and ‘Huazao-2’, which differ with respect to salt tolerance, in seedlings exposed to salt stress. Analysis of the assembled unigenes from the osmotically stressed and control libraries of ‘Hanyou-5’ and ‘Huazao-2’ showed that the expression of 21.92% (36,462/166,326) of the assembled unigenes was differentially regulated in the two cultivars after different durations of salt stress. Bioinformatics analysis showed that the main functional categories enriched in these DEGs were “metabolic process”, “response to stresses”, “plant hormone signal transduction”, “MAPK signalling”, “oxidative phosphorylation”, and the plant-pathogen interaction pathway. Some regulatory genes, such as those encoding MYB, WRKY, bHLH, and zinc finger proteins, were also found to be differentially expressed under salt stress. Physiological measurements also detected significant differences in the activities of POD (76.24 ± 1.07 Vs 81.53 ± 1.47 U/g FW) in the two genotypes in response to osmotic stress. Furthermore, differential expression of 18 of these genes was successfully validated using RNA-seq and qRT-PCR analyses. A number of stress-responsive genes were identified in both cultivars, and candidate genes with potential roles in the adaptation to salinity were proposed.
Proteomic approach for understanding milder neurotoxicity of Carfilzomib against Bortezomib
Authors: Karademir Betul , Sari Gulce , Jannuzzi Ayse Tarbin , Musunuri Sravani , Wicher Grzegorz , Grune Tilman , Mi Jia , Hacioglu-Bay Husniye , Forsberg-Nilsson Karin , Bergquist Jonas , Jung Tobias
Published: October 2018

The proteasomal system is responsible for the turnover of damaged proteins. Because of its important functions in oncogenesis, inhibiting the proteasomal system is a promising therapeutic approach for cancer treatment. Bortezomib (BTZ) is the first proteasome inhibitor approved by FDA for clinical applications. However neuropathic side effects are dose limiting for BTZ as many other chemotherapeutic agents. Therefore second-generation proteasome inhibitors have been developed including carfilzomib (CFZ). Aim of the present work was investigating the mechanisms of peripheral neuropathy triggered by the proteasome inhibitor BTZ and comparing the pathways affected by BTZ and CFZ, respectively. Neural stem cells, isolated from the cortex of E14 mouse embryos, were treated with BTZ and CFZ and mass spectrometry was used to compare the global protein pool of treated cells. BTZ was shown to cause more severe cytoskeletal damage, which is crucial in neural cell integrity. Excessive protein carbonylation and actin filament destabilization were also detected following BTZ treatment that was lower following CFZ treatment. Our data on cytoskeletal proteins, chaperone system, and protein oxidation may explain the milder neurotoxic effects of CFZ in clinical applications.
Step Sizes and Rate Constants of Single-headed Cytoplasmic Dynein Measured with Optical Tweezers
Authors: Kinoshita Yoshimi , Kambara Taketoshi , Nishikawa Kaori , Kaya Motoshi , Higuchi Hideo
Published: October 2018

A power stroke of dynein is thought to be responsible for the stepping of dimeric dynein. However, the actual size of the displacement driven by a power stroke has not been directly measured. Here, the displacements of single-headed cytoplasmic dynein were measured by optical tweezers. The mean displacement of dynein interacting with microtubule was ~8 nm at 100 µM ATP, and decreased sigmoidally with a decrease in the ATP concentration. The ATP dependence of the mean displacement was explained by a model that some dynein molecules bind to microtubule in pre-stroke conformation and generate 8-nm displacement, while others bind in the post-stroke one and detach without producing a power stroke. Biochemical assays showed that the binding affinity of the post-stroke dynein to a microtubule was ~5 times higher than that of pre-stroke dynein, and the dissociation rate was ~4 times lower. Taking account of these rates, we conclude that the displacement driven by a power stroke is 8.3 nm. A working model of dimeric dynein driven by the 8-nm power stroke was proposed.
Valence band behaviour of zirconium oxide, Photoelectron and Auger spectroscopy study
Authors: Azdad Zakaria , Marot Laurent , Moser Lucas , Steiner Roland , Meyer Ernst
Published: October 2018

In this study X-ray Photoelectron Spectroscopy and Ultraviolet Photoelectron Spectroscopy were combined to investigate the effect of oxygen incorporation on the valence band behaviour of ZrOx. The Auger transitions involving valence bands are found to mimic the self-folded density of state measured using Ultraviolet Photoelectron Spectroscopy. The valence band once constructed in a sub-oxide form, stays at a fixed energy position despite the change in the stoichiometry. This behaviour is found to be useful in setting a reference for X-ray Photoelectron Spectroscopy charge correction. The results of the charged corrected spectra were compared to other methods and found to be in great agreement. Finally, a correlation between the core-level binding energy and the structural property of ZrOxis given.
Analytical and simulation studies of driven diffusive system with asymmetric heterogeneous interactions
Authors: Wang Yu-Qing , Wang Ji-Xin , Li Wan-He , Zhou Chao-Fan , Jia Bin
Published: October 2018

Totally asymmetric simple exclusion process (namely, TASEP) is one of the most vital driven diffusive systems, which depicts stochastic dynamics of self-driven particles unidirectional updating along one-dimensional discrete lattices controlled by hard-core exclusions. Different with pre-existing results, driven diffusive system composed by multiple TASEPs with asymmetric heterogeneous interactions under two-dimensional periodic boundaries is investigated. By using detailed balance principle, particle configurations are extensively studied to obtain universal laws of characteristic order parameters of such stochastic dynamic system. By performing analytical analyses and Monte-Carlo simulations, local densities are found to be monotone increase with global density and spatially homogeneous to site locations. Oppositely, local currents are found to be non-monotonically increasing against global density and proportional to forward rate. Additionally, by calculating different cases of topologies, changing transition rates are found to have greater effects on particle configurations in adjacent subsystems. By intuitively comparing with pre-existing results, the improvement of our work also shows that introducing and considering totally heterogeneous interactions can improve the total current in such multiple TASEPs and optimize the overall transport of such driven-diffusive system. Our research will be helpful to understand microscopic dynamics and non-equilibrium dynamical behaviors of interacting particle systems.
Paper-Based Supercapacitive Mechanical Sensors
Authors: Zhang Ye , Sezen Serdar , Ahmadi Mahdi , Cheng Xiang , Rajamani Rajesh
Published: October 2018

Paper has been pursued as an interesting substrate material for sensors in applications such as microfluidics, bio-sensing of analytes and printed microelectronics. It offers advantages of being inexpensive, lightweight, environmentally friendly and easy to use. However, currently available paper-based mechanical sensors suffer from inadequate range and accuracy. Here, using the principle of supercapacitive sensing, we fabricate force sensors from paper with ultra-high sensitivity and unprecedented configurability. The high sensitivity comes from the sensitive dependence of a supercapacitor’s response on the contact area between a deformable electrolyte and a pair of electrodes. As a key component, we develop highly deformable electrolytes by coating ionic gel on paper substrates which can be cut and shaped into complex three-dimensional geometries. Paper dissolves in the ionic gel after determining the shape of the electrolytes, leaving behind transparent electrolytes with micro-structured fissures responsible for their high deformability. Exploiting this simple paper-based fabrication process, we construct diverse sensors of different configurations that can measure not just force but also its normal and shear components. The new sensors have range and sensitivity several orders of magnitude higher than traditional MEMS capacitive sensors, in spite of their being easily fabricated from paper with no cleanroom facilities.