bluuebunny/crossref_metadata_2025 huggingface dataset:
An ENU-induced splice site mutation of mouse Col1a1 causing recessive osteogenesis imperfecta and revealing a novel splicing rescue
Authors: Tabeta Koichi , Du Xin , Arimatsu Kei , Yokoji Mai , Takahashi Naoki , Amizuka Norio , Hasegawa Tomoka , Crozat Karine , Maekawa Tomoki , Miyauchi Sayuri , Matsuda Yumi , Ida Takako , Kaku Masaru , Hoebe Kasper , Ohno Kinji , Yoshie Hiromasa , Yamazaki Kazuhisa , Moresco Eva Marie Y. , Beutler Bruce
Published: September 2017

GU-AG consensus sequences are used for intron recognition in the majority of cases of pre-mRNA splicing in eukaryotes. Mutations at splice junctions often cause exon skipping, short deletions, or insertions in the mature mRNA, underlying one common molecular mechanism of genetic diseases. Using N-ethyl-N-nitrosourea, a novel recessive mutation named seal was produced, associated with fragile bones and susceptibility to fractures (spine and limbs). A single nucleotide transversion (T → A) at the second position of intron 36 of the Col1a1 gene, encoding the type I collagen, α1 chain, was responsible for the phenotype. Col1a1
seal
mRNA expression occurred at greatly reduced levels compared to the wild-type transcript, resulting in reduced and aberrant collagen fibers in tibiae of seal homozygous mice. Unexpectedly, splicing of Col1a1
seal
mRNA followed the normal pattern despite the presence of the donor splice site mutation, likely due to the action of a putative intronic splicing enhancer present in intron 25, which appeared to function redundantly with the splice donor site of intron 36. Seal mice represent a model of human osteogenesis imperfecta, and reveal a previously unknown mechanism for splicing “rescue.”
A Plastid-Localized Pentatricopeptide Repeat Protein is Required for Both Pollen Development and Plant Growth in Rice
Authors: Liu Yu-Jun , Liu Xuejiao , Chen Hao , Zheng Peng , Wang Wenyi , Wang Liangchao , Zhang Jianhua , Tu Jumin
Published: September 2017

Several mitochondrial-targeted pentatricopeptide repeat (PPR) proteins involved in pollen development have been reported to be fertility restorer (Rf) proteins. However, the roles of plastid-localized PPR proteins in plant male reproduction are poorly defined. Here, we described a plastid-localized PPR-SMR protein, OsPPR676, which is required for plant growth and pollen development in rice. In this study, OsPPR676 was confirmed to be an interacted protein with Osj10gBTF3, β-subunit of nascent polypeptide-associated complex (β-NAC), by bimolecular fluorescence complementation assays, indicating that both proteins are probably involved in the same regulatory pathway of pollen development. Compared with other chloroplast-rich tissues, OsPPR676 was only weakly expressed in anther, but in the Mei and YM stages of pollen development, its expression was relatively strong in the tapetum. Disruption of OsPPR676 resulted in growth retardation of plants and partial sterility of pollens. Phenotypic analysis of different osppr676 mutant lines implied that the SMR domain was not essential for the function of OsPPR676. We further demonstrated that OsPPR676 is essential for production of plastid atpB subunit, and then plays crucial roles in biosynthesis of fatty acids, carbohydrates, and other organic matters via affecting activity of ATP synthase.
A moso bamboo WRKY gene PeWRKY83 confers salinity tolerance in transgenic Arabidopsis plants
Authors: Wu Min , Liu Huanlong , Han Guomin , Cai Ronghao , Pan Feng , Xiang Yan
Published: September 2017

The WRKY family are transcription factors, involved in plant development, and response to biotic and abiotic stresses. Moso bamboo is an important bamboo that has high ecological, economic and cultural value and is widely distributed in the south of China. In this study, we performed a genome-wide identification of WRKY members in moso bamboo and identified 89 members. By comparative analysis in six grass genomes, we found the WRKY gene family may have experienced or be experiencing purifying selection. Based on relative expression levels among WRKY IIc members under three abiotic stresses, PeWRKY83 functioned as a transcription factor and was selected for detailed analysis. The transgenic Arabidopsis of PeWRKY83 showed superior physiological properties compared with the WT under salt stress. Overexpression plants were less sensitive to ABA at both germination and postgermination stages and accumulated more endogenous ABA under salt stress conditions. Further studies demonstrated that overexpression of PeWRKY83 could regulate the expression of some ABA biosynthesis genes (AtAAO3, AtNCED2, AtNCED3), signaling genes (AtABI1, AtPP2CA) and responsive genes (AtRD29A, AtRD29B, AtABF1) under salt stress. Together, these results suggested that PeWRKY83 functions as a novel WRKY-related TF which plays a positive role in salt tolerance by regulating stress-induced ABA synthesis.
Thermoelectricity in vertical graphene-C60-graphene architectures
Authors: Wu Qingqing , Sadeghi Hatef , García-Suárez Víctor M. , Ferrer Jaime , Lambert Colin J.
Published: September 2017

Recent studies of single-molecule thermoelectricity have identified families of high-performance molecules. However, in order to translate this discovery into practical thin-film energy-harvesting devices, there is a need for an understanding of the fundamental issues arising when such junctions are placed in parallel. This is relevant because controlled scalability might be used to boost electrical and thermoelectric performance over the current single-junction paradigm. As a first step in this direction, we investigate here the properties of two C60 molecules placed in parallel and sandwiched between top and bottom graphene electrodes. In contrast with classical conductors, we find that increasing the number of parallel junctions from one to two can cause the electrical conductance to increase by more than a factor of 2. Furthermore, we show that the Seebeck coefficient is sensitive to the number of parallel molecules sandwiched between the electrodes, whereas classically it should be unchanged. This non-classical behaviour of the electrical conductance and Seebeck coefficient are due to inter-junction quantum interference, mediated by the electrodes, which leads to an enhanced response in these vertical molecular devices.
Fine-scale harbour seal usage for informed marine spatial planning
Authors: Jones Esther L. , Sparling Carol E. , McConnell Bernie J. , Morris Christopher D. , Smout Sophie
Published: September 2017

High-resolution distribution maps can help inform conservation measures for protected species; including where any impacts of proposed commercial developments overlap the range of focal species. Around Orkney, northern Scotland, UK, the harbour seal (Phoca vitulina) population has decreased by 78% over 20 years. Concern for the declining harbour seal population has led to constraints being placed on tidal energy generation developments. For this study area, telemetry data from 54 animals tagged between 2003 and 2015 were used to produce density estimation maps. Predictive habitat models using GAM-GEEs provided robust predictions in areas where telemetry data were absent, and were combined with density estimation maps, and then scaled to population levels using August terrestrial counts between 2008 and 2015, to produce harbour seal usage maps with confidence intervals around Orkney and the North coast of Scotland. The selected habitat model showed that distance from haul out, proportion of sand in seabed sediment, and annual mean power were important predictors of space use. Fine-scale usage maps can be used in consenting and licensing of anthropogenic developments to determine local abundance. When quantifying commercial impacts through changes to species distributions, usage maps can be spatially explicitly linked to individual-based models to inform predicted movement and behaviour.
Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex
Authors: Hussain Tabish , Saha Dhurjhoti , Purohit Gunjan , Kar Anirban , Kishore Mukherjee Anand , Sharma Shalu , Sengupta Suman , Dhapola Parashar , Maji Basudeb , Vedagopuram Sreekanth , Horikoshi Nobuko T. , Horikoshi Nobuo , Pandita Raj K. , Bhattacharya Santanu , Bajaj Avinash , Riou Jean-François , Pandita Tej K. , Chowdhury Shantanu
Published: September 2017

We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells. Together these reveal for the first time role of TRF2 in REST- repressor complex mediated transcription repression.
Inhibition of Wnt/β-Catenin pathway and Histone acetyltransferase activity by Rimonabant: a therapeutic target for colon cancer
Authors: Proto Maria Chiara , Fiore Donatella , Piscopo Chiara , Franceschelli Silvia , Bizzarro Valentina , Laezza Chiara , Lauro Gianluigi , Feoli Alessandra , Tosco Alessandra , Bifulco Giuseppe , Sbardella Gianluca , Bifulco Maurizio , Gazzerro Patrizia
Published: September 2017

In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis. Increasing evidence showed that the endocannabinoids control tumor growth and progression, bothin vitroandin vivo. We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies. In these models, Rimonabant inhibited the Wnt/β-Catenin canonical pathway and increasedβ-Catenin phosphorylation; in HCT116 cells, but not in SW48, the compound also triggered the Wnt/β-Catenin non canonical pathway activation through induction of Wnt5A and activation of CaMKII. The Rimonabant-induced downregulation of Wnt/β-Catenin target genes was partially ascribable to a direct inhibition of p300/KAT3B histone acetyltransferase, a coactivator ofβ-Catenin dependent gene regulation. Finally, in HCT116 xenografts, Rimonabant significantly reduced tumor growth and destabilized the nuclear localization ofβ-Catenin. Obtained data heavily supported the rationale for the use of cannabinoids in combined therapies for metastatic CRC harbouring activating mutations ofβ-Catenin.
Maternal diabetes causes developmental delay and death in early-somite mouse embryos
Authors: Zhao Jing , Hakvoort Theodorus B. M. , Ruijter Jan M. , Jongejan Aldo , Koster Jan , Swagemakers Sigrid M. A. , Sokolovic Aleksandar , Lamers Wouter H.
Published: September 2017

Maternal diabetes causes congenital malformations and delays embryonic growth in the offspring. We investigated effects of maternal diabetes on mouse embryos during gastrulation and early organogenesis (ED7.5–11.5). Female mice were made diabetic with streptozotocin, treated with controlled-release insulin implants, and mated. Maternal blood glucose concentrations increased up to embryonic day (ED) 8.5. Maternal hyperglycemia induced severe growth retardation (approx.1 day) in 53% of the embryos on ED8.5, death in most of these embryos on ED9.5, and the termination of pregnancy on ED10.5 in litters with >20% dead embryos. Due to this selection, developmental delays and reduction in litter size were no longer observed thereafter in diabetic pregnancies. Male and female embryos were equally sensitive. High-throughput mRNA sequencing and pathway analysis of differentially expressed genes showed that retarded embryos failed to mount the adaptive suppression of gene expression that characterized non-retarded embryos (cell proliferation, cytoskeletal remodeling, oxidative phosphorylation). We conclude that failure of perigastrulation embryos of diabetic mothers to grow and survive is associated with their failure to shut down pathways that are strongly down-regulated in otherwise similar non-retarded embryos. Embryos that survive the early and generalized adverse effect of maternal diabetes, therefore, appear the subset in which malformations become manifest.
Design of Multivalent Inhibitors for Preventing Cellular Uptake
Authors: Schubertová Veronika , Martinez-Veracoechea Francisco J. , Vácha Robert
Published: September 2017

Cellular entry, the first crucial step of viral infection, can be inhibited by molecules adsorbed on the virus surface. However, apart from using stronger affinity, little is known about the properties of such inhibitors that could increase their effectiveness. Our simulations showed that multivalent inhibitors can be designed to be much more efficient than their monovalent counterparts. For example, for our particular simulation model, a single multivalent inhibitor spanning 5 to 6 binding sites is enough to prevent the uptake compared to the required 1/3 of all the receptor binding sites needed to be blocked by monovalent inhibitors. Interestingly, multivalent inhibitors are more efficient in inhibiting the uptake not only due to their increased affinity but mainly due to the co-localization of the inhibited receptor binding sites at the virion’s surface. Furthermore, we show that Janus-like inhibitors do not induce virus aggregation. Our findings may be generalized to other uptake processes including bacteria and drug-delivery.
Human histone deacetylase 6 shows strong preference for tubulin dimers over assembled microtubules
Authors: Skultetyova Lubica , Ustinova Kseniya , Kutil Zsofia , Novakova Zora , Pavlicek Jiri , Mikesova Jana , Trapl Dalibor , Baranova Petra , Havlinova Barbora , Hubalek Martin , Lansky Zdenek , Barinka Cyril
Published: September 2017

Human histone deacetylase 6 (HDAC6) is the major deacetylase responsible for removing the acetyl group from Lys40 of α-tubulin (αK40), which is located lumenally in polymerized microtubules. Here, we provide a detailed kinetic analysis of tubulin deacetylation and HDAC6/microtubule interactions using individual purified components. Our data unequivocally show that free tubulin dimers represent the preferred HDAC6 substrate, with a K
M
value of 0.23 µM and a deacetylation rate over 1,500-fold higher than that of assembled microtubules. We attribute the lower deacetylation rate of microtubules to both longitudinal and lateral lattice interactions within tubulin polymers. Using TIRF microscopy, we directly visualized stochastic binding of HDAC6 to assembled microtubules without any detectable preferential binding to microtubule tips. Likewise, indirect immunofluorescence microscopy revealed that microtubule deacetylation by HDAC6 is carried out stochastically along the whole microtubule length, rather than from the open extremities. Our data thus complement prior studies on tubulin acetylation and further strengthen the rationale for the correlation between tubulin acetylation and microtubule age.
Limits of Predictability of Cascading Overload Failures in Spatially-Embedded Networks with Distributed Flows
Authors: Moussawi A. , Derzsy N. , Lin X. , Szymanski B. K. , Korniss G.
Published: September 2017

Cascading failures are a critical vulnerability of complex information or infrastructure networks. Here we investigate the properties of load-based cascading failures in real and synthetic spatially-embedded network structures, and propose mitigation strategies to reduce the severity of damages caused by such failures. We introduce a stochastic method for optimal heterogeneous distribution of resources (node capacities) subject to a fixed total cost. Additionally, we design and compare the performance of networks with N-stable and (N-1)-stable network-capacity allocations by triggering cascades using various real-world node-attack and node-failure scenarios. We show that failure mitigation through increased node protection can be effectively achieved against single-node failures. However, mitigating against multiple node failures is much more difficult due to the combinatorial increase in possible sets of initially failing nodes. We analyze the robustness of the system with increasing protection, and find that a critical tolerance exists at which the system undergoes a phase transition, and above which the network almost completely survives an attack. Moreover, we show that cascade-size distributions measured in this region exhibit a power-law decay. Finally, we find a strong correlation between cascade sizes induced by individual nodes and sets of nodes. We also show that network topology alone is a weak predictor in determining the progression of cascading failures.
Oral fibroblasts modulate the macrophage response to bacterial challenge
Authors: Tzach-Nahman Rinat , Nashef Rizan , Fleissig Omer , Palmon Aharon , Shapira Lior , Wilensky Asaf , Nussbaum Gabriel
Published: September 2017

Tissue damage in chronic periodontal disease is driven by the host response to a dysbiotic microbiota, and not by bacteria directly. Among chronic inflammatory diseases of the oral cavity, inflammation and tissue damage around dental implants (peri-implantitis) is emerging as a major clinical challenge, since it is more severe and less responsive to treatment compared to inflammation around natural teeth. We tested whether oral fibroblasts from the periodontal ligament (PDLF), which are present around natural teeth but not around dental implants, actively regulate inflammatory responses to bacterial stimulation. We show that human PDLF down-regulate TNF-α post-transcriptionally in macrophages stimulated with the oral pathogenPorphyromonas gingivalis. Cell contact and secretion of IL-6 and IL-10 contribute to the modulation of inflammatory cytokine production. Although fibroblasts decreased TNF-α secretion, they enhanced the ability of macrophages to phagocytose bacteria. Surprisingly, donor matched oral fibroblasts from gingival tissues, or fibroblasts from peri-implant inflamed tissues were at least as active as PDLF in regulating macrophage responses to bacteria. In addition, priming fibroblasts with inflammatory mediators enhanced PDLF regulatory activity. A further understanding of the spectrum of fibroblast activities in inflammatory lesions is important in order to design ways to control inflammatory tissue damage.
Predicting clinical outcomes from large scale cancer genomic profiles with deep survival models
Authors: Yousefi Safoora , Amrollahi Fatemeh , Amgad Mohamed , Dong Chengliang , Lewis Joshua E. , Song Congzheng , Gutman David A. , Halani Sameer H. , Velazquez Vega Jose Enrique , Brat Daniel J. , Cooper Lee A. D.
Published: September 2017

Translating the vast data generated by genomic platforms into accurate predictions of clinical outcomes is a fundamental challenge in genomic medicine. Many prediction methods face limitations in learning from the high-dimensional profiles generated by these platforms, and rely on experts to hand-select a small number of features for training prediction models. In this paper, we demonstrate how deep learning and Bayesian optimization methods that have been remarkably successful in general high-dimensional prediction tasks can be adapted to the problem of predicting cancer outcomes. We perform an extensive comparison of Bayesian optimized deep survival models and other state of the art machine learning methods for survival analysis, and describe a framework for interpreting deep survival models using a risk backpropagation technique. Finally, we illustrate that deep survival models can successfully transfer information across diseases to improve prognostic accuracy. We provide an open-source software implementation of this framework called SurvivalNet that enables automatic training, evaluation and interpretation of deep survival models.
Highly potent antimicrobial modified peptides derived from the Acinetobacter baumannii phage endolysin LysAB2
Authors: Peng Shih-Yi , You Ren-In , Lai Meng-Jiun , Lin Nien-Tsung , Chen Li-Kuang , Chang Kai-Chih
Published: September 2017

The increase in the prevalence of multidrug-resistant Acinetobacter baumannii (MDRAB) strains is a serious public health concern. Antimicrobial peptides (AMPs) are a possible solution to this problem. In this study, we examined whether AMPs could be derived from phage endolysins. We synthesized four AMPs based on an amphipathic helical region in the C-terminus of endolysin LysAB2 encoded by the A. baumannii phage ΦAB2. These peptides showed potent antibacterial activity against A. baumannii (minimum inhibitory concentration, 4–64 μM), including some MDR and colistin-resistant A. baumannii. Of the four peptides, LysAB2 P3, with modifications that increased its net positive charge and decreased its hydrophobicity, showed high antibacterial activity against A. baumannii but little haemolytic and no cytotoxic activity against normal eukaryotic cells. The results of electron microscopy experiments and a fluorescein isothiocyanate staining assay indicated that this peptide killed A. baumannii through membrane permeabilization. Moreover, in a mouse intraperitoneal infection model, at 4 h after the bacterial injection, LysAB2 P3 decreased the bacterial load by 13-fold in ascites and 27-fold in blood. Additionally, LysAB2 P3 rescued sixty percent of mice heavily infected with A. baumannii from lethal bacteremia. Our results confirmed that bacteriophage endolysins are a promising resource for developing effective AMPs.
Tuning electromagnetic properties of SrRuO3 epitaxial thin films via atomic control of cation vacancies
Authors: Lee Sang A , Oh Seokjae , Lee Jegon , Hwang Jae-Yeol , Kim Jiwoong , Park Sungkyun , Bae Jong-Seong , Hong Tae Eun , Lee Suyoun , Kim Sung Wng , Kang Won Nam , Choi Woo Seok
Published: September 2017

Elemental defect in transition metal oxides is an important and intriguing subject that result in modifications in variety of physical properties including atomic and electronic structure, optical and magnetic properties. Understanding the formation of elemental vacancies and their influence on different physical properties is essential in studying the complex oxide thin films. In this study, we investigated the physical properties of epitaxial SrRuO3 thin films by systematically manipulating cation and/or oxygen vacancies, via changing the oxygen partial pressure (P(O2)) during the pulsed laser epitaxy (PLE) growth. Ru vacancies in the low-P(O2)-grown SrRuO3 thin films induce lattice expansion with the suppression of the ferromagnetic TC down to ~120 K. Sr vacancies also disturb the ferromagnetic ordering, even though Sr is not a magnetic element. Our results indicate that both A and B cation vacancies in an ABO3 perovskite can be systematically engineered via PLE, and the structural, electrical, and magnetic properties can be tailored accordingly.
Chronic kidney disease is associated with poorer in-hospital outcomes in patients hospitalized with infections: Electronic record analysis from China
Authors: Su Guobin , Xu Hong , Marrone Gaetano , Lindholm Bengt , Wen Zehuai , Liu Xusheng , Carrero Juan-Jesus , Lundborg Cecilia Stålsby
Published: September 2017

Predominantly based on studies from high-income countries, reduced estimated glomerular filtration rate (eGFR) has been associated with increased risk of infections and infection-related hospitalizations (IRHs). We here explore in-hospital outcomes of IRHs in patients with different kidney function. A total of 6,283 adults, not on renal replacement therapy, with a discharge diagnosis of infection, and with an eGFR 1–12 months before index hospitalization, were included from four hospitals in China. We compared in-hospital outcomes (death, intensive care unit (ICU) admission, length of hospital stay (LOHS) and medical expenses), between patients with and without chronic kidney disease (CKD, defined as eGFR ≤ 60 ml/min per 1.73 m2 of body surface area) by mixed-effects logistic regression model or generalized linear model. The odds for in-hospital mortality (adjusted odds ratios (OR) = 1.41; 95% CI 1.02–1.96) and ICU admission (OR = 2.18; 95% CI 1.64–2.91) were higher among patients with CKD. The median LOHS was significantly higher for CKD patients (11 days vs. 10 days in non-CKD, P < 0.001), and inferred costs were 20.0% higher adjusted for inflation rate based on costs in 2012 (P < 0.001). Patients with CKD hospitalized with infections are at increased risk of poorer in-hospital outcomes, conveying higher medical costs.
Angle-resolved stochastic photon emission in the quantum radiation-dominated regime
Authors: Li Jian-Xing , Chen Yue-Yue , Hatsagortsyan Karen Z. , Keitel Christoph H.
Published: September 2017

Signatures of stochastic effects in the radiation of a relativistic electron beam interacting with a counterpropagating superstrong short focused laser pulse are investigated in a quantum regime when the electron’s radiation dominates its dynamics. We consider the electron-laser interaction at near-reflection conditions when pronounced high-energy gamma-ray bursts arise in the backward-emission direction with respect to the initial motion of the electrons. The quantum stochastic nature of the gamma-photon emission is exhibited in the angular distributions of the radiation and explained in an intuitive picture. Although, the visibility of the stochasticity signatures depends on the laser and electron beam parameters, the signatures are of a qualitative nature and robust. The stochasticity, a fundamental quantum property of photon emission, should thus be measurable rather straightforwardly with laser technology available in near future.
MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells
Authors: Beigbeder Alice , Chartier François J. M. , Bisson Nicolas
Published: September 2017

HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized. We performed GRB2 affinity purification combined with mass spectrometry analysis of associated proteins in a HER2+ breast cancer model to delineate GRB2-nucleated protein interaction networks. We report the identification of the transmembrane protein MPZL1 as a new GRB2-associated protein. Our data show that the PTPN11 tyrosine phosphatase acts as a scaffold to bridge the association between GRB2 and MPZL1 in a phosphotyrosine-dependent manner. We further demonstrate that the formation of this MPZL1-PTPN11-GRB2 complex is triggered by cell attachment to fibronectin. Thus, our data support the importance of this new signalling complex in the control of cell adhesion of HER2+ breast cancer cells, a key feature of the metastatic process.
Hydrogen sulphate-based ionic liquid-assisted electro-polymerization of PEDOT catalyst material for high-efficiency photoelectrochemical solar cells
Authors: Carbas Buket Bezgin , Gulen Mahir , Tolu Merve Celik , Sonmezoglu Savas
Published: September 2017

This work reports the facile, one-step electro-polymerization synthesis of poly (3,4-ethylenedioxythiophene) (PEDOT) using a 1-ethyl-3-methylimidazolium hydrogen sulphate (EMIMHSO4) ionic liquid (IL) and, for the first time its utilization as a counter electrode (CE) in dye-sensitized solar cells (DSSCs). Using the IL doped PEDOT as CE, we effectively improve the solar cell efficiency to as high as 8.52%, the highest efficiency reported in 150 mC/cm2 charge capacity, an improvement of ~52% over the control device using the bare PEDOT CE (5.63%). Besides exhibiting good electrocatalytic stability, the highest efficiency reported for the PEDOT CE-based DSSCs using hydrogen sulphate [HSO4]− anion based ILs is also higher than platinum-(Pt)-based reference cells (7.87%). This outstanding performance is attributed to the enhanced charge mobility, reduced contact resistance, improved catalytic stability, smoother surface and well-adhesion. Our experimental analyses reveal that the [HSO4]− anion group of the IL bonds to the PEDOT, leading to higher electron mobility to balance the charge transport at the cathode, a better adhesion for high quality growth PEDOT CE on the substrates and superior catalytic stability. Consequently, the EMIMHSO4-doped PEDOT can successfully act as an excellent alternative green catalyst material, replacing expensive Pt catalysts, to improve performance of DSSCs.
Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation
Authors: Yu Caroline Oi-Ling , Leung Kwok-Sui , Jiang Jonney Lei , Wang Tina Bai-Yan , Chow Simon Kwoon-Ho , Cheung Wing-Hoi
Published: September 2017

Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.
The antipsychotic drugs olanzapine and haloperidol modify network connectivity and spontaneous activity of neural networks in vitro
Authors: Dzyubenko Egor , Juckel Georg , Faissner Andreas
Published: September 2017

Impaired neural synchronization is a hallmark of psychotic conditions such as schizophrenia. It has been proposed that schizophrenia-related cognitive deficits are caused by an unbalance of reciprocal inhibitory and stimulatory signaling. This supposedly leads to decreased power of induced gamma oscillations during the performance of cognitive tasks. In light of this hypothesis an efficient antipsychotic treatment should modify the connectivity and synchronization of local neural circuits. To address this issue, we investigated a model of hippocampal neuronal networks in vitro. Inhibitory and excitatory innervation of GABAergic and glutamatergic neurons was quantified using immunocytochemical markers and an automated routine to estimate network connectivity. The first generation (FGA) and second generation (SGA) antipsychotic drugs haloperidol and olanzapine, respectively, differentially modified the density of synaptic inputs. Based on the observed synapse density modifications, we developed a computational model that reliably predicted distinct changes in network activity patterns. The results of computational modeling were confirmed by spontaneous network activity measurements using the multiple electrode array (MEA) technique. When the cultures were treated with olanzapine, overall activity and synchronization were increased, whereas haloperidol had the opposite effect. We conclude that FGAs and SGAs differentially affect the balance between inhibition and excitation in hippocampal networks.
New taxa of freshwater mussels (Unionidae) from a species-rich but overlooked evolutionary hotspot in Southeast Asia
Authors: Bolotov Ivan N. , Vikhrev Ilya V. , Kondakov Alexander V. , Konopleva Ekaterina S. , Gofarov Mikhail Yu. , Aksenova Olga V. , Tumpeesuwan Sakboworn
Published: September 2017

Southeast Asia harbors a unique and diverse freshwater fauna of Mesozoic origin, which is under severe threat of extinction because of rapid economic development and urbanization. The largest freshwater basins of the region are certainly the primary evolutionary hotspots and they attract the most attention as key biodiversity areas for conservation. In contrast, medium-sized rivers are considered low-importance areas with secondary biodiversity, whose faunas originated via founder events from larger basins during the Pleistocene, although such a scenario has never been tested by using a phylogenetic approach. In this investigation, we used freshwater mussels (Unionidae) as a model to estimate the levels of endemism within the Sittaung, a little-known remote basin in Myanmar, compared with the surrounding larger rivers (Irrawaddy, Salween and Mekong). We discovered that the Sittaung represents an exceptional evolutionary hotspot with numerous endemic taxa of freshwater mussels. On the basis of our extensive dataset, we describe two new tribes, two genera, seven species and a subspecies of Unionidae. Our results highlight that medium-sized basins may represent separate evolutionary hotspots that harbor a number of endemic lineages. These basins should therefore be a focus of special conservation efforts alongside the largest Southeast Asian rivers.
A Screening Mechanism Differentiating True from False Pain during Empathy
Authors: Sun Ya-Bin , Lin Xiao-Xiao , Ye Wen , Wang Ning , Wang Jin-Yan , Luo Fei
Published: September 2017

Empathizing with another’s suffering is important in social interactions. Empathic behavior is selectively elicited from genuine, meaningful pain but not from fake, meaningless scenarios. However, the brain’s screening mechanism of false information from meaningful events and the time course for the screening process remains unclear. Using EEG combined with principle components analysis (PCA) techniques, here we compared temporal neurodynamics between the observation of pain and no-pain pictures as well as between true (painful expressions and needle-penetrated arms) and false (needle-penetrated faces with neutral expressions) pain pictures. The results revealed that pain vs. no-pain information is differentiated in the very early ERP components, i.e., the N1/P1 for the face and arm pictures categories and the VPP/N170 for the facial expression category while the mid-latency ERP components, N2 and P3, played key roles in differentiating true from false situations. The complex of N2 and P3 components may serve as a screening mechanism through which observers allocate their attentions to more important or relevant events and screen out false environmental information. This is the first study to describe and provide a time course of the screening process during pain empathy. These findings shed new light on the understanding of empathic processing.
Association among obesity, overweight and autism spectrum disorder: a systematic review and meta-analysis
Authors: Zheng Zhen , Zhang Li , Li Shiping , Zhao Fengyan , Wang Yan , Huang Lan , Huang Jinglan , Zou Rong , Qu Yi , Mu Dezhi
Published: September 2017

Obesity, overweight and autism spectrum disorder (ASD) remain serious public health problems. Although lots of studies have recently explored the association among obesity, overweight and ASD, the findings are inconsistent. Thus, we conducted a meta-analysis of epidemiological studies to examine the association among obesity, overweight and ASD. PubMed, Embase, and the Cochrane Library were used for literature searches to identify eligible studies published in English before November 15, 2016. Relevant studies estimating the association among obesity, overweight and ASD were included. Fifteen studies encompassing 49,937,078 participants and 1,045,538 individuals with ASD were included in this study. A random effects model was chosen to synthesize the effect sizes of individual studies. The prevalence of obesity was significantly higher in individuals with ASD than in controls (OR = 1.84, 95% confidence interval [CI]: 1.37–2.48, P < 0.001). However, the prevalence of overweight in individuals with ASD was not significantly different from that in controls (OR = 1.07, 95% CI: 0.83–1.38, P = 0.62). Both sensitivity analysis and publication bias testing revealed that the findings were robust. The meta-analysis showed a significant association between obesity and ASD. However, no significant association was identified between overweight and ASD.
Affected energy metabolism under manganese stress governs cellular toxicity
Authors: Kaur Gursharan , Kumar Vineet , Arora Amit , Tomar Ajay , Ashish  , Sur Runa , Dutta Dipak
Published: September 2017

Excessive manganese exposure is toxic, but a comprehensive biochemical picture of this assault is poorly understood. Whether oxidative stress or reduced energy metabolism under manganese exposure causes toxicity is still a debate. To address this, we chose ΔmntPEscherichia coli, a highly manganese-sensitive strain, in this study. Combining microarray, proteomics, and biochemical analyses, we show that the chronic manganese exposure rewires diverse regulatory and metabolic pathways. Manganese stress affects protein and other macromolecular stability, and envelope biogenesis. Most importantly, manganese exposure disrupts both iron-sulfur cluster and heme-enzyme biogenesis by depleting cellular iron level. Therefore, the compromised function of the iron-dependent enzymes in the tricarboxylic acid cycle, and electron transport chain impede ATP synthesis, leading to severe energy deficiency. Manganese stress also evokes reactive oxygen species, inducing oxidative stress. However, suppressing oxidative stress does not improve oxidative phosphorylation and cell growth. On the contrary, iron supplementation resumed cell growth stimulating oxidative phosphorylation. Therefore, we hypothesize that affected energy metabolism is the primal cause of manganese toxicity.
Using a Novel Microfabricated Model of the Alveolar-Capillary Barrier to Investigate the Effect of Matrix Structure on Atelectrauma
Authors: Higuita-Castro N. , Nelson M. T. , Shukla V. , Agudelo-Garcia P. A. , Zhang W. , Duarte-Sanmiguel S. M. , Englert J. A. , Lannutti J. J. , Hansford D. J. , Ghadiali S. N.
Published: September 2017

The alveolar-capillary barrier is composed of epithelial and endothelial cells interacting across a fibrous extracelluar matrix (ECM). Although remodeling of the ECM occurs during several lung disorders, it is not known how fiber structure and mechanics influences cell injury during cyclic airway reopening as occurs during mechanical ventilation (atelectrauma). We have developed a novelin vitroplatform that mimics the micro/nano-scale architecture of the alveolar microenvironment and have used this system to investigate how ECM microstructural properties influence epithelial cell injury during airway reopening. In addition to epithelial-endothelial interactions, our platform accounts for the fibrous topography of the basal membrane and allows for easy modulation of fiber size/diameter, density and stiffness. Results indicate that fiber stiffness and topography significantly influence epithelial/endothelial barrier function where increased fiber stiffness/density resulted in altered cytoskeletal structure, increased tight junction (TJ) formation and reduced barrier permeability. However, cells on rigid/dense fibers were also more susceptible to injury during airway reopening. These results indicate that changes in the mechanics and architecture of the lung microenvironment can significantly alter cell function and injury and demonstrate the importance of implementingin vitromodels that more closely resemble the natural conditions of the lung microenvironment.
Haplotype of the Interleukin 17A gene is associated with osteitis after Bacillus Calmette-Guerin vaccination
Authors: Korppi Matti , Teräsjärvi Johanna , Liehu-Martiskainen Milla , Lauhkonen Eero , Vuononvirta Juho , Nuolivirta Kirsi , Kröger Liisa , Pöyhönen Laura , Karjalainen Minna K. , He Qiushui
Published: September 2017

Bacillus Calmette-Guerin (BCG) osteitis was more common in Finland than elsewhere at the time when universal BCG vaccinations were given to Finnish newborns. There is evidence that IL-17 plays a role in the defense against tuberculosis. The aim of this study was to evaluate the associations of IL17A rs4711998, IL17A rs8193036 and IL17A rs2275913 single-nucleotide polymorphisms (SNPs) with the risk of BCG osteitis after newborn vaccination. IL17A rs4711998, rs8193036 and rs2275913 SNPs were determined in 131 adults had presented with BCG osteitis after newborn BCG vaccination. We analyzed, using the HaploView and PLINK programs, whether allele or haplotype frequencies of these SNPs differ between the former BCG osteitis patients and Finnish population controls. Of the three IL17A SNPs studied, rs4711998 associated nominally with BCG osteitis; minor allele frequency was 0.215 in 130 BCG osteitis cases and 0.298 in 99 controls (p = 0.034). Frequency of the second common haplotype (GTA) differed significantly between BCG osteitis cases and controls (0.296 vs. 0.184, p = 0.040 after multi-testing correction). The GTA haplotype of the IL17A SNPs rs4711998, rs8193036 and rs2275913 was associated with osteitis after BCG vaccination.
α2-adrenoceptor-mediated inhibition in the central amygdala blocks fear-conditioning
Authors: Holmes N. M. , Crane J. W. , Tang M. , Fam J. , Westbrook R. F. , Delaney A. J.
Published: September 2017

The central amygdala is critical for the acquisition and expression of fear memories. This region receives a dense innervation from brainstem noradrenergic cell groups and has a high level of α2-adrenoceptor expression. Using whole-cell electrophysiological recordings from rat brain slices, we characterise the role of pre-synaptic α2-adrenoceptor in modulating discrete inhibitory and excitatory connections within both the lateral and medial division of the central amygdala. The selective α2-adrenoceptor agonist clonidine blocked the excitatory input from the pontine parabrachial neurons onto neurons of the lateral central amygdala. In addition, clonidine blocked inhibitory connections from the medial paracapsular intercalated cell mass onto both lateral and medial central amygdala neurons. To examine the behavioural consequence of α2-adrenoceptor-mediated inhibition of these inputs, we infused clonidine into the central amygdala prior to contextual fear-conditioning. In contrast to vehicle-infused rats, clonidine-infused animals displayed reduced levels of freezing 24 hours after training, despite showing no difference in freezing during the training session. These results reveal a role for α2-adrenoceptors within the central amygdala in the modulation of synaptic transmission and the formation of fear-memories. In addition, they provide further evidence for a role of the central amygdala in fear-memory formation.
Continuous Beam Steering Through Broadside Using Asymmetrically Modulated Goubau Line Leaky-Wave Antennas
Authors: Tang Xiao-Lan , Zhang Qingfeng , Hu Sanming , Zhuang Yaqiang , Kandwal Abhishek , Zhang Ge , Chen Yifan
Published: September 2017

Goubau line is a single-conductor transmission line, featuring easy integration and low-loss transmission properties. Here, we propose a periodic leaky-wave antenna (LWA) based on planar Goubau transmission line on a thin dielectric substrate. The leaky-wave radiations are generated by introducing periodic modulations along the Goubau line. In this way, the surface wave, which is slow-wave mode supported by the Goubau line, achieves an additional momentum and hence enters the fast-wave region for radiations. By employing the periodic modulations, the proposed Goubau line LWAs are able to continuously steer the main beam from backward to forward within the operational frequency range. However, the LWAs usually suffer from a low radiation efficiency at the broadside direction. To overcome this drawback, we explore both transversally and longitudinally asymmetrical modulations to the Goubau line. Theoretical analysis, numerical simulations and experimental results are given in comparison with the symmetrical LWAs. It is demonstrated that the asymmetrical modulations significantly improve the radiation efficiency of LWAs at the broadside. Furthermore, the measurement results agree well with the numerical ones, which experimentally validates the proposed LWA structures. These novel Goubau line LWAs, experimentally demonstrated and validated at microwave frequencies, show also great potential for millimeter-wave and terahertz systems.
High-yield production of “difficult-to-express” proteins in a continuous exchange cell-free system based on CHO cell lysates
Authors: Thoring Lena , Dondapati Srujan K. , Stech Marlitt , Wüstenhagen Doreen A. , Kubick Stefan
Published: September 2017

Cell-free protein synthesis (CFPS) represents a promising technology for efficient protein production targeting especially so called “difficult-to-express” proteins whose synthesis is challenging in conventional in vivo protein production platforms. Chinese hamster ovary (CHO) cells are one of the most prominent and safety approved cell lines for industrial protein production. In this study we demonstrated the ability to produce high yields of various protein types including membrane proteins and single chain variable fragments (scFv) in a continuous exchange cell-free (CECF) system based on CHO cell lysate that contains endogenous microsomal structures. We showed significant improvement of protein yield compared to batch formatted reactions and proved biological activity of synthesized proteins using various analysis technologies. Optimized CECF reaction conditions led to membrane protein yields up to 980 µg/ml, which is the highest protein yield reached in a microsome containing eukaryotic cell-free system presented so far.
The effects of different enrofloxacin dosages on clinical efficacy and resistance development in chickens experimentally infected with Salmonella Typhimurium
Authors: Li Jun , Hao Haihong , Cheng Guyue , Wang Xu , Ahmed Saeed , Shabbir Muhammad Abu Bakr , Liu Zhenli , Dai Menghong , Yuan Zonghui
Published: September 2017

To investigate the optimal dosage which can improve clinical efficacy and minimize resistance, pharmacokinetics/pharmacodynamics model of enrofloxacin was established. Effect of enrofloxacin treatments on clearance ofSalmonellain experimentally infected chickens and simultaneously resistance selection inSalmonellaand coliforms were evaluated in three treatment groups (100, PK/PD designed dosage of 4, 0.1 mg/kg b.w.) and a control group. Treatment duration was three rounds of 7-day treatment alternated with 7-day withdrawal. Results showed that 100 mg/kg b.w. of enrofloxacin completely eradicatedSalmonella, but resistant coliforms (4.0–60.8%) were selected from the end of the second round’s withdrawal period till the end of the experiment (days 28–42). PK/PD based dosage (4 mg/kg b.w.) effectively reducedSalmonellafor the first treatment duration. However upon cessation of medication,Salmonellarepopulated chickens and persisted till the end with reduced susceptibility (MICCIP = 0.03–0.25 mg/L). Low frequency (5–9.5%) of resistant coliforms was selected (days 39–42). Enrofloxacin at dosage of 0.1 mg/kg b.w. was not able to eliminateSalmonellaand selected coliforms with slight decreased susceptibility (MICENR = 0.25 mg/L). In conclusion, short time treatment (7 days) of enrofloxacin at high dosage (100 mg/kg b.w.) could be effective in treatingSalmonellainfection while minimizing resistance selection in bothSalmonellaand coliforms.