bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of Multivalent Inhibitors for Preventing Cellular Uptake
Authors: Schubertová Veronika , Martinez-Veracoechea Francisco J. , Vácha Robert 
Published: September 2017

AbstractCellular 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

AbstractHuman 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

AbstractCascading 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

AbstractTissue 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

AbstractTranslating 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

AbstractThe 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

AbstractElemental 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

AbstractPredominantly 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

AbstractSignatures 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

AbstractHER2/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

AbstractThis 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

AbstractDelayed 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

AbstractImpaired 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

AbstractSoutheast 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

AbstractEmpathizing 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.