bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silico investigation of a KCNQ1 mutation associated with short QT syndrome
Authors: Adeniran Ismail , Whittaker Dominic G. , El Harchi Aziza , Hancox Jules C. , Zhang Henggui 
Published: August 2017

AbstractShort QT syndrome (SQTS) is a rare condition characterized by abnormally ‘short’ QT intervals on the ECG and increased susceptibility to cardiac arrhythmias and sudden death. This simulation study investigated arrhythmia dynamics in multi-scale human ventricle models associated with the SQT2-related V307L KCNQ1 ‘gain-of-function’ mutation, which increases slow-delayed rectifier potassium current (IKs). A Markov chain (MC) model recapitulating wild type (WT) and V307L mutant IKs kinetics was incorporated into a model of the human ventricular action potential (AP) for investigation of QT interval changes and arrhythmia substrates. In addition, the degree of simulated IKs inhibition necessary to normalize the QT interval and terminate re-entry in SQT2 conditions was quantified. The developed MC model accurately reproduced AP shortening and reduced effective refractory period associated with altered IKs kinetics in homozygous (V307L) and heterozygous (WT-V307L) mutation conditions, which increased the lifespan and dominant frequency of re-entry in 3D human ventricle models. IKs reductions of 58% and 65% were sufficient to terminate re-entry in WT-V307L and V307L conditions, respectively. This study further substantiates a causal link between the V307L KCNQ1 mutation and pro-arrhythmia in human ventricles, and establishes partial inhibition of IKs as a potential anti-arrhythmic strategy in SQT2.
Increased Body Exposure to New Anti-Trypanosomal Through Nanoencapsulation
Authors: Tupinambá Branquinho Renata , Pound-Lana Gwenaelle , Marques Milagre Matheus , Saúde-Guimarães Dênia Antunes , Vilela José Mário Carneiro , Spangler Andrade Margareth , de Lana Marta , Mosqueira Vanessa Carla Furtado 
Published: August 2017

AbstractLychnopholide, a lipophilic sesquiterpene lactone, is efficacious in mice at the acute and chronic phases of Chagas disease. Conventional poly-ε-caprolactone (PCL) and long-circulating poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules containing lychnopholide were developed and characterized. Lychnopholide presented high association efficiency (>90%) with the nanocapsules. A new, fast and simple HPLC-UV-based bioanalytical method was developed, validated in mouse plasma and applied to lychnopholide quantification in in vitro release kinetics and pharmacokinetics. The nanocapsules had mean hydrodynamic diameters in the range of 100–250 nm, negative zeta potentials (−30 mV to −57 mV), with good physical stability under storage. Atomic force microscopy morphological analysis revealed spherical monodispersed particles and the absence of lychnopholide crystallization or aggregation. Association of lychnopholide to PLA-PEG nanocapsules resulted in a 16-fold increase in body exposure, a 26-fold increase in plasma half-life and a dramatic reduction of the lychnopholide plasma clearance (17-fold) in comparison with free lychnopholide. The improved pharmacokinetic profile of lychnopholide in long-circulating nanocapsules is in agreement with the previously reported improved efficacy observed in Trypanosoma cruzi-infected mice. The present lychnopholide intravenous dosage form showed great potential for further pre-clinical and clinical studies in Chagas disease and cancer therapies.
Conjugated polymers mediate effective activation of the Mammalian Ion Channel Transient Receptor Potential Vanilloid 1
Authors: Lodola F. , Martino N. , Tullii G. , Lanzani G. , Antognazza M. R. 
Published: August 2017

AbstractSelective and rapid regulation of ionic channels is pivotal to the understanding of physiological processes and has a crucial impact in developing novel therapeutic strategies. Transient Receptor Potential (TRP) channels are emerging as essential cellular switches that allow animals to respond to their environment. In particular, the Vanilloid Receptor 1 (TRPV1), besides being involved in the body temperature regulation and in the response to pain, has important roles in several neuronal functions, as cytoskeleton dynamics, injured neurons regeneration, synaptic plasticity. Currently available tools to modulate TRPV1 activity suffer from limited spatial selectivity, do not allow for temporally precise control, and are usually not reversible, thus limiting their application potential. The use of optical excitation would allow for overcoming all these limitations. Here, we propose a novel strategy, based on the use of light-sensitive, conjugated polymers. We demonstrate that illumination of a polymer thin film leads to reliable, robust and temporally precise control of TRPV1 channels. Interestingly, the activation of the channel is due to the combination of two different, locally confined effects, namely the release of thermal energy from the polymer surface and the variation of the local ionic concentration at the cell/polymer interface, both mediated by the polymer photoexcitation.
Soil C and N statuses determine the effect of maize inoculation by plant growth-promoting rhizobacteria on nitrifying and denitrifying communities
Authors: Florio Alessandro , Pommier Thomas , Gervaix Jonathan , Bérard Annette , Le Roux Xavier 
Published: August 2017

AbstractMaize inoculation by Azospirillum stimulates root growth, along with soil nitrogen (N) uptake and root carbon (C) exudation, thus increasing N use efficiency. However, inoculation effects on soil N-cycling microbial communities have been overlooked. We hypothesized that inoculation would (i) increase roots-nitrifiers competition for ammonium, and thus decrease nitrifier abundance; and (ii) increase roots-denitrifiers competition for nitrate and C supply to denitrifiers by root exudation, and thus limit or benefit denitrifiers depending on the resource (N or C) mostly limiting these microorganisms. We quantified (de)nitrifiers abundance and activity in the rhizosphere of inoculated and non-inoculated maize on 4 sites over 2 years, and ancillary soil variables. Inoculation effects on nitrification and nitrifiers (AOA, AOB) were not consistent between the three sampling dates. Inoculation influenced denitrifiers abundance (nirK, nirS) differently among sites. In sites with high C limitation for denitrifiers (i.e. limitation of denitrification by C > 66%), inoculation increased nirS-denitrifier abundance (up to 56%) and gross N2O production (up to 84%), likely due to increased root C exudation. Conversely, in sites with low C limitation (<47%), inoculation decreased nirS-denitrifier abundance (down to −23%) and gross N2O production (down to −18%) likely due to an increased roots-denitrifiers competition for nitrate.
Electrochemical Hydroxylation of C3–C12
n-Alkanes by Recombinant Alkane Hydroxylase (AlkB) and Rubredoxin-2 (AlkG) from Pseudomonas putida GPo1
Authors: Tsai Yi-Fang , Luo Wen-I , Chang Jen-Lin , Chang Chun-Wei , Chuang Huai-Chun , Ramu Ravirala , Wei Guor-Tzo , Zen Jyh-Myng , Yu Steve S.-F. 
Published: August 2017

AbstractAn unprecedented method for the efficient conversion of C3–C12 linear alkanes to their corresponding primary alcohols mediated by the membrane-bound alkane hydroxylase (AlkB) from Pseudomonas putida GPo1 is demonstrated. The X-ray absorption spectroscopy (XAS) studies support that electrons can be transferred from the reduced AlkG (rubredoxin-2, the redox partner of AlkB) to AlkB in a two-phase manner. Based on this observation, an approach for the electrocatalytic conversion from alkanes to alcohols mediated by AlkB using an AlkG immobilized screen-printed carbon electrode (SPCE) is developed. The framework distortion of AlkB–AlkG adduct on SPCE surface might create promiscuity toward gaseous substrates. Hence, small alkanes including propane and n-butane can be accommodated in the hydrophobic pocket of AlkB for C–H bond activation. The proof of concept herein advances the development of artificial C–H bond activation catalysts.
Efficient generation of bispecific IgG antibodies by split intein mediated protein trans-splicing system
Authors: Han Lei , Chen Junsheng , Ding Kai , Zong Huifang , Xie Yueqing , Jiang Hua , Zhang Baohong , Lu Huili , Yin Weihan , Gilly John , Zhu Jianwei 
Published: August 2017

AbstractMany methods have been developed to produce bispecific antibodies (BsAbs) for industrial application. However, huge challenges still remain in synthesizing whole length BsAbs, including their assembly, stability, immunogenicity, and pharmacodynamics. Here we present for first time a generic technology platform of generating bispecific IgG antibodies, “Bispecific Antibody by Protein Trans-splicing (BAPTS)”. Different from published methods, we assembled two parental antibody fragments in the hinge region by the protein trans-splicing reaction of a split intein to generate BsAbs without heavy/heavy and light/heavy chain mispairing. Utilizing this simple and efficient approach, there have been several BsAbs (CD3×HER2, CD3×EGFR, EGFR×HER2) synthesized to demonstrate its broad applicability. Correctly paired mAb arms were assembled to form BsAbs that were purified through protein A affinity chromatography to demonstrate industrial applicability at large scale. Further, the products were characterized through physical-biochemistry properties and biological activities to confirm expected quality of the products from “BAPTS”. More importantly, correct pairing was confirmed by mass spectrum. Proof-of-concept studies with CD3×HER2 BsAb (T-cell recruitment) demonstrated superior bioactivity compared with trastuzumab. The results of undetectable mispairing and high biological activity have indicated that this method has the potential to be utilized to manufacture BsAbs with high efficiency at industrial scale.
Identification of Novel Non-secosteroidal Vitamin D Receptor Agonists with Potent Cardioprotective Effects and ﻿﻿devoid of Hypercalcemia
Authors: Khedkar Santosh A. , Samad Mohammed A. , Choudhury Sangita , Lee Ji Yoo , Zhang Dongsheng , Thadhani Ravi I. , Karumanchi S. Ananth , Rigby Alan C. , Kang Peter M. 
Published: August 2017

AbstractVitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models. VDR 4-1 also effectively suppressed secondary hyperparathyroidism in 1α-hydroxylase knockout mice. In contrast to 1α,25-dihydroxyvitamin D3 (1,25-D3 or calcitriol), a naturally occurring VDR agonist, VDR 4-1 therapy even at high doses did not induce hypercalcemia. These findings were accompanied by a lack of upregulation of calcium transport genes in kidney and in the gut providing a mechanism for the lack of hypercalcemia. Furthermore, VDR 4-1 therapy significantly suppressed cardiac hypertrophy and progression to heart failure in both vitamin D deficient and normal mice without inducing significant hypercalcemia. In conclusion, we have identified a unique VDR agonist compound with beneficial effects in mouse models of hyperparathyroidism and heart failure without inducing significant hypercalcemia.
Highly Active 2D Layered MoS
2

-rGO Hybrids for Energy Conversion and Storage Applications
Authors: Kamila Swagatika , Mohanty Bishnupad , Samantara Aneeya K. , Guha Puspendu , Ghosh Arnab , Jena Bijayalaxmi , Satyam Parlapalli V. , Mishra B. K. , Jena Bikash Kumar 
Published: August 2017

AbstractThe development of efficient materials for the generation and storage of renewable energy is now an urgent task for future energy demand. In this report, molybdenum disulphide hollow sphere (MoS2-HS) and its reduced graphene oxide hybrid (rGO/MoS2-S) have been synthesized and explored for energy generation and storage applications. The surface morphology, crystallinity and elemental composition of the as-synthesized materials have been thoroughly analysed. Inspired by the fascinating morphology of the MoS2-HS and rGO/MoS2-S materials, the electrochemical performance towards hydrogen evolution and supercapacitor has been demonstrated. The rGO/MoS2-S shows enhanced gravimetric capacitance values (318 ± 14 Fg−1) with higher specific energy/power outputs (44.1 ± 2.1 Whkg−1 and 159.16 ± 7.0 Wkg−1) and better cyclic performances (82 ± 0.95% even after 5000 cycles). Further, a prototype of the supercapacitor in a coin cell configuration has been fabricated and demonstrated towards powering a LED. The unique balance of exposed edge site and electrical conductivity of rGO/MoS2-S shows remarkably superior HER performances with lower onset over potential (0.16 ± 0.05 V), lower Tafel slope (75 ± 4 mVdec−1), higher exchange current density (0.072 ± 0.023 mAcm−2) and higher TOF (1.47 ± 0.085 s−1) values. The dual performance of the rGO/MoS2-S substantiates the promising application for hydrogen generation and supercapacitor application of interest.
Cerebral blood volume and oxygen supply uniformly increase following various intrathoracic pressure strains
Authors: Zhang Zhongxing , Bolz Nina , Laures Marco , Oremek Margit , Schmidt Christoph , Qi Ming , Khatami Ramin 
Published: August 2017

AbstractIntrathoracic pressure (ITP) swings challenge many physiological systems. The responses of cerebral hemodynamics to different ITP swings are still less well-known due to the complexity of cerebral circulation and methodological limitation. Using frequency-domain near-infrared spectroscopy and echocardiography, we measured changes in cerebral, muscular and cardiac hemodynamics in five graded respiratory maneuvers (RM), breath holding, moderate and strong Valsalva maneuvers (mVM/sVM) with 20 and 40 cmH2O increments in ITP, moderate and strong Mueller maneuvers (mMM/sMM) with 20 and 40 cmH2O decrements in ITP controlled by esophageal manometry. We found cerebral blood volume (CBV) maintains relative constant during the strains while it increases during the recoveries together with increased oxygen supply. By contrast changes in muscular blood volume (MBV) are mainly controlled by systemic changes. The graded changes of ITP during the maneuvers predict the changes of MBV but not CBV. Changes in left ventricular stroke volume and heart rate correlate to MBV but not to CBV. These results suggest the increased CBV after the ITP strains is brain specific, suggesting cerebral vasodilatation. Within the strains, cerebral oxygen saturation only decreases in sVM, indicating strong increment rather than decrement in ITP may be more challenging for the brain.
Pre-culture Sudan Black B treatment suppresses autofluorescence signals emitted from polymer tissue scaffolds
Authors: Qi Lin , Knapton Erin K. , Zhang Xu , Zhang Tongwen , Gu Chen , Zhao Yi 
Published: August 2017

AbstractIn tissue engineering, autofluorescence of polymer scaffolds often lowers the image contrast, making it difficult to examine cells and subcellular structures. Treating the scaffold materials with Sudan Black B (SBB) after cell fixation can effectively suppress autofluorescence, but this approach is not conducive to live cell imaging. Post-culture SBB treatment also disrupts intracellular structures and leads to reduced fluorescence intensity of the targets of interest. In this study, we introduce pre-culture SBB treatment to suppress autofluorescence, where SBB is applied to polymeric scaffold materials before cell seeding. The results show that the autofluorescence signals emitted from polycaprolactone (PCL) scaffolds in three commonly used fluorescence channels effectively decrease without diminishing the fluorescence signals emitted from the cells. The pre-culture SBB treatment does not significantly affect cell viability. The autofluorescence suppressive effect does not substantially diminish during the culturing period up to 28 days. The results also show that cell migration, proliferation, and myogenic differentiation in pre-culture SBB-treated groups do not exhibit statistical difference from the non-treated groups. As such, this approach greatly improves the fluorescence image quality for examining live cell behaviors and dynamics while the cells are cultured within autofluorescent polymer scaffolds.
MicroRNA-7641 is a regulator of ribosomal proteins and a promising targeting factor to improve the efficacy of cancer therapy
Authors: Reza Abu Musa Md. Talimur , Choi Yun-Jung , Yuan Yu-Guo , Das Joydeep , Yasuda Hideyo , Kim Jin-Hoi 
Published: August 2017

AbstractMany diseases, including myocardial infarction, autoimmune disease, viral diseases, neurodegenerative diseases, and cancers, are frequently diagnosed with aberrant expression of microRNAs (miRNAs) and their allied pathways. This indicates the crucial role of miRNAs in maintaining biological and physiological processes. miR-7641 is a miRNA whose role in disease has not been fully investigated. In the present study, we investigated the expression pattern of miR-7641 and its target genes in different cancer cells, as well as in clinical cancer patients. Our data confirmed RPS16 and TNFSF10 as two direct targets of miR-7641, while gene expression study showed that a group of genes are also deregulated by miR-7641, including many ribosomal proteins that are frequently co-expressed with RPS16 in breast cancer. Direct inhibition of miR-7641 using a locked nucleic acid upregulated the expression of its target genes, sensitized cancer cells, and enhanced the efficiency of therapeutic agents such as doxorubicin. In addition, inhibition of miR-7641 boosted doxorubicin-mediated apoptosis of cancer cells via upregulation of apoptotic molecules Caspase 9 (CAS9) and poly ADP ribose polymerase (PARP) and downregulation of anti-apoptotic molecule BCL2. Thus, miR-7641 might be a clinically important cancer biomarker. Inhibition of miR-7641 expression could be an efficient treatment strategy for clinical patients.
Identifying protein complexes in PPI network using non-cooperative sequential game
Authors: Maulik Ujjwal , Basu Srinka , Ray Sumanta 
Published: August 2017

AbstractIdentifying protein complexes from protein-protein interaction (PPI) network is an important and challenging task in computational biology as it helps in better understanding of cellular mechanisms in various organisms. In this paper we propose a noncooperative sequential game based model for protein complex detection from PPI network. The key hypothesis is that protein complex formation is driven by mechanism that eventually optimizes the number of interactions within the complex leading to dense subgraph. The hypothesis is drawn from the observed network property named small world. The proposed multi-player game model translates the hypothesis into the game strategies. The Nash equilibrium of the game corresponds to a network partition where each protein either belong to a complex or form a singleton cluster. We further propose an algorithm to find the Nash equilibrium of the sequential game. The exhaustive experiment on synthetic benchmark and real life yeast networks evaluates the structural as well as biological significance of the network partitions.
Potato spindle tuber viroid infection triggers degradation of chloride channel protein CLC-b-like and Ribosomal protein S3a-like mRNAs in tomato plants
Authors: Adkar-Purushothama Charith Raj , Iyer Pavithran Sridharan , Perreault Jean-Pierre 
Published: August 2017

AbstractIt is well established that viroid derived small RNA (vd-sRNA) induces RNA silencing of endogenous mRNA. However, it remains not clear how exactly viroid infections can lead to severe symptom induction given the fact that fewer vd-sRNAs binding the specific target mRNAs were recovered from the infected plants. To answer this question, the two least expressed (+) and (−) strand vd-sRNAs of potato spindle tuber viroid (PSTVd) binding to both the 3′ UTR and the coding region of tomato mRNAs were analyzed by infecting tomato plants with two variants of PSTVd. As products of these putative target mRNAs are involved in plant phenotype, the effect of this viroid on these genes were analyzed by infecting tomato plants with two variants of PSTVd. The direct interaction between the vd-sRNAs and putative mRNAs was validated by artificial microRNA experiments in a transient expression system and by RNA ligase-mediated rapid amplification of cDNA ends. Parallel analysis of RNA ends of viroid infected plants revealed the widespread cleavage of the target mRNAs in locations other than the vd-sRNA binding site during the viroid infection implying the viroid-infection induced vd-sRNA independent degradation of endogenous mRNAs during viroid infection.
Restriction and modification of deoxyarchaeosine (dG+)-containing phage 9 g DNA
Authors: Tsai Rebecca , Corrêa Ivan R. , Xu Michael Y. , Xu Shuang-yong 
Published: August 2017

AbstractE. coli phage 9 g contains the modified base deoxyarchaeosine (dG+) in its genome. The phage encodes its own primase, DNA ligase, DNA polymerase, and enzymes necessary to synthesize and incorporate dG+. Here we report phage 9 g DNA sensitivity to >200 Type II restriction endonucleases (REases). Among the REases tested approximately 29% generated complete or partial digestions, while the remaining 71% displayed resistance to restriction. Phage 9 g restriction fragments can be degraded by DNA exonucleases or ligated by T3 and T4 DNA ligases. In addition, we examined a number of cytosine and adenine methyltransferases to generate double base modifications. M.AluI, M.CviPI, M.HhaI, and M.EcoGII were able to introduce 5mC or
N6mA into 9 g DNA as confirmed by partial resistance to restriction and by liquid chromatography-mass spectrometry. A number of wild-type E. coli bacteria restricted phage 9 g, indicating natural restriction barriers exist in some strains. A BlastP search of GenBank sequences revealed five glutamine amidotransferase-QueC homologs in Enterobacteria and Pseudomonas phage, and distant homologs in other phage and bacterial genomes, suggesting that dG+ is not a rare modification. We also mapped phage 9 g DNA packaging (pac) site containing two 21-bp direct repeats and a major terminase cleavage site in the phage genome.
Multigenerational effects of copper nanomaterials (CuONMs) are different of those of CuCl2: exposure in the soil invertebrate Enchytraeus crypticus
Authors: Bicho Rita C. , Santos Fátima C. F. , Scott-Fordsmand Janeck J. , Amorim Mónica J. B. 
Published: August 2017

AbstractNanomaterials (NMs) are recommended to be tested in longer term exposures. Multigenerational (MG) studies are scarce and particularly important because effects can be transferred to the next generation. The current risk assessment framework does not include MG effects and this is a caveat for persistent materials. Here, the effects of copper NMs (CuONMs) and copper salt (CuCl2) were assessed in a MG exposure (4 generations in spiked soil + 2 generations in clean soil, F1 to F7 generations in total), with the standard soil model Enchytraeus crypticus, using relevant reproduction test effect concentrations (EC10, EC50), monitoring survival and reproduction. This represented ca. 1 year continuous exposure tests. MG effects varied with effect concentration and test materials: CuONMs caused increased toxicity for EC10 exposed organisms (EC50 did not change), and transfer to clean media reset effects, whereas CuCl2 reduced toxicity for EC10 and EC50, but the transfer to clean media “revived” the initial effects, i.e. close to EC50 levels in F7. Clearly CuONMs and CuCl2 cause different mechanisms of toxicity or response in the long term, not predictable based on short term or one generation studies. The present contributes for the improvement of risk assessment, adding important information for the long term exposure and effects.