bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-conductance chemo-optogenetic system based on the vertebrate channel Trpa1b
Authors: Lam Pui-Ying , Mendu Suresh K. , Mills Robert W. , Zheng Baohui , Padilla Hugo , Milan David J. , Desai Bimal N. , Peterson Randall T. 
Published: September 2017

AbstractOptogenetics is a powerful research approach that allows localized optical modulation of selected cells within an animal via the expression of genetically encoded photo-excitable ion channels. Commonly used optogenetic techniques rely on the expression of microbial opsin variants, which have many excellent features but suffer from various degrees of blue spectral overlap and limited channel conductance. Here, we expand the optogenetics toolbox in the form of a tunable, high-conductance vertebrate cation channel, zTrpa1b, coupled with photo-activated channel ligands, such as optovin and 4g6. Our results demonstrate that zTrpa1b/ligand pairing offers high light sensitivity, millisecond-scale response latency in vivo, as well as adjustable channel off latency. Exogenous in vivo expression of zTrpa1b in sensory neurons allowed subcellular photo-activation, enabling light-dependent motor control. zTrpa1b/ligand was also suitable for cardiomyocyte pacing, as shown in experiments performed on zebrafish hearts in vivo as well as in human stem cell-derived cardiomyocytes in vitro. Therefore, zTrpa1b/optovin represents a novel tool for flexible, high-conductance optogenetics.
Balance between hydration enthalpy and entropy is important for ice binding surfaces in Antifreeze Proteins
Authors: Schauperl Michael , Podewitz Maren , Ortner Teresa S. , Waibl Franz , Thoeny Alexander , Loerting Thomas , Liedl Klaus R. 
Published: September 2017

AbstractAntifreeze Proteins (AFPs) inhibit the growth of an ice crystal by binding to it. The detailed binding mechanism is, however, still not fully understood. We investigated three AFPs using Molecular Dynamics simulations in combination with Grid Inhomogeneous Solvation Theory, exploring their hydration thermodynamics. The observed enthalpic and entropic differences between the ice-binding sites and the inactive surface reveal key properties essential for proteins in order to bind ice: While entropic contributions are similar for all sites, the enthalpic gain for all ice-binding sites is lower than for the rest of the protein surface. In contrast to most of the recently published studies, our analyses show that enthalpic interactions are as important as an ice-like pre-ordering. Based on these observations, we propose a new, thermodynamically more refined mechanism of the ice recognition process showing that the appropriate balance between entropy and enthalpy facilitates ice-binding of proteins. Especially, high enthalpic interactions between the protein surface and water can hinder the ice-binding activity.
Bistability and up/down state alternations in inhibition-dominated randomly connected networks of LIF neurons
Authors: Tartaglia Elisa M. , Brunel Nicolas 
Published: September 2017

AbstractElectrophysiological recordings in cortex in vivo have revealed a rich variety of dynamical regimes ranging from irregular asynchronous states to a diversity of synchronized states, depending on species, anesthesia, and external stimulation. The average population firing rate in these states is typically low. We study analytically and numerically a network of sparsely connected excitatory and inhibitory integrate-and-fire neurons in the inhibition-dominated, low firing rate regime. For sufficiently high values of the external input, the network exhibits an asynchronous low firing frequency state (L). Depending on synaptic time constants, we show that two scenarios may occur when external inputs are decreased: (1) the L state can destabilize through a Hopf bifucation as the external input is decreased, leading to synchronized oscillations spanning d δ to β frequencies; (2) the network can reach a bistable region, between the low firing frequency network state (L) and a quiescent one (Q). Adding an adaptation current to excitatory neurons leads to spontaneous alternations between L and Q states, similar to experimental observations on UP and DOWN states alternations.
Dynamics of water bound to crystalline cellulose
Authors: O’Neill Hugh , Pingali Sai Venkatesh , Petridis Loukas , He Junhong , Mamontov Eugene , Hong Liang , Urban Volker , Evans Barbara , Langan Paul , Smith Jeremy C. , Davison Brian H. 
Published: September 2017

AbstractInteractions of water with cellulose are of both fundamental and technological importance. Here, we characterize the properties of water associated with cellulose using deuterium labeling, neutron scattering and molecular dynamics simulation. Quasi-elastic neutron scattering provided quantitative details about the dynamical relaxation processes that occur and was supported by structural characterization using small-angle neutron scattering and X-ray diffraction. We can unambiguously detect two populations of water associated with cellulose. The first is “non-freezing bound” water that gradually becomes mobile with increasing temperature and can be related to surface water. The second population is consistent with confined water that abruptly becomes mobile at ~260 K, and can be attributed to water that accumulates in the narrow spaces between the microfibrils. Quantitative analysis of the QENS data showed that, at 250 K, the water diffusion coefficient was 0.85 ± 0.04 × 10−10 m2sec−1and increased to 1.77 ± 0.09 × 10−10 m2sec−1at 265 K. MD simulations are in excellent agreement with the experiments and support the interpretation that water associated with cellulose exists in two dynamical populations. Our results provide clarity to previous work investigating the states of bound water and provide a new approach for probing water interactions with lignocellulose materials.
Core-shell heterostructured multiwalled carbon nanotubes@reduced graphene oxide nanoribbons/chitosan, a robust nanobiocomposite for enzymatic biosensing of hydrogen peroxide and nitrite
Authors: Mani Veerappan , Govindasamy Mani , Chen Shen-Ming , Chen Tse-Wei , Kumar Annamalai Senthil , Huang Sheng-Tung 
Published: September 2017

AbstractA robust nanobiocomposite based on core-shell heterostructured multiwalled carbon nanotubes@reduced graphene oxide nanoribbons (MWCNTs@rGONRs)/chitosan (CHIT) was described for the fabrication of sensitive, selective, reproducible and durable biosensor for hydrogen peroxide (H2O2) and nitrite (NO2−). The excellent physicochemical properties of MWCNTs@rGONRs such as, presence of abundant oxygen functionalities, higher area-normalized edge-plane structures and chemically active sites in combination with excellent biocompatibility of CHIT resulting in the versatile immobilization matrix for myoglobin (Mb). The most attractive property of MWCNTs@rGONRs which distinguishes it from other members of graphene family is its rich edge density and edge defects that are highly beneficial for constructing enzymatic biosensors. The direct electron transfer characteristics such as, redox properties, amount of immobilized active Mb, electron transfer efficiency and durability were studied. Being as good immobilization matrix, MWCNTs@rGONRs/CHIT is also an excellent signal amplifier which helped in achieving low detection limits to quantify H2O2 (1 nM) and NO2− (10 nM). The practical feasibility of the biosensor was successfully validated in contact lens cleaning solution and meat sample.
A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
Authors: Drummond Nicola J. , Davies Nick O. , Lovett Janet E. , Miller Mark R. , Cook Graeme , Becker Thomas , Becker Catherina G. , McPhail Donald B. , Kunath Tilo 
Published: September 2017

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and moderate mitochondrial enrichment of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against cell loss in a zebrafish model of dopaminergic neurodegeneration.
Role of chemotherapy in dedifferentiated liposarcoma of the retroperitoneum: defining the benefit and challenges of the standard
Authors: Livingston J. A. , Bugano D. , Barbo A. , Lin H. , Madewell J. E. , Wang W. L. , Lazar A. J. , Tseng W. W. , Roland C. L. , Feig B. W. , Pollock R. , Conley A. P. , Benjamin R. S. , Patel S. , Somaiah N. 
Published: September 2017

AbstractBenefit from chemotherapy for well-differentiated/de-differentiated (WD/DD) liposarcomas has been reported to be minimal, however traditional response criteria may not adequately capture positive treatment effect. In this study, we evaluate benefit from first-line chemotherapy and characterize imaging response characteristics in patients with retroperitoneal (RP) WD/DD liposarcoma treated at The University of Texas MD Anderson Cancer Center. Response was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) and an exploratory analysis of vascular response was characterized. Among 82 patients evaluable for response to first-line therapy, 31 patients received neoadjuvant chemotherapy for localized/locally advanced disease; 51 received chemotherapy for unresectable recurrent/metastatic disease. Median overall survival from the start of chemotherapy was 29 months (95% CI 24–40 months). Response rates by RECIST: partial response (PR) 21% (17/82), stable disease (SD) 40%, and progression (PD) 39%. All RECIST responses were in patients receiving combination chemotherapy. A qualitative vascular response was seen in 24 patients (31%). Combination chemotherapy yields a response rate of 24% and a clinical benefit rate (CR/PR/SD > 6 months) of 44%, higher than previously reported in DD liposarcoma. A higher percentage of patients experience a vascular response with chemotherapy that is not adequately captured by RECIST in these large heterogeneous tumors.
ArcA overexpression induces fermentation and results in enhanced growth rates of E. coli
Authors: Basan Markus , Hui Sheng , Williamson James R. 
Published: September 2017

AbstractOverflow metabolism in the presence of oxygen occurs at fast growth rates in a wide range of organisms including bacteria, yeast and cancer cells and plays an important role in biotechnology during production of proteins or metabolic compounds. As recently suggested, overflow metabolism can be understood in terms of proteome allocation, since fermentation has lower proteome cost for energy production than respiration. Here, we demonstrate that ArcA overexpression in aerobic conditions, results in downregulation of respiratory pathways and enhanced growth rates on glycolytic substrates of E. coli, coinciding with acetate excretion and increased carbon uptake rates. These results suggest that fermentation enables faster growth and demonstrate that fermentation on many glycolytic carbon sources is not limited by carbon uptake. Hence, these findings are difficult to reconcile with many alternative hypotheses that have been proposed for the origin of overflow metabolism and the growth rate dependence of fermentation and respiration, which are based on limited capacity of respiration or limitations in uptake rates and catabolic pathways. Instead, as suggested by increased lag phases of ArcA overexpression strains, respiratory energy metabolism may be related to a general preparatory response, observed for decreasing growth rates, but with limited advantages for maximizing steady-state growth rate.
Nrf2/HO-1 mediates the neuroprotective effect of mangiferin on early brain injury after subarachnoid hemorrhage by attenuating mitochondria-related apoptosis and neuroinflammation
Authors: Wang Zefeng , Guo Songxue , Wang Junxing , Shen Yuanyuan , Zhang Jianmin , Wu Qun 
Published: September 2017

AbstractEarly brain injury (EBI) is involved in the process of cerebral tissue damage caused by subarachnoid hemorrhage (SAH), and multiple mechanisms, such as apoptosis and inflammation, participate in its development. Mangiferin (MF), a natural C-glucoside xanthone, has been reported to exert beneficial effects against several types of organ injury by influencing various biological progresses. The current study aimed to investigate the potential of MF to protect against EBI following SAH via histological and biological assessments. A rat perforation model of SAH was established, and MF was subsequently administered via intraperitoneal injection at a low and a high dose. High-dose MF significantly lowered the mortality of SAH animals and ameliorated their neurological deficits and brain edema. MF also dose-relatedly attenuated SAH-induced oxidative stress and decreased cortical cell apoptosis by influencing mitochondria-apoptotic proteins. In addition, MF downregulated the activation of the NLRP3 inflammasome and NF-κB as well as the production of inflammatory cytokines, and the expression of Nrf2 and HO-1 was upregulated by MF. The abovementioned findings indicate that MF is neuroprotective against EBI after SAH and Nrf2/HO-1 cascade may play a key role in mediating its effect through regulation of the mitochondrial apoptosis pathway and activation of the NLRP3 inflammasome and NF-κB.
Enabling stop codon read-through translation in bacteria as a probe for amyloid aggregation
Authors: Molina-García Laura , Giraldo Rafael 
Published: September 2017

AbstractAmyloid aggregation of the eukaryotic translation terminator eRF3/Sup35p, the [PSI+] prion, empowers yeast ribosomes to read-through UGA stop codons. No similar functional prion, skipping a stop codon, has been found in Escherichia coli, a fact possibly due to the efficient back-up systems found in bacteria to rescue non-stop complexes. Here we report that engineering hydrophobic amyloidogenic repeats from a synthetic bacterial prion-like protein (RepA-WH1) into the E. coli releasing factor RF1 promotes its aggregation and enables ribosomes to continue with translation through a premature UAG stop codon located in a β-galactosidase reporter. To our knowledge, intended aggregation of a termination factor is a way to overcome the bacterial translation quality checkpoint that had not been reported so far. We also show the feasibility of using the amyloidogenic RF1 chimeras as a reliable, rapid and cost-effective system to screen for molecules inhibiting intracellular protein amyloidogenesis in vivo, by testing the effect on the chimeras of natural polyphenols with known anti-amyloidogenic properties. Resveratrol exhibits a clear amyloid-solubilizing effect in this assay, showing no toxicity to bacteria or interference with the enzymatic activity of β-galactosidase.
Bumetanide treatment during early development rescues maternal separation-induced susceptibility to stress
Authors: Hu Die , Yu Zhou-Long , Zhang Yan , Han Ying , Zhang Wen , Lu Lin , Shi Jie 
Published: September 2017

AbstractStress is a major risk factor for psychiatric disorders, such as depression, posttraumatic stress disorder, and schizophrenia. Early life stress, such as maternal separation, can have long-term effects on the development of the central nervous system and pathogenesis of psychiatric disorders. In the present study, we found that maternal separation increased the susceptibility to stress in adolescent rats, increased the expression of Na+/K+/2Cl− cotransporter 1 (NKCC1) on postnatal day 14, and increased the expression of K+/2Cl− cotransporter 2 (KCC2) and γ-aminobutyric acid A (GABAA) receptor subunits on postnatal day 40 in the hippocampus. NKCC1 inhibition by the U.S. Food and Drug Administration-approved drug bumetanide during the first two postnatal weeks rescued the depressive- and anxiety-like behavior that was induced by maternal separation and decreased the expression of NKCC1, KCC2 and GABAA receptor α1 and β2,3 subunits in the hippocampus. Bumetanide treatment during early development did not adversely affect body weight or normal behaviors in naive rats, or affect serum osmolality in adult rats. These results suggest that bumetanide treatment during early development may prevent the maternal separation-induced susceptibility to stress and impairments in GABAergic transmission in the hippocampus.
Local atmospheric response to warm mesoscale ocean eddies in the Kuroshio–Oyashio Confluence region
Authors: Sugimoto Shusaku , Aono Kenji , Fukui Shin 
Published: September 2017

AbstractIn the extratropical regions, surface winds enhance upward heat release from the ocean to atmosphere, resulting in cold surface ocean: surface ocean temperature is negatively correlated with upward heat flux. However, in the western boundary currents and eddy-rich regions, the warmer surface waters compared to surrounding waters enhance upward heat release–a positive correlation between upward heat release and surface ocean temperature, implying that the ocean drives the atmosphere. The atmospheric response to warm mesoscale ocean eddies with a horizontal extent of a few hundred kilometers remains unclear because of a lack of observations. By conducting regional atmospheric model experiments, we show that, in the Kuroshio–Oyashio Confluence region, wintertime warm eddies heat the marine atmospheric boundary layer (MABL), and accelerate westerly winds in the near-surface atmosphere via the vertical mixing effect, leading to wind convergence around the eastern edge of eddies. The warm-eddy-induced convergence forms local ascending motion where convective precipitation is enhanced, providing diabatic heating to the atmosphere above MABL. Our results indicate that warm eddies affect not only near-surface atmosphere but also free atmosphere, and possibly synoptic atmospheric variability. A detailed understanding of warm eddy–atmosphere interaction is necessary to improve in weather and climate projections.
Ranibizumab after laser photocoagulation failure in retinopathy of prematurity (ROP) treatment
Authors: Gotz-Więckowska Anna , Chmielarz-Czarnocińska Anna , Pawlak Marta , Gadzinowski Janusz , Mazela Jan 
Published: September 2017

AbstractThe purpose of this study was to investigate the anatomical and functional outcomes of the two-stage treatment of severe retinopathy of prematurity (ROP) using laser photocoagulation and intravitreal ranibizumab injection. The medical records of 53 eyes of 28 infants treated by conventional laser photocoagulation with deferred intravitreal 0.25 mg/0.025 mL ranibizumab injection were analysed. All patients had at least 11 months of follow-up. In the analysed group, the mean gestational age at birth was 25 weeks and mean birthweight was 790 g. The mean time of laser photocoagulation was 34 weeks of postmenstrual age (PMA). Ranibizumab injection was performed on average at 37 weeks of PMA. The mean time between interventions was 19 days. Retinal detachment occurred in 12 eyes (22.6%), in three children bilaterally. Visual responses were obtained in 23 of 28 treated children. Our results indicate that ranibizumab injection can be taken into consideration in the selected cases of laser photocoagulation failure. The unsatisfactory results of this study elicited a change in the ROP treatment protocol in our medical centre. The study gives an insight into anatomical and functional outcomes of ROP treatment in the Central and Eastern European population.
Viral outbreaks involve destabilized evolutionary networks: evidence from Ebola, Influenza and Zika
Authors: Aris-Brosou Stéphane , Ibeh Neke , Noël Jessica 
Published: September 2017

AbstractRecent history has provided us with one pandemic (Influenza A/H1N1) and two severe viral outbreaks (Ebola and Zika). In all three cases, post-hoc analyses have given us deep insights into what triggered these outbreaks, their timing, evolutionary dynamics, and phylogeography, but the genomic characteristics of outbreak viruses are still unclear. To address this outstanding question, we searched for a common denominator between these recent outbreaks, positing that the genome of outbreak viruses is in an unstable evolutionary state, while that of non-outbreak viruses is stabilized by a network of correlated substitutions. Here, we show that during regular epidemics, viral genomes are indeed stabilized by a dense network of weakly correlated sites, and that these networks disappear during pandemics and outbreaks when rates of evolution increase transiently. Post-pandemic, these evolutionary networks are progressively re-established. We finally show that destabilization is not caused by substitutions targeting epitopes, but more likely by changes in the environment sensu lato. Our results prompt for a new interpretation of pandemics as being associated with evolutionary destabilized viruses.
Functional effects of proinflammatory factors present in Sjögren’s syndrome salivary microenvironment in an in vitro model of human salivary gland
Authors: Arce-Franco Mayte , Dominguez-Luis María , Pec Martina K. , Martínez-Gimeno Carlos , Miranda Pablo , Alvarez de la Rosa Diego , Giraldez Teresa , García-Verdugo José María , Machado José David , Díaz-González Federico 
Published: September 2017

AbstractPrimary Sjögren’s syndrome (pSS) is an autoimmune exocrinopathy in which the role that the immune response plays in reducing exocrine gland function, including the glandular microenvironment of cytokines, has not been fully understood. Epithelial cells from biopsies of human parotid gland (HPG) were used to establish a model of human salivary glandin vitro. In this model, the functional consequences of several proinflammatory soluble factors present in the pSS glandular microenvironment were assessed. Stimulation with isoproterenol and calcium produced a significant increase in the basal activity of amylase in the HPG cell supernatants. Under these conditions, the presence of TNF-α and CXCL12 increased amylase mRNA cellular abundance, but reduced the amylase activity in the cell-free supernatant in a dose-dependent manner. IL-1β and IFN-γ, but not TGF-β, also diminished amylase secretion by HPG cells. These results suggest that the glandular microenvironment of cytokine, by acting post-transcriptionally, may be responsible, at least in part, for the reduced exocrine function observed in pSS patients. These data may help to a better understanding of the pathogenesis of SS, which in turn would facilitate the identification of new therapeutic targets for this disorder.