bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia tolerance, longevity and cancer-resistance in the mole rat Spalax – a liver transcriptomics approach
Authors: Schmidt Hanno , Malik Assaf , Bicker Anne , Poetzsch Gesa , Avivi Aaron , Shams Imad , Hankeln Thomas
Published: October 2017

The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxia-sensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.
Punishing second-order free riders before first-order free riders: The effect of pool punishment priority on cooperation
Authors: Ozono Hiroki , Kamijo Yoshio , Shimizu Kazumi
Published: October 2017

Second-order free riders, who do not owe punishment cost to first-order free riders in public goods games, lead to low cooperation. Previous studies suggest that for stable cooperation, it is critical to have a pool punishment system with second-order punishment, which gathers resources from group members and punishes second-order free riders as well as first-order free riders. In this study, we focus on the priority of punishment. We hypothesize that the pool punishment system that prioritizes second-order punishment is more likely to achieve cooperation than the system that prioritizes first-order punishment, because the former is more likely to obtain sufficient punishment resources. In the experiments, we compare four pool punishment systems: 1To2 (first-order punishment to second-order punishment), 2To1 (second-order punishment to first-order punishment), 1ONLY (first-order punishment only), and 2ONLY (second-order punishment only). We find that the 2To1 and 2ONLY systems can receive more support than the 1To2 and 1ONLY systems and only the 2To1 system can achieve high cooperation. However, the effect of priority of second-order punishment is observed only when the punishment ratio (PR) is low (Experiment 1), not high (Experiment 2), in which the punishment resource is relatively abundant.
Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors
Authors: Choi Won Il , Sahu Abhishek , Vilos Cristian , Kamaly Nazila , Jo Seong-Min , Lee Jin Hyung , Tae Giyoong
Published: October 2017

Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.
Shape Controlled Synthesis of Copper Vanadate Platelet Nanostructures, Their Optical Band Edges, and Solar-Driven Water Splitting Properties
Authors: Khan Ibrahim , Qurashi Ahsanulhaq
Published: October 2017

We report the morphological and size tailored rational and facile synthesis of copper vanadate nanostructures via sonication assisted sol gel method. Field emission scanning electron microscopy (FESEM), indicated irregular and nanoflakes morphologies for the as synthesized copper vanadate (CV-120) and copper vanadate calcined at 250 °C (CV-250). The semispherical platelets shaped morphology revealed for the copper vanadate calcined at 550 °C (CV-500). The XRD patterns confirm the monoclinic and triclinic crystal phases for CV-250 and CV-500, respectively. The optical properties of CV-250 and CV-500 via UV-DRS showed significant absorption in the visible regime at λ = 565 nm and 670 nm with band gap 2.2 eV and 1.84 eV, respectively as calculated from Kubelka-Munk (KM) equation via Tauc’s plot. The values of band edge positions of CV-250 and CV-550 straddle with the hydrogen (HER) and oxygen evolution reaction (OER) potentials. The photoelectrodes of CV-250 and CV-500 fabricated by adsorption desorption method to test their photoelectrochemical (PEC) water splitting performance in the three-electrode cell. The onset photocurrent potential is observed at ~0.42 V, which reached to saturation at 1.05 V. The photocurrent density at saturation is ~0.65 mA/cm2 for CV-250 and CV-500, respectively.
Leishmania infantum lipophosphoglycan induced-Prostaglandin E2 production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2
Authors: Lima Jonilson Berlink , Araújo-Santos Théo , Lázaro-Souza Milena , Carneiro Alan Brito , Ibraim Izabela Coimbra , Jesus-Santos Flávio Henrique , Luz Nívea Farias , Pontes Sara de Moura , Entringer Petter Franco , Descoteaux Albert , Bozza Patrícia Torres , Soares Rodrigo Pedro , Borges Valéria Matos
Published: October 2017

Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces ofLeishmaniapromastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2(PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation byLeishmania infantumLPG and/or its lipid and glycan motifs was evaluated with regard to PGE2induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played byL.infantum-derived LPG in the proinflammatory response seen inLeishmaniainfection.
Positioning of aquatic animals based on time-of-arrival and random walk models using YAPS (Yet Another Positioning Solver)
Authors: Baktoft Henrik , Gjelland Karl Øystein , Økland Finn , Thygesen Uffe Høgsbro
Published: October 2017

Aquatic positional telemetry offers vast opportunities to studyin vivobehaviour of wild animals, but there is room for improvement in the data quality provided by current procedures for estimating positions. Here we present a novel positioning method called YAPS (Yet Another Positioning Solver), involving Maximum Likelihood analysis of a state-space model applied directly to time of arrival (TOA) data in combination with a movement model. YAPS avoids the sequential positioning-filtering-approach applied in alternative tools by using all available data in a single model, and offers better accuracy and error control. Feasibility and performance of YAPS was rigorously tested in a simulation study and by applying YAPS to data from an acoustic transmitter towed in a receiver array. Performance was compared to an alternative positioning model and proprietary software. The simulation study and field test revealed that YAPS performance was better and more consistent than alternatives. We conclude that YAPS outperformed the compared alternative methods, and that YAPS constitute a vast improvement to currently available positioning software in acoustic telemetry. Additionally, in contrast to vendor-supplied solutions, YAPS is transparent, flexible and can easily be adapted and extended for further improvements or to meet study specific requirements such as three-dimensional positioning.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
Authors: Wang Hui , Wang Qian , Wang Jintao , Guo Chiao , Kleiman Kyle , Meng He , Knight Jason S. , Eitzman Daniel T.
Published: October 2017

The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9−/−) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9−/− mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9−/− mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9−/− mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.
Shaping the evolutionary tree of green plants: evidence from the GST family
Authors: Monticolo Francesco , Colantuono Chiara , Chiusano Maria Luisa
Published: October 2017

Glutathione-S-transferases (GSTs) are encoded by genes belonging to a wide ubiquitous family in aerobic species and catalyze the conjugation of electrophilic substrates to glutathione (GSH). GSTs are divided in different classes, both in plants and animals. In plants, GSTs function in several pathways, including those related to secondary metabolites biosynthesis, hormone homeostasis, defense from pathogens and allow the prevention and detoxification of damage from heavy metals and herbicides. 1107 GST protein sequences from 20 different plant species with sequenced genomes were analyzed. Our analysis assigns 666 unclassified GSTs proteins to specific classes, remarking the wide heterogeneity of this gene family. Moreover, we highlighted the presence of further subclasses within each class. Regarding the class GST-Tau, one possible subclass appears to be present in all the Tau members of ancestor plant species. Moreover, the results highlight the presence of members of the Tau class in Marchantiophytes and confirm previous observations on the absence of GST-Tau in Bryophytes and green algae. These results support the hypothesis regarding the paraphyletic origin of Bryophytes, but also suggest that Marchantiophytes may be on the same branch leading to superior plants, depicting an alternative model for green plants evolution.
Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues
Authors: Anand Sanjay , Desai Vidhi , Alsmadi Nesreen , Kanneganti Aswini , Nguyen Dianna Huyen-Tram , Tran Martin , Patil Lokesh , Vasudevan Srikanth , Xu Cancan , Hong Yi , Cheng Jonathan , Keefer Edward , Romero-Ortega Mario I.
Published: October 2017

Neural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively. Here, we evaluate the differential potency of NGF, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), pleiotrophin (PTN), and NT-3 in asymmetrically guiding the regeneration of sensory and motor neurons. We report that, in the absence of distal target organs, molecular guidance cues can mediate the growth of electrically conductive fascicles with normal microanatomy. Compared to Y-tube compartments with bovine serum albumin (BSA), GDNF and NGF increased the motor and sensory axon content, respectively. In addition, the sensory to motor ratio was significantly increased by PTN (12.7:1) when compared to a BDNF + GDNF choice. The differential content of motor and sensory axons modulated by selective guidance cues may provide a strategy to better define axon types in peripheral nerve interfaces.
Critical controllability analysis of directed biological networks using efficient graph reduction
Authors: Ishitsuka Masayuki , Akutsu Tatsuya , Nacher Jose C.
Published: October 2017

Network science has recently integrated key concepts from control theory and has applied them to the analysis of the controllability of complex networks. One of the proposed frameworks uses the Minimum Dominating Set (MDS) approach, which has been successfully applied to the identification of cancer-related proteins and in analyses of large-scale undirected networks, such as proteome-wide protein interaction networks. However, many real systems are better represented by directed networks. Therefore, fast algorithms are required for the application of MDS to directed networks. Here, we propose an algorithm that utilises efficient graph reduction to identify critical control nodes in large-scale directed complex networks. The algorithm is 176-fold faster than existing methods and increases the computable network size to 65,000 nodes. We then applied the developed algorithm to metabolic pathways consisting of 70 plant species encompassing major plant lineages ranging from algae to angiosperms and to signalling pathways from C. elegans, D. melanogaster and H. sapiens. The analysis not only identified functional pathways enriched with critical control molecules but also showed that most control categories are largely conserved across evolutionary time, from green algae and early basal plants to modern angiosperm plant lineages.
An Enhanced Platform to Analyse Low-Affinity Amyloid β Protein by Integration of Electrical Detection and Preconcentrator
Authors: Yoo Yong Kyoung , Yoon Dae Sung , Kim Gangeun , Kim Jinsik , Han Sung Il , Lee Junwoo , Chae Myung-Sic , Lee Sang-Myung , Lee Kyu Hyoung , Hwang Kyo Seon , Lee Jeong Hoon
Published: October 2017

Sensitivity and limit of detection (LOD) enhancement are essential criteria for the development of ultrasensitive molecular sensors. Although various sensor types have been investigated to enhance sensitivity and LOD, analyte detection and its quantification are still challenging, particularly for protein-protein interactions with low association constants. To solve this problem, here, we used ion concentration polarization (ICP)-based preconcentration to increase the local concentration of analytes in a microfluidic platform for LOD improvement. This was the first demonstration of a microfluidic device with an integrated ICP preconcentrator and interdigitated microelectrode (IME) sensor to detect small changes in surface binding between antigens and antibodies. We detected the amyloid beta (Aβ) protein, an Alzheimer’s disease marker, with low binding affinity to its antibodies by adopting ICP preconcentration phenomena. We demonstrated that a combination of ICP preconcentrator and IME sensor increased the LOD by 13.8-fold to femtomolar level (8.15 fM), which corresponds to a significant advance for clinical applications.
Erythropoietin Signaling Regulates Key Epigenetic and Transcription Networks in Fetal Neural Progenitor Cells
Authors: Sollinger Christina , Lillis Jacquelyn , Malik Jeffrey , Getman Michael , Proschel Chris , Steiner Laurie
Published: October 2017

Erythropoietin (EPO) and its receptor are highly expressed in the developing nervous system, and exogenous EPO therapy is potentially neuroprotective, however the epigenetic and transcriptional changes downstream of EPO signaling in neural cells are not well understood. To delineate epigenetic changes associated with EPO signaling, we compared histone H3 lysine 4 dimethylation (H3K4me2) in EPO treated and control fetal neural progenitor cells, identifying 1,150 differentially bound regions. These regions were highly enriched near protein coding genes and had significant overlap with H4Acetylation, a mark of active regulatory elements. Motif analyses and co-occupancy studies revealed a complex regulatory network underlying the differentially bound regions, including previously identified mediators of EPO signaling (STAT5, STAT3), and novel factors such as REST, an epigenetic modifier central to neural differentiation and plasticity, and NRF1, a key regulator of antioxidant response and mitochondrial biogenesis. Global transcriptome analyses on neural tubes isolated from E9.0 EpoR-null and littermate control embryos validated ourin vitrofindings, further suggesting a role for REST and NRF1 downstream of EPO signaling. These data support a role for EPO in regulating the survival, proliferation, and differentiation of neural progenitor cells, and suggest a basis for its function in neural development and neuroprotection.
Chimpanzees spontaneously take turns in a shared serial ordering task
Authors: Martin Christopher Flynn , Biro Dora , Matsuzawa Tetsuro
Published: October 2017

Social coordination can provide optimal solutions to many kinds of group dilemmas, and non-human subjects have been shown to perform single actions successively or simultaneously with partners to maximize food rewards in a variety of experimental settings. Less attention has been given to showing how animals are able to produce multiple (rather than single) intermixed and co-regulated actions, even though many species’ signal transmissions and social interactions rely on extended bouts of coordinated turn-taking. Here we report on coordination behaviour in three pairs of chimpanzees (mother/offspring dyads) during an experimentally induced turn-taking scenario. Participants were given a “shared” version of a computer-based serial ordering task that they had previously mastered individually. We found that minimal trial-and-error learning was necessary for the participants to solve the new social version of the task, and that information flow was more pronounced from mothers toward offspring than the reverse, mirroring characteristics of social learning in wild chimpanzees. Our experiment introduces a novel paradigm for studying behavioural coordination in non-humans, able to yield insights into the evolution of turn-taking which underlies a range of social interactions, including communication and language.
Host genotype and time dependent antigen presentation of viral peptides: predictions from theory
Authors: Eccleston R. Charlotte , Coveney Peter V. , Dalchau Neil
Published: October 2017

The rate of progression of HIV infected individuals to AIDS is known to vary with the genotype of the host, and is linked to their allele of human leukocyte antigen (HLA) proteins, which present protein degradation products at the cell surface to circulating T-cells. HLA alleles are associated with Gag-specific T-cell responses that are protective against progression of the disease. While Pol is the most conserved HIV sequence, its association with immune control is not as strong. To gain a more thorough quantitative understanding of the factors that contribute to immunodominance, we have constructed a model of the recognition of HIV infection by the MHC class I pathway. Our model predicts surface presentation of HIV peptides over time, demonstrates the importance of viral protein kinetics, and provides evidence of the importance of Gag peptides in the long-term control of HIV infection. Furthermore, short-term dynamics are also predicted, with simulation of virion-derived peptides suggesting that efficient processing of Gag can lead to a 50% probability of presentation within 3 hours post-infection, as observed experimentally. In conjunction with epitope prediction algorithms, this modelling approach could be used to refine experimental targets for potential T-cell vaccines, both for HIV and other viruses.
Accurate and efficient band gap predictions of metal halide perovskites using the DFT-1/2 method: GW accuracy with DFT expense
Authors: Tao Shu Xia , Cao Xi , Bobbert Peter A.
Published: October 2017

The outstanding optoelectronics and photovoltaic properties of metal halide perovskites, including high carrier motilities, low carrier recombination rates, and the tunable spectral absorption range are attributed to the unique electronic properties of these materials. While DFT provides reliable structures and stabilities of perovskites, it performs poorly in electronic structure prediction. The relativistic GW approximation has been demonstrated to be able to capture electronic structure accurately, but at an extremely high computational cost. Here we report efficient and accurate band gap calculations of halide metal perovskites by using the approximate quasiparticle DFT-1/2 method. Using AMX3 (A = CH3NH3, CH2NHCH2, Cs; M = Pb, Sn, X = I, Br, Cl) as demonstration, the influence of the crystal structure (cubic, tetragonal or orthorhombic), variation of ions (different A, M and X) and relativistic effects on the electronic structure are systematically studied and compared with experimental results. Our results show that the DFT-1/2 method yields accurate band gaps with the precision of the GW method with no more computational cost than standard DFT. This opens the possibility of accurate electronic structure prediction of sophisticated halide perovskite structures and new materials design for lead-free materials.
Proton-solute coupling mechanism of the maltose transporter from Saccharomyces cerevisiae
Authors: Henderson Ryan , Poolman Bert
Published: October 2017

Mal11 catalyzes proton-coupled maltose transport across the plasma membrane of Saccharomyces cerevisiae. We used structure-based design of mutants and a kinetic analysis of maltose transport to determine the energy coupling mechanism of transport. We find that wildtype Mal11 is extremely well coupled and allows yeast to rapidly accumulate maltose to dangerous levels, resulting under some conditions in self-lysis. Three protonatable residues lining the central membrane-embedded cavity of Mal11 were identified as having potential roles in proton translocation. We probed the mechanistic basis for proton coupling with uphill and downhill transport assays and found that single mutants can still accumulate maltose but with a lower coupling efficiency than the wildtype. Next, we combined the individual mutations and created double and triple mutants. We found some redundancy in the functions of the acidic residues in proton coupling and that no single residue is most critical for proton coupling to maltose uptake, unlike what is usually observed in related transporters. Importantly, the triple mutants were completely uncoupled but still fully active in downhill efflux and equilibrium exchange. Together, these results depict a concerted mechanism of proton transport in Mal11 involving multiple charged residues.
New method for the identification of arbuscular mycorrhizal fungi by proteomic-based biotyping of spores using MALDI-TOF-MS
Authors: Crossay Thomas , Antheaume Cyril , Redecker Dirk , Bon Lucie , Chedri Nicolas , Richert Clément , Guentas Linda , Cavaloc Yvon , Amir Hamid
Published: October 2017

Arbuscular mycorrhizal fungi (AMF, Glomeromycota) are mutualistic symbionts associated with majority of land plants. These fungi play an important role in plant growth, but their taxonomic identification remains a challenge for academic research, culture collections and inoculum producers who need to certify their products. Identification of these fungi was traditionally performed based on their spore morphology. DNA sequence data have successfully been used to study the evolutionary relationships of AMF, develop molecular identification tools and assess their diversity in the environment. However, these methods require considerable expertise and are not well-adapted for “routine” quality control of culture collections and inoculum production. Here, we show that Matrix-Assisted Laser Desorption Ionisation Time of Flight Mass Spectrometry proteomic-based biotyping is a highly efficient approach for AMF identification. Nineteen isolates belonging to fourteen species, seven genera and five families were clearly differentiated by MALDI biotyping at the species level, and intraspecific differentiation was achieved for the majority. AMF identification by MALDI biotyping could be highly useful, not only for research but also in agricultural and environmental applications. Fast, accurate and inexpensive molecular mass determination and the possibility of automation make MALDI-TOF-MS a real alternative to conventional morphological and molecular methods for AMF identification.
An Effective Model of the Retinoic Acid Induced HL-60 Differentiation Program
Authors: Tasseff Ryan , Jensen Holly A. , Congleton Johanna , Dai David , Rogers Katharine V. , Sagar Adithya , Bunaciu Rodica P. , Yen Andrew , Varner Jeffrey D.
Published: October 2017

In this study, we present an effective model All-Trans Retinoic Acid (ATRA)-induced differentiation of HL-60 cells. The model describes reinforcing feedback between an ATRA-inducible signalsome complex involving many proteins including Vav1, a guanine nucleotide exchange factor, and the activation of the mitogen activated protein kinase (MAPK) cascade. We decomposed the effective model into three modules; a signal initiation module that sensed and transformed an ATRA signal into program activation signals; a signal integration module that controlled the expression of upstream transcription factors; and a phenotype module which encoded the expression of functional differentiation markers from the ATRA-inducible transcription factors. We identified an ensemble of effective model parameters using measurements taken from ATRA-induced HL-60 cells. Using these parameters, model analysis predicted that MAPK activation was bistable as a function of ATRA exposure. Conformational experiments supported ATRA-induced bistability. Additionally, the model captured intermediate and phenotypic gene expression data. Knockout analysis suggested Gfi-1 and PPARg were critical to the ATRAinduced differentiation program. These findings, combined with other literature evidence, suggested that reinforcing feedback is central to hyperactive signaling in a diversity of cell fate programs.
Hydrogen Bond Variations of Influenza A Viruses During Adaptation in Human
Authors: Luo Jiejian , Deng Lizong , Ding Xiao , Quan Lijun , Wu Aiping , Jiang Taijiao
Published: October 2017

Many host specific mutations have been detected in influenza A viruses (IAVs). However, their effects on hydrogen bond (H-bond) variations have rarely been investigated. In this study, 60 host specific sites were identified in the internal proteins of avian and human IAVs, 27 of which contained mutations with effects on H-bonds. Besides, 30 group specific sites were detected in HA and NA. Twenty-six of 36 mutations existing at these group specific sites caused H-bond loss or formation in at least one subtype. The number of mutations in isolations of 2009 pandemic H1N1, human-infecting H5N1 and H7N9 varied. The combinations of mutations and H-bond changes in these three subtypes of IAVs were also different. In addition, the mutations in isolations of H5N1 distributed more scattered than those in 2009 pandemic H1N1 and H7N9. Eight wave specific mutations in isolations of the fifth H7N9 wave were also identified. Three of them, R140K in HA, Y170H in NA, and R340K in PB2, were capable of resulting in H-bond loss. As mentioned above, these host or group or wave specific H-bond variations provide us with a new field of vision for understanding the changes of structural features in the human adaptation of IAVs.
Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass
Authors: Mayeuf-Louchart Alicia , Thorel Quentin , Delhaye Stéphane , Beauchamp Justine , Duhem Christian , Danckaert Anne , Lancel Steve , Pourcet Benoit , Woldt Estelle , Boulinguiez Alexis , Ferri Lise , Zecchin Mathilde , Staels Bart , Sebti Yasmine , Duez Hélène
Published: October 2017

The nuclear receptor Rev-erb-α modulates hepatic lipid and glucose metabolism, adipogenesis and thermogenesis. We have previously demonstrated that Rev-erb-α is also an important regulator of skeletal muscle mitochondrial biogenesis and function, and autophagy. As such, Rev-erb-α over-expression in skeletal muscle or its pharmacological activation improved mitochondrial respiration and enhanced exercise capacity. Here, in gain- and loss-of function studies, we show that Rev-erb-α also controls muscle mass. Rev-erb-α-deficiency in skeletal muscle leads to increased expression of the atrophy-related genes (atrogenes), associated with reduced muscle mass and decreased fiber size. By contrast,in vivoandin vitroRev-erb-α over-expression results in reduced atrogenes expression and increased fiber size. Finally, Rev-erb-α pharmacological activation blocks dexamethasone-induced upregulation of atrogenes and muscle atrophy. This study identifies Rev-erb-α as a promising pharmacological target to preserve muscle mass.
Factors influencing the success of aerial rabies vaccination of foxes
Authors: Henning J. , Giorgi E. , Soares Magalhães R. J. , Tizzani P. , Viviani P. , Pejovic N. , Hrapović M. , Potzsch C.
Published: October 2017

Sylvatic rabies has been eradicated from most of Central Europe, but cases still occur in the Balkans. Oral rabies vaccination of foxes is an effective method for controlling the disease. The aim of this study was to evaluate the success of aerial vaccination campaigns conducted in Montenegro by identifying ecological, environmental and climatic factors that influenced the prevalence of antibodies to the rabies vaccine. To monitor the bait uptake and the serological responses to vaccination, foxes were shot by hunters. Of 175 shot foxes, 142 foxes (81.1%) had consumed baits. Of these only a total of 81 (57.0%) tested positive for rabies vaccine antibodies, possibly, due to the delayed uptake of bait in which the rabies vaccine was already inactivated. We found that low vaccination responses were associated with high fox density and bait delivery in open areas. In high fox density habitat, bait uptake might be delayed as other food and prey options for foxes are abundant. Similarly, delayed bait uptake probably occurred in open areas as such areas are less frequently used by foxes. The findings of this study suggest that efficacy of oral rabies vaccination by aerial delivery is associated with landscape features.
Quantifying the Pathway and Predicting Spontaneous Emulsification during Material Exchange in a Two Phase Liquid System
Authors: Spooner Stephen , Rahnama Alireza , Warnett Jason M. , Williams Mark A. , Li Zushu , Sridhar Seetharaman
Published: October 2017

Kinetic restriction of a thermodynamically favourable equilibrium is a common theme in materials processing. The interfacial instability in systems where rate of material exchange is far greater than the mass transfer through respective bulk phases is of specific interest when tracking the transient interfacial area, a parameter integral to short processing times for productivity streamlining in all manufacturing where interfacial reaction occurs. This is even more pertinent in high-temperature systems for energy and cost savings. Here the quantified physical pathway of interfacial area change due to material exchange in liquid metal-molten oxide systems is presented. In addition the predicted growth regime and emulsification behaviour in relation to interfacial tension as modelled using phase-field methodology is shown. The observed in-situ emulsification behaviour links quantitatively the geometry of perturbations as a validation method for the development of simulating the phenomena. Thus a method is presented to both predict and engineer the formation of micro emulsions to a desired specification.
Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction
Authors: Silva Adriana Farias , Torres Marcelo Der Torossian , Silva Leandro Souza , Alves Flavio Lopes , de Sá Pinheiro Ana Acácia , Miranda Antonio , Capurro Margareth Lara , de la Fuente-Nunez Cesar , Oliveira Vani Xavier
Published: October 2017

Angiotensin II (Ang II) is a natural mammalian hormone that has been described to exhibit antiplasmodial activity therefore constituting a promising alternative for the treatment of malaria. Despite its promise, the development of Ang II as an antimalarial is limited by its potent induction of vasoconstriction and its rapid degradation within minutes. Here, we used peptide design to perform targeted chemical modifications to Ang II to generate conformationally restricted (disulfide-crosslinked) peptide derivatives with suppressed vasoconstrictor activity and increased stability. Designed constrained peptides were synthesized chemically and then tested for antiplasmodial activity. Two lead constrained peptides were identified (i.e., peptides 1 and 2), each composed of 10 amino acid residues. These peptides exhibited very promising activity in both our Plasmodium gallinaceum (>80%) and Plasmodium falciparum (>40%) models, an activity that was equivalent to that of Ang II, and led to complete suppression of vasoconstriction. In addition, peptide 5 exhibited selective activity towards the pre-erythrocytic stage (98% of activity against P. gallinaceum), thus suggesting that it may be possible to design peptides that target specific stages of the malaria life cycle. The Ang II derived stable scaffolds presented here may provide the basis for development of a new generation of peptide-based drugs for the treatment of malaria.
HBeAg-induced miR-106b promotes cell growth by targeting the retinoblastoma gene
Authors: Samal Jasmine , Kandpal Manish , Vivekanandan Perumal
Published: October 2017

Chronic HBV infection is a major cause of hepatocellular carcinoma (HCC). The association between hepatitis B “e” antigen (HBeAg) and HCC is well-established by epidemiological studies. Nonetheless, the biological role of HBeAg in HCC remains enigmatic. We investigate the role of HBeAg in HBV-related HCC. Our findings suggest that HBeAg enhances cell proliferation and accelerates progression from G0/G1 phase to the S phase of the cell cycle in Huh7 cells. Examination of host gene expression and miRNA expression profiles reveals a total of 21 host genes and 12 host miRNAs that were differentially regulated in cells expressing HBeAg. Importantly, HBeAg induced the expression of miR-106b, an oncogenic miRNA. Interestingly, HBeAg-expression results in a significant reduction in the expression of retinoblastoma (Rb) gene, an experimentally validated target of miR-106b. Inhibition of miR-106b significantly increased the expression of the Rb gene, resulting in reduced cell proliferation and slowing of cell cycle progression from the G0/G1 phase to S phase. These observations suggest that the up-regulation of miR-106b by HBeAg contributes to the pathogenesis of HBV-related HCC by down-regulating the Rb gene. Our results highlight a role for HBeAg in HCC and provide a novel perspective on the molecular mechanisms underlying HBV-related HCC.
Rare, Intense, Big fires dominate the global tropics under drier conditions
Authors: Hantson Stijn , Scheffer Marten , Pueyo Salvador , Xu Chi , Lasslop Gitta , van Nes Egbert H. , Holmgren Milena , Mendelsohn John
Published: October 2017

Wildfires burn large parts of the tropics every year, shaping ecosystem structure and functioning. Yet the complex interplay between climate, vegetation and human factors that drives fire dynamics is still poorly understood. Here we show that on all continents, except Australia, tropical fire regimes change drastically as mean annual precipitation falls below 550 mm. While the frequency of fires decreases below this threshold, the size and intensity of wildfires rise sharply. This transition to a regime of Rare-Intense-Big fires (RIB-fires) corresponds to the relative disappearance of trees from the landscape. Most dry regions on the globe are projected to become substantially drier under global warming. Our findings suggest a global zone where this drying may have important implications for fire risks to society and ecosystem functioning.
Highly Sensitive Plasmonic Detection of the Pancreatic Cancer Biomarker CA 19-9
Authors: Jawad Zaynab A. R. , Theodorou Ioannis G. , Jiao Long R. , Xie Fang
Published: October 2017

Plasmonic gold (Au) nanotriangular arrays, functionalized with a near infrared (NIR) fluorophore-conjugated immunoassay to Carbohydrate Antigen 19-9 (CA 19-9), a pancreatic cancer biomarker, produce optically tunable substrates with two orders of magnitude fluorescence enhancement. Through nanoscale morphological control, the sensitivities of the plasmonic nanotriangular arrays are controllable, paving the way of such optical platforms for multiplexing. Here, we report a limit of detection (LOD) of 7.7 × 10−7 U.mL−1 for CA 19–9 by using such tunable Au nanotriangular arrays, a great improvement compared to commercially available CA 19–9 immunoassays. The linear dynamic range was from 1 × 10−6 U.mL−1 to 1 U.mL−1, i.e. up to six orders of magnitude. Moreover, high specificity was demonstrated, together with successful validation in serum samples. Their superior tunable sensitivity, along with efforts to combine CA 19–9 with other biomarkers for improved accuracy, open up the possibility for multiplexed NIR-fluorescence enhancement microarrays, for early cancer diagnosis and therapeutic monitoring.
CorMatrix Wrapped Around the Adventitia of the Arteriovenous Fistula Outflow Vein Attenuates Venous Neointimal Hyperplasia
Authors: Yang Binxia , Kilari Sreenivasulu , Brahmbhatt Akshaar , McCall Deborah L. , Torres Evelyn Nieves , Leof Edward B. , Mukhopadhyay Debabrata , Misra Sanjay
Published: October 2017

Venous neointimal hyperplasia (VNH) at the outflow vein of hemodialysis AVF is a major factor contributing to failure. CorMatrix is an extracellular matrix that has been used in cardiovascular procedures primarily as scaffolding during surgery. In the present study, we sought to determine whether CorMatrix wrapped around the outflow vein of arteriovenous fistula (AVF) at the time of creation could reduce VNH. In mice, the carotid artery to the ipsilateral jugular vein was connected to create an AVF, and CorMatrix scaffold was wrapped around the outflow vein compared to control mice that received no scaffolding. Immunohistochemistry, Western blot, and qRT-PCR were performed on the outflow vein at 7 and 21 days after AVF creation. In outflow veins treated with CorMatrix, there was an increase in the mean lumen vessel area with a decrease in the ratio of neointima area/media + adventitia area (P < 0.05). Furthermore, there was a significant increase in apoptosis, with a reduction in cell density and proliferation in the outflow veins treated with CorMatrix compared to controls (P < 0.05). Immunohistochemical analysis revealed a significant reduction in fibroblasts, myofibroblasts, macrophages, and leukocytes with a reduction in Tnf-α gene expression (P < 0.05). In conclusion, outflow veins treated with CorMatrix have reduced VNH.
A platform for stereological quantitative analysis of the brain-wide distribution of type-specific neurons
Authors: Zhang Chen , Yan Cheng , Ren Miao , Li Anan , Quan Tingwei , Gong Hui , Yuan Jing
Published: October 2017

Quantifying the distribution of specific neurons throughout the whole brain is crucial for understanding physiological actions, pathological alterations and pharmacological treatments. However, the precise cell number and density of specific neurons in the entire brain remain unknown because of a lack of suitable research tools. Here, we propose a pipeline to automatically acquire and analyse the brain-wide distribution of type-specific neurons in a mouse brain. We employed a Brain-wide Positioning System to collect high-throughput anatomical information with the co-localized cytoarchitecture of the whole brain at subcellular resolution and utilized the NeuroGPS algorithm to locate and count cells in the whole brain. We evaluated the data continuity of the 3D dataset and the accuracy of stereological cell counting in 3D. To apply this pipeline, we acquired and quantified the brain-wide distributions and somatic morphology of somatostatin-expressing neurons in transgenic mouse brains. The results indicated that this whole-brain cell counting pipeline has the potential to become a routine tool for cell type neuroscience studies.
Thermo-mechanical improvement of Inconel 718 using ex situ boron nitride-reinforced composites processed by laser powder bed fusion
Authors: Kim Sang Hoon , Shin Gi-Hun , Kim Byoung-Kee , Kim Kyung Tae , Yang Dong-Yeol , Aranas Clodualdo , Choi Joon-Phil , Yu Ji-Hun
Published: October 2017

Hexagonal boron nitride-reinforced Inconel 718 (h-BN/IN718) composites were fabricated using a laser powder bed fusion (LPBF) technique to treat a nanosheet-micropowder precursor mixture prepared in a mechanical blending process. Tailoring the BN in IN718 enhanced the thermal resistance of the composites, thereby dampening the sharpness of the melting temperature peak at 1364 °C. This is because the presence of the BN reinforcement, which has a low coefficient of thermal expansion (CTE), resulted in a heat-blocking effect within the matrix. Following this lead, we found that the BN (2.29 g/cm3) was uniformly distributed and strongly embedded in the IN718 (8.12 g/cm3), with the lowest alloy density value (7.03 g/cm3) being obtained after the addition of 12 vol% BN. Consequently, its specific hardness and compressive strength rose to 41.7 Hv0.5·cm3/g and 92.4 MPa·cm3/g, respectively, compared to the unreinforced IN718 alloy with 38.7 Hv0.5·cm3/g and 89.4 MPa·cm3/g, respectively. Most importantly, we discovered that the wear resistance of the composite improved compared to the unreinforced IN718, indicated by a decrease in the coefficient of friction (COF) from 0.43 to 0.31 at 2400 s. This is because the BN has an exfoliated surface and intrinsically high sliding and lubricating characteristics.
Theta and Alpha Oscillation Impairments in Autistic Spectrum Disorder Reflect Working Memory Deficit
Authors: Larrain-Valenzuela Josefina , Zamorano Francisco , Soto-Icaza Patricia , Carrasco Ximena , Herrera Claudia , Daiber Francisca , Aboitiz Francisco , Billeke Pablo
Published: October 2017

A dysfunction in the excitatory–inhibitory (E/I) coordination in neuronal assembly has been proposed as a possible neurobiological mechanism of Autistic Spectrum Disorder (ASD). However, the potential impact of this mechanism in cognitive performance is not fully explored. Since the main consequence of E/I dysfunction is an impairment in oscillatory activity and its underlying cognitive computations, we assessed the electroencephalographic activity of ASD and typically developing (TD) subjects during a working-memory task. We found that ASD subjects committed more errors than TD subjects. Moreover, TD subjects demonstrated a parametric modulation in the power of alpha and theta band while ASD subjects did not demonstrate significant modulations. The preceding leads to significant differences between the groups in both the alpha power placed on the occipital cortex and the theta power placed on the left premotor and the right prefrontal cortex. The impaired theta modulation correlated with autistic symptoms. The results indicated that ASD may present an alteration in the recruitment of the oscillatory activity during working-memory, and this alteration could be related to the physiopathology of the disorder.
Contact guidance persists under myosin inhibition due to the local alignment of adhesions and individual protrusions
Authors: Kubow Kristopher E. , Shuklis Victoria D. , Sales Dominic J. , Horwitz A. Rick
Published: October 2017

Contact guidance—cell polarization by anisotropic substrate features—is integral to numerous physiological processes; however the complexities of its regulation are only beginning to be discovered. In particular, cells polarize to anisotropic features under non-muscle myosin II (MII) inhibition, despite MII ordinarily being essential for polarized cell migration. Here, we investigate the ability of cells to sense and respond to fiber alignment in the absence of MII activity. We find that contact guidance is determined at the level of individual protrusions, which are individually guided by local fiber orientation, independent of MII. Protrusion stability and persistence are functions of adhesion lifetime, which depends on fiber orientation. Under MII inhibition, adhesion lifetime no longer depends on fiber orientation; however the ability of protrusions to form closely spaced adhesions sequentially without having to skip over gaps in adhesive area, biases protrusion formation along fibers. The co-alignment of multiple protrusions polarizes the entire cell; if the fibers are not aligned, contact guidance of individual protrusions still occurs, but does not produce overall cell polarization. These results describe how aligned features polarize a cell independently of MII and demonstrate how cellular contact guidance is built on the local alignment of adhesions and individual protrusions.
Palm vitamin E reduces locomotor dysfunction and morphological changes induced by spinal cord injury and protects against oxidative damage
Authors: Zadeh-Ardabili Parastoo Mojtahed , Rad Sima Kianpour , Rad Soheila Kianpour , Khazaài Huzwah , Sanusi Junedah , Zadeh Musa-al-Reza Haji
Published: October 2017

Spinal cord injury (SCI) occurs following different types of crushes. External and internal outcomes of SCI are including paralysis, cavity, and cyst formation. Effects of dietary derived antioxidants, such as palm vitamin E on central nervous system (CNS) encourage researchers to focus on the potential therapeutic benefits of antioxidant supplements. In the present study, experiments were carried out to evaluate the neuro-protective effect of the palm vitamin E on locomotor function and morphological damages induced SCI. Seventy-two male rats (Sprague-Dawley) were randomly divided into four groups: sham (laminectomy); control (supplemented with the palm vitamin E at a dose of 100 mg/kg/day); untreated-SCI (partial crush, 30–33% for 20 sec); treated-SCI (partial crush, 30–33% for 20 sec supplemented with the palm vitamin E at a dose of 100 mg/kg/day). The treatment with the palm vitamin E significantly improved the hind limb locomotor function, reduced the histopathological changes and the morphological damage in the spinal cord. Also, the palm vitamin E indicated a statistically significant decrease in the oxidative damage indicators, malondialdehyde (MDA) level and glutathione peroxidase (GPx) activity in the treated-SCI compared to the untreated-SCI.