bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactive Organization of the Circadian Core Regulators PER2, BMAL1, CLOCK and PML
Authors: Miki Takao , Zhao Zhaoyang , Lee Cheng Chi 
Published: July 2016

AbstractThe BMAL1 and CLOCK heterodimer in the mammalian circadian transcriptional complex is thought to be repressed by PER2 and CRY1 via direct interactions. We recently reported that PER2 is largely cytosolic in Pml−/− cells and did not co-immunoprecipitate (co-IP) with BMAL1 or CLOCK. Here, using multi-color immunofluorescence (IF) staining and co-IP, we observed a nuclear distribution of BMAL1 and a predominately cytosolic distribution of CLOCK in Pml−/− MEF. In the presence of WT PML, PER2 co-localized with BMAL1 in the nucleus. In Pml−/− MEF transfected with mutant K487R PML, we observed that BMAL1 and PER2 co-localized with K487R PML in the cytosol. Furthermore, cytosolic CLOCK and PER2 displayed a significant non-overlapping IF staining pattern. In Bmal1−/− MEF, CLOCK was primarily cytosolic while PML and PER2 were nuclear. Together, our studies suggest that PML mediates the binding of PER2 to BMAL1 in the BMAL1/CLOCK heterodimer and is an important component in the organization of a functional clock complex in the nucleus. Our studies also support that BMAL1 is important for CLOCK nuclear localization.
A novel Plasmodium falciparum rhoptry associated adhesin mediates erythrocyte invasion through the sialic-acid dependent pathway
Authors: Anand Gaurav , Reddy K. Sony , Pandey Alok Kumar , Mian Syed Yusuf , Singh Hina , Mittal Shivani Arora , Amlabu Emmanuel , Bassat Quique , Mayor Alfredo , Chauhan Virander Singh , Gaur Deepak 
Published: July 2016

AbstractErythrocyte invasion by Plasmodium falciparum merozoites is central to blood-stage infection and malaria pathogenesis. This intricate process is coordinated by multiple parasite adhesins that bind erythrocyte receptors and mediate invasion through several alternate pathways. P. falciparum expresses 2700 genes during the blood-stages, of which the identity and function of many remains unknown. Here, we have identified and characterized a novel P. falciparum rhoptry associated adhesin (PfRA) that mediates erythrocyte invasion through the sialic-acid dependent pathway. PfRA appears to play a significant functional role as it is conserved across different Plasmodium species. It is localized in the rhoptries and further translocated to the merozoite surface. Both native and recombinant PfRA specifically bound erythrocytes in a sialic-acid dependent, chymotrypsin and trypsin resistant manner, which was abrogated by PfRA antibodies confirming a role in erythrocyte invasion. PfRA antibodies inhibited erythrocyte invasion and in combination with antibodies against other parasite ligands produced an additive inhibitory effect, thus validating its important role in erythrocyte invasion. We have thus identified a novel P. falciparum adhesin that binds with a sialic acid containing erythrocyte receptor. Our observations substantiate the strategy to block P. falciparum erythrocyte invasion by simultaneously targeting multiple conserved merozoite antigens involved in alternate invasion pathways.
Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis
Authors: Simonett Joseph M. , Huang Russell , Siddique Nailah , Farsiu Sina , Siddique Teepu , Volpe Nicholas J. , Fawzi Amani A. 
Published: July 2016

AbstractAmyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests.
Estimation of brain network ictogenicity predicts outcome from epilepsy surgery
Authors: Goodfellow M. , Rummel C. , Abela E. , Richardson M. P. , Schindler K. , Terry J. R. 
Published: July 2016

AbstractSurgery is a valuable option for pharmacologically intractable epilepsy. However, significant post-operative improvements are not always attained. This is due in part to our incomplete understanding of the seizure generating (ictogenic) capabilities of brain networks. Here we introduce an in silico, model-based framework to study the effects of surgery within ictogenic brain networks. We find that factors conventionally determining the region of tissue to resect, such as the location of focal brain lesions or the presence of epileptiform rhythms, do not necessarily predict the best resection strategy. We validate our framework by analysing electrocorticogram (ECoG) recordings from patients who have undergone epilepsy surgery. We find that when post-operative outcome is good, model predictions for optimal strategies align better with the actual surgery undertaken than when post-operative outcome is poor. Crucially, this allows the prediction of optimal surgical strategies and the provision of quantitative prognoses for patients undergoing epilepsy surgery.
Production of dumbbell probe through hairpin cleavage-ligation and increasing RCA sensitivity and specificity by circle to circle amplification
Authors: Wei Hua , Tang Suming , Hu Tianyu , Zhao Guojie , Guan Yifu 
Published: July 2016

AbstractDumbbell probe (DP) attracts increasing interests in rolling circle amplification (RCA). A universal DP production method through cleavage-ligation of hairpin was proposed and optimized. The production is characterized by restriction endonuclease (RE)-induced cleavage ends ligation. It has the advantage of phosphorylation-free, splint-free and purification-free. To optimize designing, we found that the position of RE cleavage sequence in the stem and the primer position in the loop affected the formation and amplification of DP obviously. Both sticky and blunt ends cleaved by RE produce DP efficiently. Moreover, we introduced this DP into circle to circle (C2C) RCA based on the same cleavage-ligation principle and acquired high sensitivity. By combining a two-ligation design and the C2C strategy, specificity for detecting let-7 family members was increased extremely. Furthermore, coreaction of different steps facilitated convenient formation and amplification process of DP.
Inverse scattering transform analysis of rogue waves using local periodization procedure
Authors: Randoux Stéphane , Suret Pierre , El Gennady 
Published: July 2016

AbstractThe nonlinear Schrödinger equation (NLSE) stands out as the dispersive nonlinear partial differential equation that plays a prominent role in the modeling and understanding of the wave phenomena relevant to many fields of nonlinear physics. The question of random input problems in the one-dimensional and integrable NLSE enters within the framework of integrable turbulence and the specific question of the formation of rogue waves (RWs) has been recently extensively studied in this context. The determination of exact analytic solutions of the focusing 1D-NLSE prototyping RW events of statistical relevance is now considered as the problem of central importance. Here we address this question from the perspective of the inverse scattering transform (IST) method that relies on the integrable nature of the wave equation. We develop a conceptually new approach to the RW classification in which appropriate, locally coherent structures are specifically isolated from a globally incoherent wave train to be subsequently analyzed by implementing a numerical IST procedure relying on a spatial periodization of the object under consideration. Using this approach we extend the existing classifications of the prototypes of RWs from standard breathers and their collisions to more general nonlinear modes characterized by their nonlinear spectra.
A high-sensitivity HPLC assay for measuring intracellular Na+ and K+ and its application to Plasmodium falciparum infected erythrocytes
Authors: Winterberg Markus , Kirk Kiaran 
Published: July 2016

AbstractThe measurement of intracellular ion concentrations, and the screening of chemical agents to identify molecules targeting ion transport, has traditionally involved low-throughput techniques. Here we present a novel HPLC method that allows the rapid, high-sensitivity measurement of cell Na+ and K+ content, demonstrating its utility by monitoring the ionic changes induced in the intracellular malaria parasite by the new spiroindolone antimalarial KAE609.
The role of interconnectivity in control of an Ebola epidemic
Authors: Blackwood J. C. , Childs L. M. 
Published: July 2016

AbstractSeveral West African countries - Liberia, Sierra Leone and Guinea - experienced significant morbidity and mortality during the largest Ebola epidemic to date, from late 2013 through 2015. The extent of the epidemic was fueled by outbreaks in large urban population centers as well as movement of the pathogen between populations. During the epidemic there was no known vaccine or drug, so effective disease control required coordinated efforts that include both standard medical and community practices such as hospitalization, quarantine and safe burials. Due to the high connectivity of the region, control of the epidemic not only depended on internal strategies but also was impacted by neighboring countries. In this paper, we use a deterministic framework to examine the role of movement between two populations in the overall success of practices designed to minimize the extent of Ebola epidemics. We find that it is possible for even small amounts of intermixing between populations to positively impact the control of an epidemic on a more global scale.
Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients
Authors: Mameli Giuseppe , Cocco Eleonora , Frau Jessica , Arru Giannina , Caggiu Elisa , Marrosu Maria Giovanna , Sechi Leonardo A. 
Published: July 2016

AbstractElevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.
Caenorhabditis elegans employs innate and learned aversion in response to bacterial toxic metabolites tambjamine and violacein
Authors: Ballestriero Francesco , Nappi Jadranka , Zampi Giuseppina , Bazzicalupo Paolo , Di Schiavi Elia , Egan Suhelen 
Published: July 2016

AbstractBacteriovorus eukaryotes such as nematodes are one of the major natural predators of bacteria. In their defense bacteria have evolved a number of strategies to avoid predation, including the production of deterrent or toxic metabolites, however little is known regarding the response of predators towards such bacterial defenses. Here we use the nematode C. elegans as a model to study a predators’ behavioral response towards two toxic bacterial metabolites, tambjamine YP1 and violacein. We found that C. elegans displays an innate avoidance behavior towards tambjamine YP1, however requires previous exposure to violacein before learning to avoid this metabolite. The learned avoidance of violacein is specific, reversible, is mediated via the nematode olfactory apparatus (aversive olfactory learning) and is reduced in the absence of the neurotransmitter serotonin. These multiple strategies to evade bacterial toxic metabolites represent a valuable behavioral adaptation allowing bacteriovorus predators to distinguish between good and bad food sources, thus contributing to the understanding of microbial predator-prey interactions.
Conditional ablation of myeloid TNF increases lesion volume after experimental stroke in mice, possibly via altered ERK1/2 signaling
Authors: Clausen Bettina Hjelm , Degn Matilda , Sivasaravanaparan Mithula , Fogtmann Torben , Andersen Maria Gammelstrup , Trojanowsky Michelle D. , Gao Han , Hvidsten Svend , Baun Christina , Deierborg Tomas , Finsen Bente , Kristensen Bjarne Winther , Bak Sara Thornby , Meyer Morten , Lee Jae , Nedospasov Sergei A. , Brambilla Roberta , Lambertsen Kate Lykke 
Published: July 2016

AbstractMicroglia are activated following cerebral ischemia and increase their production of the neuro- and immunomodulatory cytokine tumor necrosis factor (TNF). To address the function of TNF from this cellular source in focal cerebral ischemia we used TNF conditional knock out mice (LysMcreTNFfl/fl) in which the TNF gene was deleted in cells of the myeloid lineage, including microglia. The deletion reduced secreted TNF levels in lipopolysaccharide-stimulated cultured primary microglia by ~93%. Furthermore, phosphorylated-ERK/ERK ratios were significantly decreased in naïve LysMcreTNFfl/fl mice demonstrating altered ERK signal transduction. Micro-PET using 18[F]-fluorodeoxyglucose immediately after focal cerebral ischemia showed increased glucose uptake in LysMcreTNFfl/fl mice, representing significant metabolic changes, that translated into increased infarct volumes at 24 hours and 5 days compared to littermates (TNFfl/fl). In naïve LysMcreTNFfl/fl mice cytokine levels were low and comparable to littermates. At 6 hours, TNF producing microglia were reduced by 56% in the ischemic cortex in LysMcreTNFfl/fl mice compared to littermate mice, whereas no TNF+ leukocytes were detected. At 24 hours, pro-inflammatory cytokine (TNF, IL-1β, IL-6, IL-5 and CXCL1) levels were significantly lower in LysMcreTNFfl/fl mice, despite comparable infiltrating leukocyte populations. Our results identify microglial TNF as beneficial and neuroprotective in the acute phase and as a modulator of neuroinflammation at later time points after experimental ischemia, which may contribute to regenerative recovery.
Point contact resistive switching memory based on self-formed interface of Al/ITO
Authors: Li Qiuhong , Qiu Linjun , Wei Xianhua , Dai Bo , Zeng Huizhong 
Published: July 2016

AbstractPoint contact resistive switching random access memory (RRAM) has been achieved by directly sputtering Al electrodes on indium tin oxide (ITO) conductive glasses. The room-temperature deposited Al/ITO shows an asymmetrical bipolar resistive switching (BRS) behavior after a process of initialization which induces a stable high resistive state (HRS). It might be caused by the in-situ formation of an ultra-thin layer (≈4 nm) at the interface. By comparison, the Al/ITO device after vacuum annealed exhibits typical symmetrical BRS without an initiation or electroforming process. This can be ascribed to the ex-situ thickening of the interfacial layer (≈9.2 nm) to achieve the stable HRS after heat treatment. This work suggests that the self-formed interface of active Al electrode/ITO would provide the simplest geometry to construct RRAM.
Adaptive immunity against gut microbiota enhances apoE-mediated immune regulation and reduces atherosclerosis and western-diet-related inflammation
Authors: Saita Diego , Ferrarese Roberto , Foglieni Chiara , Esposito Antonio , Canu Tamara , Perani Laura , Ceresola Elisa Rita , Visconti Laura , Burioni Roberto , Clementi Massimo , Canducci Filippo 
Published: July 2016

AbstractCommon features of immune-metabolic and inflammatory diseases such as metabolic syndrome, diabetes, obesity and cardiovascular diseases are an altered gut microbiota composition and a systemic pro-inflammatory state. We demonstrate that active immunization against the outer membrane protein of bacteria present in the gut enhances local and systemic immune control via apoE-mediated immune-modulation. Reduction of western-diet-associated inflammation was obtained for more than eighteen weeks after immunization. Immunized mice had reduced serum cytokine levels, reduced insulin and fasting glucose concentrations; and gene expression in both liver and visceral adipose tissue confirmed a reduced inflammatory steady-state after immunization. Moreover, both gut and atherosclerotic plaques of immunized mice showed reduced inflammatory cells and an increased M2 macrophage fraction. These results suggest that adaptive responses directed against microbes present in our microbiota have systemic beneficial consequences and demonstrate the key role of apoE in this mechanism that could be exploited to treat immune-metabolic diseases.
Structural Signature of Plasticity Unveiled by Nano-Scale Viscoelastic Contact in a Metallic Glass
Authors: Lu Y. M. , Zeng J. F. , Wang S. , Sun B. A. , Wang Q. , Lu J. , Gravier S. , Bladin J. J. , Wang W. H. , Pan M. X. , Liu C. T. , Yang Y. 
Published: July 2016

AbstractRoom-temperature plasticity in metallic glasses (MGs) is commonly associated with local structural heterogeneity; however, direct observation of the subtle structural change caused by plasticity is vitally important but the data are extremely scarce. Based on dynamic atomic force microscopy (DAFM), here we show that plasticity-induced structural evolution in a Zr-Ni MG can be revealed via nano-scale viscoelastic contacts between an AFM tip and plastically deformed MG surface layers. Our experimental results clearly show a spatial amplification of the nano-scale structural heterogeneity caused by the distributed plastic flow, which can be linked to the limited growth, reorientation and agglomeration of some nano-scale energy-absorbing regions, which are reminiscent of the behavior of the defect-like regions with non-affine deformation as conceived in many theories and models. Furthermore, we are able to experimentally extract the thermodynamic properties of these nano-scale regions, which possess an energy barrier of 0.3–0.5 eV, about half of that for a typical shear transformation event that usually occurs at the onset of plasticity. The outcome of our current work sheds quantitative insights into the correlation between plasticity and structural heterogeneity in MGs.
In-situ coupling between kinase activities and protein dynamics within single focal adhesions
Authors: Wu Yiqian , Zhang Kaiwen , Seong Jihye , Fan Jason , Chien Shu , Wang Yingxiao , Lu Shaoying 
Published: July 2016

AbstractThe dynamic activation of oncogenic kinases and regulation of focal adhesions (FAs) are crucial molecular events modulating cell adhesion in cancer metastasis. However, it remains unclear how these events are temporally coordinated at single FA sites. Therefore, we targeted fluorescence resonance energy transfer (FRET)-based biosensors toward subcellular FAs to report local molecular events during cancer cell adhesion. Employing single FA tracking and cross-correlation analysis, we quantified the dynamic coupling characteristics between biochemical kinase activities and structural FA within single FAs. We show that kinase activations and FA assembly are strongly and sequentially correlated, with the concurrent FA assembly and Src activation leading focal adhesion kinase (FAK) activation by 42.6 ± 12.6 sec. Strikingly, the temporal coupling between kinase activation and individual FA assembly reflects the fate of FAs at later stages. The FAs with a tight coupling tend to grow and mature, while the less coupled FAs likely disassemble. During FA disassembly, however, kinase activations lead the disassembly, with FAK being activated earlier than Src. Therefore, by integrating subcellularly targeted FRET biosensors and computational analysis, our study reveals intricate interplays between Src and FAK in regulating the dynamic life of single FAs in cancer cells.
Regional differences in health, diet and weaning patterns amongst the first Neolithic farmers of central Europe
Authors: Ash Abigail , Francken Michael , Pap Ildikó , Tvrdý Zdeněk , Wahl Joachim , Pinhasi Ron 
Published: July 2016

AbstractAcross much of central Europe, theLinearbandkeramik(LBK) represents the first Neolithic communities. Arising in Transdanubia around 5500 cal. BC the LBK spread west to the Rhine within two to three hundred years, carrying elements of a mixed agricultural economy and a relatively homogeneous material culture. Colonisation of new regions during this progress would have required economic adaptations to varied ecological conditions within the landscape. This paper investigates whether such adaptation at a local scale affected health patterns and altered the dietary habits of populations that otherwise shared a common cultural and biological origin. Analysis of non-specific stress (linear enamel hypoplasia, porotic hyperostosis, cribra orbitalia) within five LBK populations from across central Europe in conjunction with published carbon and nitrogen stable isotope data from each site revealed a high prevalence of porotic hyperostosis and cribra orbitalia in western populations that was associated with a lower animal protein intake. Hypoplastic enamel was more frequently observed in eastern populations however, and may reflect geographic differences in childhood morbidity and mortality as a result of variation in social practices relating to weaning. Local socio-economic adaptations within the LBK were therefore an important factor in the exposure of populations to non-specific stress.