bluuebunny/crossref_metadata_2025_split huggingface dataset:
Portal protein functions akin to a DNA-sensor that couples genome-packaging to icosahedral capsid maturation
Authors: Lokareddy Ravi K. , Sankhala Rajeshwer S. , Roy Ankoor , Afonine Pavel V. , Motwani Tina , Teschke Carolyn M. , Parent Kristin N. , Cingolani Gino 
Published: January 2017

AbstractTailed bacteriophages and herpesviruses assemble infectious particles via an empty precursor capsid (or ‘procapsid’) built by multiple copies of coat and scaffolding protein and by one dodecameric portal protein. Genome packaging triggers rearrangement of the coat protein and release of scaffolding protein, resulting in dramatic procapsid lattice expansion. Here, we provide structural evidence that the portal protein of the bacteriophage P22 exists in two distinct dodecameric conformations: an asymmetric assembly in the procapsid (PC-portal) that is competent for high affinity binding to the large terminase packaging protein, and a symmetric ring in the mature virion (MV-portal) that has negligible affinity for the packaging motor. Modelling studies indicate the structure of PC-portal is incompatible with DNA coaxially spooled around the portal vertex, suggesting that newly packaged DNA triggers the switch from PC- to MV-conformation. Thus, we propose the signal for termination of ‘Headful Packaging’ is a DNA-dependent symmetrization of portal protein.
Bacillus subtilis biofilm extends Caenorhabditis elegans longevity through downregulation of the insulin-like signalling pathway
Authors: Donato Verónica , Ayala Facundo Rodríguez , Cogliati Sebastián , Bauman Carlos , Costa Juan Gabriel , Leñini Cecilia , Grau Roberto 
Published: January 2017

AbstractBeneficial bacteria have been shown to affect host longevity, but the molecular mechanisms mediating such effects remain largely unclear. Here we show that formation of Bacillus subtilis biofilms increases Caenorhabditis elegans lifespan. Biofilm-proficient B. subtilis colonizes the C. elegans gut and extends worm lifespan more than biofilm-deficient isogenic strains. Two molecules produced by B. subtilis — the quorum-sensing pentapeptide CSF and nitric oxide (NO) — are sufficient to extend C. elegans longevity. When B. subtilis is cultured under biofilm-supporting conditions, the synthesis of NO and CSF is increased in comparison with their production under planktonic growth conditions. We further show that the prolongevity effect of B. subtilis biofilms depends on the DAF-2/DAF-16/HSF-1 signalling axis and the downregulation of the insulin-like signalling (ILS) pathway.
Inhibition of the integrin/FAK signaling axis and c-Myc synergistically disrupts ovarian cancer malignancy
Authors: Xu B , Lefringhouse J , Liu Z , West D , Baldwin L A , Ou C , Chen L , Napier D , Chaiswing L , Brewer L D , St. Clair D , Thibault O , van Nagell J R , Zhou B P , Drapkin R , Huang J-A , Lu M L , Ueland F R , Yang X H 
Published: January 2017

AbstractIntegrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor. From this screening, JQ1, a potent inhibitor of Myc oncogenic network, emerged as the most robust collaborator. Treatment with a combination of VS-6063 and JQ1 synergistically caused an arrest of tumor cells at the G2/M phase and a decrease in the XIAP-linked cell survival. Our subsequent mechanistic analyses indicate that this functional cooperation was strongly associated with the concomitant disruption of activation or expression of FAK and c-Myc as well as their downstream signaling through the PI3K/Akt pathway. In line with these observations, we detected a strong co-amplification or upregulation at genomic or protein level for FAK and c-Myc in a large portion of primary tumors in the TCGA or a local HGSOC patient cohort. Taken together, our results suggest that the integrin–FAK signaling axis and c-Myc synergistically drive cell proliferation, survival and oncogenic potential in HGSOC. As such, our study provides key genetic, functional and signaling bases for the small-molecule-based co-targeting of these two distinct oncogenic drivers as a new line of targeted therapy against human ovarian cancer.
Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells
Authors: Peng W-x , Wan Y-y , Gong A-h , Ge L , Jin J , Xu M , Wu C-y 
Published: January 2017

AbstractAlthough hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy.
Elevated 5hmC levels characterize DNA of the cerebellum in Parkinson’s disease
Authors: Stöger Reinhard , Scaife Paula J. , Shephard Freya , Chakrabarti Lisa 
Published: January 2017

Abstract5-methylcytosine and the oxidation product 5-hydroxymethylcytosine are two prominent epigenetic variants of the cytosine base in nuclear DNA of mammalian brains. We measured levels of 5-methylcytosine and 5-hydroxymethylcytosine by enzyme-linked immunosorbent assay in DNA from post-mortem cerebella of individuals with Parkinson’s disease and age-matched controls. 5-methylcytosine levels showed no significant differences between Parkinson’s disease and control DNA sample sets. In contrast, median 5-hydroxymethylcytosine levels were almost twice as high (p < 0.001) in both male and female Parkinson’s disease individuals compared with controls. The distinct epigenetic profile identified in cerebellar DNA of Parkinson’s disease patients raises the question whether elevated 5-hydroxymethylcytosine levels are a driver or a consequence of Parkinson’s disease.
Genetics and educational attainment
Authors: Cesarini David , Visscher Peter M. 
Published: January 2017

AbstractWe explore how advances in our understanding of the genetics of complex traits such as educational attainment could constructively be leveraged to advance research on education and learning. We discuss concepts and misconceptions about genetic findings with regard to causes, consequences, and policy. Our main thesis is that educational attainment as a measure that varies between individuals in a population can be subject to exactly the same experimental biological designs as other outcomes, for example, those studied in epidemiology and medical sciences, and the same caveats about interpretation and implication apply.
Low-dose acetaminophen induces early disruption of cell-cell tight junctions in human hepatic cells and mouse liver
Authors: Gamal Wesam , Treskes Philipp , Samuel Kay , Sullivan Gareth J. , Siller Richard , Srsen Vlastimil , Morgan Katie , Bryans Anna , Kozlowska Ada , Koulovasilopoulos Andreas , Underwood Ian , Smith Stewart , del-Pozo Jorge , Moss Sharon , Thompson Alexandra Inés , Henderson Neil C. , Hayes Peter C. , Plevris John N. , Bagnaninchi Pierre-Olivier , Nelson Leonard J. 
Published: January 2017

AbstractDysfunction of cell-cell tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. Liver TJs preserve cellular polarity by delimiting functional bile-canalicular structures, forming the blood-biliary barrier. In acetaminophen-hepatotoxicity, the mechanism by which tissue cohesion and polarity are affected remains unclear. Here, we demonstrate that acetaminophen, even at low-dose, disrupts the integrity of TJ and cell-matrix adhesions, with indicators of cellular stress with liver injury in the human hepatic HepaRG cell line, and primary hepatocytes. In mouse liver, at human-equivalence (therapeutic) doses, dose-dependent loss of intercellular hepatic TJ-associated ZO-1 protein expression was evident with progressive clinical signs of liver injury. Temporal, dose-dependent and specific disruption of the TJ-associated ZO-1 and cytoskeletal-F-actin proteins, correlated with modulation of hepatic ultrastructure. Real-time impedance biosensing verified in vitro early, dose-dependent quantitative decreases in TJ and cell-substrate adhesions. Whereas treatment with NAPQI, the reactive metabolite of acetaminophen, or the PKCα-activator and TJ-disruptor phorbol-12-myristate-13-acetate, similarly reduced TJ integrity, which may implicate oxidative stress and the PKC pathway in TJ destabilization. These findings are relevant to the clinical presentation of acetaminophen-hepatotoxicity and may inform future mechanistic studies to identify specific molecular targets and pathways that may be altered in acetaminophen-induced hepatic depolarization.
Discovery of a junctional epitope antibody that stabilizes IL-6 and gp80 protein:protein interaction and modulates its downstream signaling
Authors: Adams Ralph , Burnley Rebecca J. , Valenzano Chiara R. , Qureshi Omar , Doyle Carl , Lumb Simon , del Carmen Lopez Maria , Griffin Robert , McMillan David , Taylor Richard D. , Meier Chris , Mori Prashant , Griffin Laura M. , Wernery Ulrich , Kinne Jörg , Rapecki Stephen , Baker Terry S. , Lawson Alastair D. G. , Wright Michael , Ettorre Anna 
Published: January 2017

AbstractProtein:protein interactions are fundamental in living organism homeostasis. Here we introduce VHH6, a junctional epitope antibody capable of specifically recognizing a neo-epitope when two proteins interact, albeit transiently, to form a complex. Orthogonal biophysical techniques have been used to prove the “junctional epitope” nature of VHH6, a camelid single domain antibody recognizing the IL-6–gp80 complex but not the individual components alone. X-ray crystallography, HDX-MS and SPR analysis confirmed that the CDR regions of VHH6 interact simultaneously with IL-6 and gp80, locking the two proteins together. At the cellular level, VHH6 was able to alter the response of endothelial cells to exogenous IL-6, promoting a sustained STAT3 phosphorylation signal, an accumulation of IL-6 in vesicles and an overall pro-inflammatory phenotype supported further by transcriptomic analysis. Junctional epitope antibodies, like VHH6, not only offer new opportunities in screening and structure-aided drug discovery, but could also be exploited as therapeutics to modulate complex protein:protein interactions.
The iSelect 9 K SNP analysis revealed polyploidization induced revolutionary changes and intense human selection causing strong haplotype blocks in wheat
Authors: Hao Chenyang , Wang Yuquan , Chao Shiaoman , Li Tian , Liu Hongxia , Wang Lanfen , Zhang Xueyong 
Published: January 2017

AbstractA Chinese wheat mini core collection was genotyped using the wheat 9 K iSelect SNP array. Total 2420 and 2396 polymorphic SNPs were detected on the A and the B genome chromosomes, which formed 878 haplotype blocks. There were more blocks in the B genome, but the average block size was significantly (P < 0.05) smaller than those in the A genome. Intense selection (domestication and breeding) had a stronger effect on the A than on the B genome chromosomes. Based on the genetic pedigrees, many blocks can be traced back to a well-known Strampelli cross, which was made one century ago. Furthermore, polyploidization of wheat (both tetraploidization and hexaploidization) induced revolutionary changes in both the A and the B genomes, with a greater increase of gene diversity compared to their diploid ancestors. Modern breeding has dramatically increased diversity in the gene coding regions, though obvious blocks were formed on most of the chromosomes in both tetraploid and hexaploid wheats. Tag-SNP markers identified in this study can be used for marker assisted selection using haplotype blocks as a wheat breeding strategy. This strategy can also be employed to facilitate genome selection in other self-pollinating crop species.
Computational predictors fail to identify amino acid substitution effects at rheostat positions
Authors: Miller M. , Bromberg Y. , Swint-Kruse L. 
Published: January 2017

AbstractMany computational approaches exist for predicting the effects of amino acid substitutions. Here, we considered whether the protein sequence position class – rheostat or toggle – affects these predictions. The classes are defined as follows: experimentally evaluated effects of amino acid substitutions at toggle positions are binary, while rheostat positions show progressive changes. For substitutions in the LacI protein, all evaluated methods failed two key expectations: toggle neutrals were incorrectly predicted as more non-neutral than rheostat non-neutrals, while toggle and rheostat neutrals were incorrectly predicted to be different. However, toggle non-neutrals were distinct from rheostat neutrals. Since many toggle positions are conserved, and most rheostats are not, predictors appear to annotate position conservation better than mutational effect. This finding can explain the well-known observation that predictors assign disproportionate weight to conservation, as well as the field’s inability to improve predictor performance. Thus, building reliable predictors requires distinguishing between rheostat and toggle positions.
Time-reversing a monochromatic subwavelength optical focus by optical phase conjugation of multiply-scattered light
Authors: Park Jongchan , Park Chunghyun , Lee KyeoReh , Cho Yong-Hoon , Park YongKeun 
Published: January 2017

AbstractDue to its time-reversal nature, optical phase conjugation generates a monochromatic light wave which retraces its propagation paths. Here, we demonstrate the regeneration of a subwavelength optical focus by phase conjugation. Monochromatic light from a subwavelength source is scattered by random nanoparticles, and the scattered light is phase conjugated at the far-field region by coupling its wavefront into a single-mode optical reflector using a spatial light modulator. Then the conjugated beam retraces its propagation paths and forms a refocus on the source at the subwavelength scale. This is the first direct experimental realisation of subwavelength focusing beyond the diffraction limit with far-field time reversal in the optical domain.
Tree cover in Central Africa: determinants and sensitivity under contrasted scenarios of global change
Authors: Aleman Julie C. , Blarquez Olivier , Gourlet-Fleury Sylvie , Bremond Laurent , Favier Charly 
Published: January 2017

AbstractTree cover is a key variable for ecosystem functioning, and is widely used to study tropical ecosystems. But its determinants and their relative importance are still a matter of debate, especially because most regional and global analyses have not considered the influence of agricultural practices. More information is urgently needed regarding how human practices influence vegetation structure. Here we focused in Central Africa, a region still subjected to traditional agricultural practices with a clear vegetation gradient. Using remote sensing data and global databases, we calibrated a Random Forest model to correlatively link tree cover with climatic, edaphic, fire and agricultural practices data. We showed that annual rainfall and accumulated water deficit were the main drivers of the distribution of tree cover and vegetation classes (defined by the modes of tree cover density), but agricultural practices, especially pastoralism, were also important in determining tree cover. We simulated future tree cover with our model using different scenarios of climate and land-use (agriculture and population) changes. Our simulations suggest that tree cover may respond differently regarding the type of scenarios, but land-use change was an important driver of vegetation change even able to counterbalance the effect of climate change in Central Africa.
A novel approach to analyze lysosomal dysfunctions through subcellular proteomics and lipidomics: the case of NPC1 deficiency
Authors: Tharkeshwar Arun Kumar , Trekker Jesse , Vermeire Wendy , Pauwels Jarne , Sannerud Ragna , Priestman David A. , te Vruchte Danielle , Vints Katlijn , Baatsen Pieter , Decuypere Jean-Paul , Lu Huiqi , Martin Shaun , Vangheluwe Peter , Swinnen Johannes V. , Lagae Liesbet , Impens Francis , Platt Frances M. , Gevaert Kris , Annaert Wim 
Published: January 2017

AbstractSuperparamagnetic iron oxide nanoparticles (SPIONs) have mainly been used as cellular carriers for genes and therapeutic products, while their use in subcellular organelle isolation remains underexploited. We engineered SPIONs targeting distinct subcellular compartments. Dimercaptosuccinic acid-coated SPIONs are internalized and accumulate in late endosomes/lysosomes, while aminolipid-SPIONs reside at the plasma membrane. These features allowed us to establish standardized magnetic isolation procedures for these membrane compartments with a yield and purity permitting proteomic and lipidomic profiling. We validated our approach by comparing the biomolecular compositions of lysosomes and plasma membranes isolated from wild-type and Niemann-Pick disease type C1 (NPC1) deficient cells. While the accumulation of cholesterol and glycosphingolipids is seen as a primary hallmark of NPC1 deficiency, our lipidomics analysis revealed the buildup of several species of glycerophospholipids and other storage lipids in selectively late endosomes/lysosomes of NPC1-KO cells. While the plasma membrane proteome remained largely invariable, we observed pronounced alterations in several proteins linked to autophagy and lysosomal catabolism reflecting vesicular transport obstruction and defective lysosomal turnover resulting from NPC1 deficiency. Thus the use of SPIONs provides a major advancement in fingerprinting subcellular compartments, with an increased potential to identify disease-related alterations in their biomolecular compositions.
CASCADE, a platform for controlled gene amplification for high, tunable and selection-free gene expression in yeast
Authors: Strucko Tomas , Buron Line Due , Jarczynska Zofia Dorota , Nødvig Christina Spuur , Mølgaard Louise , Halkier Barbara Ann , Mortensen Uffe Hasbro 
Published: January 2017

AbstractOver-expression of a gene by increasing its copy number is often desirable in the model yeast Saccharomyces cerevisiae. It may facilitate elucidation of enzyme functions, and in cell factory design it is used to increase production of proteins and metabolites. Current methods are typically exploiting expression from the multicopy 2 μ-derived plasmid or by targeting genes repeatedly into sequences like Ty or rDNA; in both cases, high gene expression levels are often reached. However, with 2 μ-based plasmid expression, the population of cells is very heterogeneous with respect to protein production; and for integration into repeated sequences it is difficult to determine the genetic setup of the resulting strains and to achieve specific gene doses. For both types of systems, the strains often suffer from genetic instability if proper selection pressure is not applied. Here we present a gene amplification system, CASCADE, which enables construction of strains with defined gene copy numbers. One or more genes can be amplified simultaneously and the resulting strains can be stably propagated on selection-free medium. As proof-of-concept, we have successfully used CASCADE to increase heterologous production of two fluorescent proteins, the enzyme β-galactosidase the fungal polyketide 6-methyl salicylic acid and the plant metabolite vanillin glucoside.
Solar-Pumping Upconversion of Interfacial Coordination Nanoparticles
Authors: Ishii Ayumi , Hasegawa Miki 
Published: January 2017

AbstractAn interfacial coordination nanoparticle successfully exhibited an upconversion blue emission excited by very low-power light irradiation, such as sunlight. The interfacial complex was composed of Yb ions and indigo dye, which formed a nano-ordered thin shell layer on a Tm2O3 nanoparticle. At the surface of the Tm2O3 particle, the indigo dye can be excited by non-laser excitation at 640 nm, following the intramolecular energy transfer from the indigo dye to the Yb ions. Additionally, the excitation energy of the Yb ion was upconverted to the blue emission of the Tm ion at 475 nm. This upconversion blue emission was achieved by excitation with a CW Xe lamp at an excitation power of 0.14 mW/cm2, which is significantly lower than the solar irradiation power of 1.4 mW/cm2 at 640 ± 5 nm.
Guided magnonic Michelson interferometer
Authors: Ahmed Muhammad H. , Jeske Jan , Greentree Andrew D. 
Published: January 2017

AbstractMagnonics is an emerging field with potential applications in classical and quantum information processing. Freely propagating magnons in two-dimensional media are subject to dispersion, which limits their effective range and utility as information carriers. We show the design of a confining magnonic waveguide created by two surface current carrying wires placed above a spin-sheet, which can be used as a primitive for reconfigurable magnonic circuitry. We theoretically demonstrate the ability of such guides to counter the transverse dispersion of the magnon in a spin-sheet, thus extending the range of the magnon. A design of a magnonic directional coupler and controllable Michelson interferometer is shown, demonstrating its utility for information processing tasks.
Time-domain analysis for extracting fast-paced pupil responses
Authors: Zénon Alexandre 
Published: January 2017

AbstractThe eye pupil reacts to cognitive processes, but its analysis is challenging when luminance varies or when stimulation is fast-paced. Current approaches relying on deconvolution techniques do not account for the strong low-frequency spontaneous changes in pupil size or the large interindividual variability in the shape of the responses. Here a system identification framework is proposed in which the pupil responses to different parameters are extracted by means of an autoregressive model with exogenous inputs. In an example application of this technique, pupil size was shown to respond to the luminance and arousal scores of affective pictures presented in rapid succession. This result was significant in each subject (N = 5), but the pupil response varied between individuals both in amplitude and latency, highlighting the need for determining impulse responses subjectwise. The same method was also used to account for pupil size variations caused by respiration, illustrating the possibility to model the relation between pupil size and other continuous signals. In conclusion, this new framework for the analysis of pupil size data allows us to dissociate the response of the eye pupil from intermingled sources of influence and can be used to study the relation between pupil size and other physiological signals.