bluuebunny/crossref_metadata_2025 huggingface dataset:
Positively interacting strains that co-circulate within a network structured population induce cycling epidemics of Mycoplasma pneumoniae
Authors: Zhang Xu-Sheng , Zhao Hongxin , Vynnycky Emilia , Chalker Vicki
Published: January 2019

Mycoplasma pneumoniae(MP) is considered a common cause of pneumonia, causing about 15–20% of adult community-acquired pneumonia (CAP) and up to 40% of cases in children. It has often been observed that MP epidemics last approximately 1–2 years and occur every 3–7 years, with the dominant strains alternating between epidemics. However, the underlying mechanism by which these cycles and changes in the dominant strains occur remains unclear. The traditional models for the periodicity of MP epidemics neglected two phenomena: structured contact patterns among people and co-circulating strains of MP. We also believe that the two distinctive aspects of MP epidemics: prevalent serotype shifts among epidemics and incidence cycling of MP, are interconnected. We propose a network transmission model that assumes two strains of MP are transmitted within a network structured population and they can interact as secondary infections with primary infections. Our studies show that multiple strains that co-circulate within a network structured population and interact positively generate the observed patterns of recurrent epidemics of MP. Hence our study provides a possible mechanism for the cycling epidemics of MP, and could provide useful information for future vaccine design and vaccine evaluation/monitoring processes.
Collaborative efforts to forecast seasonal influenza in the United States, 2015–2016
Authors: McGowan Craig J. , Biggerstaff Matthew , Johansson Michael , Apfeldorf Karyn M. , Ben-Nun Michal , Brooks Logan , Convertino Matteo , Erraguntla Madhav , Farrow David C. , Freeze John , Ghosh Saurav , Hyun Sangwon , Kandula Sasikiran , Lega Joceline , Liu Yang , Michaud Nicholas , Morita Haruka , Niemi Jarad , Ramakrishnan Naren , Ray Evan L. , Reich Nicholas G. , Riley Pete , Shaman Jeffrey , Tibshirani Ryan , Vespignani Alessandro , Zhang Qian , Reed Carrie ,   The Influenza Forecasting Working Group, Rosenfeld Roni , Ulloa Nehemias , Will Katie , Turtle James , Bacon David , Riley Steven , Yang Wan
Published: January 2019

Since 2013, the Centers for Disease Control and Prevention (CDC) has hosted an annual influenza season forecasting challenge. The 2015–2016 challenge consisted of weekly probabilistic forecasts of multiple targets, including fourteen models submitted by eleven teams. Forecast skill was evaluated using a modified logarithmic score. We averaged submitted forecasts into a mean ensemble model and compared them against predictions based on historical trends. Forecast skill was highest for seasonal peak intensity and short-term forecasts, while forecast skill for timing of season onset and peak week was generally low. Higher forecast skill was associated with team participation in previous influenza forecasting challenges and utilization of ensemble forecasting techniques. The mean ensemble consistently performed well and outperformed historical trend predictions. CDC and contributing teams will continue to advance influenza forecasting and work to improve the accuracy and reliability of forecasts to facilitate increased incorporation into public health response efforts.
TaCAMTA4, a Calmodulin-Interacting Protein, Involved in Defense Response of Wheat to Puccinia triticina
Authors: Wang Yuelin , Wei Fengju , Zhou Hui , Liu Na , Niu Xiaonan , Yan Chao , Zhang Lifeng , Han Shengfang , Hou Chunyan , Wang Dongmei
Published: January 2019

Leaf rust caused by Puccinia triticina is one of the main diseases affecting wheat (Triticum aestivum) production worldwide. Calmodulin (CaM) was found involved in the early stage of signal transduction pathway in response to P. triticina in wheat. To study the function and molecular mechanism of calmodulin (CaM) in signal transduction of wheat against P. triticina, we cloned a putative calmodulin-binding transcription activator (TaCAMTA4), and characterized its molecular structure and functions by using the CaM-encoding gene (TaCaM4-1) as a bait to screen the cDNA library from P. triticina infected wheat leaves. The open reading frame of TaCAMTA4 was 2505 bp encoding a protein of 834 aa, which contained all the four conserved domains of family (CG-1 domain, TIG domain, ANK repeats and CaM-binding domain). TaCaM4-1 bound to TaCAMTA4 by the C-terminal CaM-binding domain in Ca2+-dependent manner in the electrophoretic mobility shift assay (EMSA). Bimolecular fluorescence complementation (BiFC) analysis indicated that the interaction of TaCAMTA4 and TaCaM4-1 took place in the cytoplasm and nucleus of epidermal leaf cells in N. benthamiana. The expression level of TaCAMTA4 genes was down-regulated in incompatible combination after P. triticina infection. Furthermore, virus-induced gene silencing (VIGS)-based knockdown of TaCAMTA4 and disease assays verified that silencing of TaCAMTA4 resulted in enhanced resistance to P. triticina race 165. These results suggested that TaCAMTA4 function as negative regulator of defense response against P. triticina.
Design factors for determining the radula shape of Euhadra Peliomphala
Authors: Miura Satoshi , Saito Rikako , Parque Victor , Miyashita Tomoyuki
Published: January 2019

Biomimetics present useful ideas for various product designs. However, most biomimetics only mimic the features of living organisms. It has not been clarified how a given shape is attained through natural selection. This paper presents the design factors that optimize the radula shape of Euhadra peliomphala. Clarifying the important design factors would help designers in solving several problems simultaneously in order to adapt to complicated and multi-functionalized design mechanisms. We measured the radula of Euhadra peliomphala by using a microscope and modeled the grinding/cutting force using the finite element analysis (FEA). We reproduced the natural selection using multi-objective genetic algorithm (MOGA). We compared the solutions when optimizing the radula shape using objective functions of each combination of stress, cutting force, abrasion, or volume. The results show that the solution obtained through two-objective optimization with stress and cutting force was the closest to the actual radula shape.
Molecular ontogeny of the stomach in the catshark Scyliorhinus canicula
Authors: Gonçalves Odete , Freitas Renata , Ferreira Patrícia , Araújo Mafalda , Zhang GuangJun , Mazan Sylvie , Cohn Martin J. , Castro L. Filipe C. , Wilson Jonathan M.
Published: January 2019

The origin of extracellular digestion in metazoans was accompanied by structural and physiological alterations of the gut. These adaptations culminated in the differentiation of a novel digestive structure in jawed vertebrates, the stomach. Specific endoderm/mesenchyme signalling is required for stomach differentiation, involving the growth and transcription factors: 1) Shh and Bmp4, required for stomach outgrowth; 2) Barx1, Sfrps and Sox2, required for gastric epithelium development and 3) Cdx1 and Cdx2, involved in intestinal versus gastric identity. Thus, modulation of endoderm/mesenchyme signalling emerges as a plausible mechanism linked to the origin of the stomach. In order to gain insight into the ancient mechanisms capable of generating this structure in jawed vertebrates, we characterised the development of the gut in the catshark Scyliorhinus canicula. As chondrichthyans, these animals retained plesiomorphic features of jawed vertebrates, including a well-differentiated stomach. We identified a clear molecular regionalization of their embryonic gut, characterised by the expression of barx1 and sox2 in the prospective stomach region and expression of cdx1 and cdx2 in the prospective intestine. Furthermore, we show that gastric gland development occurs close to hatching, accompanied by the onset of gastric proton pump activity. Our findings favour a scenario in which the developmental mechanisms involved in the origin of the stomach were present in the common ancestor of chondrichthyans and osteichthyans.
An inverse free electron laser acceleration-driven Compton scattering X-ray source
Authors: Gadjev I. , Sudar N. , Babzien M. , Duris J. , Hoang P. , Fedurin M. , Kusche K. , Malone R. , Musumeci P. , Palmer M. , Pogorelsky I. , Polyanskiy M. , Sakai Y. , Swinson C. , Williams O. , Rosenzweig J. B.
Published: January 2019

The generation of X-rays and γ-rays based on synchrotron radiation from free electrons, emitted in magnet arrays such as undulators, forms the basis of much of modern X-ray science. This approach has the drawback of requiring very high energy, up to the multi-GeV-scale, electron beams, to obtain the required photon energy. Due to the limit in accelerating gradients in conventional particle accelerators, reaching high energy typically demands use of instruments exceeding 100’s of meters in length. Compact, less costly, monochromatic X-ray sources based on very high field acceleration and very short period undulators, however, may enable diverse, paradigm-changing X-ray applications ranging from novel X-ray therapy techniques to active interrogation of sensitive materials, by making them accessible in energy reach, cost and size. Such compactness and enhanced energy reach may be obtained by an all-optical approach, which employs a laser-driven high gradient accelerator based on inverse free electron laser (IFEL), followed by a collision point for inverse Compton scattering (ICS), a scheme where a laser is used to provide undulator fields. We present an experimental proof-of-principle of this approach, where a TW-class CO2 laser pulse is split in two, with half used to accelerate a high quality electron beam up to 84 MeV through the IFEL interaction, and the other half acts as an electromagnetic undulator to generate up to 13 keV X-rays via ICS. These results demonstrate the feasibility of this scheme, which can be joined with other techniques such as laser recirculation to yield very compact photon sources, with both high peak and average brilliance, and with energies extending from the keV to MeV scale. Further, use of the IFEL acceleration with the ICS interaction produces a train of high intensity X-ray pulses, thus enabling a unique tool synchronized with a laser pulse for ultra-fast strobe, pump-probe experimental scenarios.
Bacteriophage biodistribution and infectivity from honeybee to bee larvae using a T7 phage model
Authors: Ribeiro Henrique G. , Correia Rossana , Moreira Tiago , Vilas Boas Diana , Azeredo Joana , Oliveira Ana
Published: January 2019

Bacteriophages (phages) or viruses that specifically infect bacteria have widely been studied as biocontrol agents against animal and plant bacterial diseases. They offer many advantages compared to antibiotics. The American Foulbrood (AFB) is a bacterial disease affecting honeybee larvae caused byPaenibacillus larvae. Phages can be very significant in fighting it mostly due to European restrictions to the use of antibiotics in beekeeping. New phages able to controlP. larvaein hives have already been reported with satisfactory results. However, the efficacy and feasibility of administering phages indirectly to larvae through their adult workers only by providing phages in bees’ feeders has never been evaluated. This strategy is considered herein the most feasible as far as hive management is concerned. Thisin vivostudy investigated the ability of a phage to reach larvae in an infective state after oral administration to honeybees. The screening (by direct PFU count) and quantification (by quantitative PCR) of the phage in bee organs and in larvae after ingestion allowed us to conclude that despite 104phages reaching larvae only an average of 32 were available to control the spread of the disease. The fast inactivation of many phages in royal jelly could compromise this therapeutic approach. The protection of phages from hive-derived conditions should be thus considered in further developments for AFB treatment.
Exposure to Pb impairs breeding success and is associated with longer lifespan in urban European blackbirds
Authors: Fritsch Clémentine , Jankowiak Łukasz , Wysocki Dariusz
Published: January 2019

Although several factors have been highlighted to explain the influence of urbanization on bird fitness and survival, the role of persistent toxicants such as lead (Pb), which is typically present in urban areas worldwide, has seldom been studied despite the ecological importance of such a widespread stressor. Studying free-living European blackbirds (Turdus merula) in city parks, we tested the hypothesis that low-dose chronic exposure to Pb could shape the life-history traits of urban birds. The feather concentrations of Pb and cadmium were typical of urban areas and low-to-moderate contamination of sites. Although the lifetime breeding success of females decreased with increasing exposure to Pb, the lifespan and survival probabilities of blackbirds increased with Pb contamination regardless of gender. Breeding effort-dependent patterns in the relationship between lifespan and Pb levels were highlighted. No significant relationships were detected between cadmium and life-history traits. The results suggest a possible trade-off between self-maintenance and reproduction, with the most affected birds redirecting allocations towards their own survival, which is consistent with the “stress hormone hypothesis”. These findings suggest that Pb pollution in urban environments may shape avian ecological features and be one of the drivers of wildlife responses to urbanization and that some urban areas may function as ecological traps driven by pollutants.
Mechanisms for lyssavirus persistence in non-synanthropic bats in Europe: insights from a modeling study
Authors: Colombi Davide , Serra-Cobo Jordi , Métras Raphaëlle , Apolloni Andrea , Poletto Chiara , López-Roig Marc , Bourhy Hervé , Colizza Vittoria
Published: January 2019

Bats are natural reservoirs of the largest proportion of viral zoonoses among mammals, thus understanding the conditions for pathogen persistence in bats is essential to reduce human risk. Focusing on the European Bat Lyssavirus subtype 1 (EBLV-1), causing rabies disease, we develop a data-driven spatially explicit metapopulation model to investigate EBLV-1 persistence inMyotis myotisandMiniopterus schreibersiibat species in Catalonia. We find that persistence relies on host spatial structure through the migratory nature ofM. schreibersii, on cross-species mixing withM. myotis, and on survival of infected animals followed by temporary immunity. The virus would not persist in the single colony ofM. myotis. Our study provides for the first time epidemiological estimates for EBLV-1 progression inM. schreibersii. Our approach can be readily adapted to other zoonoses of public health concern where long-range migration and habitat sharing may play an important role.
Gibbsian Thermodynamic Study of Capillary Meniscus Depth
Authors: Eslami Fatemeh , Elliott Janet A. W.
Published: January 2019

In the presence of gravity or other external fields, liquid surface curvature deviates from a spherical shape and the surface configuration can be found by numerical integration of the Young–Laplace equation and the typical initial point for integration is the apex of the interface. The meniscus shape in large Bond number systems, which have the central portion of the interface flattened, cannot be determined with the apex as the initial point for integration. Here we find the depth of capillary menisci by considering an initial point for integration to be at the three-phase-contact-line (TPCL) and evaluate the curvature at the TPCL by free energy analysis and inspect the effect of different parameters on the interface shape. A new parameter—which is the deviation of equilibrium curvature at the TPCL from the spherical shape (SR)—is introduced and inspected and it was found that at a Bond number of 13 the maximum deviation, approximately 0.8 of spherical curvature, takes place while for large enough Bond numbers the curvature at the three-phase contact line is near the spherical shape (0.95 < SR < 1). A potential application of this approach is to measure the capillary rise at the TPCL to find the surface tension in high Bond number systems such as those with low surface/interfacial tensions.
Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae Isolated from Lebanon
Authors: Arabaghian Harout , Salloum Tamara , Alousi Sahar , Panossian Balig , Araj George F. , Tokajian Sima
Published: January 2019

Klebsiella pneumoniae is a Gram-negative organism and a major public health threat. In this study, we used whole-genome sequences to characterize 32 carbapenem-resistant K. pneumoniae (CRKP) and two carbapenem-resistant K. quasipneumoniae (CRKQ). Antimicrobial resistance was assessed using disk diffusion and E-test, while virulence was assessed in silico. The capsule type was determined by sequencing the wzi gene. The plasmid diversity was assessed by PCR-based replicon typing to detect the plasmid incompatibility (Inc) groups. The genetic relatedness was determined by multilocus sequence typing, pan-genome, and recombination analysis. All of the isolates were resistant to ertapenem together with imipenem and/or meropenem. Phenotypic resistance was due to blaOXA-48,blaNDM-1, blaNDM-7, or the coupling of ESBLs and outer membrane porin modifications. This is the first comprehensive study reporting on the WGS of CRKP and the first detection of CRKQ in the region. The presence and dissemination of CRKP and CRKQ, with some additionally having characteristics of hypervirulent clones such as the hypermucoviscous phenotype and the capsular type K2, are particularly concerning. Additionally, mining the completely sequenced K. pneumoniae genomes revealed the key roles of mobile genetic elements in the spread of antibiotic resistance and in understanding the epidemiology of these clinically significant pathogens.
Smoothelin-like 1 deletion enhances myogenic reactivity of mesenteric arteries with alterations in PKC and myosin phosphatase signaling
Authors: Turner Sara R. , Chappellaz Mona , Popowich Brittany , Wooldridge Anne A. , Haystead Timothy A. J. , Cole William C. , MacDonald Justin A.
Published: January 2019

The role of the smoothelin-like 1 (SMTNL1) protein in mediating vascular smooth muscle contractile responses to intraluminal pressure was examined in resistance vessels. Mesenteric arterioles from wild type (WT) and SMTNL1 global knock-out (KO) mice were examined with pressure myography. SMTNL1 deletion was associated with enhanced myogenic tone in vessels isolated from male, but not female, mice. Intraluminal pressures greater than 40 mmHg generated statistically significant differences in myogenic reactivity between WT and KO vessels. No overt morphological differences were recorded for vessels dissected from KO animals, but SMTNL1 deletion was associated with loss of myosin phosphatase-targeting protein MYPT1 and increase in the myosin phosphatase inhibitor protein CPI-17. Additionally, we observed altered contractile responses of isolated arteries from SMTNL1 KO mice to phenylephrine, KCl-dependent membrane depolarization and phorbol 12,13-dibutyrate (PDBu). Using pharmacological approaches, myogenic responses of both WT and KO vessels were equally affected by Rho-associated kinase (ROCK) inhibition; however, augmented protein kinase C (PKC) signaling was found to contribute to the increased myogenic reactivity of SMTNL1 KO vessels across the 60–120 mmHg pressure range. Based on these findings, we conclude that deletion of SMTNL1 contributes to enhancement of pressure-induced contractility of mesenteric resistance vessels by influencing the activity of myosin phosphatase.
C/EBPβ regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats
Authors: Shinagawa Masahiro , Tamura Isao , Maekawa Ryo , Sato Shun , Shirafuta Yuichiro , Mihara Yumiko , Okada - Matsumoto Maki , Taketani Toshiaki , Asada Hiromi , Tamura Hiroshi , Sugino Norihiro
Published: January 2019

The ovulatory LH-surge increases Vegf gene expression in granulosa cells (GCs) undergoing luteinization during ovulation. To understand the factors involved in this increase, we examined the roles of two transcription factors and epigenetic mechanisms in rat GCs. GCs were obtained from rats treated with eCG before, 4 h, 8 h, 12 h and 24 h after hCG injection. Vegf mRNA levels gradually increased after hCG injection and reached a peak at 12 h. To investigate the mechanism by which Vegf is up-regulated after hCG injection, we focused on C/EBPβ and HIF1α. Their protein expression levels were increased at 12 h. The binding activity of C/EBPβ to the Vegf promoter region increased after hCG injection whereas that of HIF1α did not at this time point. The C/EBPβ binding site had transcriptional activities whereas the HIF1α binding sites did not have transcriptional activities under cAMP stimulation. The levels of H3K9me3 and H3K27me3, which are transcriptional repression markers, decreased in the C/EBPβ binding region after hCG injection. The chromatin structure of this region becomes looser after hCG injection. These results show that C/EBPβ regulates Vegf gene expression with changes in histone modifications and chromatin structure of the promoter region in GCs undergoing luteinization during ovulation.
Spatio-temporal overview of neuroinflammation in an experimental mouse stroke model
Authors: Buscemi Lara , Price Melanie , Bezzi Paola , Hirt Lorenz
Published: January 2019

After ischemic stroke, in the lesion core as well as in the ischemic penumbra, evolution of tissue damage and repair is strongly affected by neuroinflammatory events that involve activation of local specialized glial cells, release of inflammatory mediators, recruiting of systemic cells and vascular remodelling. To take advantage of this intricate response in the quest to devise new protective therapeutic strategies we need a better understanding of the territorial and temporal interplay between stroke-triggered inflammatory and cell death-inducing processes in both parenchymal and vascular brain cells. Our goal is to describe structural rearrangements and functional modifications occurring in glial and vascular cells early after an acute ischemic stroke. Low and high scale mapping of the glial activation on brain sections of mice subjected to 30 minutes middle cerebral artery occlusion (MCAO) was correlated with that of the neuronal cell death, with markers for microvascular changes and with markers for pro-inflammatory (IL-1β) and reparative (TGFβ1) cytokines. Our results illustrate a time-course of the neuroinflammatory response starting at early time-points (1 h) and up to one week after MCAO injury in mice, with an accurate spatial distribution of the observed phenomena.
Two-Parameter Quasi-Ballistic Transport Model for Nanoscale Transistors
Authors: Lee Ji Ung , Cuduvally Ramya , Dhakras Prathamesh , Nguyen Phung , Hughes Harold L.
Published: January 2019

We show that by adding only two fitting parameters to a purely ballistic transport model, we can accurately characterize the current-voltage characteristics of nanoscale MOSFETs. The model is an extension of Natori’s model and includes transmission probability and drain-channel coupling parameter. The latter parameter gives rise to a theoretical RON that is significantly larger than those predicted previously. To validate our model, we fabricated n-channel MOSFETs with varying channel lengths. We show the length dependence of these parameters to support a quasi-ballistic description of our devices.
The highly GABARAP specific rat monoclonal antibody 8H5 visualizes GABARAP in immunofluorescence imaging at endogenous levels
Authors: Simons Indra M. , Mohrlüder Jeannine , Feederle Regina , Kremmer Elisabeth , Zobel Thomas , Dobner Jochen , Bleffert Nicole , Hoffmann Silke , Willbold Dieter
Published: January 2019

The determination of unique functions of GABARAP (gamma-aminobutyric acid type A receptor-associated protein), a member of the highly conserved protein family of mammalian autophagy-related 8 protein (mATG8), within diverse cellular processes remains challenging. Because available anti-GABARAP antibodies perform inadequate, especially within various microscopy-based applications, we aimed to develop an antibody that targets GABARAP but not its close orthologs. Following the latest recommendations for antibody validation including fluorescence protein tagging, genetic and orthogonal strategies, we characterized the resulting anti-GABARAP (8H5) antibody during confocal immunofluorescence imaging in-depth. We compared the antibody staining pattern with that obtained for fluorescence protein tagged GABARAP, GABARAPL1 or GABARAPL2 each ectopically expressed in GABARAP knockout cells. Furthermore, we imaged cells expressing all mATG8 family members at endogenous levels and checked GABARAP knockout cells for unspecific staining under fed or macroautophagy-inducing conditions. Finally, we simultaneously stained cells for endogenous GABARAP and the common autophagosomal marker LC3B. Summarized, the presented antibody shows high specificity for GABARAP without cross-reactivity to other mATG8 family members in immunofluorescence imaging making it a valuable tool for the identification of unique GABARAP functions.
Epidermal growth factor receptor promotes cerebral and retinal invasion by Toxoplasma gondii
Authors: Corcino Yalitza Lopez , Portillo Jose-Andres C. , Subauste Carlos S.
Published: January 2019

Little is known about strategies used by pathogens to facilitate CNS invasion.Toxoplasma gondiireaches the CNS by circulating in blood within leukocytes or as extracellular tachyzoites.T. gondiiinduces EGFR signalingin vitroduring invasion of mammalian cells. We examined the effects of endothelial cell EGFR on CNS invasion. Transgenic mice whose endothelial cells expressed a dominant negative (DN) EGFR (inhibits EGFR signaling) exhibited diminished parasite load and histopathology in the brain and retina afterT. gondiiinfection. I.V. administration of infected leukocytes or extracellular tachyzoites led to reduced parasite loads in mice with DN EGFR. This was not explained by enhanced immunity or reduced leukocyte recruitment. Endothelial cell infection is key for CNS invasion. Parasite foci in brain endothelial cells were reduced by DN EGFR. DN EGFR in these cells led to recruitment of the autophagy protein LC3 aroundT. gondiiand spontaneous parasite killing dependent on the autophagy protein ULK1 and lysosomal enzymes. The autophagy inhibitor 3-MA prevented DN EGFR mice from exhibiting reduced CNS invasion. Altogether, EGFR is a novel regulator ofT. gondiiinvasion of neural tissue, enhancing invasion likely by promoting survival of the parasite within endothelial cells.
Learning from Longitudinal Data in Electronic Health Record and Genetic Data to Improve Cardiovascular Event Prediction
Authors: Zhao Juan , Feng QiPing , Wu Patrick , Lupu Roxana A. , Wilke Russell A. , Wells Quinn S. , Denny Joshua C. , Wei Wei-Qi
Published: January 2019

Current approaches to predicting a cardiovascular disease (CVD) event rely on conventional risk factors and cross-sectional data. In this study, we applied machine learning and deep learning models to 10-year CVD event prediction by using longitudinal electronic health record (EHR) and genetic data. Our study cohort included 109, 490 individuals. In the first experiment, we extracted aggregated and longitudinal features from EHR. We applied logistic regression, random forests, gradient boosting trees, convolutional neural networks (CNN) and recurrent neural networks with long short-term memory (LSTM) units. In the second experiment, we applied a late-fusion approach to incorporate genetic features. We compared the performance with approaches currently utilized in routine clinical practice – American College of Cardiology and the American Heart Association (ACC/AHA) Pooled Cohort Risk Equation. Our results indicated that incorporating longitudinal feature lead to better event prediction. Combining genetic features through a late-fusion approach can further improve CVD prediction, underscoring the importance of integrating relevant genetic data whenever available.
Revisiting the Maxillary Teeth in 384 Subjects Reveals A Deviation From the Classical Aesthetic Dimensions
Authors: Melo María , Ata-Ali Fadi , Huertas Julia , Cobo Teresa , Shibli Jamil Awad , Galindo-Moreno Pablo , Ata-Ali Javier
Published: January 2019

Dental esthetics need to be defined from the scientific perspective in order to obtain predictable treatment outcomes and avoid the effects of subjectivisms on the part of the dental profesional. It can be deduced that the ideal dimensions in the maxillary anterior sector are difficult to establish. Therefore, the primary purpose of this study was to define the dimensions of the maxillary anterior teeth and the relationships between them. In addition, an analysis was made to reinvestigate whether they complied with the Golden proportion, the RED (Recurrent Esthetic Dental) proportion and the Golden percentage. A total of 2304 tooth corresponding to 384 subjects were evaluated. The central incisor presented a mean width of 8.58 mm and a height of 9.35 mm, while the lateral incisor presented a width of 6.69 mm and a height of 7.75 mm. The mean width of the canine was 7.69 mm, with a height of 8.68 mm. The teeth revisited in this study did not comply with the ideal dimensions in the anterior maxillary sector as established by the Golden proportion, Golden percentage and RED. The information obtained from this study can be clinically applied to restore the dimensions during periodontal surgery, restorative dentistry and prosthetic rehabilitation.
Working memory performance in the elderly relates to theta-alpha oscillations and is predicted by parahippocampal and striatal integrity
Authors: Steiger Tineke K. , Herweg Nora A. , Menz Mareike M. , Bunzeck Nico
Published: January 2019

The ability to maintain information for a short period of time (i.e. working memory, WM) tends to decrease across the life span with large inter-individual variability; the underlying neuronal bases, however, remain unclear. To address this issue, we used a multimodal imaging approach (voxel-based morphometry, diffusion-tensor imaging, electroencephalography) to test the contribution of brain structures and neural oscillations in an elderly population. Thirty-one healthy elderly participants performed a change-detection task with different load conditions. As expected, accuracy decreased with increasing WM load, reflected by power modulations in the theta-alpha band (5–12 Hz). Importantly, these power changes were directly related to the tract strength between parahippocampus and parietal cortex. Furthermore, between-subject variance in gray matter volume of the parahippocampus and dorsal striatum predicted WM accuracy. Together, our findings provide new evidence that WM performance critically depends on parahippocampal and striatal integrity, while theta-alpha oscillations may provide a mechanism to bind the nodes within the WM network.
STC1 and PTHrP Modify Carbohydrate and Lipid Metabolism in Liver of a Teleost Fish
Authors: Palma Pedro F. S. , Bock Christian , Silva Tomé S. , Guerreiro Pedro M. , Power Deborah M. , Pörtner Hans-Otto , Canário Adelino V. M.
Published: January 2019

Stanniocalcin 1 (STC1) and parathyroid hormone-related protein (PTHrP) are calciotropic hormones in vertebrates. Here, a recently hypothesized metabolic role for these hormones is tested on European sea bass treated with: (i) teleost PTHrP(1–34), (ii) PTHrP(1–34) and anti-STC1 serum (pro-PTHrP groups), (iii) a PTHrP antagonist PTHrP(7–34) or (iv) PTHrP(7–34) and STC1 (pro-STC1 groups). Livers were analysed using untargeted metabolic profiling based on proton nuclear magnetic resonance (1H-NMR) spectroscopy. Concentrations of branched-chain amino acid (BCAA), alanine, glutamine and glutamate increased in pro-STC1 groups suggesting their mobilization from the muscle to the liver for degradation and gluconeogenesis from alanine and glutamine. In addition, only STC1 treatment decreased the concentrations of succinate, fumarate and acetate, indicating slowing of the citric acid cycle. In the pro-PTHrP groups the concentrations of glucose, erythritol and lactate decreased, indicative of gluconeogenesis from lactate. Taurine, trimethylamine, trimethylamine N-oxide and carnitine changed in opposite directions in the pro-STC1 versus the pro-PTHrP groups, suggesting opposite effects, with STC1 stimulating lipogenesis and PTHrP activating lipolysis/β-oxidation of fatty acids. These findings suggest a role for STC1 and PTHrP related to strategic energy mechanisms that involve the production of glucose and safeguard of liver glycogen reserves for stressful situations.
Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-111
Authors: Rinne Sara S. , Leitao Charles Dahlsson , Mitran Bogdan , Bass Tarek Z. , Andersson Ken G. , Tolmachev Vladimir , Ståhl Stefan , Löfblom John , Orlova Anna
Published: January 2019

Radionuclide molecular imaging of human epidermal growth factor receptor 3 (HER3) expression using affibody molecules could be used for patient stratification for HER3-targeted cancer therapeutics. We hypothesized that the properties of HER3-targeting affibody molecules might be improved through modification of the radiometal-chelator complex. Macrocyclic chelators NOTA (1,4,7-triazacyclononane-N,N′,N′′-triacetic acid), NODAGA (1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), and DOTAGA (1,4,7,10-tetraazacyclododececane,1-(glutaric acid)−4,7,10-triacetic acid) were conjugated to the C-terminus of anti-HER3 affibody molecule Z08698 and conjugates were labeled with indium-111. All conjugates bound specifically and with picomolar affinity to HER3 in vitro. In mice bearing HER3-expressing xenografts, no significant difference in tumor uptake between the conjugates was observed. Presence of the negatively charged 111In-DOTAGA-complex resulted in the lowest hepatic uptake and the highest tumor-to-liver ratio. In conclusion, the choice of chelator influences the biodistribution of indium-111 labeled anti-HER3 affibody molecules. Hepatic uptake of anti-HER3 affibody molecules could be reduced by the increase of negative charge of the radiometal-chelator complex on the C-terminus without significantly influencing the tumor uptake.
Mutual action by Gγ and Gβ for optimal activation of GIRK channels in a channel subunit-specific manner
Authors: Tabak Galit , Keren-Raifman Tal , Kahanovitch Uri , Dascal Nathan
Published: January 2019

The tetrameric G protein-gated K+ channels (GIRKs) mediate inhibitory effects of neurotransmitters that activate Gi/o-coupled receptors. GIRKs are activated by binding of the Gβγ dimer, via contacts with Gβ. Gγ underlies membrane targeting of Gβγ, but has not been implicated in channel gating. We observed that, in Xenopus oocytes, expression of Gγ alone activated homotetrameric GIRK1* and heterotetrameric GIRK1/3 channels, without affecting the surface expression of GIRK or Gβ. Gγ and Gβ acted interdependently: the effect of Gγ required the presence of ambient Gβ and was enhanced by low doses of coexpressed Gβ, whereas excess of either Gβ or Gγ imparted suboptimal activation, possibly by sequestering the other subunit “away” from the channel. The unique distal C-terminus of GIRK1, G1-dCT, was important but insufficient for Gγ action. Notably, GIRK2 and GIRK1/2 were not activated by Gγ. Our results suggest that Gγ regulates GIRK1* and GIRK1/3 channel’s gating, aiding Gβ to trigger the channel’s opening. We hypothesize that Gγ helps to relax the inhibitory effect of a gating element (“lock”) encompassed, in part, by the G1-dCT; GIRK2 acts to occlude the effect of Gγ, either by setting in motion the same mechanism as Gγ, or by triggering an opposing gating effect.
Search for efficient inhibitors of myotoxic activity induced by ophidian phospholipase A2-like proteins using functional, structural and bioinformatics approaches
Authors: Salvador Guilherme H. M. , Cardoso Fábio Florença , Gomes Antoniel A. , Cavalcante Walter L. G. , Gallacci Márcia , Fontes Marcos R. M.
Published: January 2019

Ophidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America,Bothropssnakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A2-like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However,in vitromyographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA2-like toxins and, eventually, may complement serum therapy.
Novel pseudo-aspartic peptidase from the midgut of the tick Rhipicephalus microplus
Authors: Lu S. , Parizi L. F. , Torquato R. J. S. , Vaz Junior I. S. , Tanaka A. S.
Published: January 2019

The characterization of Rhipicephalus microplus tick physiology can support efforts to develop and improve the efficiency of control methods. A sequence containing a domain with similarity to one derived from the aspartic peptidase family was isolated from the midgut of engorged female R. microplus. The lack of the second catalytic aspartic acid residue suggest that it may be a pseudo-aspartic peptidase, and it was named RmPAP. In this work we confirm the lack of proteolytic activity of RmPAP and investigate it’s non-proteolytic interaction with bovine hemoglobin by Surface Plasmon Resonance and phage display. Moreover we carried out RNAi interference and artificial feeding of ticks with anti-RmPAP antibodies to assess it’s possible biological role, although no changes were observed in the biological parameters evaluated. Overall, we hypothesize that RmPAP may act as a carrier of hemoglobin/heme between the tick midgut and the ovaries.
Relationship between ultraviolet index (UVI) and first-, second- and third-degree sunburn using the Probit methodology
Authors: Sánchez-Pérez J. F. , Vicente-Agullo D. , Barberá M. , Castro-Rodríguez E. , Cánovas M.
Published: January 2019

In this paper, a relation between the ultraviolet index (UVI) as a Sun exposure time and its effects in the form of burns according to the skin type has been elaborated. Moreover, we present a new expression that relates the intensity of solar radiation and the UVI, as well as expressions to obtain the percentage of population affected both by first and second degree lllsunburn for every skin-type. The results have been adjusted and validated through experimental results taken from the bibliography. Finally, this paper presents a table where the population can easily interpret the UVI values and calculate the maximum time one can be exposed to solar radiation without getting sunburn. In addition, this article aims to raise awareness of the potential harm caused by solar radiation by indicating the percentage of population affected by different types of sunburn depending on skin-type. Moreover, ultraviolet exposure to sunlight could not just result in sunburn, but also have long-term effects on eyes, or even cause immune system disorders or melanoma. Therefore, managing risk perception with this useful table could familiarize the population with actual harm prevention.
BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo
Authors: Schleiss Cédric , Ilias Wassila , Tahar Ouria , Güler Yonca , Miguet Laurent , Mayeur-Rousse Caroline , Mauvieux Laurent , Fornecker Luc-Matthieu , Toussaint Elise , Herbrecht Raoul , Bertrand Frédéric , Maumy-Bertrand Myriam , Martin Thierry , Fournel Sylvie , Georgel Philippe , Bahram Seiamak , Vallat Laurent
Published: January 2019

A chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway
Authors: Asselman Jana , Van Acker Emmanuel , De Rijcke Maarten , Tilleman Laurentijn , Van Nieuwerburgh Filip , Mees Jan , De Schamphelaere Karel A. C. , Janssen Colin R.
Published: January 2019

Sea spray aerosols (SSAs) have profound effects on our climate and ecosystems. They also contain microbiota and biogenic molecules which could affect human health. Yet the exposure and effects of SSAs on human health remain poorly studied. Here, we exposed human lung cancer cells to extracts of a natural sea spray aerosol collected at the seashore in Belgium, a laboratory-generated SSA, the marine algal toxin homoyessotoxin and a chemical inhibitor of the mammalian target of rapamycin (mTOR) pathway. We observed significant increased expression of genes related to the mTOR pathway and Proprotein convertase subtilisin/kexin type 9 (PCSK9) after exposure to homoyessotoxin and the laboratory-generated SSA. In contrast, we observed a significant decrease in gene expression in the mTOR pathway and of PCSK9 after exposure to the natural SSA and the mTOR inhibitor, suggesting induction of apoptosis. Our results indicate that marine biogenics in SSAs interact with PCSK9 and the mTOR pathway and can be used in new potential pharmaceutical applications. Overall, our results provide a substantial molecular evidence base for potential beneficial health effects at environmentally relevant concentrations of natural SSAs.
Soil parameters, land use, and geographical distance drive soil bacterial communities along a European transect
Authors: Plassart Pierre , Prévost-Bouré Nicolas Chemidlin , Uroz Stéphane , Dequiedt Samuel , Stone Dorothy , Creamer Rachel , Griffiths Robert I. , Bailey Mark J. , Ranjard Lionel , Lemanceau Philippe
Published: January 2019

To better understand the relationship between soil bacterial communities, soil physicochemical properties, land use and geographical distance, we considered for the first time ever a European transect running from Sweden down to Portugal and from France to Slovenia. We investigated 71 sites based on their range of variation in soil properties (pH, texture and organic matter), climatic conditions (Atlantic, alpine, boreal, continental, Mediterranean) and land uses (arable, forest and grassland). 16S rRNA gene amplicon pyrosequencing revealed that bacterial communities highly varied in diversity, richness, and structure according to environmental factors. At the European scale, taxa area relationship (TAR) was significant, supporting spatial structuration of bacterial communities. Spatial variations in community diversity and structure were mainly driven by soil physicochemical parameters. Within soil clusters (k-means approach) corresponding to similar edaphic and climatic properties, but to multiple land uses, land use was a major driver of the bacterial communities. Our analyses identified specific indicators of land use (arable, forest, grasslands) or soil conditions (pH, organic C, texture). These findings provide unprecedented information on soil bacterial communities at the European scale and on the drivers involved; possible applications for sustainable soil management are discussed.
Emergence of Topological insulator and Nodal line semi-metal states in XX′Bi (X = Na, K, Rb, Cs; X′ = Ca, Sr)
Authors: Mondal Chiranjit , Barman C. K. , Kumar Sourabh , Alam Aftab , Pathak Biswarup
Published: January 2019

In this article, we predict the emergence of non-trivial band topology in the family of XX′Bi compounds having $$P\overline{6}2m$$
P

6

¯

2
m
(# 189) space group. Using first principles calculations within hybrid functional framework, we demonstrate that NaSrBi and NaCaBi are strong topological insulator under controlled band engineering. Here, we propose three different ways to engineer the band topology to get a non-trivial order: (i) hydrostatic pressure, (ii) biaxial strain (due to epitaxial mismatch), and (iii) doping. Non-triviality is confirmed by investigating bulk band inversion, topological Z2 invariant, surface dispersion and spin texture. Interestingly, some of these compounds also show a three dimensional topological nodal line semi-metal (NLS) state in the absence of spin orbit coupling (SOC). In these NLS phases, the closed loop of band degeneracy in the Brillouin zone lie close to the Fermi level. Moreover, a drumhead like flat surface state is observed on projecting the bulk state on the [001] surface. The inclusion of SOC opens up a small band gap making them behave like a topological insulator.
Social isolation impairs the persistence of social recognition memory by disturbing the glutamatergic tonus and the olfactory bulb-dorsal hippocampus coupling
Authors: Almeida-Santos Ana F. , Carvalho Vinícius R. , Jaimes Laura F. , de Castro Caio M. , Pinto Hyorrana P. , Oliveira Tadeu P. D. , Vieira Luciene B. , Moraes Márcio F. D. , Pereira Grace S.
Published: January 2019

The absence of companion may jeopardize mental health in social animals. Here, we tested the hypothesis that social isolation impairs social recognition memory by altering the excitability and the dialog between the olfactory bulb (OB) and the dorsal hippocampus (dHIP). Adult male Swiss mice were kept grouped (GH) or isolated (SI) for 7 days. Social memory (LTM) was evaluated using social recognition test. SI increased glutamate release in the OB, while decreased in the dHIP. Blocking AMPA and NMDA receptors into the OB or activating AMPA into the dHIP rescued LTM in SI mice, suggesting a cause-effect relationship between glutamate levels and LTM impairment. Additionally, during memory retrieval, phase-amplitude coupling between OB and dHIP decreased in SI mice. Our results indicate that SI impaired the glutamatergic signaling and the normal communication between OB and HIP, compromising the persistence of social memory.