bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling
Authors: Rider Paul J. F. , Coghill Lyndon M. , Naderi Misagh , Brown Jeremy M. , Brylinski Michal , Kousoulas Konstantin G. 
Published: October 2019

AbstractAlphaherpesviruses are a subfamily of herpesviruses that include the significant human pathogens herpes simplex viruses (HSV) and varicella zoster virus (VZV). Glycoprotein K (gK), conserved in all alphaherpesviruses, is a multi-membrane spanning virion glycoprotein essential for virus entry into neuronal axons, virion assembly, and pathogenesis. Despite these critical functions, little is known about which gK domains and residues are most important for maintaining these functions across all alphaherpesviruses. Herein, we employed phylogenetic and structural analyses including the use of a novel model for evolutionary rate variation across residues to predict conserved gK functional domains. We found marked heterogeneity in the evolutionary rate at the level of both individual residues and domains, presumably as a result of varying selective constraints. To clarify the potential role of conserved sequence features, we predicted the structures of several gK orthologs. Congruent with our phylogenetic analysis, slowly evolving residues were identified at potentially structurally significant positions across domains. We found that using a quantitative measure of amino acid rate variation combined with molecular modeling we were able to identify amino acids predicted to be critical for gK protein structure/function. This analysis yields targets for the design of anti-herpesvirus therapeutic strategies across all alphaherpesvirus species that would be absent from more traditional analyses of conservation.
Full-wave electromagnetic modes and hybridization in nanoparticle dimers
Authors: Pascale Mariano , Miano Giovanni , Tricarico Roberto , Forestiere Carlo 
Published: October 2019

AbstractThe plasmon hybridization theory is based on a quasi-electrostatic approximation of the Maxwell’s equations. It does not take into account magnetic interactions, retardation effects, and radiation losses. Magnetic interactions play a dominant role in the scattering from dielectric nanoparticles. The retardation effects play a fundamental role in the coupling of the modes with the incident radiation and in determining their radiative strength; their exclusion may lead to erroneous predictions of the excited modes and of the scattered power spectra. Radiation losses may lead to a significant broadening of the scattering resonances. We propose a hybridization theory for non-Hermitian composite systems based on the full-Maxwell equations that, overcoming all the limitations of the plasmon hybridization theory, unlocks the description of dielectric dimers. As an example, we decompose the scattered field from silicon and silver dimers, under different excitation conditions and gap-sizes, in terms of dimer modes, pinpointing the hybridizing isolated-sphere modes behind them.
Experimental validation of force inference in epithelia from cell to tissue scale
Authors: Kong Weiyuan , Loison Olivier , Chavadimane Shivakumar Pruthvi , Chan Eunice HoYee , Saadaoui Mehdi , Collinet Claudio , Lenne Pierre-François , Clément Raphaël 
Published: October 2019

AbstractMorphogenesis relies on the active generation of forces, and the transmission of these forces to surrounding cells and tissues. Hence measuring forces directly in developing embryos is an essential task to study the mechanics of development. Among the experimental techniques that have emerged to measure forces in epithelial tissues, force inference is particularly appealing. Indeed it only requires a snapshot of the tissue, as it relies on the topology and geometry of cell contacts, assuming that forces are balanced at each vertex. However, establishing force inference as a reliable technique requires thorough validation in multiple conditions. Here we performed systematic comparisons of force inference with laser ablation experiments in four epithelial tissues from two animals, the fruit fly and the quail. We show that force inference accurately predicts single junction tension, tension patterns in stereotyped groups of cells, and tissue-scale stress patterns, in wild type and mutant conditions. We emphasize its ability to capture the distribution of forces at different scales from a single image, which gives it a critical advantage over perturbative techniques such as laser ablation. Overall, our results demonstrate that force inference is a reliable and efficient method to quantify the mechanical state of epithelia during morphogenesis, especially at larger scales when inferred tensions and pressures are binned into a coarse-grained stress tensor.
Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice
Authors: Martines Anne-Claire M. F. , Gerding Albert , Stolle Sarah , Vieira-Lara Marcel A. , Wolters Justina C. , Jurdzinski Angelika , Bongiovanni Laura , de Bruin Alain , van der Vlies Pieter , van der Vries Gerben , Bloks Vincent W. , Derks Terry G. J. , Reijngoud Dirk-Jan , Bakker Barbara M. 
Published: October 2019

AbstractDuring fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse. WT and KO mice were given a high- or low-fat diet and subsequently fasted. We analyzed histology, mitochondrial function, targeted mitochondrial proteomics, and transcriptome in liver tissue. Loss of MCAD led to a decreased capacity to oxidize octanoyl-CoA. This was not compensated for by altered protein levels of the short- and long-chain isoenzymes SCAD and LCAD. In the transcriptome, we identified subtle adaptations in the expression of genes encoding enzymes catalyzing CoA- and NAD(P)(H)-involving reactions and of genes involved in detoxification mechanisms. We discuss how these processes may contribute to robustness in MCAD-KO mice and potentially also in asymptomatic human subjects with a complete loss of MCAD activity.
Three-Dimensional Microscopy by Milling with Ultraviolet Excitation
Authors: Guo Jiaming , Artur Camille , Eriksen Jason L. , Mayerich David 
Published: October 2019

AbstractAnalysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are difficult to explore using two-dimensional histology. While three-dimensional techniques such as confocal and light-sheet microscopy are well-established, they are time consuming, require expensive instrumentation, and are limited to small tissue volumes. Three-dimensional microscopy is therefore impractical in clinical settings and often limited to core facilities at major research institutions. There would be a tremendous benefit to providing clinicians and researchers with the ability to routinely image large three-dimensional tissue volumes at cellular resolution. In this paper, we propose an imaging methodology that enables fast and inexpensive three-dimensional imaging that can be readily integrated into current histology pipelines. This method relies on block-face imaging of paraffin-embedded samples using deep-ultraviolet excitation. The imaged surface is then ablated to reveal the next tissue section for imaging. The final image stack is then aligned and reconstructed to provide tissue models that exceed the depth and resolution achievable with modern three-dimensional imaging systems.
The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma
Authors: Lee A. T. J. , Chew W. , Wilding C. P. , Guljar N. , Smith M. J. , Strauss D. C. , Fisher C. , Hayes A. J. , Judson I. , Thway K. , Jones R. L. , Huang P. H. 
Published: October 2019

AbstractThe characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.
Frictional Damping from Biomimetic Scales
Authors: Ali Hessein , Ebrahimi Hossein , Ghosh Ranajay 
Published: October 2019

AbstractStiff scales adorn the exterior surfaces of fishes, snakes, and many reptiles. They provide protection from external piercing attacks and control over global deformation behavior to aid locomotion, slithering, and swimming across a wide range of environmental condition. In this report, we investigate the dynamic behavior of biomimetic scale substrates for further understanding the origins of the nonlinearity that involve various aspect of scales interaction, sliding kinematics, interfacial friction, and their combination. Particularly, we study the vibrational characteristics through an analytical model and numerical investigations for the case of a simply supported scale covered beam. Our results reveal for the first time that biomimetic scale beams exhibit viscous damping behavior even when only Coulomb friction is postulated for free vibrations. We anticipate and quantify the anisotropy in the damping behavior with respect to curvature. We also find that unlike static pure bending where friction increases bending stiffness, a corresponding increase in natural frequency for the dynamic case does not arise for simply supported beam. Since both scale geometry, distribution and interfacial properties can be easily tailored, our study indicates a biomimetic strategy to design exceptional synthetic materials with tailorable damping behavior.
Interactive spatial scale effects on species distribution modeling: The case of the giant panda
Authors: Connor Thomas , Viña Andrés , Winkler Julie A. , Hull Vanessa , Tang Ying , Shortridge Ashton , Yang Hongbo , Zhao Zhiqiang , Wang Fang , Zhang Jindong , Zhang Zejun , Zhou Caiquan , Bai Wenke , Liu Jianguo 
Published: October 2019

AbstractResearch has shown that varying spatial scale through the selection of the total extent of investigation and the grain size of environmental predictor variables has effects on species distribution model (SDM) results and accuracy, but there has been minimal investigation into the interactive effects of extent and grain. To do this, we used a consistently sampled range-wide dataset of giant panda occurrence across southwest China and modeled their habitat and distribution at 4 extents and 7 grain sizes. We found that increasing grain size reduced model accuracy at the smallest extent, but that increasing extent negated this effect. Increasing extent also generally increased model accuracy, but the models built at the second-largest (mountain range) extent were more accurate than those built at the largest, geographic range-wide extent. When predicting habitat suitability in the smallest nested extents (50 km2), we found that the models built at the next-largest extent (500 km2) were more accurate than the smallest-extent models but that further increases in extent resulted in large decreases in accuracy. Overall, this study highlights the impacts of the selection of spatial scale when evaluating species’ habitat and distributions, and we suggest more explicit investigations of scale effects in future modeling efforts.
The explant developmental stage profoundly impacts small RNA-mediated regulation at the dedifferentiation step of maize somatic embryogenesis
Authors: Juárez-González Vasti T. , López-Ruiz Brenda A. , Baldrich Patricia , Luján-Soto Eduardo , Meyers Blake C. , Dinkova Tzvetanka D. 
Published: October 2019

AbstractMaize somatic embryogenesis (SE) requires the induction of embryogenic callus and establishment of proliferation before plant regeneration. The molecular mechanisms underlying callus embryogenic potential are not well understood. Here we explored the role of small RNAs (sRNAs) and the accumulation of their target transcripts in maize SE at the dedifferentiation step using VS-535 zygotic embryos collected at distinct developmental stages and displaying contrasting in vitro embryogenic potential and morphology. MicroRNAs (miRNAs), trans-acting siRNAs (tasiRNAs), heterochromatic siRNAs (hc-siRNAs) populations and their RNA targets were analyzed by high-throughput sequencing. Abundances of specific miRNAs, tasiRNAs and targets were validated by qRT-PCR. Unique accumulation patterns were found for immature embryo at 15 Days After Pollination (DAP) and for the callus induction from this explant, as compared to 23 DAP and mature embryos. miR156, miR164, miR166, tasiARFs and the 24 nt hc-siRNAs displayed the most strikingly different patterns between explants and during dedifferentiation. According to their role in auxin responses and developmental cues, we conclude that sRNA-target regulation operating within the 15 DAP immature embryo explant provides key molecular hints as to why this stage is relevant for callus induction with successful proliferation and plant regeneration.
Risk of end-stage renal disease in patients with hypertrophic cardiomyopathy: A nationwide population-based cohort study
Authors: Lee Heesun , Han Kyungdo , Park Jun-Bean , Hwang In-Chang , Yoon Yeonyee E. , Park Hyo Eun , Choi Su-Yeon , Kim Yong-Jin , Cho Goo-Yeong , Kim Hyung-Kwan , Ommen Steve R. 
Published: October 2019

AbstractAlthough hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p < 0.001). In the HCM, the incidence rate for ESRD gradually increased with age, but an initial peak and subsequent plateau in age-specific risk were observed. HCM was a significant predictor for ESRD (unadjusted HR 6.90, 95% CI 5.21–9.15, p < 0.001), as comparable to hypertension and diabetes mellitus. Furthermore, after adjusting for all variables showing the association in univariate analysis, HCM itself remained a robust predictor of ESRD development (adjusted HR 3.93, 95% CI 2.82–5.46, p < 0.001). The consistent associations between HCM and ESRD were shown in almost all subgroups other than smokers and subjects with a history of stroke. Conclusively, HCM increased the risk of ESRD, regardless of known prognosticators. It provides new insight into worsening renal function in HCM, and active surveillance for renal function should be considered.
Comparative Analysis of Midgut Regeneration Capacity and Resistance to Oral Infection in Three Disease-Vector Mosquitoes
Authors: Janeh Maria , Osman Dani , Kambris Zakaria 
Published: October 2019

AbstractMosquitoes acquire the pathogens they transmit through ingestion, and the insects’ gut constitutes the first line of defense against invading pathogens. Indeed the gut epithelium acts as a physical barrier, activates local antimicrobial peptides production and triggers the systemic immune response. Consequently, gut epithelium is constantly confronted to stress and often suffers cellular damage. We have previously shown that regenerative cells are present in the guts of adultAedes albopictus, and that chemical damage or bacterial infection leads to the proliferation of these regenerative cells in the midgut. In this study, we extended the analysis of gut cells response to stress to two other important disease vector mosquitoes:Culex pipiensandAnopheles gambiae. We fed mosquitoes on sucrose solutions or on sucrose supplemented with pathogenic bacteria or with damage-inducing chemicals. We also assayed the survival of mosquitoes following the ingestion of pathogenic bacteria. We found that in adultC. pipiens, dividing cells exist in the digestive tract and that these cells proliferate in the midgut after bacterial or chemical damage, similarly to what we previously observed inA. albopictus. In sharp contrast, we did not detect any mitotic cell in the midguts ofA. gambiaemosquitoes, neither in normal situation nor after the induction of gut damage. In agreement with this observation,A. gambiaemosquitoes were more sensitive to oral bacterial infections compared toA. albopictusandC. pipiens. This work provides evidence that major differences in gut physiological responses exist between different mosquitoes. The presence of regenerative cells in the mosquito guts and their ability to multiply after gut damage affect the mosquito survival to oral infections, and is also likely to affect its vectorial capacity.
Biarticular muscles are most responsive to upper-body pitch perturbations in human standing
Authors: Schumacher Christian , Berry Andrew , Lemus Daniel , Rode Christian , Seyfarth André , Vallery Heike 
Published: October 2019

AbstractBalancing the upper body is pivotal for upright and efficient gait. While models have identified potentially useful characteristics of biarticular thigh muscles for postural control of the upper body, experimental evidence for their specific role is lacking. Based on theoretical findings, we hypothesised that biarticular muscle activity would increase strongly in response to upper-body perturbations. To test this hypothesis, we used a novel Angular Momentum Perturbator (AMP) that, in contrast to existing methods, perturbs the upper-body posture with only minimal effect on Centre of Mass (CoM) excursions. The impulse-like AMP torques applied to the trunk of subjects resulted in upper-body pitch deflections of up to 17° with only small CoM excursions below 2 cm. Biarticular thigh muscles (biceps femoris long head and rectus femoris) showed the strongest increase in muscular activity (mid- and long-latency reflexes, starting 100 ms after perturbation onset) of all eight measured leg muscles which highlights the importance of biarticular muscles for restoring upper-body balance. These insights could be used for improving technological aids like rehabilitation or assistive devices, and the effectiveness of physical training for fall prevention e.g. for elderly people.
Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells
Authors: Fontaine Margaux A. C. , Westra Marijke M. , Bot Ilze , Jin Han , Franssen Aimée J. P. M. , Bot Martine , de Jager Saskia C. A. , Dzhagalov Ivan , He You-Wen , van Vlijmen Bart J. M. , Gijbels Marion J. J. , Reutelingsperger Chris P. , van Berkel Theo J. C. , Sluimer Judith C. , Temmerman Lieve , Biessen Erik A. L. 
Published: October 2019

AbstractThe anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of myeloid Mcl-1 deletion in atherosclerosis. Western type diet fed LDL receptor-deficient mice were transplanted with either wild-type (WT) or LysMCre Mcl-1fl/fl (Mcl-1−/−) bone marrow. Mcl-1 myeloid deletion resulted in enhanced apoptosis and lipid accumulation in atherosclerotic plaques. In vitro, Mcl-1 deficient macrophages also showed increased lipid accumulation, resulting in increased sensitivity to lipid-induced cell death. However, plaque size, necrotic core and macrophage content were similar in Mcl-1−/− compared to WT mice, most likely due to decreased circulating and plaque-residing neutrophils. Interestingly, Mcl-1−/− peritoneal foam cells formed up to 45% more multinucleated giant cells (MGCs) in vitro compared to WT, which concurred with an increased MGC presence in atherosclerotic lesions of Mcl-1−/− mice. Moreover, analysis of human unstable atherosclerotic lesions also revealed a significant inverse correlation between MGC lesion content and Mcl-1 gene expression, coinciding with the mouse data. Taken together, these findings suggest that myeloid Mcl-1 deletion leads to a more apoptotic, lipid and MGC-enriched phenotype. These potentially pro-atherogenic effects are however counteracted by neutropenia in circulation and plaque.
Fucosylated α1-acid glycoprotein as a biomarker to predict prognosis following tumor immunotherapy of patients with lung cancer
Authors: Yokobori Takehiko , Yazawa Shin , Asao Takayuki , Nakazawa Nobuhiro , Mogi Akira , Sano Rie , Kuwano Hiroyuki , Kaira Kyoichi , Shirabe Ken 
Published: October 2019

AbstractImmunotherapy targeting immune checkpoint molecules has provided remarkable clinical benefits in cancer patients but no clinically relevant biomarker for predicting treatment outcomes exists. Recently, we demonstrated that glycan structures of serum α1-acid glycoprotein (AGP) changed dramatically in cancer patients and that α1,3fucosylated AGP (fAGP) levels increased along with disease progression and decreased responding to chemotherapy treatments. Here, the fAGP was analyzed in sera prospectively obtained from 39 patients with advanced lung cancer who underwent immunotherapy with anti-PD-1 antibody, nivolumab. Twenty-three patients had significantly high fAGP levels above the cut-off value (H-fAGP) at one month after starting the treatment and 20 patients in this group, whose tumor sizes did not decrease, maintained high fAGP levels continuously and subsequently died. However, the other 16 patients, whose fAGP levels decreased or maintained below the cut-off value (L-fAGP), survived during a 2-year observation even though 5 patients in this group had no tumor shrinkage. Accordingly, the overall survival rate was found to significantly correlate with the fAGP level. Multivariate analyses revealed that the H-fAGP was an independent risk factor for cancer progression. Therefore, the fAGP level appeared to be a reliable biomarker for predicting clinical efficacy of immunotherapy with nivolumab.