bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metal–peptide rings form highly entangled topologically inequivalent frameworks with the same ring- and crossing-numbers
Authors: Sawada Tomohisa , Saito Ami , Tamiya Kenki , Shimokawa Koya , Hisada Yutaro , Fujita Makoto 
Published: February 2019

AbstractWith increasing ring-crossing number (c), knot theory predicts an exponential increase in the number of topologically different links of these interlocking structures, even for structures with the same ring number (n) and c. Here, we report the selective construction of two topologies of 12-crossing peptide [4]catenanes (n = 4, c = 12) from metal ions and pyridine-appended tripeptide ligands. Two of the 100 possible topologies for this structure are selectively created from related ligands in which only the tripeptide sequence is changed: one catenane has a T2-tetrahedral link and the other a three-crossed tetrahedral link. Crystallographic studies illustrate that a conformational difference in only one of the three peptide residues in the ligand causes the change in the structure of the final tetrahedral link. Our results thus reveal that peptide-based folding and assembly can be used for the facile bottom-up construction of 3D molecular objects containing polyhedral links.
Supercluster-coupled crystal growth in metallic glass forming liquids
Authors: Xie Yujun , Sohn Sungwoo , Wang Minglei , Xin Huolin , Jung Yeonwoong , Shattuck Mark D. , O’Hern Corey S. , Schroers Jan , Cha Judy J. 
Published: February 2019

AbstractWhile common growth models assume a structure-less liquid composed of atomic flow units, structural ordering has been shown in liquid metals. Here, we conduct in situ transmission electron microscopy crystallization experiments on metallic glass nanorods, and show that structural ordering strongly affects crystal growth and is controlled by nanorod thermal history. Direct visualization reveals structural ordering as densely populated small clusters in a nanorod heated from the glass state, and similar behavior is found in molecular dynamics simulations of model metallic glasses. At the same growth temperature, the asymmetry in growth rate for rods that are heated versus cooled decreases with nanorod diameter and vanishes for very small rods. We hypothesize that structural ordering enhances crystal growth, in contrast to assumptions from common growth models. The asymmetric growth rate is attributed to the difference in the degree of the structural ordering, which is pronounced in the heated glass but sparse in the cooled liquid.
Somatic mutations of PREX2 gene in patients with hepatocellular carcinoma
Authors: Yang Ming-Hui , Yen Chia-Hung , Chen Yen-Fu , Fang Cheng-Chieh , Li Chung-Hsien , Lee Kuo-Jui , Lin Yi-Hsiung , Weng Chien-Hui , Liu Tze-Tze , Huang Shiu-Feng , Teh Bin Tean , Chen Yi-Ming Arthur 
Published: February 2019

AbstractCharacterized with a high recurrence rate and low detection rate, prevention is the best approach to reduce mortality in hepatocellular carcinoma (HCC). The overexpression of Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) is observed in various tumors, including HCC; and the frequent PREX2 mutations in melanoma are associated with invasiveness. We sought to identify somatic mutations and the functional changes in mutational signatures of PREX2. Genomic DNA sequencing was performed in 68 HCC samples with three types of hepatitis viral infection status: HBs Ag-positive, anti-HCV Ab-positive, and negative for any hepatitis B or C markers. Stabilities and interactions of proteins as well as cell proliferation and migration were evaluated. Fourteen non-silent point mutations in PREX2 were detected, with 16 of 68 HCC patients harboring at least one non-silent mutation. All mutant forms of PREX2, except for K400f, had an extended half-life compared with wild-type PREX2. Moreover, only the half-life of S1113R was twice that of the wild-type. PREX2 mutant-S1113R also promoted migration and activated the AKT pathway as well as impaired HectH9-mediated ubiquitination. Our study identified a gain-of-function mutation of PREX2 – S1113R in HCC. Such mutation enhanced PREX2 protein stability, promoted cell proliferation, and was associated with aggressiveness of HCC.
Human-attacks by an urban raptor are tied to human subsidies and religious practices
Authors: Kumar Nishant , Jhala Yadvendradev V. , Qureshi Qamar , Gosler Andrew G. , Sergio Fabrizio 
Published: February 2019

AbstractGrowing urbanization is increasing human-wildlife interactions, including attacks towards humans by vertebrate predators, an aspect that has received extremely scarce investigation. Here, we examined the ecological, landscape and human factors that may promote human-aggression by raptorial Black kitesMilvus migransin the 16-millions inhabitants megacity of Delhi (India). Physical attacks depended on human activities such as unhygienic waste management, ritual-feeding of kites (mainly operated by Muslims), human density, and presence of a balcony near the nest, suggesting an association between aggression and frequent-close exposure to humans and derived food-rewards. Surprisingly, while more than 100,000 people could be at risk of attack in any given moment, attitudes by local inhabitants were strikingly sympathetic towards the birds, even by injured persons, likely as a result of religious empathy. These results highlight the importance of socio-cultural factors for urban biota and how these may radically differentiate the under-studied cities of developing countries from those of western nations, thus broadening our picture of human-wildlife interactions in urban environments. The rapid sprawling of urban and suburban areas with their associated food-subsidies is likely to increase proximity and exposure of large predators to humans, and vice versa, leading to heightened worldwide conflicts.
Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting
Authors: Lee Jong Geol , Ha Chang Hoon , Yoon Bohyun , Cheong Seung-A. , Kim Globinna , Lee Doo Jae , Woo Dong-Cheol , Kim Young-Hak , Nam Sang-Yoon , Lee Sang-wook , Sung Young Hoon , Baek In-Jeoung 
Published: February 2019

AbstractThe rat is a time-honored traditional experimental model animal, but its use is limited due to the difficulty of genetic modification. Although engineered endonucleases enable us to manipulate the rat genome, it is not known whether the newly identified endonuclease Cpf1 system is applicable to rats. Here we report the first application of CRISPR-Cpf1 in rats and investigate whether Apoe knockout rat can be used as an atherosclerosis model. We generated Apoe- and/or Ldlr-deficient rats via CRISPR-Cpf1 system, characterized by high efficiency, successful germline transmission, multiple gene targeting capacity, and minimal off-target effect. The resulting Apoe knockout rats displayed hyperlipidemia and aortic lesions. In partially ligated carotid arteries of rats and mice fed with high-fat diet, in contrast to Apoe knockout mice showing atherosclerotic lesions, Apoe knockout rats showed only adventitial immune infiltrates comprising T lymphocytes and mainly macrophages with no plaque. In addition, adventitial macrophage progenitor cells (AMPCs) were more abundant in Apoe knockout rats than in mice. Our data suggest that the Cpf1 system can target single or multiple genes efficiently and specifically in rats with genetic heritability and that Apoe knockout rats may help understand initial-stage atherosclerosis.
Functional expression of a peritrophin A-like SfPER protein is required for larval development in Spodoptera frugiperda (Lepidoptera: Noctuidae)
Authors: Rodríguez-de la Noval Claudia , Rodríguez-Cabrera Lianet , Izquierdo Laurent , Espinosa Luis A. , Hernandez Daily , Ponce Milagro , Moran-Bertot Ivis , Tellez-Rodríguez Pilar , Borras-Hidalgo Orlando , Huang Siliang , Kan Yunchao , Wright Denis J. , Ayra-Pardo Camilo 
Published: February 2019

AbstractPeritrophins are associated with structural and functional integrity of peritrophic membranes (PM), structures composed of chitin and proteins. PM lines the insect midgut and has roles in digestion and protection from toxins. We report the full-length cDNA cloning, molecular characterization and functional analysis of SfPER, a novel PM peritrophin A protein, in Spodoptera frugiperda. The predicted amino acid sequence indicated SfPER’s domain structure as a CMCMC-type, consisting of a signal peptide and three chitin-binding (C) domains with two intervening mucin-like (M) domains. Phylogenetic analysis determined a close relationship between SfPER and another S. frugiperda PM peritrophin partial sequence. SfPER transcripts were found in larvae and adults but were absent from eggs and pupae. Chitin affinity studies with a recombinant SfPER-C1 peritrophin A-type domain fused to SUMO/His-tag confirmed that SfPER binds to chitin. Western blots of S. frugiperda larval proteins detected different sized variants of SfPER along the PM, with larger variants found towards the posterior PM. In vivo suppression of SfPER expression did not affect susceptibility of larvae to Bacillus thuringiensis toxin, but significantly decreased pupal weight and adult emergence, possibly due to PM structural alterations impairing digestion. Our results suggest SfPER could be a novel target for insect control.
Vitamin D Receptor Polymorphism and DHCR7 Contribute to the Abnormal Interplay Between Vitamin D and Lipid Profile in Rheumatoid Arthritis
Authors: Rodríguez-Carrio Javier , Alperi-López Mercedes , Naves-Díaz Manuel , Dusso Adriana , López Patricia , Ballina-García Francisco Javier , Cannata-Andía Jorge B. , Suárez Ana 
Published: February 2019

AbstractEmerging evidence suggests a role for 7-dehydrocholesterol reductase (DHCR7) in the crosstalk between cholesterol and vitamin D. Our aim was to evaluate the impact of vitamin D-related polymorphisms and DHCR7 levels in the association between vitamin D deficiency and altered lipid profile in rheumatoid arthritis (RA). Serum 25(OH)-vitamin D, DHCR7 levels and vitamin D-related polymorphisms (VDR-rs2228570, CYP27A1-rs933994, CYP2R1-rs10741657 and DHCR7-rs12785878) were analyzed in 211 RA patients,94 controls and in a prospective cohort of 13 RA patients undergoing TNFα-blockade. Vitamin D was decreased in RA (p < 0.001), correlated to HDL-cholesterol (r = 0.217, p < 0.001) and total-/HDL-cholesterol ratio (r = −0.227, p = 0.004). These correlations were restricted to the VDR-rs2228570 status. Vitamin D deficiency was associated with lower HDL-cholesterol (p = 0.028), higher tender (p = 0.005) and swollen (p = 0.002) joint counts, higher DAS28 (p = 0.018) and HAQ (p = 0.024) in AG/AA-patients but not in their GG-counterparts. The associations among DHCR7, vitamin D and lipid profile followed a seasonal pattern, decreased DHCR7 (p = 0.008) and vitamin D (p < 0.001) and increased total-cholesterol (p = 0.025) being found in winter/spring. Increasing vitamin D upon TNFα-blockade paralleled RA clinical improvement (r = −0.610, p = 0.027) and DHCR7 elevation (r = 0.766, p = 0.002). In conclusion, vitamin D-related polymorphisms and DHCR7 are pivotal to understand the complex, seasonal associations between vitamin D and lipid profile in RA.
Coffee tree architecture and its interactions with microclimates drive the dynamics of coffee berry disease in coffee trees
Authors: Motisi Natacha , Ribeyre Fabienne , Poggi Sylvain 
Published: February 2019

AbstractCoffee berry disease (CBD), which is widespread in Africa, has been responsible for massive yield losses of Coffea arabica. In Cameroon, C. arabica is mainly planted in agroforestry systems on smallholder farms, where low incomes hinder the use of chemicals to manage the disease. Novel agroecological strategies for controlling CBD are expected to be implemented and even increase in the current context of global changes. In this study, we showed that coffee tree architecture and its interactions with microclimates were important to CBD cluster symptom appearance (CSA), with notable CSA increasing along the tree branch away from the trunk to the tip of the branch. As shade trees can modify microclimates, we further investigated scenarios of various microclimatic conditions under shade to explore the effects of agroforestry systems on CBD dynamics in coffee trees. We showed that shade could result in contrasting effects on disease dynamics, decreasing CSA along the branch and increasing epidemic duration. We suggest that the contrasting effects of shade on disease dynamics need further evaluation of the possible trade-offs among the variables at play, and we recommend a combination of epidemiological and architectural modelling to help design more cost-effective and environmentally friendly CBD management strategies.
Using resting-state DMN effective connectivity to characterize the neurofunctional architecture of empathy
Authors: Esménio Sofia , Soares José M. , Oliveira-Silva P. , Zeidman Peter , Razi Adeel , Gonçalves Óscar F. , Friston Karl , Coutinho Joana 
Published: February 2019

AbstractNeuroimaging studies in social neuroscience have largely relied on functional connectivity (FC) methods to characterize the functional integration between different brain regions. However, these methods have limited utility in social-cognitive studies that aim to understand the directed information flow among brain areas that underlies complex psychological processes. In this study we combined functional and effective connectivity approaches to characterize the functional integration within the Default Mode Network (DMN) and its role in self-perceived empathy. Forty-two participants underwent a resting state fMRI scan and completed a questionnaire of dyadic empathy. Independent Component Analysis (ICA) showed that higher empathy scores were associated with an increased contribution of the medial prefrontal cortex (mPFC) to the DMN spatial mode. Dynamic causal modelling (DCM) combined with Canonical Variance Analysis (CVA) revealed that this association was mediated indirectly by the posterior cingulate cortex (PCC) via the right inferior parietal lobule (IPL). More specifically, in participants with higher scores in empathy, the PCC had a greater effect on bilateral IPL and the right IPL had a greater influence on mPFC. These results highlight the importance of using analytic approaches that address directed and hierarchical connectivity within networks, when studying complex psychological phenomena, such as empathy.
Increased susceptibility of airway epithelial cells from ataxia-telangiectasia to S. pneumoniae infection due to oxidative damage and impaired innate immunity
Authors: Yeo Abrey J. , Henningham Anna , Fantino Emmanuelle , Galbraith Sally , Krause Lutz , Wainwright Claire E. , Sly Peter D. , Lavin Martin F. 
Published: February 2019

AbstractRespiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that the upper airway microbiome in patients with A-T is different from that to healthy controls, with S. pneumoniae detected largely in patients only. Patient-specific airway epithelial cells and differentiated air-liquid interface cultures derived from these were hypersensitive to infection which was at least in part due to oxidative damage since it was partially reversed by catalase. We also observed increased levels of the pro-inflammatory cytokines IL-8 and TNF-α (inflammasome-independent) and a decreased level of the inflammasome-dependent cytokine IL-β in patient cells. Further investigation revealed that the ASC-Caspase 1 signalling pathway was defective in A-T airway epithelial cells. These data suggest that the heightened susceptibility of these cells to S. pneumoniae infection is due to both increased oxidative damage and a defect in inflammasome activation, and has implications for lung disease in these patients.
Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration
Authors: Parmeggiani Francesco , Gallenga Carla Enrica , Costagliola Ciro , Semeraro Francesco , Romano Mario R. , Dell’Omo Roberto , Russo Andrea , De Nadai Katia , Gemmati Donato , D’Angelo Sergio , Bolletta Elena , Sorrentino Francesco Saverio 
Published: February 2019

AbstractThe most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12–0.32] and 0.09 [95% CI, 0.04–0.21] (P < 0.001), and odd ratios of 0.24 [95% CI, 0.15–0.39] and 0.03 [95% CI, 0.01–0.11] (P < 0.001). These pharmacogenetic findings indicate a rational basis to optimize the future clinical application of PDT-V during the combined treatments of AMD-related CNV, highlighting the role of thrombophilia to be aware of the efficacy profile of photodynamic therapy.
Transcriptome-wide analysis of filarial extract-primed human monocytes reveal changes in LPS-induced PTX3 expression levels
Authors: Buerfent B. C. , Gölz L. , Hofmann A. , Rühl H. , Stamminger W. , Fricker N. , Hess T. , Oldenburg J. , Nöthen M. M. , Schumacher J. , Hübner M. P. , Hoerauf A. 
Published: February 2019

AbstractFilarial nematodes modulate immune responses in their host to enable their survival and mediate protective effects against autoimmunity and allergies. In this study, we examined the immunomodulatory capacity of extracts from the human pathogenic filaria Brugia malayi (BmA) on human monocyte responses in a transcriptome-wide manner to identify associated pathways and diseases. As previous transcriptome studies often observed quiescent responses of innate cells to filariae, the potential of BmA to alter LPS driven responses was investigated by analyzing >47.000 transcripts of monocytes from healthy male volunteers stimulated with BmA, Escherichia coli LPS or a sequential stimulation of both. In comparison to ~2200 differentially expressed genes in LPS-only stimulated monocytes, only a limited number of differentially expressed genes were identified upon BmA priming before LPS re-stimulation with only PTX3↓ reaching statistical significance after correcting for multiple testing. Nominal significant differences were reached for metallothioneins↑, MMP9↑, CXCL5/ENA-78↑, CXCL6/GCP-2↑, TNFRSF21↓, and CCL20/MIP3α↓ and were confirmed by qPCR or ELISA. Flow cytometric analysis of activation markers revealed a reduced LPS-induced expression of HLA-DR and CD86 on BmA-primed monocytes as well as a reduced apoptosis of BmA-stimulated monocytes. While our experimental design does not allow a stringent extrapolation of our results to the development of filarial pathology, several genes that were identified in BmA-primed monocytes had previously been associated with filarial pathology, supporting the need for further research.
Mediation Effect of Neutrophil Lymphocyte Ratio on Cardiometabolic Risk Factors and Cardiovascular Events
Authors: Angkananard Teeranan , Anothaisintawee Thunyarat , Ingsathit Atiporn , McEvoy Mark , Silapat Kongpop , Attia John , Sritara Piyamitr , Thakkinstian Ammarin 
Published: February 2019

AbstractNeutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, is associated with cardiovascular events (CVEs), but its causal pathway is unknown. We aimed to explore the extent to which NLR is directly associated with CVEs or mediated through diabetes mellitus (DM), hypertension (HT) and creatinine (Cr). The study used data on 2,501 subjects from the Electricity Generating Authority of Thailand cohort 2002–2012. Two causal pathways A: NLR→(DM→Cr→HT)→CVEs and B: NLR→(DM → HT→Cr)→CVEs were constructed. A generalized structural equation model and 1,000-replication bootstrapping were applied. The incidence rate of CVE was 8.8/1000/year. Prevalence rates of HT, DM, and chronic kidney disease were 45.1%, 23.6%, and 16.5%, respectively. The total effect of NLR on CVEs was explained partly (44%) by a direct effect and partly (56%) by an indirect effect through DM, HT and Cr. For pathway A, the direct OR of NLR on CVE was 1.25 (95% CI: 1.13, 1.39); the ORs for the indirect effects of NLR on CVEs mediated through DM, Cr, and poor-controlled HT were 1.06 (95% CI: 1.01, 1.11), 1.01 (95% CI: 1.00, 1.02), and 1.07 (95% CI: 1.01, 1.14) respectively. Results were similar for pathway B. Our findings demonstrate that roughly half of the relationship between NLR and CVEs may be mediated through DM, HT and Cr.
Above and belowground community strategies respond to different global change drivers
Authors: Adair Karen L. , Lindgreen Stinus , Poole Anthony M. , Young Laura M. , Bernard-Verdier Maud , Wardle David A. , Tylianakis Jason M. 
Published: February 2019

AbstractEnvironmental changes alter the diversity and structure of communities. By shifting the range of species traits that will be successful under new conditions, environmental drivers can also dramatically impact ecosystem functioning and resilience. Above and belowground communities jointly regulate whole-ecosystem processes and responses to change, yet they are frequently studied separately. To determine whether these communities respond similarly to environmental changes, we measured taxonomic and trait-based responses of plant and soil microbial communities to four years of experimental warming and nitrogen deposition in a temperate grassland. Plant diversity responded strongly to N addition, whereas soil microbial communities responded primarily to warming, likely via an associated decrease in soil moisture. These above and belowground changes were associated with selection for more resource-conservative plant and microbe growth strategies, which reduced community functional diversity. Functional characteristics of plant and soil microbial communities were weakly correlated (P = 0.07) under control conditions, but not when above or belowground communities were altered by either global change driver. These results highlight the potential for global change drivers operating simultaneously to have asynchronous impacts on above and belowground components of ecosystems. Assessment of a single ecosystem component may therefore greatly underestimate the whole-system impact of global environmental changes.