bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure determination from single molecule X-ray scattering with three photons per image
Authors: von Ardenne Benjamin , Mechelke Martin , Grubmüller Helmut 
Published: June 2018

AbstractScattering experiments with femtosecond high-intensity free-electron laser pulses provide a new route to macromolecular structure determination. While currently limited to nano-crystals or virus particles, the ultimate goal is scattering on single biomolecules. The main challenges in these experiments are the extremely low signal-to-noise ratio due to the very low expected photon count per scattering image, often well below 100, as well as the random orientation of the molecule in each shot. Here we present a de novo correlation-based approach and show that three coherently scattered photons per image suffice for structure determination. Using synthetic scattering data of a small protein, we demonstrate near-atomic resolution of  3.3 Å using 3.3 × 1010 coherently scattered photons from 3.3 × 109 images, which is within experimental reach. Further, our three-photon correlation approach is robust to additional noise from incoherent scattering; the number of disordered solvent molecules attached to the macromolecular surface should be kept small.
Evolution of thiolate-stabilized Ag nanoclusters from Ag-thiolate cluster intermediates
Authors: Cao Yitao , Guo Jiahao , Shi Run , Waterhouse Geoffrey I. N. , Pan Jinheng , Du Zhenxia , Yao Qiaofeng , Wu Li-Zhu , Tung Chen-Ho , Xie Jianping , Zhang Tierui 
Published: June 2018

AbstractThe synthesis of atomically precise thiolate-stabilized silver (Ag) nanoclusters is the subject of intense research interest, yet the formation mechanism of such nanoclusters remains obscure. Here, electrospray ionization mass spectrometry is successfully applied to monitor the reaction intermediates formed during the sodium-borohydride-reduction of silver 4-tert-butylbenzenethiolate (AgSPh-tBu). We demonstrate a unique evolution route to thiolate-stabilized Ag nanoclusters mediated by Ag-thiolate clusters. The Ag-thiolate clusters form in the initial stage of reduction contain tens of Ag atoms and similar number of ligands, and they are transformed into Ag17(SPh-tBu)123− and Ag44(SPh-tBu)304− nanoclusters in the later reduction process. The number of Ag atoms in the Ag-thiolate clusters determines the reaction path to each final nanocluster product. A similar mechanism is found when silver 2,4-dimethylbenzenethiolate (AgSPhMe2) is used as precursor. This mechanism differs markedly from the long-established bottom-up evolution process, providing valuable new insights into the synthesis of metal nanoclusters.
Antibody targeting of a specific region of Pfs47 blocks Plasmodium falciparum malaria transmission
Authors: Canepa Gaspar E. , Molina-Cruz Alvaro , Yenkoidiok-Douti Lampouguin , Calvo Eric , Williams Adeline E. , Burkhardt Martin , Peng Fangni , Narum David , Boulanger Martin J. , Valenzuela Jesus G. , Barillas-Mury Carolina 
Published: June 2018

AbstractTransmission-blocking vaccines are based on eliciting antibody responses in the vertebrate host that disrupt parasite development in the mosquito vector and prevent malaria transmission. The surface protein Pfs47 is present in Plasmodium falciparum gametocytes and female gametes. The potential of Pfs47 as a vaccine target was evaluated. Soluble full-length recombinant protein, consisting of three domains, was expressed in E. coli as a thioredoxin fusion (T-Pfs47). The protein was immunogenic, and polyclonal and monoclonal antibodies (mAb) were obtained, but they did not confer transmission blocking activity (TBA). All fourteen mAb targeted either domains 1 or 3, but not domain 2 (D2), and immune reactivity to D2 was also very low in polyclonal mouse IgG after T-Pfs47 immunization. Disruption of the predicted disulfide bond in D2, by replacing cysteines for alanines (C230A and C260A), allowed expression of recombinant D2 protein in E. coli. A combination of mAbs targeting D2, and deletion proteins from this domain, allowed us to map a central 52 amino acid (aa) region where antibody binding confers strong TBA (78-99%). This 52 aa antigen is immunogenic and well conserved, with only seven haplotypes world-wide that share 96–98% identity. Neither human complement nor the mosquito complement-like system are required for the observed TBA. A dramatic reduction in ookinete numbers and ookinete-specific transcripts was observed, suggesting that the antibodies are interacting with female gametocytes and preventing fertilization.
Value of multilocus genetic risk score for atrial fibrillation in end-stage kidney disease patients in a Polish population
Authors: Saracyn Marek , Kisiel Bartłomiej , Bachta Artur , Franaszczyk Maria , Brodowska-Kania Dorota , Żmudzki Wawrzyniec , Szymański Konrad , Sokalski Antoni , Klatko Wiesław , Stopiński Marek , Grochowski Janusz , Papliński Marek , Goździk Zdzisław , Niemczyk Longin , Bober Barbara , Kołodziej Maciej , Tłustochowicz Witold , Kamiński Grzegorz , Płoski Rafał , Niemczyk Stanisław 
Published: June 2018

AbstractGenetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.
Assessment of Lower-limb Vascular Endothelial Function Based on Enclosed Zone Flow-mediated Dilation
Authors: Hirano Harutoyo , Takama Renjo , Matsumoto Ryo , Tanaka Hiroshi , Hirano Hiroki , Soh Zu , Ukawa Teiji , Takayanagi Tsuneo , Morimoto Haruka , Nakamura Ryuji , Saeki Noboru , Hashimoto Haruki , Matsui Shogo , Kishimoto Shinji , Oda Nozomu , Kajikawa Masato , Maruhashi Tatsuya , Kawamoto Masashi , Yoshizumi Masao , Higashi Yukihito , Tsuji Toshio 
Published: June 2018

AbstractThis paper proposes a novel non-invasive method for assessing the vascular endothelial function of lower-limb arteries based on the dilation rate of air-cuff plethysmograms measured using the oscillometric approach. The principle of evaluating vascular endothelial function involves flow-mediated dilation. In the study conducted, blood flow in the dorsal pedis artery was first monitored while lower-limb cuff pressure was applied using the proposed system. The results showed blood flow was interrupted when the level of pressure was at least 50 mmHg higher than the subject’s lower-limb systolic arterial pressure and that blood flow velocity increased after cuff release. Next, values of the proposed index, %ezFMDL, for assessing the vascular endothelial function of lower-limb arteries were determined from 327 adult subjects: 87 healthy subjects, 150 subjects at high risk of arteriosclerosis and 90 patients with cardiovascular disease (CAD). The mean values and standard deviations calculated using %ezFMDL were 30.5 ± 12.0% for the healthy subjects, 23.6 ± 12.7% for subjects at high risk of arteriosclerosis and 14.5 ± 15.4% for patients with CAD. The %ezFMDL values for the subjects at high risk of arteriosclerosis and the patients with CAD were significantly lower than those for the healthy subjects (p < 0.01). The proposed method may have potential for clinical application.
Ab initio inspired design of ternary boride thin films
Authors: Moraes Vincent , Riedl Helmut , Fuger Christoph , Polcik Peter , Bolvardi Hamid , Holec David , Mayrhofer P. H. 
Published: June 2018

AbstractThe demand to discover new materials is scientifically as well as industrially a continuously present topic, covering all different fields of application. The recent scientific work on thin film materials has shown, that especially for nitride-based protective coatings, computationally-driven understanding and modelling serves as a reliable trend-giver and can be used for target-oriented experiments. In this study, semi-automated density functional theory (DFT) calculations were used, to sweep across transition metal diborides in order to characterize their structure, phase stability and mechanical properties. We show that early transition metal diborides (TiB2, VB2, etc.) tend to be chemically more stable in the AlB2 structure type, whereas late transition metal diborides (WB2, ReB2, etc.) are preferably stabilized in the W2B5−x structure type. Closely related, we could prove that point defects such as vacancies significantly influence the phase stability and even can reverse the preference for the AlB2 or W2B5−x structure. Furthermore, investigations on the brittle-ductile behavior of the various diborides reveal, that the metastable structures are more ductile than their stable counterparts (WB2, TcB2, etc.). To design thin film materials, e.g. ternary or layered systems, this study is important for application oriented coating development to focus experimental studies on the most perspective systems.
Genome-wide assessment of gene-by-smoking interactions in COPD
Authors: Park Boram , Koo So-My , An Jaehoon , Lee MoonGyu , Kang Hae Yeon , Qiao Dandi , Cho Michael H. , Sung Joohon , Silverman Edwin K. , Yang Hyeon-Jong , Won Sungho 
Published: June 2018

AbstractCigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables—forced expiratory volume in 1 s (FEV1). We found that variations in FEV1were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus nearSOX9on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV1values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.
Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the Cftr-F508del mouse
Authors: Philp Amber R. , Riquelme Texia T. , Millar-Büchner Pamela , González Rodrigo , Sepúlveda Francisco V. , Cid L. Pablo , Flores Carlos A. 
Published: June 2018

AbstractNearly 70% of cystic fibrosis (CF) patients bear the phenylalanine-508 deletion but disease severity differs greatly, and is not explained by the existence of different mutations in compound heterozygous. Studies demonstrated that genes other than CFTR relate to intestinal disease in humans and CF-mouse. Kcnn4, the gene encoding the calcium-activated potassium channel KCa3.1, important for intestinal secretion, is present in a locus linked with occurrence of intestinal CF-disease in mice and humans. We reasoned that it might be a CF-modifier gene and bred a CF-mouse with Kcnn4 silencing, finding that lethality was almost abolished. Silencing of Kcnn4 did not improve intestinal secretory functions, but rather corrected increased circulating TNF-α level and reduced intestinal mast cell increase. Given the importance of mast cells in intestinal disease additional double mutant CF-animals were tested, one lacking mast cells (C-kitW-sh/W-sh) and Stat6−/− to block IgE production. While mast cell depletion had no effect, silencing Stat6 significantly reduced lethality. Our results show that Kcnn4 is an intestinal CF modifier gene partially acting through a STAT6-dependent mechanism.
Non-communicable disease risk factor profile among public employees in a regional city in northern Ethiopia
Authors: Gebremariam Lemlem Weldegerima , Chiang Chifa , Yatsuya Hiroshi , Hilawe Esayas Haregot , Kahsay Alemayehu Bayray , Godefay Hagos , Abraham Loko , Hirakawa Yoshihisa , Iso Hiroyasu , Aoyama Atsuko 
Published: June 2018

AbstractThe burden of non-communicable diseases (NCDs) is increasing in Ethiopia. This study aims to describe the prevalence of NCD risk factors of public employees in a regional city in northern Ethiopia. We conducted a cross-sectional epidemiological study targeting men and women aged 25–64 years employed by public offices in Mekelle. The prevalence was age-standardized to the Ethiopian 2007 population. Among the 1380 subjects (823 men and 557 women), 68.7% had less than 1 serving of fruits and vegetables per day, 41.0% were physically inactive, and 57.3% observed religious fast. The age-standardised prevalence of abdominal obesity was 29.3% in men and 58.5% in women, but that of metabolic syndrome was comparable between men (39.2%) and women (39.0%). The prevalence of diabetes was underestimated if only fasting blood glucose (FBG) was used for the diagnosis compared to combination of FBG and glycated haemoglobin (HbA1c) (6.7% in men and 3.8% in women vs. 12.1% in men and 5.6% in women). More than a quarter (26.1%) of men and 8.7% of women had estimated 10-year risk of cardiovascular disease of 10% or more. This study revealed the high prevalence of NCD metabolic risk factors among the urban public employees in the highland of Ethiopia.
Ossification of the Ligamentum Flavum in a Nineteenth-Century Skeletal Population Sample from Ireland: Using Bioarchaeology to Reveal a Neglected Spine Pathology
Authors: Geber Jonny , Hammer Niels 
Published: June 2018

AbstractOssification of the ligamentum flavum of the spine (OLF) is rarely reported in individuals of European ancestry. It has, however, been observed in archaeological skeletons from Europe. The aim of this study was to revisit OLF rates, utilising a mid-nineteenth-century skeletal sample from Ireland. The hypothesis was that the OLF prevalence rate was similar to studies on non-Europeans. Spines from 345 individuals were analysed, and the extent of OLF recorded on the cranial and caudal attachment sites of each vertebra using the following classification system: Grade 0 (no change); Grade 1 (<2 mm); Grade 2 (2–4 mm); Grade 3 (≥4 mm). OLF was observed at prevalence rates of 83.6%. There was no disparity in prevalence based on sex, except for individuals aged 36–45 years at death in which the male rate was higher. Advancing age was a determining factor in the OLF occurrence with an onset in young adulthood (18–25 years), and most severe grades occurring over the age of 25 years. OLF coincides with spinal osteoarthritis, spondylosis deformans and Schmorl’s nodes in both sexes, and with intervertebral osteochondrosis in females. The results of this study indicate that OLF is likely to be an understudied rather than rare condition in European populations.
QSAR-based molecular signatures of prenylated (iso)flavonoids underlying antimicrobial potency against and membrane-disruption in Gram positive and Gram negative bacteria
Authors: Araya-Cloutier Carla , Vincken Jean-Paul , van de Schans Milou G. M. , Hageman Jos , Schaftenaar Gijs , den Besten Heidy M. W. , Gruppen Harry 
Published: June 2018

AbstractPrenylated flavonoids and isoflavonoids are phytochemicals with remarkable antibacterial activity. In this study, 30 prenylated (iso)flavonoids were tested against Listeria monocytogenes and Escherichia coli (the latter in combination with an efflux pump inhibitor). Minimum inhibitory concentrations of the most active compounds ranged between 6.3–15.0 µg/mL. Quantitative structure-activity relationships (QSAR) analysis was performed and linear regression models were proposed with R2 between 0.77–0.80, average R2m between 0.70–0.75, Q2LOO between 0.66–0.69, and relatively low amount of descriptors. Shape descriptors (related to flexibility and globularity), together with hydrophilic/hydrophobic volume and surface area descriptors, were identified as important molecular characteristics related to activity. A 3D pharmacophore model explaining the effect of the prenyl position on the activity of compounds was developed for each bacterium. These models predicted active compounds with an accuracy of 71–88%. With regard to the mode of action, good antibacterial prenylated (iso)flavonoids with low relative hydrophobic surface area caused remarkable membrane permeabilization, whereas those with higher relative hydrophobic surface area did not. Based on the QSAR and membrane permeabilization studies, the mode of action of antibacterial prenylated (iso)flavonoids was putatively rationalized.
Highly accurate model for prediction of lung nodule malignancy with CT scans
Authors: Causey Jason L. , Zhang Junyu , Ma Shiqian , Jiang Bo , Qualls Jake A. , Politte David G. , Prior Fred , Zhang Shuzhong , Huang Xiuzhen 
Published: June 2018

AbstractComputed tomography (CT) examinations are commonly used to predict lung nodule malignancy in patients, which are shown to improve noninvasive early diagnosis of lung cancer. It remains challenging for computational approaches to achieve performance comparable to experienced radiologists. Here we present NoduleX, a systematic approach to predict lung nodule malignancy from CT data, based on deep learning convolutional neural networks (CNN). For training and validation, we analyze >1000 lung nodules in images from the LIDC/IDRI cohort. All nodules were identified and classified by four experienced thoracic radiologists who participated in the LIDC project. NoduleX achieves high accuracy for nodule malignancy classification, with an AUC of ~0.99. This is commensurate with the analysis of the dataset by experienced radiologists. Our approach, NoduleX, provides an effective framework for highly accurate nodule malignancy prediction with the model trained on a large patient population. Our results are replicable with software available at http://bioinformatics.astate.edu/NoduleX.
Protein and DNA synthesis demonstrated in cell-free Ehrlichia chaffeensis organisms in axenic medium
Authors: Eedunuri Vijay K. , Zhang Yuntao , Cheng Chuanmin , Chen Li , Liu Huitao , Omsland Anders , Boyle Dan , Ganta Roman R. 
Published: June 2018

AbstractEhrlichia chaffeensis, a tick-transmitted rickettsial bacterium, is the causative agent of human monocytic ehrlichiosis. Biochemical characterization of this and other related Rickettsiales remains a major challenge, as they require a host cell for their replication. We investigated the use of an axenic medium for E. chaffeensis growth, assessed by protein and DNA synthesis, in the absence of a host cell. E. chaffeensis organisms harvested from in vitro cultures grown in a vertebrate cell line were fractionated into infectious dense-core cells (DC) and the non-infectious replicating form, known as reticulate cells (RC) by renografin density gradient centrifugation and incubated in the axenic medium containing amino acids, nucleotides, and different energy sources. Bacterial protein and DNA synthesis were observed in RCs in response to glucose-6-phosphate, although adenosine triphosphate, alpha-ketoglutarate or sodium acetate supported protein synthesis. The biosynthetic activity could not be detected in DCs in the axenic medium. While the data demonstrate de novo protein and DNA synthesis under axenic conditions for E. chaffeensis RCs, additional modifications are required in order to establish conditions that support bacterial replication, and transition to DCs.
Gallic acid improves cardiac dysfunction and fibrosis in pressure overload-induced heart failure
Authors: Jin Li , Sun Simei , Ryu Yuhee , Piao Zhe Hao , Liu Bin , Choi Sin Young , Kim Gwi Ran , Kim Hyung-Seok , Kee Hae Jin , Jeong Myung Ho 
Published: June 2018

AbstractGallic acid is a trihydroxybenzoic acid found in tea leaves and some plants. Here, we report the effect of gallic acid on cardiac dysfunction and fibrosis in a mouse model of pressure overload-induced heart failure and in primary rat cardiac fibroblasts, and compare the effects of gallic acid with those of drugs used in clinics. Gallic acid reduces cardiac hypertrophy, dysfunction, and fibrosis induced by transverse aortic constriction (TAC) stimuli in vivo and transforming growth factor β1 (TGF-β1) in vitro. It decreases left ventricular end-diastolic and end-systolic diameter, and recovers the reduced fractional shortening in TAC. In addition, it suppresses the expression of atrial natriuretic peptide, brain natriuretic peptide, skeletal α-actin, and β-myosin heavy chain. Administration of gallic acid decreases perivascular fibrosis, as determined by Trichrome II Blue staining, and reduces the expression of collagen type I and connective tissue growth factor. However, administration of losartan, carvedilol, and furosemide does not reduce cardiac dysfunction and fibrosis in TAC. Moreover, treatment with gallic acid inhibits fibrosis-related genes and deposition of collagen type I in TGF-β1-treated cardiac fibroblasts. These results suggest that gallic acid is a therapeutic agent for cardiac dysfunction and fibrosis in chronic heart failure.
A pivotal role for starch in the reconfiguration of 14C-partitioning and allocation in Arabidopsis thaliana under short-term abiotic stress
Authors: Dong Shaoyun , Zhang Joshua , Beckles Diane M. 
Published: June 2018

AbstractPlant carbon status is optimized for normal growth but is affected by abiotic stress. Here, we used14C-labeling to provide the first holistic picture of carbon use changes during short-term osmotic, salinity, and cold stress inArabidopsis thaliana. This could inform on the early mechanisms plants use to survive adverse environment, which is important for efficient agricultural production. We found that carbon allocation from source to sinks, and partitioning into major metabolite pools in the source leaf, sink leaves and roots showed both conserved and divergent responses to the stresses examined. Carbohydrates changed under all abiotic stresses applied; plants re-partitioned14C to maintain sugar levels under stress, primarily by reducing14C into the storage compounds in the source leaf, and decreasing14C into the pools used for growth processes in the roots. Salinity and cold increased14C-flux into protein, but as the stress progressed, protein degradation increased to produce amino acids, presumably for osmoprotection. Our work also emphasized that stress regulated the carbon channeled into starch, and its metabolic turnover. These stress-induced changes in starch metabolism and sugar export in the source were partly accompanied by transcriptional alteration in the T6P/SnRK1 regulatory pathway that are normally activated by carbon starvation.