bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Sulfo-Sialic Acid Analogues: Potent Neuraminidase Inhibitors in Regards to Anomeric Functionality
Authors: Vavricka Christopher J. , Muto Chiaki , Hasunuma Tomohisa , Kimura Yoshinobu , Araki Michihiro , Wu Yan , Gao George F. , Ohrui Hiroshi , Izumi Minoru , Kiyota Hiromasa 
Published: August 2017

AbstractThe design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. While 2-decarboxy-2-deoxy-2-sulfo-N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors.
Localization of photoperiod responsive circadian oscillators in the mouse suprachiasmatic nucleus
Authors: Yoshikawa Tomoko , Inagaki Natsuko F. , Takagi Seiji , Kuroda Shigeru , Yamasaki Miwako , Watanabe Masahiko , Honma Sato , Honma Ken-ichi 
Published: August 2017

AbstractThe circadian pacemaker in the suprachiasmatic nucleus (SCN) yields photoperiodic response to transfer seasonal information to physiology and behavior. To identify the precise location involved in photoperiodic response in the SCN, we analyzed circadianPeriod1and PERIOD2 rhythms in horizontally sectioned SCN of mice exposed to a long or short day. Statistical analyses of bioluminescence images with respective luciferase reporters on pixel level enabled us to identify the distinct localization of three oscillating regions; a large open-ring-shape region, the region at the posterior end and a sharply demarcated oval region at the center of the SCN. The first two regions are the respective sites for the so-called evening and morning oscillators, and the third region is possibly a site for mediating photic signals to the former oscillators. In these regions, there are two classes of oscillating cells in whichPer1andPer2could play differential roles in photoperiodic responses.
CO2 and temperature decoupling at the million-year scale during the Cretaceous Greenhouse
Authors: Barral Abel , Gomez Bernard , Fourel François , Daviero-Gomez Véronique , Lécuyer Christophe 
Published: August 2017

AbstractCO2 is considered the main greenhouse gas involved in the current global warming and the primary driver of temperature throughout Earth’s history. However, the soundness of this relationship across time scales and during different climate states of the Earth remains uncertain. Here we explore how CO2 and temperature are related in the framework of a Greenhouse climate state of the Earth. We reconstruct the long-term evolution of atmospheric CO2 concentration (pCO2) throughout the Cretaceous from the carbon isotope compositions of the fossil conifer Frenelopsis. We show that pCO2 was in the range of ca. 150–650 ppm during the Barremian–Santonian interval, far less than what is usually considered for the mid Cretaceous. Comparison with available temperature records suggest that although CO2 may have been a main driver of temperature and primary production at kyr or smaller scales, it was a long-term consequence of the climate-biological system, being decoupled or even showing inverse trends with temperature, at Myr scales. Our analysis indicates that the relationship between CO2 and temperature is time scale-dependent at least during Greenhouse climate states of the Earth and that primary productivity is a key factor to consider in both past and future analyses of the climate system.
Totipotency segregates between the sister blastomeres of two-cell stage mouse embryos
Authors: Casser E. , Israel S. , Witten A. , Schulte K. , Schlatt S. , Nordhoff V. , Boiani M. 
Published: August 2017

AbstractFollowing fertilization in mammals, it is generally accepted that totipotent cells are exclusive to the zygote and to each of the two blastomeres originating from the first mitotic division. This model of totipotency was inferred from a minority of cases in which blastomeres produced monozygotic twins in mice. Was this due to experimental limitation or biological constraint? Here we removed experimental obstacles and achieved reliable quantification of the prevalence of dual totipotency among mouse two-cell stage blastomeres. We separated the blastomeres of 1,252 two-cell embryos, preserving 1,210 of the pairs. Two classes of monozygotic twins became apparent at the blastocyst stage: 27% formed a functional epiblast in both members (concordant), and 73% did so in only one member of the pair (discordant) – a partition that proved insensitive to oocyte quality, sperm-entry point, culture environment and pattern of cleavage. In intact two-cell embryos, the ability of sister blastomeres to generate epiblast was also skewed. Class discovery clustering of the individual blastomeres’ and blastocysts’ transcriptomes points to an innate origin of concordance and discordance rather than developmental acquisition. Our data place constraints on the commonly accepted idea that totipotency is allocated equally between the two-cell stage blastomeres in mice.
Atomic-scale study of the amorphous-to-crystalline phase transition mechanism in GeTe thin films
Authors: Mantovan R. , Fallica R. , Mokhles Gerami A. , Mølholt T. E. , Wiemer C. , Longo M. , Gunnlaugsson H. P. , Johnston K. , Masenda H. , Naidoo D. , Ncube M. , Bharuth-Ram K. , Fanciulli M. , Gislason H. P. , Langouche G. , Ólafsson S. , Weyer G. 
Published: August 2017

AbstractThe underlying mechanism driving the structural amorphous-to-crystalline transition in Group VI chalcogenides is still a matter of debate even in the simplest GeTe system. We exploit the extreme sensitivity of 57Fe emission Mössbauer spectroscopy, following dilute implantation of 57Mn (T½ = 1.5 min) at ISOLDE/CERN, to study the electronic charge distribution in the immediate vicinity of the 57Fe probe substituting Ge (FeGe), and to interrogate the local environment of FeGe over the amorphous-crystalline phase transition in GeTe thin films. Our results show that the local structure of as-sputtered amorphous GeTe is a combination of tetrahedral and defect-octahedral sites. The main effect of the crystallization is the conversion from tetrahedral to defect-free octahedral sites. We discover that only the tetrahedral fraction in amorphous GeTe participates to the change of the FeGe-Te chemical bonds, with a net electronic charge density transfer of  ~ 1.6 e/a0 between FeGe and neighboring Te atoms. This charge transfer accounts for a lowering of the covalent character during crystallization. The results are corroborated by theoretical calculations within the framework of density functional theory. The observed atomic-scale chemical-structural changes are directly connected to the macroscopic phase transition and resistivity switch of GeTe thin films.
Mutations in the promoter, intron and CDS of two FAD2 generate multiple alleles modulating linoleic acid level in yellow mustard
Authors: Zeng Fangqin , Roslinsky Vicky , Cheng Bifang 
Published: August 2017

AbstractLinoleic acid (C18:2) is an important polyunsaturated fatty acid in the seed oil of many crops. Here, we report that mutations in the promoter, intron and CDS of the FAD2 genes SalFAD2.LIA1 and SalFAD2.LIA2 generate three alleles LIA1a
, LIA
1b
and lia
1
and two alleles LIA2 and lia2, respectively, controlling the C18:2 variation (4.4–32.7%) in yellow mustard. The allelic effect on increasing C18:2 content is LIA
1a
> LIA
1b
> lia
1
, LIA2 > lia2, and LIA
1a
> LIA2. The five FAD2 alleles each contain two exons, one intron and a promoter adjacent to exon 1. LIA1a
has a 1152 bp CDS, a 1221 bp intron with promoter function and a 607 bp promoter. Compared with LIA
1a
, the intron of LIA
1b
has reduced promoter activity and that of LIA2 and lia2 has no promoter function due to extensive SNP and indel mutations. lia1 differed from LIA1b
by having an insertion of 1223 bp retrotransposon in its intron. lia
2
with mutations in the promoter has reduced promoter activity compared with LIA
2
. This study revealed that complex quantitative variation of trait phenotype in plants could be modulated by multiple alleles of oligogenic loci resulting from mutations in the regulatory region and CDS.
A new method to investigate the catalytic mechanism of YhdE pyrophosphatase by using a pyrophosphate fluorescence probe
Authors: Shen Qingya , Tan Hongwei , Xing Guo-wen , Zheng Jimin , Jia Zongchao 
Published: August 2017

AbstractYhdE is a Maf (multicopy associated filamentation) proteins from Escherichia coli which exhibits pyrophosphatase activity towards selected nucleotides, although its catalytic mechanism remains unclear. Herein we used a novel fluorescence probe (4-isoACBA–Zn(II) complex) to characterize the enzymatic properties of YhdE and its mutant, establishing a new method for assaying pyrophosphatase catalytic function. Our results reveal for the first time that the new fluorescence sensor confers high sensitivity and specificity and pyrophosphate (PPi) is the direct catalytic product of YhdE. Crystal structures of a mutant in the active-site loop (YhdE_E33A) show conformational flexibility implicated in the catalytic mechanism of YhdE. ITC experiments and computational docking further reveal that Asp70 and substrate dTTP coordinate Mn2+. Quantum mechanics calculations indicate that YhdE hydrolysis appears to follow a stepwise pathway in which a water molecule first attacks the α-phosphorus atom in the substrate, followed by the release of PPi from the pentavalent intermediate.
Interactions count: plant origin, herbivory and disturbance jointly explain seedling recruitment and community structure
Authors: Korell Lotte , Lang Birgit R. , Hensen Isabell , Auge Harald , Bruelheide Helge 
Published: August 2017

AbstractHerbivory and disturbance are major drivers of biological invasions, but it is unclear how they interact to determine exotic vs. native seedling recruitment and what consequences arise for biodiversity and ecosystem functioning. Previous studies neglected the roles of different, potentially interacting, guilds of generalist herbivores such as rodents and gastropods. We therefore set up a full-factorial rodent exclusion x gastropod exclusion x disturbance x seed-addition experiment in a grassland community in Central Germany and measured early seedling recruitment, as well as species richness, species composition and aboveground biomass. Gastropod herbivory reduced the positive effect of disturbance on seedling recruitment, particularly for exotic species. Rodent herbivory had weak positive effects on seedling recruitment at undisturbed sites, irrespective of species origin. This effect was likely driven by their strong negative effect on productivity. Interactive effects between both herbivore guilds became only evident for species richness and composition. How many species established themselves depended on disturbance, but was independent of species origin. The fewer exotic species that established themselves increased productivity to a stronger extent compared to native species. Our study highlights that joint effects of disturbance, herbivory and species origin shape early recruitment, while they only weakly affect biodiversity and ecosystem functioning.
Overexpressed somatic alleles are enriched in functional elements in Breast Cancer
Authors: Restrepo Paula , Movassagh Mercedeh , Alomran Nawaf , Miller Christian , Li Muzi , Trenkov Chris , Manchev Yulian , Bahl Sonali , Warnken Stephanie , Spurr Liam , Apanasovich Tatiyana , Crandall Keith , Edwards Nathan , Horvath Anelia 
Published: August 2017

AbstractAsymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent allele-specific overexpression of variants in tumor-suppressor genes. We also report a list of over-expressed variants from non-CGC genes. Overall, our analysis presents an integrated set of features of somatic allele expression and points to the vast information content of the asymmetric alleles in the cancer transcriptome.
Solid-state 31P and 1H chemical MR micro-imaging of hard tissues and biomaterials with magic angle spinning at very high magnetic field
Authors: Yon Maxime , Sarou-Kanian Vincent , Scheler Ulrich , Bouler Jean-Michel , Bujoli Bruno , Massiot Dominique , Fayon Franck 
Published: August 2017

AbstractIn this work, we show that it is possible to overcome the limitations of solid-state MRI for rigid tissues due to large line broadening and short dephasing times by combining Magic Angle Spinning (MAS) with rotating pulsed field gradients. This allows recordingex vivo31P 3D and 2D slice-selected images of rigid tissues and related biomaterials at very high magnetic field, with greatly improved signal to noise ratio and spatial resolution when compared to static conditions. Cross-polarization is employed to enhance contrast and to further depict spatially localized chemical variations in reduced experimental time. In these materials, very high magnetic field and moderate MAS spinning rate directly provide high spectral resolution and enable the use of frequency selective excitation schemes for chemically selective imaging. These new possibilities are exemplified with experiments probing selectively the 3D spatial distribution of apatitic hydroxyl protons inside a mouse tooth with attached jaw bone with a nominal isotropic resolution nearing 100 µm.
Crosstalk between diurnal rhythm and water stress reveals an altered primary carbon flux into soluble sugars in drought-treated rice leaves
Authors: Kim Seo-Woo , Lee Sang-Kyu , Jeong Hee-Jeong , An Gynheung , Jeon Jong-Seong , Jung Ki-Hong 
Published: August 2017

AbstractPlants retain rhythmic physiological responses when adapting to environmental challenges. However, possible integrations between drought conditions and those responses have not received much focus, especially regarding crop plants, and the relationship between abiotic stress and the diurnal cycle is generally not considered. Therefore, we conducted a genome-wide analysis to identify genes showing both diurnal regulation and water-deficiency response in rice (Oryza sativa). Among the 712 drought-responsive genes primary identified, 56.6% are diurnally expressed while 47.6% of the 761 that are down-regulated by drought are also diurnal. Using the β-glucuronidase reporter system and qRT-PCR analyses, we validated expression patterns of two candidate genes, thereby supporting the reliability of our transcriptome data. MapMan analysis indicated that diurnal genes up-regulated by drought are closely associated with the starch-sucrose pathway while those that are down-regulated are involved in photosynthesis. We then confirmed that starch-sucrose contents and chlorophyll fluorescence are altered in a diurnal manner under drought stress, suggesting these metabolic diurnal alterations as a novel indicator to evaluate the drought response in rice leaves. We constructed a functional gene network associated with the starch-sucrose KEGG metabolic pathway for further functional studies, and also developed a regulatory pathway model that includes OsbZIP23 transcription factor.
Spin-Selective Transmission and Devisable Chirality in Two-Layer Metasurfaces
Authors: Li Zhancheng , Liu Wenwei , Cheng Hua , Chen Shuqi , Tian Jianguo 
Published: August 2017

AbstractChirality is a nearly ubiquitous natural phenomenon. Its minute presence in most naturally occurring materials makes it incredibly difficult to detect. Recent advances in metasurfaces indicate that they exhibit devisable chirality in novel forms; this finding offers an effective opening for studying chirality and its features in such nanostructures. These metasurfaces display vast possibilities for highly sensitive chirality discrimination in biological and chemical systems. Here, we show that two-layer metasurfaces based on twisted nanorods can generate giant spin-selective transmission and support engineered chirality in the near-infrared region. Two designed metasurfaces with opposite spin-selective transmission are proposed for treatment as enantiomers and can be used widely for spin selection and enhanced chiral sensing. Specifically, we demonstrate that the chirality in these proposed metasurfaces can be adjusted effectively by simply changing the orientation angle between the twisted nanorods. Our results offer simple and straightforward rules for chirality engineering in metasurfaces and suggest intriguing possibilities for the applications of such metasurfaces in spin optics and chiral sensing.
Joint inflammation related citrullination of functional arginines in extracellular proteins
Authors: Sipilä Kalle H. , Ranga Vipin , Rappu Pekka , Mali Markku , Pirilä Laura , Heino Ilona , Jokinen Johanna , Käpylä Jarmo , Johnson Mark S. , Heino Jyrki 
Published: August 2017

AbstractWe report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction. Citrullination of integrin ligands was selected for further studies since fibronectin R234 in isoDGR was among the most frequently citrullinated arginines in synovial fluid. Assays with synovial fibroblasts and integrin αVβ3 indicated decreased affinity to the enzymatically citrullinated integrin binding sites. To conclude, our data indicate that in inflamed joints extensive citrullination affects the functional arginine residues in extracellular proteins.
Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients
Authors: Al-Daghri Nasser M. , Mohammed Abdul Khader , Al-Attas Omar S. , Ansari Mohammed Ghouse Ahmed , Wani Kaiser , Hussain Syed D. , Sabico Shaun , Tripathi Gyanendra , Alokail Majed S. 
Published: August 2017

AbstractThere is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.
A Tissue Engineered Blood Vessel Model of Hutchinson-Gilford Progeria Syndrome Using Human iPSC-derived Smooth Muscle Cells
Authors: Atchison Leigh , Zhang Haoyue , Cao Kan , Truskey George A. 
Published: August 2017

AbstractHutchison-Gilford Progeria Syndrome (HGPS) is a rare, accelerated aging disorder caused by nuclear accumulation of progerin, an altered form of the Lamin A gene. The primary cause of death is cardiovascular disease at about 14 years. Loss and dysfunction of smooth muscle cells (SMCs) in the vasculature may cause defects associated with HGPS. Due to limitations of 2D cell culture and mouse models, there is a need to develop improved models to discover novel therapeutics. To address this need, we produced a functional three-dimensional model of HGPS that replicates an arteriole-scale tissue engineered blood vessel (TEBV) using induced pluripotent stem cell (iPSC)-derived SMCs from an HGPS patient. To isolate the effect of the HGPS iSMCs, the endothelial layer consisted of human cord blood-derived endothelial progenitor cells (hCB-EPCs) from a separate, healthy donor. TEBVs fabricated from HGPS iSMCs and hCB-EPCs show reduced vasoactivity, increased medial wall thickness, increased calcification and apoptosis relative to TEBVs fabricated from normal iSMCs or primary MSCs. Additionally, treatment of HGPS TEBVs with the proposed therapeutic Everolimus, increases HGPS TEBV vasoactivity and increases iSMC differentiation in the TEBVs. These results show the ability of this iPSC-derived TEBV to reproduce key features of HGPS and respond to drugs.
Autonomic versus perceptual accounts for tactile hypersensitivity in autism spectrum disorder
Authors: Fukuyama Hiroshi , Kumagaya Shin-ichiro , Asada Kosuke , Ayaya Satsuki , Kato Masaharu 
Published: August 2017

AbstractTactile atypicality in individuals with autism spectrum disorder (ASD) has harmful effects on their everyday lives including social interactions. However, whether tactile atypicality in ASD reflects perceptual and/or autonomic processes is unknown. Here, we show that adults with ASD have hypersensitivity to tactile stimuli in the autonomic but not perceptual domain. In particular, adults with ASD showed a greater skin conductance response (SCR) to tactile stimuli compared to typically developing (TD) adults, despite an absence of differences in subjective responses. Furthermore, the level of the SCR was correlated with sensory sensitivity in daily living. By contrast, in perceptual discriminative tasks that psychophysically measured thresholds to tactile stimuli, no differences were found between the ASD and TD groups. These results favor the hypothesis that atypical autonomic processing underlies tactile hypersensitivity in ASD.