bluuebunny/crossref_metadata_2025_split huggingface dataset:
KoVariome: Korean National Standard Reference Variome database of whole genomes with comprehensive SNV, indel, CNV, and SV analyses
Authors: Kim Jungeun , Weber Jessica A. , Jho Sungwoong , Jang Jinho , Jun JeHoon , Cho Yun Sung , Kim Hak-Min , Kim Hyunho , Kim Yumi , Chung OkSung , Kim Chang Geun , Lee HyeJin , Kim Byung Chul , Han Kyudong , Koh InSong , Chae Kyun Shik , Lee Semin , Edwards Jeremy S. , Bhak Jong 
Published: March 2018

AbstractHigh-coverage whole-genome sequencing data of a single ethnicity can provide a useful catalogue of population-specific genetic variations, and provides a critical resource that can be used to more accurately identify pathogenic genetic variants. We report a comprehensive analysis of the Korean population, and present the Korean National Standard Reference Variome (KoVariome). As a part of the Korean Personal Genome Project (KPGP), we constructed the KoVariome database using 5.5 terabases of whole genome sequence data from 50 healthy Korean individuals in order to characterize the benign ethnicity-relevant genetic variation present in the Korean population. In total, KoVariome includes 12.7M single-nucleotide variants (SNVs), 1.7M short insertions and deletions (indels), 4K structural variations (SVs), and 3.6K copy number variations (CNVs). Among them, 2.4M (19%) SNVs and 0.4M (24%) indels were identified as novel. We also discovered selective enrichment of 3.8M SNVs and 0.5M indels in Korean individuals, which were used to filter out 1,271 coding-SNVs not originally removed from the 1,000 Genomes Project when prioritizing disease-causing variants. KoVariome health records were used to identify novel disease-causing variants in the Korean population, demonstrating the value of high-quality ethnic variation databases for the accurate interpretation of individual genomes and the precise characterization of genetic variations.
Ribosome-dependent conformational flexibility changes and RNA dynamics of IRES domains revealed by differential SHAPE
Authors: Lozano Gloria , Francisco-Velilla Rosario , Martinez-Salas Encarnacion 
Published: March 2018

AbstractInternal ribosome entry site (IRES) elements are RNA regions that recruit the translation machinery internally. Here we investigated the conformational changes and RNA dynamics of a picornavirus IRES upon incubation with distinct ribosomal fractions. Differential SHAPE analysis of the free RNA showed that nucleotides reaching the final conformation on long timescales were placed at domains 4 and 5, while candidates for long-range interactions were located in domain 3. Salt-washed ribosomes induced a fast RNA local flexibility modification of domains 2 and 3, while ribosome-associated factors changed domains 4 and 5. Consistent with this, modeling of the three-dimensional RNA structure indicated that incubation of the IRES with native ribosomes induced a local rearrangement of the apical region of domain 3, and a reorientation of domains 4 and 5. Furthermore, specific motifs within domains 2 and 3 showed a decreased flexibility upon incubation with ribosomal subunits in vitro, and presence of the IRES enhanced mRNA association to the ribosomal subunits in whole cell lysates. The finding that RNA modules can provide direct IRES-ribosome interaction suggests that linking these motifs to additional sequences able to recruit trans-acting factors could be useful to design synthetic IRESs with novel activities.
State-dependent representation of stimulus-evoked activity in high-density recordings of neural cultures
Authors: Nieus Thierry , D’Andrea Valeria , Amin Hayder , Di Marco Stefano , Safaai Houman , Maccione Alessandro , Berdondini Luca , Panzeri Stefano 
Published: March 2018

AbstractNeuronal responses to external stimuli vary from trial to trial partly because they depend on continuous spontaneous variations of the state of neural circuits, reflected in variations of ongoing activity prior to stimulus presentation. Understanding how post-stimulus responses relate to the pre-stimulus spontaneous activity is thus important to understand how state dependence affects information processing and neural coding, and how state variations can be discounted to better decode single-trial neural responses. Here we exploited high-resolution CMOS electrode arrays to record simultaneously from thousands of electrodes in in-vitro cultures stimulated at specific sites. We used information-theoretic analyses to study how ongoing activity affects the information that neuronal responses carry about the location of the stimuli. We found that responses exhibited state dependence on the time between the last spontaneous burst and the stimulus presentation and that the dependence could be described with a linear model. Importantly, we found that a small number of selected neurons carry most of the stimulus information and contribute to the state-dependent information gain. This suggests that a major value of large-scale recording is that it individuates the small subset of neurons that carry most information and that benefit the most from knowledge of its state dependence.
Systemic and specific effects of antihypertensive and lipid-lowering medication on plasma protein biomarkers for cardiovascular diseases
Authors: Enroth Stefan , Maturi Varun , Berggrund Malin , Enroth Sofia Bosdotter , Moustakas Aristidis , Johansson Åsa , Gyllensten Ulf 
Published: March 2018

AbstractA large fraction of the adult population is on lifelong medication for cardiovascular disorders, but the metabolic consequences are largely unknown. This study determines the effects of common anti-hypertensive and lipid lowering drugs on circulating plasma protein biomarkers. We studied 425 proteins in plasma together with anthropometric and lifestyle variables, and the genetic profile in a cross-sectional cohort. We found 8406 covariate-protein associations, and a two-stage GWAS identified 17253 SNPs to be associated with 109 proteins. By computationally removing variation due to lifestyle and genetic factors, we could determine that medication, per se, affected the abundance levels of 35.7% of the plasma proteins. Medication either affected a single, a few, or a large number of protein, and were found to have a negative or positive influence on known disease pathways and biomarkers. Anti-hypertensive or lipid lowering drugs affected 33.1% of the proteins. Angiotensin-converting enzyme inhibitors showed the strongest lowering effect by decreasing plasma levels of myostatin. Cell-culture experiments showed that angiotensin-converting enzyme inhibitors reducted myostatin RNA levels. Thus, understanding the effects of lifelong medication on the plasma proteome is important both for sharpening the diagnostic precision of protein biomarkers and in disease management.
A porcine ex vivo model of pigmentary glaucoma
Authors: Dang Yalong , Waxman Susannah , Wang Chao , Loewen Ralitsa T. , Sun Ming , Loewen Nils A. 
Published: March 2018

AbstractPigment dispersion can lead to pigmentary glaucoma, a poorly understood condition of younger myopic eyes with fluctuating high intraocular pressure. It has been difficult to investigate its pathogenesis without a model similar to human eyes in size and behavior. Here we present a porcine ex vivo model that recreates several features of pigmentary glaucoma, including intraocular hypertension, accumulation of pigment in the trabecular meshwork, and declining phagocytosis. We found that trabecular meshwork cells regulate outflow, form actin stress fibers, and have a decreased phagocytic activity. Gene expression microarrays and a pathway analysis of TM monolayers as well as ex vivo anterior segment perfusion cultures indicated that RhoA plays a central role in regulating the cytoskeleton, motility, and phagocytosis in the trabecular meshwork, providing new insights and targets to investigate in pigmentary glaucoma.
Effect of magnetic fullerene on magnetization reversal created at the Fe/C60 interface
Authors: Mallik Srijani , Mattauch Stefan , Dalai Manas Kumar , Brückel Thomas , Bedanta Subhankar 
Published: March 2018

AbstractProbing the hybridized magnetic interface between organic semiconductor (OSC) and ferromagnetic (FM) layers has drawn significant attention in recent years because of their potential in spintronic applications. Recent studies demonstrate various aspects of organic spintronics such as magnetoresistance, induced interface moment etc. However, not much work has been performed to investigate the implications of such OSC/FM interfaces on the magnetization reversal and domain structure which are the utmost requirements for any applications. Here, we show that non-magnetic Fullerene can obtain non-negligible magnetic moment at the interface of Fe(15 nm)/C60(40 nm) bilayer. This leads to substantial effect on both the magnetic domain structure as well as the magnetization reversal when compared to a single layer of Fe(15 nm). This is corroborated by the polarized neutron reflectivity (PNR) data which indicates presence of hybridization at the interface by the reduction of magnetic moment in Fe. Afterwards, upto 1.9 nm of C60 near the interface exhibits magnetic moment. From the PNR measurements it was found that the magnetic C60 layer prefers to be aligned anti-parallel with the Fe layer at the remanant state. The later observation has been confirmed by domain imaging via magneto-optic Kerr microscopy.
NMR Structure, Dynamics and Interactions of the Integrin β2 Cytoplasmic Tail with Filamin Domain IgFLNa21
Authors: Chatterjee Deepak , Zhiping Lewis Lu , Tan Suet-Mien , Bhattacharjya Surajit 
Published: March 2018

AbstractIntegrins are transmembrane proteins that mediate cell adhesion and migration. Each integrin is a heterodimer formed by an α and a β subunit. A large number of cytoplasmic proteins interact with the cytoplasmic tails (CTs) of integrins. The actin-binding cytoskeletal protein filamin A is a negative regulator of integrin activation. The IgFLNa21 domain of filamin A binds to the C-terminus of β2 CT that contains a TTT-motif. Based on x-ray crystallography, it has been reported that the integrin β2 CT forms a β strand that docks into the β strands C and D of IgFLNa21. In this study, we performed solution NMR analyses of IgFLNa21 in the presence of integrin β2 CT peptides, and hybrid IgFLNa21, a construct of covalently linked IgFLNa21 and β2 CT. The atomic resolution structure of the hybrid IgFLNa21 demonstrated conserved binding mode with β2 CT. Although,15N relaxation, model free analyses and H-D exchange studies have uncovered important insights into the conformational dynamics and stability of β2 CT in complex with IgFLNa21. Such dynamical characteristics are likely to be necessary for the TTT-motif to serve as a phosphorylation switch that regulates filamin A binding to integrin β2 CT.
Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker
Authors: Iwasawa Kentaro , Suda Wataru , Tsunoda Tomoyuki , Oikawa-Kawamoto Manari , Umetsu Shuichiro , Takayasu Lena , Inui Ayano , Fujisawa Tomoo , Morita Hidetoshi , Sogo Tsuyoshi , Hattori Masahira 
Published: March 2018

AbstractPrimary sclerosing cholangitis (PSC) is a liver disease known for its frequent concurrence with inflammatory bowel disease. Dysbiosis of the gut microbiota in PSC was reported in several studies, but the microbiological features of the salivary microbiota in PSC have not been established. Here we compared the salivary microbial communities of 24 pediatric-onset PSC patients, 16 age-matched ulcerative colitis (UC) patients, and 24 healthy controls (HCs) by analyzing the bacterial 16S rRNA gene sequence data. The species-richness (α-diversity) showed no significant between-group differences, whereas the overall salivary microbiota structure (β-diversity) showed significant differences among the three groups. Taxonomic assignment revealed that the PSC salivary microbiota were characterized by significant decreases in the abundance of Rothia and Haemophilus compared to the HC group, and significantly decreased Haemophilus and increased Oribacterium compared to the UC group. By combining the genera selected by the random forest algorithm in machine learning, followed by confirmation with 10-fold cross-validation, we were able to distinguish the PSC group from the HC group with the area under the curve (AUC) of 0.7423, and from the UC group with the AUC of 0.8756. Our results indicate the potential of salivary microbiota as biomarkers for a noninvasive diagnosis of PSC.
Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis
Authors: Wall Richard J. , Ferguson David J. P. , Freville Aline , Franke-Fayard Blandine , Brady Declan , Zeeshan Mohammad , Bottrill Andrew R. , Wheatley Sally , Fry Andrew M. , Janse Chris J. , Yamano Hiroyuki , Holder Anthony A. , Guttery David S. , Tewari Rita 
Published: March 2018

AbstractThe anaphase promoting complex/cyclosome (APC/C) is a highly conserved multi-subunit E3 ubiquitin ligase that controls mitotic division in eukaryotic cells by tagging cell cycle regulators for proteolysis. APC3 is a key component that contributes to APC/C function. Plasmodium, the causative agent of malaria, undergoes atypical mitotic division during its life cycle. Only a small subset of APC/C components has been identified in Plasmodium and their involvement in atypical cell division is not well understood. Here, using reverse genetics we examined the localisation and function of APC3 in Plasmodium berghei. APC3 was observed as a single focus that co-localised with the centriolar plaque during asexual cell division in schizonts, whereas it appeared as multiple foci in male gametocytes. Functional studies using gene disruption and conditional knockdown revealed essential roles of APC3 during these mitotic stages with loss resulting in a lack of chromosome condensation, abnormal cytokinesis and absence of microgamete formation. Overall, our data suggest that Plasmodium utilises unique cell cycle machinery to coordinate various processes during endomitosis, and this warrants further investigation in future studies.
Disturbed retrieval network and prospective memory decline in postpartum women
Authors: Shin Na-Young , Bak Yunjin , Nah Yoonjin , Han Sanghoon , Kim Dong Joon , Kim Se Joo , Lee Jong Eun , Lee Sang-Guk , Lee Seung-Koo 
Published: March 2018

AbstractProspective memory (PM) refers to the ability to remember to execute an intended action in the future. For successful PM performance, both top-down strategic monitoring and bottom-up spontaneous retrieval processes need to be appropriately recruited. We assessed PM performance and used fMRI to discover relevant neural correlates and possible predictors for PM performance in 25 postpartum and 26 nulliparous age- and education-matched women. Postpartum women showed decreased PM performance, a higher number of nocturnal awakenings, and lower estradiol level. The postpartum women had decreased functional connectivity (FC) in the right hippocampus and ventral frontoparietal networks (FPN) during retrieval-dominant PM trials relative to maintenance-dominant ongoing trials in the PM block. On multivariate analyses, decreased FC between the right hippocampus and ventral FPN and a higher number of nocturnal awakenings were independent predictors for poor PM performance after adjusting for age, education, estradiol level, and depressive symptoms. On mediation analyses, the estradiol level was found to have an indirect effect on PM accuracy via altered FC as a mediator. This suggests that decreased FC within the spontaneous retrieval-related regions including the right hippocampus and ventral FPN, disrupted sleep rhythms, and decreased estradiol level may contribute to poor PM performance in postpartum women.
Mixture toxicity assisting the design of eco-friendlier plant protection products: a case-study using a commercial herbicide combining nicosulfuron and terbuthylazine
Authors: Queirós Libânia , Vidal Tânia , Nogueira António J. A. , Gonçalves Fernando J. M. , Pereira Joana Luísa 
Published: March 2018

AbstractThe development of environmentally friendly plant protection products (PPPs), including pesticides, is a challenge nowadays. A commercial herbicide combining terbuthylazine and nicosulfuron as active substances (a.s.) was selected as a model PPP. The suitability of manipulating the ratio between a.s. towards alternative formulations with reduced impacts in a non-target indicator (Lemna minor) was assessed. The efficacy of such eco-friendlier a.s. ratios was then assessed using a target weed,Portulaca oleracea. Single and mixture toxicity testing withL. minorrevealed an antagonistic joint action of the a.s., suggesting an environmentally protective effect of the combination compared to single dosing of a.s. The efficacy testing against the target weed of single and combined treatments of the a.s. showed that (i) the a.s. behave antagonistically throughout the wholeP. oleracearesponse surface; (ii) there were no environmentally safe a.s. combinations ensuring target-efficacy; (iii) terbuthylazine alone was effective in controllingP. oleraceawith no environmental hazardous potential, dosed at concentrations 10-fold lower than those involved in commercially recommended application doses. Overall, this case-study suggests that modelling tools widely used in the field of environmental risk assessment of PPPs may also have application in PPP design stages for a more efficient meeting of efficacy and environmental friendliness requirements.
Structure-function analysis and therapeutic efficacy of antibodies to fungal melanin for melanoma radioimmunotherapy
Authors: Nosanchuk J. D. , Jeyakumar A. , Ray A. , Revskaya E. , Jiang Z. , Bryan R. A. , Allen K. J. H. , Jiao R. , Malo M. E. , Gómez B. L. , Morgenstern A. , Bruchertseifer F. , Rickles D. , Thornton G. B. , Bowen A. , Casadevall A. , Dadachova E. 
Published: March 2018

AbstractMetastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to humanization and cGMP (current Good Manufacturing Practice) manufacturing than IgMs. We performed comparative structural analysis of melanin-binding IgM 6D2 and IgG 8C3. The therapeutic efficacy of213Bi- and188Re-labeled 8C3 and its comparison with anti-CTLA4 immunotherapy was performed in B16-F10 murine melanoma model. The primary structures of these antibodies revealed significant homology, with the CDRs containing a high percentage of positively charged amino acids. The 8C3 model has a negatively charged binding surface and significant number of aromatic residues in its H3 domain, suggesting that hydrophobic interactions contribute to the antibody-melanin interaction. Radiolabeled IgG 8C3 showed significant therapeutic efficacy in murine melanoma, safety towards healthy melanin-containing tissues and favorable comparison with the anti-CTLA4 antibody. We have demonstrated that antibody binding to melanin relies on both charge and hydrophobic interactions while thein vivodata supports further development of 8C3 IgG as radioimmunotherapy reagent for metastatic melanoma.
Human Sertoli cells support high levels of Zika virus replication and persistence
Authors: Kumar Anil , Jovel Juan , Lopez-Orozco Joaquin , Limonta Daniel , Airo Adriana M. , Hou Shangmei , Stryapunina Iryna , Fibke Chad , Moore Ronald B. , Hobman Tom C. 
Published: March 2018

AbstractZika virus is a teratogenic mosquito-transmitted flavivirus that is associated with birth defects in newborns and Guillain–Barré syndrome in adults. The virus can also be sexually transmitted, but currently, very little is known about the cell types supporting virus replication and persistence in human testes. Using primary cell cultures, we observed that Sertoli but not Leydig cells are highly susceptible to Zika virus infection, a process that is dependent on the TAM family receptor Axl. In cell culture, Sertoli cells could be productively infected with Zika virus for at least 6-weeks. Infection of Sertoli cells resulted in dramatic changes to the transcriptional profile of these cells. The most upregulated mRNA in infected cells was basic fibroblast growth factor (FGF2), a cytokine that was found to enhance Zika virus replication and support viral persistence. Together these findings provide key insights into understanding how Zika virus persists in the male reproductive tract and in turn may aid in developing antiviral therapies or strategies to minimize sexual transmission of this pathogen.
A comparative analysis of rod bipolar cell transcriptomes identifies novel genes implicated in night vision
Authors: Woods Sasha M. , Mountjoy Edward , Muir Duncan , Ross Sarah E. , Atan Denize 
Published: March 2018

AbstractIn the mammalian retina, rods and a specialised rod-driven signalling pathway mediate visual responses under scotopic (dim light) conditions. As rods primarily signal to rod bipolar cells (RBCs) under scoptic conditions, disorders that affect rod or RBC function are often associated with impaired night vision. To identify novel genes expressed by RBCs and, therefore, likely to be involved in night vision, we took advantage of the adultBhlhe23−/−mouse retina (that lacks RBCs) to derive the RBC transcriptome. We found that genes expressed by adult RBCs are mainly involved in synaptic structure and signalling, whereas genes that influence RBC development are also involved in the cell cycle and transcription/translation. By comparing our data with other published retinal and bipolar cell transcriptomes (where we identify RBCs by the presence ofPrkcaand/orPcp2transcripts), we have derived a consensus for the adult RBC transcriptome. These findings ought to facilitate further research into physiological mechanisms underlying mammalian night vision as well as proposing candidate genes for patients with inherited causes of night blindness.
Simple Method for De Novo Structural Determination of Underivatised Glucose Oligosaccharides
Authors: Hsu Hsu Chen , Liew Chia Yen , Huang Shih-Pei , Tsai Shang-Ting , Ni Chi-Kung 
Published: March 2018

AbstractCarbohydrates have various functions in biological systems. However, the structural analysis of carbohydrates remains challenging. Most of the commonly used methods involve derivatization of carbohydrates or can only identify part of the structure. Here, we report a de novo method for completely structural identification of underivatised oligosaccharides. This method, which can provide assignments of linkages, anomeric configurations, and branch locations, entails low-energy collision-induced dissociation (CID) of sodium ion adducts that enable the cleavage of selective chemical bonds, a logical procedure to identify structurally decisive fragment ions for subsequent CID, and the specially prepared disaccharide CID spectrum databases. This method was first applied to determine the structures of four underivatised glucose oligosaccharides. Then, high-performance liquid chromatography and a mass spectrometer with a built-in logical procedure were established to demonstrate the capability of the in situ CID spectrum measurement and structural determination of the oligosaccharides in chromatogram. This consolidation provides a simple, rapid, sensitive method for the structural determination of glucose oligosaccharides, and applications to oligosaccharides containing hexoses other than glucose can be made provided the corresponding disaccharide databases are available.