bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hidden genomic MHC disparity between HLA-matched sibling pairs in hematopoietic stem cell transplantation
Authors: Koskela Satu , Ritari Jarmo , Hyvärinen Kati , Kwan Tony , Niittyvuopio Riitta , Itälä-Remes Maija , Pastinen Tomi , Partanen Jukka 
Published: March 2018

AbstractMatching classical HLA alleles between donor and recipient is an important factor in avoiding adverse immunological effects in HSCT. Siblings with no differences in HLA alleles, either due to identical-by-state or identical-by-descent status, are considered to be optimal donors. We carried out a retrospective genomic sequence and SNP analysis of 336 fully HLA-A, -B, -DRB1 matched and 14 partially HLA-matched sibling HSCT pairs to determine the level of undetected mismatching within the MHC segment as well as to map their recombination sites. The genomic sequence of 34 genes locating in the MHC region revealed allelic mismatching at 1 to 8 additional genes in partially HLA-matched pairs. Also, fully matched pairs were found to have mismatching either at HLA-DPB1 or at non-HLA region within the MHC segment. Altogether, 3.9% of fully HLA-matched HSCT pairs had large genomic mismatching in the MHC segment. Recombination sites mapped to certain restricted locations. The number of mismatched nucleotides correlated with the risk of GvHD supporting the central role of full HLA matching in HSCT. High-density genome analysis revealed that fully HLA-matched siblings may not have identical MHC segments and even single allelic mismatching at any classical HLA gene often implies larger genomic differences along MHC.
The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair
Authors: Hensen Fenna , Moretton Amandine , van Esveld Selma , Farge Géraldine , Spelbrink Johannes N. 
Published: March 2018

AbstractEXD2 is a recently identified exonuclease that has been implicated in nuclear double-strand break repair. Given our long standing interest in mitochondrial DNA maintenance and indications that EXD2 could also be a mitochondrial protein we sought to determine its cellular localization and possible mitochondrial associated functions. Our results show that EXD2 indeed shows mitochondrial localization, but, surprisingly, is found predominantly associated with the mitochondrial outer-membrane. Gradient purified nuclei show only the faintest hint of EXD2 presence while overexpression of the predicted full-length protein shows exclusive mitochondrial localization. Importantly, induction of double-strand DNA breaks via X-irradiation or Zeocin treatment does not support the notion that EXD2 re-locates to the nucleus following double-strand breaks and thus is unlikely to have a direct role in nuclear DNA repair. Knockdown or overexpression of EXD2 affects the cellular distribution of mitochondria. These results suggest that the reported defects in nuclear DNA repair following EXD2 depletion are likely an indirect consequence of altered mitochondrial dynamics and/or function.
Identification of individual subjects on the basis of their brain anatomical features
Authors: Valizadeh Seyed Abolfazl , Liem Franziskus , Mérillat Susan , Hänggi Jürgen , Jäncke Lutz 
Published: March 2018

AbstractWe examined whether it is possible to identify individual subjects on the basis of brain anatomical features. For this, we analyzed a dataset comprising 191 subjects who were scanned three times over a period of two years. Based on FreeSurfer routines, we generated three datasets covering 148 anatomical regions (cortical thickness, area, volume). These three datasets were also combined to a dataset containing all of these three measures. In addition, we used a dataset comprising 11 composite anatomical measures for which we used larger brain regions (11LBR). These datasets were subjected to a linear discriminant analysis (LDA) and a weighted K-nearest neighbors approach (WKNN) to identify single subjects. For this, we randomly chose a data subset (training set) with which we calculated the individual identification. The obtained results were applied to the remaining sample (test data). In general, we obtained excellent identification results (reasonably good results were obtained for 11LBR using WKNN). Using different data manipulation techniques (adding white Gaussian noise to the test data and changing sample sizes) still revealed very good identification results, particularly for the LDA technique. Interestingly, using the small 11LBR dataset also revealed very good results indicating that the human brain is highly individual.
Attenuated Notch signaling in schizophrenia and bipolar disorder
Authors: Hoseth Eva Z. , Krull Florian , Dieset Ingrid , Mørch Ragni H. , Hope Sigrun , Gardsjord Erlend S. , Steen Nils Eiel , Melle Ingrid , Brattbakk Hans-Richard , Steen Vidar M. , Aukrust Pål , Djurovic Srdjan , Andreassen Ole A. , Ueland Thor 
Published: March 2018

AbstractThe Notch signaling pathway plays a crucial role in neurodevelopment and in adult brain homeostasis. We aimed to further investigate Notch pathway activity in bipolar disorder (BD) and schizophrenia (SCZ) by conducting a pathway analysis. We measured plasma levels of Notch ligands (DLL1 and DLK1) using enzyme immunoassays in a large sample of patients (SCZ n = 551, BD n = 246) and healthy controls (HC n = 639). We also determined Notch pathway related gene expression levels by microarray analyses from whole blood in a subsample (SCZ n = 338, BD n = 241 and HC n = 263). We found significantly elevated Notch ligand levels in plasma in both SCZ and BD compared to HC. Significant gene expression findings included increased levels of RFNG and KAT2B (p < 0.001), and decreased levels of PSEN1 and CREBBP in both patient groups (p < 0.001). RBPJ was significantly lower in SCZ vs HC (p < 0.001), and patients using lithium had higher levels of RBPJ (p < 0.001). We provide evidence of altered Notch signaling in both SCZ and BD compared to HC, and suggest that Notch signaling pathway may be disturbed in these disorders. Lithium may ameliorate aberrant Notch signaling. We propose that drugs targeting Notch pathway could be relevant in the treatment of psychotic disorders.
Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase
Authors: Meseda Clement A. , Atukorale Vajini , Soto Jackeline , Eichelberger Maryna C. , Gao Jin , Wang Wei , Weiss Carol D. , Weir Jerry P. 
Published: March 2018

AbstractInfluenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages – A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). These vectors were evaluated for immunogenicity and protective efficacy against H7N3 virus in a murine model of intranasal challenge. High levels of H7-, N3-, and N9-specific antibodies, including neutralizing antibodies, were induced by the MVA-HA and MVA-NA vectors. Mice vaccinated with MVA vectors expressing any of the H7 antigens were protected, suggesting cross-protection among H7 viruses. In addition, MVA vectors expressing N3 but not N9 elicited protection against H7N3 virus challenge. Similar outcomes were obtained when immune sera from MVA vector-immunized mice were passively transferred to naïve mice prior to challenge with the H7N3 virus. The results support the further development of an MVA vector platform as a candidate vaccine for influenza strains with pandemic potential.
Endophytes of Withania somnifera modulate in planta content and the site of withanolide biosynthesis
Authors: Pandey Shiv S. , Singh Sucheta , Pandey Harshita , Srivastava Madhumita , Ray Tania , Soni Sumit , Pandey Alok , Shanker Karuna , Babu C. S. Vivek , Banerjee Suchitra , Gupta M. M. , Kalra Alok 
Published: March 2018

AbstractTissue specific biosynthesis of secondary metabolites is a distinguished feature of medicinal plants. Withania somnifera, source of pharmaceutically important withanolides biosynthesizes withaferin-A in leaves and withanolide-A in roots. To increase the in planta withanolides production, a sustainable approach needs to be explored. Here, we isolated endophytes from different parts of W. somnifera plants and their promising role in in planta withanolide biosynthesis was established in both in-vivo grown as well in in-vitro raised composite W. somnifera plants. Overall, the fungal endophytes improved photosynthesis, plant growth and biomass, and the root-associated bacterial endophytes enhanced the withanolide content in both in-vivo and in-vitro grown plants by modulating the expression of withanolide biosynthesis genes in leaves and roots. Surprisingly, a few indole-3-acetic acid (IAA)-producing and nitrogen-fixing root-associated endophytes could induce the biosynthesis of withaferin-A in roots by inducing in planta IAA-production and upregulating the expression of withanolide biosynthesis genes especially MEP-pathway genes (DXS and DXR) in roots as well. Results indicate the role of endophytes in modulating the synthesis and site of withanolides production and the selected endophytes can be used for enhancing the in planta withanolide production and enriching roots with pharmaceutically important withaferin-A which is generally absent in roots.
Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies
Authors: Noh Soo Min , Shin Seunghyeon , Lee Gyun Min 
Published: March 2018

AbstractTo characterize a glutamine synthetase (GS)-based selection system, monoclonal antibody (mAb) producing recombinant CHO cell clones were generated by a single round of selection at various methionine sulfoximine (MSX) concentrations (0, 25, and 50 μM) using two different host cell lines (CHO-K1 and GS-knockout CHO). Regardless of the host cell lines used, the clones selected at 50 μM MSX had the lowest average specific growth rate and the highest average specific production rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high producing clones could be generated in the absence of MSX using GS-knockout CHO with an improved selection stringency. Regardless of the host cell lines used, the clones selected at various MSX concentrations showed no significant difference in the GS, heavy chain, and light chain gene copies (P > 0.05). Furthermore, there was no correlation between the specific mAb productivity and these three gene copies (R2 ≤ 0.012). Taken together, GS-mediated gene amplification does not occur in a single round of selection at a MSX concentration up to 50 μM. The use of the GS-knockout CHO host cell line facilitates the rapid generation of high producing clones with reduced production of lactate and ammonia in the absence of MSX.
Src signaling in a low-complexity unicellular kinome
Authors: Suga Hiroshi , Miller W. Todd 
Published: March 2018

AbstractCreolimax fragrantissima is a member of the ichthyosporean clade, the earliest branching holozoan lineage. The kinome of Creolimax is markedly reduced as compared to those of metazoans. In particular, Creolimax possesses a single non-receptor tyrosine kinase: CfrSrc, the homolog of c-Src kinase. CfrSrc is an active tyrosine kinase, and it is expressed throughout the lifecycle of Creolimax. In animal cells, the regulatory mechanism for Src involves tyrosine phosphorylation at a C-terminal site by Csk kinase. The lack of Csk in Creolimax suggests that a different mode of negative regulation must exist for CfrSrc. We demonstrate that CfrPTP-3, one of the 7 tyrosine-specific phosphatases (PTPs) in Creolimax, suppresses CfrSrc activity in vitro and in vivo. Transcript levels of CfrPTP-3 and two other PTPs are significantly higher than that of CfrSrc in the motile amoeboid and sessile multinucleate stages of the Creolimax life cycle. Thus, in the context of a highly reduced kinome, a pre-existing PTP may have been co-opted for the role of Src regulation. Creolimax represents a unique model system to study the adaptation of tyrosine kinase signaling and regulatory mechanisms.
Exome Sequencing Identifies Genetic Variants Associated with Circulating Lipid Levels in Mexican Americans: The Insulin Resistance Atherosclerosis Family Study (IRASFS)
Authors: Gao Chuan , Tabb Keri L. , Dimitrov Latchezar M. , Taylor Kent D. , Wang Nan , Guo Xiuqing , Long Jirong , Rotter Jerome I. , Watanabe Richard M. , Curran Joanne E. , Blangero John , Langefeld Carl D. , Bowden Donald W. , Palmer Nicholette D. 
Published: March 2018

AbstractGenome-wide association studies have identified numerous variants associated with lipid levels; yet, the majority are located in non-coding regions with unclear mechanisms. In the Insulin Resistance Atherosclerosis Family Study (IRASFS), heritability estimates suggest a strong genetic basis: low-density lipoprotein (LDL, h2 = 0.50), high-density lipoprotein (HDL, h2 = 0.57), total cholesterol (TC, h2 = 0.53), and triglyceride (TG, h2 = 0.42) levels. Exome sequencing of 1,205 Mexican Americans (90 pedigrees) from the IRASFS identified 548,889 variants and association and linkage analyses with lipid levels were performed. One genome-wide significant signal was detected inAPOA5with TG (rs651821, PTG = 3.67 × 10−10, LODTG = 2.36, MAF = 14.2%). In addition, two correlated SNPs (r2 = 1.0) rs189547099 (PTG = 6.31 × 10−08, LODTG = 3.13, MAF = 0.50%) and chr4:157997598 (PTG = 6.31 × 10−08, LODTG = 3.13, MAF = 0.50%) reached exome-wide significance (P < 9.11 × 10−08). rs189547099 is an intronic SNP inFNIP2and SNP chr4:157997598 is intronic inGLRB. Linkage analysis revealed 46 SNPs with a LOD > 3 with the strongest signal at rs1141070 (LODLDL = 4.30, PLDL = 0.33, MAF = 21.6%) inDFFB. A total of 53 nominally associated variants (P < 5.00 × 10−05, MAF ≥ 1.0%) were selected for replication in six Mexican-American cohorts (N = 3,280). The strongest signal observed was a synonymous variant (rs1160983, PLDL = 4.44 × 10−17, MAF = 2.7%) inTOMM40. Beyond primary findings, previously reported lipid loci were fine-mapped using exome sequencing in IRASFS. These results support that exome sequencing complements and extends insights into the genetics of lipid levels.
An accessible visible-light actinometer for the determination of photon flux and optical pathlength in flow photo microreactors
Authors: Roibu Anca , Fransen Senne , Leblebici M. Enis , Meir Glen , Van Gerven Tom , Kuhn Simon 
Published: March 2018

AbstractCoupling photochemistry with flow microreactors enables novel synthesis strategies with higher efficiencies compared to batch systems. Improving the reproducibility and understanding of the photochemical reaction mechanisms requires quantitative tools such as chemical actinometry. However, the choice of actinometric systems which can be applied in microreactors is limited, due to their short optical pathlength in combination with a large received photon flux. Furthermore, actinometers for the characterization of reactions driven by visible light between 500 and 600 nm (e.g. photosensitized oxidations) are largely missing. In this paper, we propose a new visible-light actinometer which can be applied in flow microreactors between 480 and 620 nm. This actinometric system is based on the photoisomerization reaction of a diarylethene derivative from its closed to the open form. The experimental protocol for actinometric measurements is facile and characterized by excellent reproducibility and we also present an analytical estimation to calculate the photon flux. Furthermore, we propose an experimental methodology to determine the average pathlength in microreactors using actinometric measurements. In the context of a growing research interest on using flow microreactors for photochemical reactions, the proposed visible-light actinometer facilitates the determination of the received photon flux and average pathlength in confined geometries.
Immunotoxicity of Silver Nanoparticles (AgNPs) on the Leukocytes of Common Bottlenose Dolphins (Tursiops truncatus)
Authors: Li Wen-Ta , Chang Hui-Wen , Yang Wei-Cheng , Lo Chieh , Wang Lei-Ya , Pang Victor Fei , Chen Meng-Hsien , Jeng Chian-Ren 
Published: March 2018

AbstractSilver nanoparticles (AgNPs) have been extensively used and are considered as an emerging contaminant in the ocean. The environmental contamination of AgNPs is expected to increase greatly over time, and cetaceans, as the top ocean predators, will suffer the negative impacts of AgNPs. In the present study, we investigate the immunotoxicity of AgNPs on the leukocytes of cetaceans using several methods, including cytomorphology, cytotoxicity, and functional activity assays. The results reveal that 20 nm Citrate-AgNPs (C-AgNP20) induce different cytomorphological alterations and intracellular distributions in cetacean polymorphonuclear cells (cPMNs) and peripheral blood mononuclear cells (cPBMCs). At high concentrations of C-AgNP20 (10 and 50 μg/ml), the time- and dose-dependent cytotoxicity in cPMNs and cPBMCs involving apoptosis is demonstrated. C-AgNP20 at sub-lethal doses (0.1 and 1 μg/ml) negatively affect the functional activities of cPMNs (phagocytosis and respiratory burst) and cPBMCs (proliferative activity). The current study presents the first evidence of the cytotoxicity and immunotoxicity of AgNPs on the leukocytes of cetaceans and improves our understanding of environmental safety concerning AgNPs. The dose-response data of AgNPs on the leukocytes of cetaceans are invaluable for evaluating the adverse health effects in cetaceans and for proposing a conservation plan for marine mammals.
A powerful on line ABTS+–CE-DAD method to screen and quantify major antioxidants for quality control of Shuxuening Injection
Authors: Ma Huifen , Li Jin , An Mingrui , Gao Xiu-mei , Chang Yan-xu 
Published: March 2018

AbstractA novel method of on-line 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)-Capillary Electrophoresis-Diode Array Detector (on-line ABTS+-CE-DAD) was developed to screen the major antioxidants from complex herbal medicines. ABTS+, one of well-known oxygen free radicals was firstly integrated into the capillary. For simultaneously detecting and separating ABTS+ and chemical components of herb medicines, some conditions were optimized. The on-line ABTS+-CE-DAD method has successfully been used to screen the main antioxidants from Shuxuening injection (SI), an herbal medicines injection. Under the optimum conditions, nine ingredients of SI including clitorin, rutin, isoquercitrin, Quercetin-3-O-D-glucosyl]-(1-2)-L-rhamnoside, kaempferol-3-O-rutinoside, kaempferol-7-O-β-D-glucopyranoside, apigenin-7-O-Glucoside, quercetin-3-O-[2-O-(6-O-p-hydroxyl-E-coumaroyl)-D-glucosyl]-(1-2)-L-rhamnoside, 3-O-{2-O-[6-O-(p-hydroxyl-E-coumaroyl)-glucosyl]}-(1-2) rhamnosyl kaempfero were separated and identified as the major antioxidants. There is a linear relationship between the total amount of major antioxidants and total antioxidative activity of SI with a linear correlation coefficient of 0.9456. All the Relative standard deviations of recovery, precision and stability were below 7.5%. Based on these results, these nine ingredients could be selected as combinatorial markers to evaluate quality control of SI. It was concluded that on-line ABTS+-CE-DAD method was a simple, reliable and powerful tool to screen and quantify active ingredients for evaluating quality of herbal medicines.
Entropic effect of macromolecular crowding enhances binding between nucleosome clutches in heterochromatin, but not in euchromatin
Authors: Oh Inrok , Choi Saehyun , Jung YounJoon , Kim Jun Soo 
Published: March 2018

AbstractSharp increase in macromolecular crowding induces abnormal chromatin compaction in the cell nucleus, suggesting its non-negligible impact on chromatin structure and function. However, the details of the crowding-induced chromatin compaction remain poorly understood. In this work, we present a computer simulation study on the entropic effect of macromolecular crowding on the interaction between chromatin structural units called nucleosome clutches. Nucleosome clutches were modeled by a chain of nucleosomes collapsed by harmonic restraints implicitly mimicking the nucleosome association mediated by histone tails and linker histones. The nucleosome density of the clutches was set close to either that of high-density heterochromatin or that of low-density euchromatin. The effective interactions between these nucleosome clutches were calculated in various crowding conditions, and it was found that the increase in the degree of macromolecular crowding induced attractive interaction between two clutches with high nucleosome density. Interestingly, the increased degree of macromolecular crowding did not induce any attraction between two clutches with low nucleosome density. Our results suggest that the entropic effect of macromolecular crowding can enhance binding between nucleosome clutches in heterochromatin, but not in euchromatin, as a result of the difference in nucleosome packing degrees.
Long-term response of forest productivity to climate change is mostly driven by change in tree species composition
Authors: Morin Xavier , Fahse Lorenz , Jactel Hervé , Scherer-Lorenzen Michael , García-Valdés Raúl , Bugmann Harald 
Published: March 2018

AbstractClimate change affects ecosystem functioning directly through impacts on plant physiology, resulting in changes of global productivity. However, climate change has also an indirect impact on ecosystems, through changes in the composition and diversity of plant communities. The relative importance of these direct and indirect effects has not been evaluated within a same generic approach yet. Here we took advantage of a novel approach for disentangling these two effects in European temperate forests across a large climatic gradient, through a large simulation-based study using a forest succession model. We first showed that if productivity positively correlates with realized tree species richness under a changed climate, indirect effects appear pivotal to understand the magnitude of climate change impacts on forest productivity. We further detailed how warmer and drier conditions may affect the diversity-productivity relationships (DPRs) of temperate forests in the long term, mostly through effects on species recruitment, ultimately enhancing or preventing complementarity in resource use. Furthermore, losing key species reduced the strength of DPRs more severely in environments that are becoming climatically harsher. By disentangling direct and indirect effects of climate change on ecosystem functioning, these findings explain why high-diversity forests are expected to be more resilient to climate change.