bluuebunny/crossref_metadata_2025_split huggingface dataset:
De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy
Authors: Buena-Atienza Elena , Rüther Klaus , Baumann Britta , Bergholz Richard , Birch David , De Baere Elfride , Dollfus Helene , Greally Marie T. , Gustavsson Peter , Hamel Christian P. , Heckenlively John R. , Leroy Bart P. , Plomp Astrid S. , Pott Jan Willem R. , Rose Katherine , Rosenberg Thomas , Stark Zornitza , Verheij Joke B. G. M. , Weleber Richard , Zobor Ditta , Weisschuh Nicole , Kohl Susanne , Wissinger Bernd 
Published: June 2016

AbstractX-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree.
A Synthetic Pseudo-Rh: NOx Reduction Activity and Electronic Structure of Pd–Ru Solid-solution Alloy Nanoparticles
Authors: Sato Katsutoshi , Tomonaga Hiroyuki , Yamamoto Tomokazu , Matsumura Syo , Zulkifli Nor Diana Binti , Ishimoto Takayoshi , Koyama Michihisa , Kusada Kohei , Kobayashi Hirokazu , Kitagawa Hiroshi , Nagaoka Katsutoshi 
Published: June 2016

AbstractRh is one of the most important noble metals for industrial applications. A major fraction of Rh is used as a catalyst for emission control in automotive catalytic converters because of its unparalleled activity toward NOxreduction. However, Rh is a rare and extremely expensive element; thus, the development of Rh alternative composed of abundant elements is desirable. Pd and Ru are located at the right and left of Rh in the periodic table, respectively, nevertheless this combination of elements is immiscible in the bulk state. Here, we report a Pd–Ru solid-solution-alloy nanoparticle (PdxRu1-xNP) catalyst exhibiting better NOxreduction activity than Rh. Theoretical calculations show that the electronic structure of Pd0.5Ru0.5is similar to that of Rh, indicating that Pd0.5Ru0.5can be regarded as a pseudo-Rh. Pd0.5Ru0.5exhibits better activity than natural Rh, which implies promising applications not only for exhaust-gas cleaning but also for various chemical reactions.
Conditioning adaptive combination of P-values method to analyze case-parent trios with or without population controls
Authors: Lin Wan-Yu , Liang Yun-Chieh 
Published: June 2016

AbstractDetection of rare causal variants can help uncover the etiology of complex diseases. Recruiting case-parent trios is a popular study design in family-based studies. If researchers can obtain data from population controls, utilizing them in trio analyses can improve the power of methods. The transmission disequilibrium test (TDT) is a well-known method to analyze case-parent trio data. It has been extended to rare-variant association testing (abbreviated as “rvTDT”), with the flexibility to incorporate population controls. The rvTDT method is robust to population stratification. However, power loss may occur in the conditioning process. Here we propose a “conditioning adaptive combination of P-values method” (abbreviated as “conADA”), to analyze trios with/without unrelated controls. By first truncating the variants with larger P-values, we decrease the vulnerability of conADA to the inclusion of neutral variants. Moreover, because the test statistic is developed by conditioning on parental genotypes, conADA generates valid statistical inference in the presence of population stratification. With regard to statistical methods for next-generation sequencing data analyses, validity may be hampered by population stratification, whereas power may be affected by the inclusion of neutral variants. We recommend conADA for its robustness to these two factors (population stratification and the inclusion of neutral variants).
STARD6 on steroids: solution structure, multiple timescale backbone dynamics and ligand binding mechanism
Authors: Létourneau Danny , Bédard Mikaël , Cabana Jérôme , Lefebvre Andrée , LeHoux Jean-Guy , Lavigne Pierre 
Published: June 2016

AbstractSTART domain proteins are conserved α/β helix-grip fold that play a role in the non-vesicular and intracellular transport of lipids and sterols. The mechanism and conformational changes permitting the entry of the ligand into their buried binding sites is not well understood. Moreover, their functions and the identification of cognate ligands is still an active area of research. Here, we report the solution structure of STARD6 and the characterization of its backbone dynamics on multiple time-scales through15N spin-relaxation and amide exchange studies. We reveal for the first time the presence of concerted fluctuations in the Ω1loop and the C-terminal helix on the microsecond-millisecond time-scale that allows for the opening of the binding site and ligand entry. We also report that STARD6 binds specifically testosterone. Our work represents a milestone for the study of ligand binding mechanism by other START domains and the elucidation of the biological function of STARD6.
Dual-pump Kerr Micro-cavity Optical Frequency Comb with varying FSR spacing
Authors: Wang Weiqiang , Chu Sai T. , Little Brent E. , Pasquazi Alessia , Wang Yishan , Wang Leiran , Zhang Wenfu , Wang Lei , Hu Xiaohong , Wang Guoxi , Hu Hui , Su Yulong , Li Feitao , Liu Yuanshan , Zhao Wei 
Published: June 2016

AbstractIn this paper, we demonstrate a novel dual-pump approach to generate robust optical frequency comb with varying free spectral range (FSR) spacing in a CMOS-compatible high-Q micro-ring resonator (MRR). The frequency spacing of the comb can be tuned by an integer number FSR of the MRR freely in our dual-pump scheme. The dual pumps are self-oscillated in the laser cavity loop and their wavelengths can be tuned flexibly by programming the tunable filter embedded in the cavity. By tuning the pump wavelength, broadband OFC with the bandwidth of >180 nm and the frequency-spacing varying from 6 to 46-fold FSRs is realized at a low pump power. This approach could find potential and practical applications in many areas, such as optical metrology, optical communication and signal processing systems, for its excellent flexibility and robustness.
Different Effects of sgRNA Length on CRISPR-mediated Gene Knockout Efficiency
Authors: Zhang Jian-Ping , Li Xiao-Lan , Neises Amanda , Chen Wanqiu , Hu Lin-Ping , Ji Guang-Zhen , Yu Jun-Yao , Xu Jing , Yuan Wei-Ping , Cheng Tao , Zhang Xiao-Bing 
Published: June 2016

AbstractCRISPR-Cas9 is a powerful genome editing technology, yet with off-target effects. Truncated sgRNAs (17nt) have been found to decrease off-target cleavage without affecting on-target disruption in 293T cells. However, the potency of 17nt sgRNAs relative to the full-length 20nt sgRNAs in stem cells, such as human mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), has not been assessed. Using a GFP reporter system, we found that both 17nt and 20nt sgRNAs expressed by lentiviral vectors induce ~95% knockout (KO) in 293T cells, whereas the KO efficiencies are significantly lower in iPSCs (60–70%) and MSCs (65–75%). Furthermore, we observed a decrease of 10–20 percentage points in KO efficiency with 17nt sgRNAs compared to full-length sgRNAs in both iPSCs and MSCs. Off-target cleavage was observed in 17nt sgRNAs with 1-2nt but not 3-4nt mismatches; whereas 20nt sgRNAs with up to 5nt mismatches can still induce off-target mutations. Of interest, we occasionally observed off-target effects induced by the 17nt but not the 20nt sgRNAs. These results indicate the importance of balancing on-target gene cleavage potency with off-target effects: when efficacy is a major concern such as genome editing in stem cells, the use of 20nt sgRNAs is preferable.
Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model
Authors: Otte Anna , Marriott Anthony C. , Dreier Carola , Dove Brian , Mooren Kyra , Klingen Thorsten R. , Sauter Martina , Thompson Katy-Anne , Bennett Allan , Klingel Karin , van Riel Debby , McHardy Alice C. , Carroll Miles W. , Gabriel Gülsah 
Published: June 2016

AbstractThere is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses.
SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector
Authors: Wall Richard J. , Roques Magali , Katris Nicholas J. , Koreny Ludek , Stanway Rebecca R. , Brady Declan , Waller Ross F. , Tewari Rita 
Published: June 2016

AbstractThe SAS6-like (SAS6L) protein, a truncated paralogue of the ubiquitous basal body/centriole protein SAS6, has been characterised recently as a flagellum protein in trypanosomatids, but associated with the conoid in apicomplexan Toxoplasma. The conoid has been suggested to derive from flagella parts, but is thought to have been lost from some apicomplexans including the malaria-causing genus Plasmodium. Presence of SAS6L in Plasmodium, therefore, suggested a possible role in flagella assembly in male gametes, the only flagellated stage. Here, we have studied the expression and role of SAS6L throughout the Plasmodium life cycle using the rodent malaria model P. berghei. Contrary to a hypothesised role in flagella, SAS6L was absent during gamete flagellum formation. Instead, SAS6L was restricted to the apical complex in ookinetes and sporozoites, the extracellular invasive stages that develop within the mosquito vector. In these stages SAS6L forms an apical ring, as we show is also the case in Toxoplasma tachyzoites. The SAS6L ring was not apparent in blood-stage invasive merozoites, indicating that the apical complex is differentiated between the different invasive forms. Overall this study indicates that a conoid-associated apical complex protein and ring structure is persistent in Plasmodium in a stage-specific manner.
Photochromic switching of the DNA helicity induced by azobenzene derivatives
Authors: Deiana Marco , Pokladek Ziemowit , Olesiak-Banska Joanna , Młynarz Piotr , Samoc Marek , Matczyszyn Katarzyna 
Published: June 2016

AbstractThe photochromic properties of azobenzene, involving conformational changes occurring upon interaction with light, provide an excellent tool to establish new ways of selective regulation applied to biosystems. We report here on the binding of two water-soluble 4-(phenylazo)benzoic acid derivatives (Azo-2N and Azo-3N) with double stranded DNA and demonstrate that the photoisomerization of Azo-3N leads to changes in DNA structure. In particular, we show that stabilization and destabilization of the B-DNA secondary structure can be photochemically induced in situ by light. This photo-triggered process is fully reversible and could be an alternative pathway to control a broad range of biological processes. Moreover, we found that the bicationic Azo-3N exhibited a higher DNA-binding constant than the monocationic Azo-2N pointing out that the number of positive charges along the photosensitive polyamines chain plays a pivotal role in stabilizing the photochrome-DNA complex.
Gene Expression Profiling of Breast Cancer Brain Metastasis
Authors: Lee Ji Yun , Park Kyunghee , Lee Eunjin , Ahn TaeJin , Jung Hae Hyun , Lim Sung Hee , Hong Mineui , Do In-Gu , Cho Eun Yoon , Kim Duk-Hwan , Kim Ji-Yeon , Ahn Jin Seok , Im Young-Hyuck , Park Yeon Hee 
Published: June 2016

AbstractThe biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM. Five of these genes,CXCL12,MMP2,MMP11,VCAM1, andMME, which have previously been associated with tumor progression, angiogenesis, and metastasis, clearly discriminated between primary BC and BCBM. Notably, the five genes were significantly upregulated in primary BC compared to BCBM. Conversely,SOX2andOLIG2genes were upregulated in BCBM. These genes may participate in metastatic colonization but not in primary tumor development. Among patient-matched paired samples (n = 17), a PAM50 molecular subtype conversion was observed in eight cases (47.1%), with a trend toward unfavorable subtypes in patients with the distinct gene expression. Our findings, although not conclusive, reveal differentially expressed genes that might mediate the brain metastasis process.
Systems pathway engineering of Corynebacterium crenatum for improved L-arginine production
Authors: Man Zaiwei , Xu Meijuan , Rao Zhiming , Guo Jing , Yang Taowei , Zhang Xian , Xu Zhenghong 
Published: June 2016

AbstractL-arginine is an important amino acid in food and pharmaceutical industries. Until now, the main production method of L-arginine in China is the highly polluting keratin acid hydrolysis. The industrial level L-arginine production by microbial fermentation has become an important task. In previous work, we obtained a new L-arginine producing Corynebacterium crenatum (subspecies of Corynebacterium glutamicum) through screening and mutation breeding. In this work, we performed systems pathway engineering of C. crenatum for improved L-arginine production, involving amplification of L-arginine biosynthetic pathway flux by removal of feedback inhibition and overexpression of arginine operon; optimization of NADPH supply by modulation of metabolic flux distribution between glycolysis and pentose phosphate pathway; increasing glucose consumption by strengthening the preexisting glucose transporter and exploitation of new glucose uptake system; channeling excess carbon flux from glycolysis into tricarboxylic acid cycle to alleviate the glucose overflow metabolism; redistribution of carbon flux at α-ketoglutarate metabolic node to channel more flux into L-arginine biosynthetic pathway; minimization of carbon and cofactor loss by attenuation of byproducts formation. The final strain could produce 87.3 g L−1 L-arginine with yield up to 0.431 g L-arginine g−1 glucose in fed-batch fermentation.
Ventromedial prefrontal cortex, adding value to autobiographical memories
Authors: Lin Wen-Jing , Horner Aidan J. , Burgess Neil 
Published: June 2016

AbstractThe medial prefrontal cortex (mPFC) has been consistently implicated in autobiographical memory recall and decision making. Its function in decision making tasks is believed to relate to value representation, but its function in autobiographical memory recall is not yet clear. We hypothesised that the mPFC represents the subjective value of elements during autobiographical memory retrieval. Using functional magnetic resonance imaging during an autobiographical memory recall task, we found that the blood oxygen level dependent (BOLD) signal in ventromedial prefrontal cortex (vmPFC) was parametrically modulated by the affective values of items in participants’ memories when they were recalling and evaluating these items. An unrelated modulation by the participant’s familiarity with the items was also observed. During retrieval of the event, the BOLD signal in the same region was modulated by the personal significance and emotional intensity of the memory, which was correlated with the values of the items within them. These results support the idea that vmPFC processes self-relevant information and suggest that it is involved in representing the personal emotional values of the elements comprising autobiographical memories.
REAC technology and hyaluron synthase 2, an interesting network to slow down stem cell senescence
Authors: Maioli Margherita , Rinaldi Salvatore , Pigliaru Gianfranco , Santaniello Sara , Basoli Valentina , Castagna Alessandro , Fontani Vania , Ventura Carlo 
Published: June 2016

AbstractHyaluronic acid (HA) plays a fundamental role in cell polarity and hydrodynamic processes, affording significant modulation of proliferation, migration, morphogenesis and senescence, with deep implication in the ability of stem cells to execute their differentiating plans. The Radio Electric Asymmetric Conveyer (REAC) technology is aimed to optimize the ions fluxes at the molecular level in order to optimize the molecular mechanisms driving cellular asymmetry and polarization. Here, we show that treatment with 4-methylumbelliferone (4-MU), a potent repressor of type 2 HA synthase and endogenous HA synthesis, dramatically antagonized the ability of REAC to recover the gene and protein expression of Bmi1, Oct4, Sox2, and Nanog in ADhMSCs that had been made senescent by prolonged culture up to the 30th passage. In senescent ADhMSCs, 4-MU also counteracted the REAC ability to rescue the gene expression of TERT, and the associated resumption of telomerase activity. Hence, the anti-senescence action of REAC is largely dependent upon the availability of endogenous HA synthesis. Endogenous HA and HA-binding proteins with REAC technology create an interesting network that acts on the modulation of cell polarity and intracellular environment. This suggests that REAC technology is effective on an intracellular niche level of stem cell regulation.
Using oriented peptide array libraries to evaluate methylarginine-specific antibodies and arginine methyltransferase substrate motifs
Authors: Gayatri Sitaram , Cowles Martis W. , Vemulapalli Vidyasiri , Cheng Donghang , Sun Zu-Wen , Bedford Mark T. 
Published: June 2016

AbstractSignal transduction in response to stimuli relies on the generation of cascades of posttranslational modifications that promote protein-protein interactions and facilitate the assembly of distinct signaling complexes. Arginine methylation is one such modification, which is catalyzed by a family of nine protein arginine methyltransferases, or PRMTs. Elucidating the substrate specificity of each PRMT will promote a better understanding of which signaling networks these enzymes contribute to. Although many PRMT substrates have been identified and their methylation sites mapped, the optimal target motif for each of the nine PRMTs has not been systematically addressed. Here we describe the use of Oriented Peptide Array Libraries (OPALs) to methodically dissect the preferred methylation motifs for three of these enzymes – PRMT1, CARM1 and PRMT9. In parallel, we show that an OPAL platform with a fixed methylarginine residue can be used to validate the methyl-specific and sequence-specific properties of antibodies that have been generated against different PRMT substrates and can also be used to confirm the pan nature of some methylarginine-specific antibodies.
Photo-derived transformation from modified chitosan@calcium carbonate nanohybrids to nanosponges
Authors: Byeon Jeong Hoon 
Published: June 2016

AbstractZwitterionic chitosan (ZC)@calcium carbonate (CC) nanoparticles were conveniently obtained and transformed to biocompatible nanosponges by continuous gas-phase photo-derived transformation in a single-pass configuration, and their potential use for biomedical applications was investigated. The mean diameter of the ZC@CC sponges was ~166 nm (~72 nm for CC and, ~171 nm for ZC), and the sponges had a mesoporous structure (i.e., an average pore diameter of ~13 nm). Measurements of the sponge cytotoxicity were performed and only a slight decrease was observed (>78% in cell viability) when compared with pure ZC (>80%). The ZC@CC sponges had a similar transfection ability to lipofectamine (~2.7 × 109RLU mg−1protein) at a 50:1 ratio of sponge:DNA weight. Because of a porous structure, the sponges showed remarkably higher transfection efficiencies than pure ZC.
The dynamics of human behavior in the public goods game with institutional incentives
Authors: Dong Yali , Zhang Boyu , Tao Yi 
Published: June 2016

AbstractThe empirical research on the public goods game (PGG) indicates that both institutional rewards and institutional punishment can curb free-riding and that the punishment effect is stronger than the reward effect. Self-regarding models that are based on Nash equilibrium (NE) strategies or evolutionary game dynamics correctly predict which incentives are best at promoting cooperation, but individuals do not play these rational strategies overall. The goal of our study is to investigate the dynamics of human decision making in the repeated PGG with institutional incentives. We consider that an individual’s contribution is affected by four factors, which are self-interest, the behavior of others, the reaction to rewards and the reaction to punishment. We find that people on average do not react to rewards and punishment and that self-interest and the behavior of others sufficiently explain the dynamics of human behavior. Further analysis suggests that institutional incentives promote cooperation by affecting the self-regarding preference and that the other-regarding preference seems to be independent of incentive schemes. Because individuals do not change their behavioral patterns even if they were not rewarded or punished, the mere potential to punish defectors and reward cooperators can lead to considerable increases in the level of cooperation.