bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis
Authors: Wang Wenyuan , Org Tonis , Montel-Hagen Amélie , Pioli Peter D. , Duan Dan , Israely Edo , Malkin Daniel , Su Trent , Flach Johanna , Kurdistani Siavash K. , Schiestl Robert H. , Mikkola Hanna K. A. 
Published: August 2016

AbstractDNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF2C enhances the expression of DNA repair and recombination factors in B-cell progenitors, promoting DSB repair, V(D)J recombination and cell survival. Although Mef2c-deficient mice maintain relatively intact peripheral B-lymphoid cellularity during homeostasis, they exhibit poor B-lymphoid recovery after sub-lethal irradiation and 5-fluorouracil injection. MEF2C binds active regulatory regions with high-chromatin accessibility in DNA repair and V(D)J genes in both mouse B-cell progenitors and human B lymphoblasts. Loss of Mef2c in pre-B cells reduces chromatin accessibility in multiple regulatory regions of the MEF2C-activated genes. MEF2C therefore protects B lymphopoiesis during stress by ensuring proper expression of genes that encode DNA repair and B-cell factors.
Southward autumn migration of waterfowl facilitates cross-continental transmission of the highly pathogenic avian influenza H5N1 virus
Authors: Xu Yanjie , Gong Peng , Wielstra Ben , Si Yali 
Published: August 2016

AbstractThe highly pathogenic avian influenza subtype H5N1 (HPAI H5N1) is a worldwide zoonotic infectious disease, threatening humans, poultry and wild birds. The role of wild birds in the spread of HPAI H5N1 has previously been investigated by comparing disease spread patterns with bird migration routes. However, the different roles that the southward autumn and northward spring migration might play in virus transmission have hardly been explored. Using direction analysis, we analyze HPAI H5N1 transmission directions and angular concentration of currently circulating viral clades, and compare these with waterfowl seasonal migration directions along major waterfowl flyways. Out of 22 HPAI H5N1 transmission directions, 18 had both a southward direction and a relatively high concentration. Differences between disease transmission and waterfowl migration directions were significantly smaller for autumn than for spring migration. The four northward transmission directions were found along Asian flyways, where the initial epicenter of the virus was located. We suggest waterfowl first picked up the virus from East Asia, then brought it to the north via spring migration, and then spread it to other parts of world mainly by autumn migration. We emphasize waterfowl autumn migration plays a relatively important role in HPAI H5N1 transmission compared to spring migration.
The CD4+ T cell methylome contributes to a distinct CD4+ T cell transcriptional signature in Mycobacterium bovis-infected cattle
Authors: Doherty Rachael , Whiston Ronan , Cormican Paul , Finlay Emma K. , Couldrey Christine , Brady Colm , O’Farrelly Cliona , Meade Kieran G. 
Published: August 2016

AbstractWe hypothesised that epigenetic regulation of CD4+ T lymphocytes contributes to a shift toward a dysfunctional T cell phenotype which may impact on their ability to clear mycobacterial infection. Combined RNA-seq transcriptomic profiling and Reduced Representation Bisulfite Sequencing identified 193 significantly differentially expressed genes and 760 differentially methylated regions (DMRs), between CD4+ T cells from M. bovis infected and healthy cattle. 196 DMRs were located within 10 kb of annotated genes, including GATA3 and RORC, both of which encode transcription factors that promote TH2 and TH17 T helper cell subsets respectively. Gene-specific DNA methylation and gene expression levels for the TNFRSF4 and Interferon-γ genes were significantly negatively correlated suggesting a regulatory relationship. Pathway analysis of DMRs identified enrichment of genes involved in the anti-proliferative TGF-β signaling pathway and TGFB1 expression was significantly increased in peripheral blood leukocytes from TB-infected cattle. This first analysis of the bovine CD4+ T cell methylome suggests that DNA methylation directly contributes to a distinct gene expression signature in CD4+ T cells from cattle infected with M. bovis. Specific methylation changes proximal to key inflammatory gene loci may be critical to the emergence of a non-protective CD4+ T cell response during mycobacterial infection in cattle.
The use of T-DNA insertional mutagenesis to improve cellulase production by the thermophilic fungus Humicola insolens Y1
Authors: Xu Xinxin , Li Jinyang , Shi Pengjun , Ji Wangli , Liu Bo , Zhang Yuhong , Yao Bin , Fan Yunliu , Zhang Wei 
Published: August 2016

AbstractHumicola insolens is an excellent producer of pH-neutral active, thermostable cellulases that find many industrial applications. In the present study, we developed an efficient Agrobacterium tumefaciens-mediated transformation system for H. insolens. We transformed plasmids carrying the promoter of the glyceraldehyde-3-phosphate dehydrogenase gene of H. insolens driving the transcription of genes encoding neomycin phosphotransferase, hygromycin B phosphotransferase and enhanced green fluorescent protein. We optimized transformation efficiency to obtain over 300 transformants/106 conidia. T-DNA insertional mutagenesis was employed to generate an H. insolens mutant library and we isolated a transformant termed T4 with enhanced cellulase and hemicellulase activities. The FPase, endoglucanase, cellobiohydrolase, β-glucosidase and xylanase activities of T4, measured at the end of fermentation, were 60%, 440%, 320%, 41% and 81% higher than those of the wild-type strain, respectively. We isolated the sequences flanking the T-DNA insertions and thus identified new genes potentially involved in cellulase and hemicellulase production. Our results show that it is feasible to use T-DNA insertional mutagenesis to identify novel candidate genes involved in cellulase production. This will be valuable when genetic improvement programs seeking to enhance cellulase production are planned and will also allow us to gain a better understanding of the genetics of the thermophilic fungus H. insolens.
“A novel highly stable and injectable hydrogel based on a conformationally restricted ultrashort peptide”
Authors: Thota Chaitanya Kumar , Yadav Nitin , Chauhan Virander Singh 
Published: August 2016

AbstractNanostructures including hydrogels based on peptides containing non protein amino acids are being considered as platform for drug delivery because of their inherent biocompatibility and additional proteolytic stability. Here we describe instantaneous self-assembly of a conformationally restricted dipeptide, LeuΔPhe, containing an α,β-dehydrophenylalanine residue into a highly stable and mechanically strong hydrogel, under mild physiological aqueous conditions. The gel successfully entrapped several hydrophobic and hydrophilic drug molecules and released them in a controlled manner. LeuΔPhe was highly biocompatible and easily injectable. Administration of an antineoplastic drug entrapped in the gel in tumor bearing mice significantly controlled growth of tumors. These characteristics make LeuΔPhe an attractive candidate for further development as a delivery platform for various biomedical applications.
Non-absorbable apple procyanidins prevent obesity associated with gut microbial and metabolomic changes
Authors: Masumoto Saeko , Terao Akari , Yamamoto Yuji , Mukai Takao , Miura Tomisato , Shoji Toshihiko 
Published: August 2016

AbstractSeveral studies have suggested that flavan-3-ols/procyanidins are associated with a reduced risk of developing obesity and metabolic syndrome. However, the role of highly polymeric procyanidins (PP), which are major non-absorbable flavonoids, in the biological effects, is not completely understood. Here, we show that 0.5% PP administration for 20 weeks alleviated obesity and regulate expression of genes related to lipid metabolism in C57BL/6J mice fed a high-fat/high-sucrose diet. PP-treatment attenuated weight gain and inflammatory effects including lipopolysaccharide and gut permeability. Additionally, metabolic urine profiling using high-performance liquid chromatography–quadrupole time-of-flight/mass spectrometry demonstrated that PP-treatment decreased the levels of endogenous metabolites associated with insulin resistance. Furthermore, microbial 16S rRNA gene sequencing of the cecum demonstrated that PP administration markedly decreased the Firmicutes/Bacteroidetes ratio and increased eight times the proportion of Akkermansia. These data suggest that PPs influence the gut microbiota and the intestinal metabolome to produce beneficial effects on metabolic homeostasis.
Novel ligands of Choline Acetyltransferase designed by in silico molecular docking, hologram QSAR and lead optimization
Authors: Kumar Rajnish , Långström Bengt , Darreh-Shori Taher 
Published: August 2016

AbstractRecent reports have brought back the acetylcholine synthesizing enzyme, choline acetyltransferase in the mainstream research in dementia and the cholinergic anti-inflammatory pathway. Here we report, a specific strategy for the design of novel ChAT ligands based on molecular docking, Hologram Quantitative Structure Activity Relationship (HQSAR) and lead optimization. Molecular docking was performed on a series of ChAT inhibitors to decipher the molecular fingerprint of their interaction with the active site of ChAT. Then robust statistical fragment HQSAR models were developed. A library of novel ligands was generated based on the pharmacophoric and shape similarity scoring function, and evaluated in silico for their molecular interactions with ChAT. Ten of the top scoring invented compounds are reported here. We confirmed the activity of α-NETA, the only commercially available ChAT inhibitor, and one of the seed compounds in our model, using a new simple colorimetric ChAT assay (IC50 ~ 88 nM). In contrast, α-NETA exhibited an IC50 of ~30 μM for the ACh-degrading cholinesterases. In conclusion, the overall results may provide useful insight for discovering novel ChAT ligands and potential positron emission tomography tracers as in vivo functional biomarkers of the health of central cholinergic system in neurodegenerative disorders, such as Alzheimer’s disease.
The secondary frame in spider orb webs: the detail that makes the difference
Authors: Soler Alejandro , Zaera Ramón 
Published: August 2016

AbstractSpider orb webs are multifunctional structures, the main function of which is to dissipate the kinetic energy of the impacting prey, while minimizing structural damage. There is no single explanation for their remarkable strength and ductility. However, it is clear that topology is decisive in the structural performance upon impact and the arrangement of the different silk threads in the web must also exert an effect. The aim of this study is to show how a slight variation in the geometry markedly affects the prey-capture ability of spider orb webs. The study is focused on the secondary frame, a thread interposed between radial and primary frame strands, the importance of which has not been examined until now. The simulation of the impact performance of webs using different lengths of the secondary frame clarifies its structural role, which has proven to be decisive. Furthermore, the study explains why secondary frame threads of moderate length, as commonly encountered, enable the capture of prey with higher energy without a marked increase in the volume of silk used.
Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions
Authors: Biller Armin , Pflugmann Isabella , Badde Stephanie , Diem Ricarda , Wildemann Brigitte , Nagel Armin M. , Jordan J. , Benkhedah Nadia , Kleesiek Jens 
Published: August 2016

AbstractThe cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ2(1) = 27.89, p < 0.001) and fluid-attenuated (χ2(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation.
Prediction of Quantum Anomalous Hall Insulator in half-fluorinated GaBi Honeycomb
Authors: Chen Sung-Ping , Huang Zhi-Quan , Crisostomo Christian P. , Hsu Chia-Hsiu , Chuang Feng-Chuan , Lin Hsin , Bansil Arun 
Published: August 2016

AbstractUsing first-principles electronic structure calculations, we predict half-fluorinated GaBi honeycomb under tensile strain to harbor a quantum anomalous Hall (QAH) insulator phase. We show that this QAH phase is driven by a single inversion in the band structure at the Γ point. Moreover, we have computed the electronic spectrum of a half-fluorinated GaBi nanoribbon with zigzag edges, which shows that only one edge band crosses the Fermi level within the band gap. Our results suggest that half-fluorination of the GaBi honeycomb under tensile strain could provide a new platform for developing novel spintronics devices based on the QAH effect.
Multifunctional metal-polymer nanoagglomerates from single-pass aerosol self-assembly
Authors: Byeon Jeong Hoon 
Published: August 2016

AbstractIn this study, gold (Au)-iron (Fe) nanoagglomerates were capped by a polymer mixture (PM) consisting of poly(lactide-co-glycolic acid), protamine sulfate, and poly-l-lysine via floating self-assembly in a single-pass aerosol configuration as multibiofunctional nanoplatforms. The Au-Fe nanoagglomerates were directly injected into PM droplets (PM dissolved in dichloromethane) in a collison atomizer and subsequently heat-treated to liberate the solvent from the droplets, resulting in the formation of PM-capped Au-Fe nanoagglomerates. Measured in vitro, the cytotoxicities of the nanoagglomerates (>98.5% cell viability) showed no significant differences compared with PM particles alone (>98.8%), thus implying that the nanoagglomerates are suitable for further testing of biofunctionalities. Measurements of gene delivery performance revealed that the incorporation of the Au-Fe nanoagglomerates enhanced the gene delivery performance (3.2 × 106 RLU mg−1) of the PM particles alone (2.1 × 106 RLU mg−1), which may have been caused by the PM structural change from a spherical to a hairy structure (i.e., the change followed the agglomerated backbone). Combining the X-ray-absorbing ability of Au and the magnetic property of Fe led to magnetic resonance (MR)-computed tomography (CT) contrast ability in a phantom; and the signal intensities [which reached 64 s−1T2-relaxation in MR and 194 Hounsfield units (HUs) in CT at 6.0 mg mL−1] depended on particle concentration (0.5–6.0 mg mL−1).
Three-dimensional facial analysis of Chinese children with repaired unilateral cleft lip and palate
Authors: Othman Siti Adibah , Aidil Koay Noor Airin 
Published: August 2016

AbstractWe analyzed the facial features of Chinese children with repaired unilateral cleft lip and palate (UCLP) and compared them with a normal control group using a three-dimensional (3D) stereophotogrammetry camera. This cross-sectional study examined 3D measurements of the facial surfaces of 20 Chinese children with repaired UCLP and 40 unaffected Chinese children aged 7 to 12 years old, which were captured using the VECTRA 3D five-pod photosystem and analyzed using Mirror software. Twenty-five variables and two ratios were compared between both groups using independent t-test. Intra- and inter-observer reliability was determined using ten randomly selected images and analyzed using intra-class correlation coefficient test (ICC). The level of significance was set at p < 0.0018. Intra- and inter-observers’ reliability was considered fair to excellent with an ICC value ranging from 0.54 to 0.99. Statistically significant differences (p < 0.0018) were found mainly in the nasolabial region. The cleft group exhibited wider alar base root width, flattened nose and broader nostril floor width on the cleft side. They tended to have shorter upper lip length and thinner upper vermillion thickness. Faces of Chinese children with repaired UCLP displayed meaningful differences when compared to the normal group especially in the nasolabial regions.
Structural basis for cytokinin production by LOG from Corynebacterium glutamicum
Authors: Seo Hogyun , Kim Sangwoo , Sagong Hye-Young , Son Hyeoncheol Francis , Jin Kyeong Sik , Kim Il-Kwon , Kim Kyung-Jin 
Published: August 2016

Abstract“Lonely guy” (LOG) has been identified as a cytokinin-producing enzyme in plants and plant-interacting fungi. The gene product ofCg2612from the soil-dwelling bacteriumCorynebacterium glutamicumwas annotated as an LDC. However, the facts thatC. glutamicumlacks an LDC andCg2612 has high amino acid similarity with LOG proteins suggest thatCg2612 is possibly an LOG protein. To investigate the function ofCg2612, we determined its crystal structure at a resolution of 2.3 Å.Cg2612 functions as a dimer and shows an overall structure similar to other known LOGs, such as LOGs fromArabidopsis thaliana(AtLOG),Claviceps purpurea(CpLOG), andMycobacterium marinum(MmLOG).Cg2612 also contains a “PGGXGTXXE” motif that contributes to the formation of an active site similar to other LOGs. Moreover, biochemical studies onCg2612 revealed that the protein has phosphoribohydrolase activity but not LDC activity. Based on these structural and biochemical studies, we propose thatCg2612 is not an LDC family enzyme, but instead belongs to the LOG family. In addition, the prenyl-binding site ofCg2612 (CgLOG) comprised residues identical to those seen inAtLOG andCpLOG, albeit dissimilar to those inMmLOG. The work provides structural and functional implications for LOG-like proteins from other microorganisms.
Altered lipid metabolism in Drosophila model of Huntington’s disease
Authors: Aditi Kumari , Shakarad Mallikarjun N. , Agrawal Namita 
Published: August 2016

AbstractHuntington’s disease (HD) is late-onset, progressive neurodegenerative disorder caused by expansion of polyglutamine (polyQ) repeat within Huntingtin (Htt) protein. In HD patients, energy-related manifestations such as modulation of weight during entire course of disease with energy deficit at terminal stage have been reported, however, underlying reason remains elusive till date. Lipids, carbohydrate and protein constitute a predominant fraction of body’s energy reservoir and perturbation in their homeostasis may influence weight. To discern role of these energy molecules in weight alteration, we quantified them in an in vivo transgenic Drosophila model of HD. We document that diseased flies exhibit change in weight due to an altered lipid metabolism, as evident from considerably high lipid levels at the time of disease onset followed by a pathologic decline at end-stage. An alteration in intracellular lipid droplet size suggested altered cellular lipid turnover. Furthermore, diseased flies displayed substantial changes in carbohydrate and protein content. Interestingly, alteration in weight and lipid levels are independent of the feeding pattern in diseased condition and exhibit weak correlation with insulin-like peptide or adipokinetic hormone producing cells. We propose that therapeutic intervention aimed at restoring lipid levels and associated metabolic pathways may improve longevity and quality of patient’s life.
Assessing the temporal stability of surface functional groups introduced by plasma treatments on the outer shells of carbon nanotubes
Authors: Merenda Andrea , Ligneris Elise des , Sears Kallista , Chaffraix Thomas , Magniez Kevin , Cornu David , Schütz Jürg A. , Dumée Ludovic F. 
Published: August 2016

AbstractPlasma treatments are emerging as superior efficiency treatment for high surface to volume ratio materials to tune functional group densities and alter crystallinity due to their ability to interact with matter at the nanoscale. The purpose of this study is to assess for the first time the long term stability of surface functional groups introduced across the surface of carbon nanotube materials for a series of oxidative, reductive and neutral plasma treatment conditions. Both plasma duration dose matrix based exposures and time decay experiments, whereby the surface energy of the materials was evaluated periodically over a one-month period, were carried out. Although only few morphological changes across the graphitic planes of the carbon nanotubes were found under the uniform plasma treatment conditions, the time dependence of pertinent work functions, supported by Raman analysis, suggested that the density of polar groups decreased non-linearly over time prior to reaching saturation from 7 days post treatment. This work provides critical considerations on the understanding of the stability of functional groups introduced across high specific surface area nano-materials used for the design of nano-composites, adsorptive or separation systems, or sensing materials and where interfacial interactions are key to the final materials performance.
Is the Employers’ Liability (Compulsory Insurance) Act 1969 Fit for Purpose?
Authors: Barrett Brenda , Lewis David 
Published: August 2016

Abstract
This article explains the origin of the concept of employers’ liability in 1837 and notes the various reasons for the failure of this liability to be developed during the 19th century. It proceeds to look at the context in which the Employers’ Liability (Compulsory Insurance) Act 1969 was enacted, looking at the content of the Act and considering the environment at the time of its enactment, noting the then apparent imperfections in the legislation. The account then moves fast forward to the 21st century and questions whether the Act is now fit for purpose.