bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel protein kinase inhibitor IMB-YH-8 with anti-tuberculosis activity
Authors: Xu Jian , Wang Ju-xian , Zhou Jin-ming , Xu Chang-liang , Huang Bin , Xing Yun , Wang Bin , Luo Rui , Wang Yu-cheng , You Xue-fu , Lu Yu , Yu Li-yan 
Published: July 2017

AbstractProtein kinase B (PknB) is one of the Mycobacterium tuberculosis serine/threonine protein kinases and has an essential role in sustaining mycobacterial growth. Here, we identified and characterized a novel small molecule compound named IMB-YH-8 that inhibited PknB and served as anti-mycobacteria lead compound. IMB-YH-8 inhibited PknB auto-phosphorylation and the phosphorylation of GarA by PknB in a dose-dependent manner. The compound did not inhibit human Akt1 or other serine/threonine kinases in M. tuberculosis except for the highly homologous PknA. IMB-YH-8 bound to PknB with a moderate affinity. Molecular docking revealed that IMB-YH-8 interacts with the catalytic domain of PknB. Observations of electron microscopy showed that IMB-YH-8 changed the morphology of H37Rv and disrupted the cell wall. The differential transcriptional response of M. tuberculosis to IMB-YH-8 revealed changes in SigH regulatory pathways modulated by PknB. Notably IMB-YH-8 not only potently inhibited drug-sensitive and multidrug-resistant clinical isolates but also exhibited a dose dependent inhibition of intracellular M. tuberculosis. Taken together, these in vitro data demonstrate that IMB-YH-8 is a novel inhibitor of PknB, which potently prevents growth of M. tuberculosis. It is as yet unclear whether inhibition of PknA contributes to the anti-tubercular action of IMB-YH-8.
The genetic architecture of water-soluble protein content and its genetic relationship to total protein content in soybean
Authors: Zhang Dan , Lü Haiyan , Chu Shanshan , Zhang Huairen , Zhang Hengyou , Yang Yuming , Li Hongyan , Yu Deyue 
Published: July 2017

AbstractWater-soluble protein content (WSPC) is a critical factor in both soybean protein quality and functionality. However, the underlying genetic determinants are unclear. Here, we used 219 soybean accessions and 152 recombinant inbred lines genotyped with high-density markers and phenotyped in multi-environments to dissect the genetic architectures of WSPC and protein content (PC) using single- and multi-locus genome-wide association studies. In the result, a total of 32 significant loci, including 10 novel loci, significantly associated with WSPC and PC across multi-environments were identified, which were subsequently validated by linkage mapping. Among these loci, only four exhibited pleiotropic effects for PC and WSPC, explaining the low correlation coefficient between the two traits. The largest-effect WSPC-specific loci, GqWSPC8, was stably identified across all six environments and tagged to a linkage disequilibrium block comprising two promising candidate genes AAP8 and 2 S albumin, which might contribute to the high level of WSPC in some soybean varieties. In addition, two genes, Glyma.13G123500 and Glyma.13G194400 with relatively high expression levels at seed development stage compared with other tissues were regarded as promising candidates associated with the PC and WSPC, respectively. Our results provide new insights into the genetic basis of WSPC affecting soybean protein quality and yield.
Influence of the Body Schema on Multisensory Integration: Evidence from the Mirror Box Illusion
Authors: Liu Yuqi , Medina Jared 
Published: July 2017

AbstractWhen placing one hand on each side of a mirror and making synchronous bimanual movements, the mirror-reflected hand feels like one’s own hand that is hidden behind the mirror. We developed a novel mirror box illusion to investigate whether motoric, but not spatial, visuomotor congruence is sufficient for inducing multisensory integration, and importantly, if biomechanical constraints encoded in the body schema influence multisensory integration. Participants placed their hands in a mirror box in opposite postures (palm up, palm down), creating a conflict between visual and proprioceptive feedback for the hand behind the mirror. After synchronous bimanual hand movements in which the viewed and felt movements were motorically congruent but spatially in the opposite direction, participants felt that the hand behind the mirror rotated or completely flipped towards matching the hand reflection (illusory displacement), indicating facilitation of multisensory integration by motoric visuomotor congruence alone. Some wrist rotations are more difficult due to biomechanical constraints. We predicted that these biomechanical constraints would influence illusion effectiveness, even though the illusion does not involve actual limb movement. As predicted, illusory displacement increased as biomechanical constraints and angular disparity decreased, providing evidence that biomechanical constraints are processed in multisensory integration.
Aerobic fitness associates with mnemonic discrimination as a mediator of physical activity effects: evidence for memory flexibility in young adults
Authors: Suwabe Kazuya , Hyodo Kazuki , Byun Kyeongho , Ochi Genta , Fukuie Takemune , Shimizu Takeshi , Kato Morimasa , Yassa Michael A. , Soya Hideaki 
Published: July 2017

AbstractA physically active lifestyle has beneficial effects on hippocampal memory function. A potential mechanism for this effect is exercise-enhanced hippocampal plasticity, particularly in the dentate gyrus (DG). Within hippocampal memory formation, the DG plays a crucial role in pattern separation, which is the ability to discriminate among similar experiences. Computational models propose a theoretical hypothesis that enhanced DG-mediated pattern separation leads to “memory flexibility”–a selective improvement in the ability to overcome moderate levels of mnemonic interference. Thus, in the current cross-sectional study of healthy young adults, we tested the working hypothesis that aerobic fitness, as a physiological indicator of endurance capacity associated with physical activity, is strongly associated with mnemonic discrimination at moderate interference levels. When divided the sample (n = 75) based on a median split of aerobic fitness, the higher fitness group had better discrimination performance for moderate interference levels compared to the lower fitness group, namely, exhibited memory flexibility. Moreover, aerobic fitness levels were positively associated with discrimination performance for moderate interference levels, as a mediator of physical activity effects. This evidence suggests that aerobic fitness levels are associated with hippocampal DG-related memory, which is consistent with literature showing positive effect of physical exercise on hippocampal memory.
Laminin-511 and -521-based matrices for efficient ex vivo-expansion of human limbal epithelial progenitor cells
Authors: Polisetti Naresh , Sorokin Lydia , Okumura Naoki , Koizumi Noriko , Kinoshita Shigeru , Kruse Friedrich E. , Schlötzer-Schrehardt Ursula 
Published: July 2017

AbstractOptimization of culture conditions for human limbal epithelial stem/progenitor cells (LEPC) that incorporate the in vivo cell-matrix interactions are essential to enhance LEPC ex vivo-expansion and transplantation efficiency. Here, we investigate the efficacy of laminin (LN) isoforms preferentially expressed in the limbal niche as culture matrices for epithelial tissue engineering. Analyses of expression patterns of LN chains in the human limbal niche provided evidence for enrichment of LN-α2, -α3, -α5, -β1, -β2, -β3, -γ1, -γ2 and -γ3 chains in the limbal basement membrane, with LN-α5 representing a signature component specifically produced by epithelial progenitor cells. Recombinant human LN-521 and LN-511 significantly enhanced in vitro LEPC adhesion, migration and proliferation compared to other isoforms, and maintained phenotype stability. The bioactive LN-511-E8 fragment carrying only C-terminal domains showed similar efficacy as full-length LN-511. Functional blocking of α3β1 and α6β1 integrins suppressed adhesion of LEPC to LN-511/521-coated surfaces. Cultivation of LEPC on fibrin-based hydrogels incorporating LN-511-E8 resulted in firm integrin-mediated adhesion to the scaffold and well-stratified epithelial constructs, with maintenance of a progenitor cell phenotype in their (supra)basal layers. Thus, the incorporation of chemically defined LN-511-E8 into biosynthetic scaffolds represents a promising approach for xeno-free corneal epithelial tissue engineering for ocular surface reconstruction.
Tudor Domain Containing Protein 3 Promotes Tumorigenesis and Invasive Capacity of Breast Cancer Cells
Authors: Morettin Alan , Paris Geneviève , Bouzid Younes , Baldwin R. Mitchell , Falls Theresa J. , Bell John C. , Côté Jocelyn 
Published: July 2017

AbstractTudor domain containing protein 3 (TDRD3) is a modular protein identified based on its ability to recognize methylated arginine motifs through its Tudor domain. We have previously shown that TDRD3 localizes to cytoplasmic stress granules, a structure shown to promote survival upon treatment with chemotherapeutic drugs in cancer cells. Here, we report TDRD3 as a novel regulator of cell proliferation and invasion in breast cancer cells. Our study also demonstrates that TDRD3 depletion inhibits tumor formation and metastasis to the lung in vivo. Furthermore, we show that TDRD3 regulates the expression of a number of key genes associated with promotion of breast cancer tumorigenesis and disease progression. Strikingly, we report that TDRD3 regulates some of these key targets at the level of translation. These findings provide the first experimental demonstration of a functional role for TDRD3 in promoting breast cancer development and progression, and identify TDRD3 as a potential new therapeutic target for breast cancer.
Dual non-contiguous peptide occupancy of HLA class I evoke antiviral human CD8 T cell response and form neo-epitopes with self-antigens
Authors: Xiao Ziwei , Ye Zhiyong , Tadwal Vikeramjeet Singh , Shen Meixin , Ren Ee Chee 
Published: July 2017

AbstractHost CD8 T cell response to viral infections involves recognition of 8–10-mer peptides presented by MHC-I molecules. However, proteasomes generate predominantly 2–7-mer peptides, but the role of these peptides is largely unknown. Here, we show that single short peptides of <8-mer from Latent Membrane Protein 2 (LMP2) of Epstein Barr Virus (EBV) can bind HLA-A*11:01 and stimulate CD8+cells. Surprisingly, two peptide fragments between 4–7-mer derived from LMP2(340–349)were able to complement each other, forming combination epitopes that can stimulate specific CD8+T cell responses. Moreover, peptides from self-antigens can complement non-self peptides within the HLA binding cleft, forming neoepitopes. Solved structures of a tetra-complex comprising two peptides, HLA and β2-microglobulin revealed the free terminals of the two peptides to adopt an upward conformation directed towards the T cell receptor. Our results demonstrate a previously unknown mix-and-match combination of dual peptide occupancy in HLA that can generate vast combinatorial complexity.
Investigating gene flow between the blind cavefish Garra barreimiae and its conspecific surface populations
Authors: Kirchner Sandra , Sattmann Helmut , Haring Elisabeth , Plan Lukas , Victor Reginald , Kruckenhauser Luise 
Published: July 2017

AbstractCave-dwelling taxa often share the same phenotypic modifications like absence of eyes and pigmentation. These “troglomorphic characters” are expressed in the populations of Garra barreimiae from the Al Hoota Cave and nearby Hoti Pit in Northern Oman. Surface morphotypes of this cyprinid species are common throughout the distribution area. Very rarely individuals with intermediate phenotypes can be found. In the present study, potential gene flow between cave and surface populations was tested and population structure within five sampling sites was assessed. Overall, 213 individuals were genotyped at 18 microsatellite loci. We found that the cave populations have lower genetic diversity and are clearly isolated from the surface populations, which seem to be sporadically in contact with each other. The results indicate a recent genetic bottleneck in the cave populations. Thus, it can be assumed that during climatic changes the connection between cave and surface water bodies was disjoined, leaving a subpopulation trapped inside. Nevertheless, occasional gene flow between the morphotypes is detectable, but hybridisation seems only possible in cave habitat with permanent connection to surface water. Individuals from surface sites bearing intermediate phenotypes but cave genotypes imply that phenotypic plasticity might play a role in the development of the phenotype.
Molecular dynamics study on the mechanism of polynucleotide encapsulation by chitosan
Authors: Shen Jia-Wei , Li Jiachen , Zhao Zhennan , Zhang Li , Peng Guoteng , Liang Lijun 
Published: July 2017

AbstractThe safe and effective delivery of therapeutic genes into target cell interiors is of great importance in gene therapy. Chitosan has been extensively studied as a gene delivery carrier due to its good biocompatibility and biodegradability. Understanding the atomic interaction mechanism between chitosan and DNA is important in the design and application of chitosan-based drug and gene delivery systems. In this work, the interactions between single-stranded polynucleotides and different types of chitosan were systematically investigated by using molecular dynamics (MD) simulation. Our results demonstrate that the functional groups of chitosan, the types of base and length of polynucleotides regulate the interaction behavior between chitosan and polynucleotides. The encapsulation capacity of polynucleotide by chitosan is mainly balanced by two factors: the strength of polynucleotide binding to chitosan and the tendency of self-aggregation of polynucleotide in the solution. For –NH3+ chitosan, due to the strong electrostatic interaction, especially the H-bond between –NH3+ groups in chitosan and phosphate groups in polynucleotide, the aggregation effect could be partially eliminated. The good dispersal capacity of polynucleotides may improve the encapsulation of polynucleotides by chitosan, and hence increase the delivery and transfection efficiency of chitosan-based gene carrier.
Identification of FBXL4 as a Metastasis Associated Gene in Prostate Cancer
Authors: Stankiewicz Elzbieta , Mao Xueying , Mangham D. Chas , Xu Lei , Yeste-Velasco Marc , Fisher Gabrielle , North Bernard , Chaplin Tracy , Young Bryan , Wang Yuqin , Kaur Bansal Jasmin , Kudahetti Sakunthala , Spencer Lucy , Foster Christopher S. , Møller Henrik , Scardino Peter , Oliver R. Tim , Shamash Jonathan , Cuzick Jack , Cooper Colin S. , Berney Daniel M. , Lu Yong-Jie 
Published: July 2017

AbstractProstate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1–16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH). Loss of FBXL4 was also detected in primary tumours and it was highly associated with prognostic factors including high Gleason score, clinical stage, prostate-specific antigen (PSA) and extent of disease, as well as poor patient survival, suggesting that FBXL4 loss contributes to prostate cancer progression. We also demonstrated that FBXL4 deletion is detectable in circulating tumour cells (CTCs), making it a potential prognostic biomarker by ‘liquid biopsy’. In vitro analysis showed that FBXL4 plays a role in regulating the migration and invasion of prostate cancer cells. FBXL4 potentially controls cancer metastasis through regulation of ERLEC1 levels. Therefore, FBXL4 could be a potential novel prostate cancer suppressor gene, which may prevent cancer progression and metastasis through controlling cell invasion.
Regional and local environmental conditions do not shape the response to warming of a marine habitat-forming species
Authors: Crisci C. , Ledoux J.-B. , Mokhtar- Jamaï K. , Bally M. , Bensoussan N. , Aurelle D. , Cebrian E. , Coma R. , Féral J.- P. , La Rivière M. , Linares C. , López-Sendino P. , Marschal C. , Ribes M. , Teixidó N. , Zuberer F. , Garrabou J. 
Published: July 2017

AbstractThe differential response of marine populations to climate change remains poorly understood. Here, we combine common garden thermotolerance experiments in aquaria and population genetics to disentangle the factors driving the population response to thermal stress in a temperate habitat-forming species: the octocoral Paramuricea clavata. Using eight populations separated from tens of meters to hundreds of kilometers, which were differentially impacted by recent mortality events, we identify 25 °C as a critical thermal threshold. After one week of exposure at this temperature, seven of the eight populations were affected by tissue necrosis and after 30 days of exposure at this temperature, the mean % of affected colonies increased gradually from 3 to 97%. We then demonstrate the weak relation between the observed differential phenotypic responses and the local temperature regimes experienced by each population. A significant correlation was observed between these responses and the extent of genetic drift impacting each population. Local adaptation may thus be hindered by genetic drift, which seems to be the main driver of the differential response. Accordingly, conservation measures should promote connectivity and control density erosion in order to limit the impact of genetic drift on marine populations facing climate change.
Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo
Authors: Lee Byung Cheon , Lee Sang-Goo , Choo Min-Kyung , Kim Ji Hyung , Lee Hae Min , Kim Sorah , Fomenko Dmitri E. , Kim Hwa-Young , Park Jin Mo , Gladyshev Vadim N. 
Published: July 2017

AbstractPost-translational redox modification of methionine residues often triggers a change in protein function. Emerging evidence points to this reversible protein modification being an important regulatory mechanism under various physiological conditions. Reduction of oxidized methionine residues is catalyzed by methionine sulfoxide reductases (Msrs). Here, we show that one of these enzymes, a selenium-containing MsrB1, is highly expressed in immune-activated macrophages and contributes to shaping cellular and organismal immune responses. In particular, lipopolysaccharide (LPS) induces expression of MsrB1, but not other Msrs. Genetic ablation of MsrB1 did not preclude LPS-induced intracellular signaling in macrophages, but resulted in attenuated induction of anti-inflammatory cytokines, such as interleukin (IL)-10 and the IL-1 receptor antagonist. This anomaly was associated with excessive pro-inflammatory cytokine production as well as an increase in acute tissue inflammation in mice. Together, our findings suggest that MsrB1 controls immune responses by promoting anti-inflammatory cytokine expression in macrophages. MsrB1-dependent reduction of oxidized methionine in proteins may be a heretofore unrecognized regulatory event underlying immunity and inflammatory disease, and a novel target for clinical applications.
Efficient Characterization and Classification of Contrast Sensitivity Functions in Aging
Authors: Yan Fang-Fang , Hou Fang , Lu Zhong-Lin , Hu Xiaopeng , Huang Chang-Bing 
Published: July 2017

AbstractThe contrast sensitivity function (CSF), delineating contrast sensitivity over a wide range of spatial frequencies, provides a comprehensive characterization of spatial vision and a sensitive test for many physiological and pathological processes. A precise CSF measurement tool for the aging population is of great theoretical and practical importance. In the current study, we tested whether the assumptions of the newly developed quick CSF method were valid and whether it can rapidly, reliably, and effectively evaluate CSFs in the aging population. The quick CSF method combines Bayesian adaptive inference with an information gain strategy to directly estimate four parameters that define the observer’s CSF. Eighteen young and twenty-five old observers participated in the evaluation of the quick CSF method. All observers were screened for ophthalmological and mental diseases. Our results showed that the CSFs derived from the quick CSF method well matched with those from the traditional Ψ method, with excellent test-retest reliability. More importantly, the quick CSF method can accurately detect the difference of CSFs between the young and old groups. Aging significantly degrades contrast sensitivity. The quick CSF method demonstrates great potentials for both laboratory research and clinical applications in the aging population.
Optimization of hormone combinations for root growth and bud germination in Chinese fir (Cunninghamia lanceolata) clone leaf cuttings
Authors: Li Shubin , Huang Peng , Ding Guochang , Zhou Lili , Tang Piao , Sun Min , Zheng Yingying , Lin Sizu 
Published: July 2017

AbstractIn order to ascertain the optimal hormone combination for Chinese fir (Cunninghamia lanceolata) leaf cuttings, an L16(4)4 orthogonal test of 6-benzylaminopurine (6-BA), 1-naphthaleneacetic acid (NAA), and indole-3-butyric acid (IBA) (0, 10, 30, or 50 mg · L−1 of each exogenous hormone) immersion for 5, 10, 15, or 20 min was conducted. Callus initiation rate and rooting promotion rate were mainly affected by treatment time, root length increase by 6-BA concentration, and bud germination rate and plantlet formation rate by NAA concentration. The expected optimal combination for callus initiation rate was 50 mg · L−1 6-BA + 0 mg · L−1 NAA + 30 mg · L−1 IBA + 10 min; for rooting promotion rate, it was 0–10 mg · L−1 6-BA + 10 mg · L−1 NAA + 30 mg · L−1 IBA + 20 min; for bud germination rate, it was 50 mg · L−1 6-BA + 0–10 mg · L−1 NAA + 0–30 mg · L−1 IBA + 20 min; and for seedling formation rate for No. 4, it was 10 mg · L−1 6-BA + 10 mg · L−1 NAA + 0 mg · L−1 IBA + 20 min. Light microscopy image analysis revealed that a cluster of primordial cells was produced 40 days after cutting, and mastoid cells developed into peninsula cells in calli that were cultured for 50 days.
An intragenic mutagenesis strategy in Physcomitrella patens to preserve intron splicing
Authors: Ako Ako Eugene , Perroud Pierre-François , Innocent Joseph , Demko Viktor , Olsen Odd-Arne , Johansen Wenche 
Published: July 2017

AbstractGene targeting is a powerful reverse genetics technique for site-specific genome modification. Intrinsic homologous recombination in the moss Physcomitrella patens permits highly effective gene targeting, a characteristic that makes this organism a valuable model for functional genetics. Functional characterization of domains located within a multi-domain protein depends on the ability to generate mutants harboring genetic modifications at internal gene positions while maintaining the reading-frames of the flanking exons. In this study, we designed and evaluated different gene targeting constructs for targeted gene manipulation of sequences corresponding to internal domains of the DEFECTIVE KERNEL1 protein in Physcomitrella patens. Our results show that gene targeting-associated mutagenesis of introns can have adverse effects on splicing, corrupting the normal reading frame of the transcript. We show that successful genetic modification of internal sequences of multi-exon genes depends on gene-targeting strategies which insert the selection marker cassette into the 5′ end of the intron and preserve the nucleotide sequence of the targeted intron.