bluuebunny/crossref_metadata_2025_split huggingface dataset:
A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus
Authors: Mobuchon Lenha , Battistella Aude , Bardel Claire , Scelo Ghislaine , Renoud Alexia , Houy Alexandre , Cassoux Nathalie , Milder Maud , Cancel-Tassin Géraldine , Cussenot Olivier , Delattre Olivier , Besse Céline , Boland Anne , Deleuze Jean-François , Cox David G. , Stern Marc-Henri 
Published: March 2017

AbstractUveal melanoma, a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. A genome-wide association study of 259 uveal melanoma patients compared to 401 controls all of European ancestry revealed a candidate locus at chromosome 5p15.33 (region rs421284: OR = 1.7, CI 1.43–2.05). This locus was replicated in an independent set of 276 cases and 184 controls. In addition, risk variants from this region were positively associated with higher expression of CLPTM1L. In conclusion, the CLPTM1L region contains risk alleles for uveal melanoma susceptibility, suggesting that CLPTM1L could play a role in uveal melanoma oncogenesis.
CRISPR-Cas9 cleavage efficiency correlates strongly with target-sgRNA folding stability: from physical mechanism to off-target assessment
Authors: Xu Xiaojun , Duan Dongsheng , Chen Shi-Jie 
Published: March 2017

AbstractThe CRISPR/Cas9 complex, a bacterial immune response system, has been widely adopted for RNA-guided genome editing and transcription regulation in applications such as targeted genome modification and site-directed mutagenesis. However, the physical basis for its target specificity is not fully understood. In this study, based on a statistical mechanical analysis for the whole ensemble of sgRNA-target complex conformations, we identify a strong correlation between Cas9 cleavage efficiency and the stability of the DNA-RNA (R-loop) complex structures, with a Pearson correlation coefficient ranging from 0.775 to 0.886 for the tested systems. The finding leads to quantitative insights into important experimental results, such as the greater Cas9 tolerance to single-base mismatches in PAM-distal region than to PAM-proximal region and the high specificity and efficiency for shorter protospacers. Moreover, the results from the genome-wide off-target assessments, compared with other off-target scoring tools, indicate that the statistical mechanics-based approach provides more reliable off-target analyses and sgRNA design. To facilitate the genome engineering applications, a new web-based tool for genome-wide off-target assessment is established.
Control of fault plane geometry on the formation of a normal fault-related anticline: an experimental approach
Authors: Long Wei , Li Zhongquan , Li Ying , Chen Junliang , Li Hongkui , Wan Shuangshuang 
Published: March 2017

AbstractIn one of the largest oil-gas fields in Daqing, China, the anticlines are important structures that hold natural gas. The origin of the symmetric anticlines, which have bends on both the limbs, remains under debate. This is especially true in the case of the anticline in Xujiaweizi (XJWZ), which has recently been the focus of gas exploration. A compressive force introduced by a ramp/flat fault was suggested as its origin of formation; however, this is inconsistent with the reconstruction of the regional stress fields, which show an extensive environment. An alternative explanation suggests a normal fault-related fold under extensive stress. However, this mechanism has difficulty explaining the very localized, rather than wide-spread, development of the anticline along the proposed controlling normal fault. The well-developed bends on both limbs of the anticline are also very different from the typical roll-over anticline. Here, we conduct an experimental study showing that the very localized development of the bent-on-both-limbs anticline is controlled by the geometry of the underlying fault-plane. A ramp/flat fault plane can introduce an anticline with bends on both limbs, while a smooth fault plane will develop a roll-over anticline with a bend on only one limb.
Microbial transformation of ginsenoside Rb1, Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng
Authors: Yu Shanshan , Zhou Xiaoli , Li Fan , Xu Chunchun , Zheng Fei , Li Jing , Zhao Huanxi , Dai Yulin , Liu Shuying , Feng Yan 
Published: March 2017

AbstractMicrobial transformation of ginsenosides to increase its pharmaceutical effect is gaining increasing attention in recent years. In this study, Cellulosimicrobium sp. TH-20, which was isolated from soil samples on which ginseng grown, exhibited effective ginsenoside-transforming activity. After protopanaxadiol (PPD)-type ginsenoside (Rb1) and protopanaxatriol (PPT)-type ginsenosides (Re and Rg1) were fed to C. sp. TH20, a total of 12 metabolites, including 6 new intermediate metabolites, were identified. Stepwise deglycosylation and dehydrogenation on the feeding precursors have been observed. The final products were confirmed to be rare ginsenosides Rd, GypXVII, Rg2 and PPT after 96 h transformation with 38–96% yields. The four products showed improved anti-inflammatory activities by using lipopolysaccharide (LPS)-induced murine RAW 264.7 macrophages and the xylene-induced acute inflammatory model of mouse ear edema. The results indicated that they could dramatically attenuate the production of TNF-α more effectively than the precursors. Our study would provide an example of a unique and powerful microbial cell factory for efficiently converting both PPD-type and PPT-type ginsenosides to rare natural products, which extends the drug candidates as novel anti-inflammatory remedies.
Universal slip dynamics in metallic glasses and granular matter – linking frictional weakening with inertial effects
Authors: Denisov Dmitry V. , Lőrincz Kinga A. , Wright Wendelin J. , Hufnagel Todd C. , Nawano Aya , Gu Xiaojun , Uhl Jonathan T. , Dahmen Karin A. , Schall Peter 
Published: March 2017

AbstractSlowly strained solids deform via intermittent slips that exhibit a material-independent critical size distribution. Here, by comparing two disparate systems - granular materials and bulk metallic glasses - we show evidence that not only the statistics of slips but also their dynamics are remarkably similar, i.e. independent of the microscopic details of the material. By resolving and comparing the full time evolution of avalanches in bulk metallic glasses and granular materials, we uncover a regime of universal deformation dynamics. We experimentally verify the predicted universal scaling functions for the dynamics of individual avalanches in both systems, and show that both the slip statistics and dynamics are independent of the scale and details of the material structure and interactions, thus settling a long-standing debate as to whether or not the claim of universality includes only the slip statistics or also the slip dynamics. The results imply that the frictional weakening in granular materials and the interplay of damping, weakening and inertial effects in bulk metallic glasses have strikingly similar effects on the slip dynamics. These results are important for transferring experimental results across scales and material structures in a single theory of deformation dynamics.
Real-time analysis of arc-induced Long Period Gratings under gamma irradiation
Authors: Esposito Flavio , Ranjan Rajeev , Stăncălie Andrei , Sporea Dan , Neguţ Daniel , Becherescu Nicu , Campopiano Stefania , Iadicicco Agostino 
Published: March 2017

AbstractIn this paper, we present a comparative experimental and theoretical study on gamma radiation sensitivity of Long Period Gratings (LPGs), fabricated by electric arc discharge technique, as monitored in three single mode optical fibers supplied by different manufacturers. A real-time measurement of LPGs’ wavelength shift was performed until a total dose of 35 kGy was reached, with average dose rate of 0.18 kGy/h, the irradiation being done at room temperature. In one case, a maximum radiation sensitivity of 1.34 nm/kGy was recorded for doses up to 0.5 kGy. Moreover, by combining experimental results with numerical simulations, it was found that changes occurred in the core refractive index of the irradiated optical fibers up to 2.5 ∙ 10−5. The increase of the core thermo-optic coefficient up to 1.5 ∙ 10−8/°C was observed as well.
Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties
Authors: Ma Shaocheng , Goh En Lin , Jin Andi , Bhattacharya Rajarshi , Boughton Oliver R. , Patel Bhavi , Karunaratne Angelo , Vo Nghia T. , Atwood Robert , Cobb Justin P. , Hansen Ulrich , Abel Richard L. 
Published: March 2017

AbstractOsteoporosis is characterised by trabecular bone loss resulting from increased osteoclast activation and unbalanced coupling between resorption and formation, which induces a thinning of trabeculae and trabecular perforations. Bisphosphonates are the frontline therapy for osteoporosis, which act by reducing bone remodelling, and are thought to prevent perforations and maintain microstructure. However, bisphosphonates may oversuppress remodelling resulting in accumulation of microcracks. This paper aims to investigate the effect of bisphosphonate treatment on microstructure and mechanical strength. Assessment of microdamage within the trabecular bone core was performed using synchrotron X-ray micro-CT linked to image analysis software. Bone from bisphosphonate-treated fracture patients exhibited fewer perforations but more numerous and larger microcracks than both fracture and non-fracture controls. Furthermore, bisphosphonate-treated bone demonstrated reduced tensile strength and Young’s Modulus. These findings suggest that bisphosphonate therapy is effective at reducing perforations but may also cause microcrack accumulation, leading to a loss of microstructural integrity and consequently, reduced mechanical strength.
Population genomics of an endemic Mediterranean fish: differentiation by fine scale dispersal and adaptation
Authors: Carreras Carlos , Ordóñez Víctor , Zane Lorenzo , Kruschel Claudia , Nasto Ina , Macpherson Enrique , Pascual Marta 
Published: March 2017

AbstractThe assessment of the genetic structuring of biodiversity is crucial for management and conservation. For species with large effective population sizes a low number of markers may fail to identify population structure. A solution of this shortcoming can be high-throughput sequencing that allows genotyping thousands of markers on a genome-wide approach while facilitating the detection of genetic structuring shaped by selection. We used Genotyping-by-Sequencing (GBS) on 176 individuals of the endemic East Atlantic peacock wrasse (Symphodus tinca), from 6 locations in the Adriatic and Ionian seas. We obtained a total of 4,155 polymorphic SNPs and we observed two strong barriers to gene flow. The first one differentiated Tremiti Islands, in the northwest, from all the other locations while the second one separated east and south-west localities. Outlier SNPs potentially under positive selection and neutral SNPs both showed similar patterns of structuring, although finer scale differentiation was unveiled with outlier loci. Our results reflect the complexity of population genetic structure and demonstrate that both habitat fragmentation and positive selection are on play. This complexity should be considered in biodiversity assessments of different taxa, including non-model yet ecologically relevant organisms.
IL-33/ST2 immune responses to respiratory bacteria in pediatric asthma
Authors: Hentschke Isabell , Graser Anna , Melichar Volker O. , Kiefer Alexander , Zimmermann Theodor , Kroß Bettina , Haag Patricia , Xepapadaki Paraskevi , Papadopoulos Nikolaos G. , Bogdan Christian , Finotto Susetta 
Published: March 2017

AbstractHere we investigated the relationship between local bacterial colonization and anti-bacterial immune responses in pre-school asthmatic and control children within the EU-wide study PreDicta. In this cohort of pre-school asthmatic children, nasopharyngeal colonization with Gram-negative bacteria such as Haemophilus influenzae and Moraxella catarrhalis was found to be associated with the highest interferon beta (IFNβ) and IL-33 levels in the nasal pharyngeal fluids (NPF). IL33R-ST2 was found induced in the blood of asthmatic children with additional Gram + bacteria in the nasopharynx (Gr+/−). Furthermore, asthmatic children had more episodes of infection that required antibiotic therapy than the control group. Treatment with antibiotics associated with reduced ST2 in blood cells of both asthmatic and control children and reduced IL-33 levels in the airways of asthmatic children. In the absence of Staphylococcus (S.) aureus in NPF, antibiotic therapy associated with decreased IL-33 levels in the NPF and lower ST2 values in the blood of control children but not of asthmatic children. These data suggest that, in asthmatic children, Gram- bacteria, which persist after antibiotic therapy, contributes to IL-33 locally and associated with Gr + bacteria colonization in the airways, inhibited IFN-β and in the absence of Staphylococcus (S.) aureus, induced ST2 bearing cells in their blood.
Antithymocyte globulin improves the survival of patients with myelodysplastic syndrome undergoing HLA-matched unrelated donor and haplo-identical donor transplants
Authors: Wang Hong , Liu Hong , Zhou Jin-Yi , Zhang Tong-Tong , Jin Song , Zhang Xiang , Chen Su-Ning , Li Wei-Yang , Xu Yang , Miao Miao , Wu De-Pei 
Published: March 2017

AbstractSignificant advances have been achieved in the outcomes of patients with myelodysplastic syndromes (MDS) after both HLA-matched sibling donor transplants (MSDT) and non-MSDT, the latter including HLA-matched unrelated donor (MUDT) and haplo-identical donor transplants (HIDT). In this retrospective study, we analyzed the data of 85 consecutive patients with MDS who received allogeneic HSCT between Dec 2007 and Apr 2014 in our center. These patients comprised 38 (44.7%) who received MSDT, 29 (34.1%) MUDT, and 18 (21.2%) HIDT. The median overall survival (OS) was 60.2 months, the probabilities of OS being 63%, 57%, and 48%, at the first, second, and fifth year, respectively. Median OS post-transplant (OSPT) was 57.2 months, the probabilities of OSPT being 58%, 55%, and 48% at the first, second, and fifth year, respectively. The survival of patients receiving non-MSDT was superior to that of MSDT, median OSPT being 84.0 months and 23.6 months, respectively (P = 0.042); the findings for OS were similar (P = 0.028). We also found that using ATG in conditioning regimens significantly improved survival after non-MSDT, with better OS and OSPT (P = 0.016 and P = 0.025). These data suggest that using ATG in conditioning regimens may improve the survival of MDS patients after non-MSDT.
CTCF participates in DNA damage response via poly(ADP-ribosyl)ation
Authors: Han Deqiang , Chen Qian , Shi Jiazhong , Zhang Feng , Yu Xiaochun 
Published: March 2017

AbstractCCCTC-binding factor (CTCF) plays an essential role in regulating the structure of chromatin by binding DNA strands for defining the boundary between active and heterochromatic DNA. However, the role of CTCF in DNA damage response remains elusive. Here, we show that CTCF is quickly recruited to the sites of DNA damage. The fast recruitment is mediated by the zinc finger domain and poly (ADP-ribose) (PAR). Further analyses show that only three zinc finger motifs are essential for PAR recognition. Moreover, CTCF-deficient cells are hypersensitive to genotoxic stress such as ionizing radiation (IR). Taken together, these results suggest that CTCF participate in DNA damage response via poly(ADP-ribosylation).
Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway
Authors: Huang Miao-Tzu , Chen Yi-Lien , Lien Chia-I , Liu Wei-Liang , Hsu Li-Chung , Yagita Hideo , Chiang Bor-Luen 
Published: March 2017

AbstractNotch is a pleiotropic signaling family that has been implicated in pathogenesis of allergic airway diseases; however, the distinct function of individual Notch ligands remains elusive. We investigated whether Notch ligands, Jagged1 and DLL4, exert differential effects in OVA-induced allergic asthma. We found that whilst Jagged1 inhibition mitigated Th2-dominated airway inflammation, blockage of DLL4 aggravated the Th2-mediated asthma phenotypes. Additionally, Jagged1 signaling blockage enhanced IL-17 production and neutrophilic airway infiltration. In vitro, exogenous Jagged1 induced Th2-skewed responses, whereas augmented DLL4 signaling displayed a dual role by promoting expansion of both Tregs and Th17. In vivo, DLL4 blockage impaired Treg differentiation which plausibly resulted in exaggerated asthma phenotypes. On the contrary, administration of DLL4-expressing antigen-presenting cells promoted endogenous Treg expansion and ameliorated the allergic responses. Therefore, whilst Jagged1 induces Th2-skewed inflammation, DLL4 elicits an essential self-regulatory mechanism via Treg-mediated pathway that counterbalances Jagged1-induced Th2 responses and facilitates resolution of the airway inflammation to restore homeostasis. These findings uncover a disparate function of Jagged1 and DLL4 in allergic airway diseases, hinting feasibility of Notch ligand-specific targeting in therapy of allergic airway diseases.
Contribution of engineered nanomaterials physicochemical properties to mast cell degranulation
Authors: Johnson Monica M. , Mendoza Ryan , Raghavendra Achyut J. , Podila Ramakrishna , Brown Jared M. 
Published: March 2017

AbstractThe rapid development of engineered nanomaterials (ENMs) has grown dramatically in the last decade, with increased use in consumer products, industrial materials, and nanomedicines. However, due to increased manufacturing, there is concern that human and environmental exposures may lead to adverse immune outcomes. Mast cells, central to the innate immune response, are one of the earliest sensors of environmental insult and have been shown to play a role in ENM-mediated immune responses. Our laboratory previously determined that mast cells are activated via a non-FcεRI mediated response following silver nanoparticle (Ag NP) exposure, which was dependent upon key physicochemical properties. Using bone marrow-derived mast cells (BMMCs), we tested the hypothesis that ENM physicochemical properties influence mast cell degranulation. Exposure to 13 physicochemically distinct ENMs caused a range of mast degranulation responses, with smaller sized Ag NPs (5 nm and 20 nm) causing the most dramatic response. Mast cell responses were dependent on ENMs physicochemical properties such as size, apparent surface area, and zeta potential. Surprisingly, minimal ENM cellular association by mast cells was not correlated with mast cell degranulation. This study suggests that a subset of ENMs may elicit an allergic response and contribute to the exacerbation of allergic diseases.
Epigenetic modifications of interleukin-6 in synovial fibroblasts from osteoarthritis patients
Authors: Yang Fei , Zhou Song , Wang Chuandong , Huang Yan , Li Huiwu , Wang You , Zhu Zhenan , Tang Jian , Yan Mengning 
Published: March 2017

AbstractOsteoarthritis (OA) is the most common degenerative disease of the synovial joint. The synovial membrane is responsible for the inflammatory reaction leading to the secretion of macrophage-derived pro-inflammatory cytokines, such as IL-6. Suppressing IL-6 over-expression in synovial fibroblasts (SF) is a promising method to prevent OA development and progression, in which the prerequisite is the elucidation of the molecular mechanisms underlying IL-6 over-expression in SF. Currently, there are few reports concerning epigenetic modifications in IL-6 in OA SF. In the present study, we attempted to investigate this phenomenon. SF over-expressing IL-6 was collected from OA patients. DNA hypomethylation and histone hyperacetylation were observed in the IL-6 promoter regions in OA SF compared with normal SF. No differences in the status of H3K9 di-methylation, H3K27 tri-methylation and H3K4 tri-methylation were observed in the IL-6 promoter regions between normal and OA SF. DNA (cytosine-5-)-methyltransferase 3 alpha (Dnmt3a) overexpression and anacardic acid (histone acetyltransferase inhibitor) treatment increased DNA methylation and decreased histone acetylation in the IL-6 promoter, and IL-6 over-expression in OA SF was suppressed. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic methods to treat OA.
Timing of global regression and microbial bloom linked with the Permian-Triassic boundary mass extinction: implications for driving mechanisms
Authors: Baresel Björn , Bucher Hugo , Bagherpour Borhan , Brosse Morgane , Guodun Kuang , Schaltegger Urs 
Published: March 2017

AbstractNew high-resolution U-Pb dates indicate a duration of 89 ± 38 kyr for the Permian hiatus and of 14 ± 57 kyr for the overlying Triassic microbial limestone in shallow water settings of the Nanpanjiang Basin, South China. The age and duration of the hiatus coincides with the Permian-Triassic boundary (PTB) and the extinction interval in the Meishan Global Stratotype Section and Point, and strongly supports a glacio-eustatic regression, which best explains the genesis of the worldwide hiatus straddling the PTB in shallow water records. In adjacent deep marine troughs, rates of sediment accumulation display a six-fold decrease across the PTB compatible with a dryer and cooler climate as indicated by terrestrial plants. Our model of the Permian-Triassic boundary mass extinction (PTBME) hinges on the synchronicity of the hiatus with the onset of the Siberian Traps volcanism. This early eruptive phase released sulfur-rich volatiles into the stratosphere, thus simultaneously eliciting a short-lived ice age responsible for the global regression and a brief but intense acidification. Abrupt cooling, shrunk habitats on shelves and acidification may all have synergistically triggered the PTBME. Subsequently, the build-up of volcanic CO2 induced a transient cool climate whose early phase saw the deposition of the microbial limestone.
Chemical or genetic Pin1 inhibition exerts potent anticancer activity against hepatocellular carcinoma by blocking multiple cancer-driving pathways
Authors: Liao Xin-Hua , Zhang Arina Li , Zheng Min , Li Mei-Qing , Chen Champ Peng , Xu Huijuan , Chu Qing-Song , Yang Dayun , Lu Wenxian , Tsai Ting-Fen , Liu Hekun , Zhou Xiao Zhen , Lu Kun Ping 
Published: March 2017

AbstractHepatocellular carcinoma (HCC) is one of the most prevalent and malignant cancers with high inter- and intra-tumor heterogeneity. A central common signaling mechanism in cancer is proline-directed phosphorylation, which is further regulated by the unique proline isomerase Pin1. Pin1 is prevalently overexpressed in human cancers including ~70% of HCC, and promotes tumorigenesis by activating multiple cancer-driving pathways. However, it was challenging to evaluate the significance of targeting Pin1 in cancer treatment until the recent identification of all-trans retinoic acid (ATRA) as a Pin1 inhibitor. Here we systematically investigate functions of Pin1 and its inhibitor ATRA in the development and treatment of HCC. Pin1 knockdown potently inhibited HCC cell proliferation and tumor growth in mice. ATRA-induced Pin1 degradation inhibited the growth of HCC cells, although at a higher IC50 as compared with breast cancer cells, likely due to more active ATRA metabolism in liver cells. Indeed, inhibition of ATRA metabolism enhanced the sensitivity of HCC cells to ATRA. Moreover, slow-releasing ATRA potently and dose-dependently inhibited HCC growth in mice. Finally, chemical or genetic Pin1 ablation blocked multiple cancer-driving pathways simultaneously in HCC cells. Thus, targeting Pin1 offers a promising therapeutic approach to simultaneously stop multiple cancer-driving pathways in HCC.