bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification
Authors: Park Jong Ho , Yang Seung Wook , Park Jung Mi , Ka Seung Hyeun , Kim Ji-Hoon , Kong Young-Yun , Jeon Young Joo , Seol Jae Hong , Chung Chin Ha 
Published: August 2016

Abstractp53 plays a pivotal role in tumour suppression under stresses, such as DNA damage. ISG15 has been implicated in the control of tumorigenesis. Intriguingly, the expression of ISG15, UBE1L and UBCH8 is induced by DNA-damaging agents, such as ultraviolet and doxorubicin, which are known to induce p53. Here, we show that the genes encoding ISG15, UBE1L, UBCH8 and EFP, have the p53-responsive elements and their expression is induced in a p53-dependent fashion under DNA damage conditions. Furthermore, DNA damage induces ISG15 conjugation to p53 and this modification markedly enhances the binding of p53 to the promoters of its target genes (for example, CDKN1 and BAX) as well as of its own gene by promoting phosphorylation and acetylation, leading to suppression of cell growth and tumorigenesis. These findings establish a novel feedback circuit between p53 and ISG15-conjugating system for positive regulation of the tumour suppressive function of p53 under DNA damage conditions.
Fscn1 is required for the trafficking of TGF-β family type I receptors during endoderm formation
Authors: Liu Zhaoting , Ning Guozhu , Xu Ranran , Cao Yu , Meng Anming , Wang Qiang 
Published: August 2016

AbstractMicrotubules function in TGF-β signalling by facilitating the cytoplasmic trafficking of internalized receptors and the nucleocytoplasmic shuttling of Smads. However, nothing is known about whether actin filaments are required for these processes. Here we report that zebrafish actin-bundling protein fscn1a is highly expressed in mesendodermal precursors and its expression is directly regulated by the TGF-β superfamily member Nodal. Knockdown or knockout of fscn1a leads to a reduction of Nodal signal transduction and endoderm formation in zebrafish embryos. Fscn1 specifically interacts with TGF-β family type I receptors, and its depletion disrupts the association between receptors and actin filaments and sequesters the internalized receptors into clathrin-coated vesicles. Therefore, Fscn1 acts as a molecular linker between TGF-β family type I receptors and the actin filaments to promote the trafficking of internalized receptors from clathrin-coated vesicles to early endosomes during zebrafish endoderm formation.
Association between impaired fasting glycaemia in pediatric obesity and type 2 diabetes in young adulthood
Authors: Hagman E , Danielsson P , Brandt L , Ekbom A , Marcus C 
Published: August 2016

Abstract
Objectives:
In adults, impaired fasting glycemia (IFG) increases the risk for type 2 diabetes mellitus (T2DM). This study aimed to investigate to which extent children with obesity develop T2DM during early adulthood, and to determine whether IFG and elevated hemoglobin A1c (HbA1c) in obese children are risk markers for early development of T2DM.

Methods:
In this prospective cohort study, 1620 subjects from the Swedish Childhood Obesity Treatment Registry – BORIS who were ⩾18 years at follow-up and 8046 individuals in a population-based comparison group, matched on gender age and living area, were included. IFG was defined according to both ADA (cut-off 5.6 mmol l−1) and WHO (6.1 mmol l−1). Elevated HbA1c was defined according to ADA (cut-off 39 mmol l−1). Main outcome was T2DM medication, as a proxy for T2DM. Data on medications were retrieved from a national registry.

Results:
The childhood obesity cohort were 24 times more likely to receive T2DM medications in early adulthood compared with the comparison group (95% confidence interval (CI): 12.52–46). WHO-defined IFG predicted future use of T2DM medication with an adjusted hazard ratio (HR) of 3.73 (95% CI: 1.87–7.45) compared with those who had fasting glucose levels <5.6 mmol l−1. A fasting glucose level of 5.6–6.0 mmol l−1, that is, the IFG-interval added by American Diabetes Association (ADA), did not increase the use of T2DM medication more than pediatric obesity itself, adjusted HR=1.72 (0.84–3.52). Elevated levels of HbA1c resulted in an adjusted HR=3.12 (1.50–6.52). More severe degree of obesity also increased the future T2DM risk.

CONCLUSION:
IFG according to WHO and elevated HbA1c (39–48 mmol l−1), but not the additional fasting glucose interval added by ADA (5.6–6.0 mmol l−1), can be considered as prediabetes in the obese pediatric population in Sweden.
Global terrestrial Human Footprint maps for 1993 and 2009
Authors: Venter Oscar , Sanderson Eric W. , Magrach Ainhoa , Allan James R. , Beher Jutta , Jones Kendall R. , Possingham Hugh P. , Laurance William F. , Wood Peter , Fekete Balázs M. , Levy Marc A. , Watson James E.M. 
Published: August 2016

AbstractRemotely-sensed and bottom-up survey information were compiled on eight variables measuring the direct and indirect human pressures on the environment globally in 1993 and 2009. This represents not only the most current information of its type, but also the first temporally-consistent set of Human Footprint maps. Data on human pressures were acquired or developed for: 1) built environments, 2) population density, 3) electric infrastructure, 4) crop lands, 5) pasture lands, 6) roads, 7) railways, and 8) navigable waterways. Pressures were then overlaid to create the standardized Human Footprint maps for all non-Antarctic land areas. A validation analysis using scored pressures from 3114×1 km2 random sample plots revealed strong agreement with the Human Footprint maps. We anticipate that the Human Footprint maps will find a range of uses as proxies for human disturbance of natural systems. The updated maps should provide an increased understanding of the human pressures that drive macro-ecological patterns, as well as for tracking environmental change and informing conservation science and application.
Multi-marker metabarcoding of coral skeletons reveals a rich microbiome and diverse evolutionary origins of endolithic algae
Authors: Marcelino Vanessa Rossetto , Verbruggen Heroen 
Published: August 2016

AbstractBacteria, fungi and green algae are common inhabitants of coral skeletons. Their diversity is poorly characterized because they are difficult to identify with microscopy or environmental sequencing, as common metabarcoding markers have low phylogenetic resolution and miss a large portion of the biodiversity. We used a cost-effective protocol and a combination of markers (tufA, 16S rDNA, 18S rDNA and 23S rDNA) to characterize the microbiome of 132 coral skeleton samples. We identified a wide range of prokaryotic and eukaryotic organisms, many never reported in corals before. We additionally investigated the phylogenetic diversity of the green algae—the most abundant eukaryotic member of this community, for which previous literature recognizes only a handful of endolithic species. We found more than 120 taxonomic units (near species level), including six family-level lineages mostly new to science. The results suggest that the existence of lineages with an endolithic lifestyle predates the existence of modern scleractinian corals by ca. 250my and that this particular niche was independently invaded by over 20 lineages in green algae evolution. These results highlight the potential of the multi-marker approach to assist in species discovery and, when combined with a phylogenetic framework, clarify the evolutionary origins of host-microbiota associations.
Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy
Authors: Godar Marie , Morello Virginia , Sadi Ava , Hultberg Anna , De Jonge Natalie , Basilico Cristina , Hanssens Valérie , Saunders Michael , Lambrecht Bart N. , El Khattabi Mohamed , de Haard Hans , Michieli Paolo , Blanchetot Christophe 
Published: August 2016

AbstractBispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.
Necrotising enterocolitis and mortality in preterm infants after introduction of probiotics: a quasi-experimental study
Authors: Samuels Noor , van de Graaf Rob , Been Jasper V. , de Jonge Rogier C. J. , Hanff Lidwien M. , Wijnen René M. H. , Kornelisse René F. , Reiss Irwin K. M. , Vermeulen Marijn J. 
Published: August 2016

AbstractEvidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran®) on the primary outcome ‘NEC or death’. Preterm infants (gestational age <32 weeks or birth weight <1500 gram) admitted before (Jan 2008–Sep 2012; n = 1288) and after (Oct 2012–Dec 2014; n = 673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in ‘NEC or death’ between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42–0.93, p = 0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for ‘NEC or sepsis or death’ in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21–0.93, p = 0.03) only. We conclude that introduction of probiotics was not associated with a reduction in ‘NEC or death’ and that type of feeding seems to modify the effects of probiotics.
Optical characterization of red blood cells from individuals with sickle cell trait and disease in Tanzania using quantitative phase imaging
Authors: Jung JaeHwang , Matemba Lucas E. , Lee KyeoReh , Kazyoba Paul E. , Yoon Jonghee , Massaga Julius J. , Kim Kyoohyun , Kim Dong-Jin , Park YongKeun 
Published: August 2016

AbstractSickle cell disease (SCD) is common across Sub-Saharan Africa. However, the investigation of SCD in this area has been significantly limited mainly due to the lack of research facilities and skilled personnel. Here, we present optical measurements of individual red blood cells from healthy individuals and individuals with SCD and sickle cell trait in Tanzania using the quantitative phase imaging technique. By employing a quantitative phase imaging unit, an existing microscope in a clinic is transformed into a powerful quantitative phase microscope providing measurements on the morphological, biochemical, and biomechanical properties of individual cells. The present approach will open up new opportunities for cost-effective investigation and diagnosis of several diseases in low resource environments.
Optical coherence microscopy in 1700 nm spectral band for high-resolution label-free deep-tissue imaging
Authors: Yamanaka Masahito , Teranishi Tatsuhiro , Kawagoe Hiroyuki , Nishizawa Norihiko 
Published: August 2016

AbstractOptical coherence microscopy (OCM) is a label-free, high-resolution, three-dimensional (3D) imaging technique based on optical coherence tomography (OCT) and confocal microscopy. Here, we report that the 1700-nm spectral band has the great potential to improve the imaging depth in high-resolution OCM imaging of animal tissues. Recent studies to improve the imaging depth in OCT revealed that the 1700-nm spectral band is a promising choice for imaging turbid scattering tissues due to the low attenuation of light in the wavelength region. In this study, we developed high-resolution OCM by using a high-power supercontinuum source in the 1700-nm spectral band and compared the attenuation of signal-to-noise ratio between the 1700-nm and 1300-nm OCM imaging of a mouse brain under the condition of the same sensitivity. The comparison clearly showed that the 1700-nm OCM provides larger imaging depth than the 1300-nm OCM. In this 1700-nm OCM, the lateral resolution of 1.3 μm and the axial resolution of 2.8 μm, when a refractive index was assumed to be 1.38, was achieved.
Reconciling Local Structure Disorder and the Relaxor State in (Bi1/2Na1/2)TiO3-BaTiO3
Authors: Groszewicz Pedro B. , Gröting Melanie , Breitzke Hergen , Jo Wook , Albe Karsten , Buntkowsky Gerd , Rödel Jürgen 
Published: August 2016

AbstractLead-based relaxor ferroelectrics are key functional materials indispensable for the production of multilayer ceramic capacitors and piezoelectric transducers. Currently there are strong efforts to develop novel environmentally benign lead-free relaxor materials. The structural origins of the relaxor state and the role of composition modifications in these lead-free materials are still not well understood. In the present contribution, the solid-solution (100-x)(Bi1/2Na1/2)TiO3-xBaTiO3 (BNT-xBT), a prototypic lead-free relaxor is studied by the combination of solid-state nuclear magnetic resonance (NMR) spectroscopy, dielectric measurements and ab-initio density functional theory (DFT). For the first time it is shown that the peculiar composition dependence of the EFG distribution width (ΔQISwidth) correlates strongly to the dispersion in dielectric permittivity, a fingerprint of the relaxor state. Significant disorder is found in the local structure of BNT-xBT, as indicated by the analysis of the electric field gradient (EFG) in 23Na 3QMAS NMR spectra. Aided by DFT calculations, this disorder is attributed to a continuous unimodal distribution of octahedral tilting. These results contrast strongly to the previously proposed coexistence of two octahedral tilt systems in BNT-xBT. Based on these results, we propose that considerable octahedral tilt disorder may be a general feature of these oxides and essential for their relaxor properties.
Identification of cellular senescence-specific genes by comparative transcriptomics
Authors: Nagano Taiki , Nakano Masayuki , Nakashima Akio , Onishi Kengo , Yamao Shunsuke , Enari Masato , Kikkawa Ushio , Kamada Shinji 
Published: August 2016

AbstractCellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence.
Infection-induced behavioural changes reduce connectivity and the potential for disease spread in wild mice contact networks
Authors: Lopes Patricia C. , Block Per , König Barbara 
Published: August 2016

AbstractInfection may modify the behaviour of the host and of its conspecifics in a group, potentially altering social connectivity. Because many infectious diseases are transmitted through social contact, social connectivity changes can impact transmission dynamics. Previous approaches to understanding disease transmission dynamics in wild populations were limited in their ability to disentangle different factors that determine the outcome of disease outbreaks. Here we ask how social connectivity is affected by infection and how this relationship impacts disease transmission dynamics. We experimentally manipulated disease status of wild house mice using an immune challenge and monitored social interactions within this free-living population before and after manipulation using automated tracking. The immune-challenged animals showed reduced connectivity to their social groups, which happened as a function of their own behaviour, rather than through conspecific avoidance. We incorporated these disease-induced changes of social connectivity among individuals into models of disease outbreaks over the empirically-derived networks. The models revealed that changes in host behaviour frequently resulted in the disease being contained to very few animals, as opposed to becoming widespread. Our results highlight the importance of considering the role that behavioural alterations during infection can have on social dynamics when evaluating the potential for disease outbreaks.
A bivariate genome-wide association study identifies ADAM12 as a novel susceptibility gene for Kashin-Beck disease
Authors: Hao Jingcan , Wang Wenyu , Wen Yan , Xiao Xiao , He Awen , Guo Xiong , Yang Tielin , Liu Xiaogang , Shen Hui , Chen Xiangding , Tian Qing , Deng Hong-Wen , Zhang Feng 
Published: August 2016

AbstractKashin-Beck disease (KBD) is a chronic osteoarthropathy, which manifests as joint deformities and growth retardation. Only a few genetic studies of growth retardation associated with the KBD have been carried out by now. In this study, we conducted a two-stage bivariate genome-wide association study (BGWAS) of the KBD using joint deformities and body height as study phenotypes, totally involving 2,417 study subjects. Articular cartilage specimens from 8 subjects were collected for immunohistochemistry. In the BGWAS, ADAM12 gene achieved the most significant association (rs1278300 p-value = 9.25 × 10−9) with the KBD. Replication study observed significant association signal at rs1278300 (p-value = 0.007) and rs1710287 (p-value = 0.002) of ADAM12 after Bonferroni correction. Immunohistochemistry revealed significantly decreased expression level of ADAM12 protein in the KBD articular cartilage (average positive chondrocyte rate = 47.59 ± 7.79%) compared to healthy articular cartilage (average positive chondrocyte rate = 64.73 ± 5.05%). Our results suggest that ADAM12 gene is a novel susceptibility gene underlying both joint destruction and growth retardation of the KBD.
Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration
Authors: Ma Shiqing , Adayi Aidina , Liu Zihao , Li Meng , Wu Mingyao , Xiao Linghao , Sun Yingchun , Cai Qing , Yang Xiaoping , Zhang Xu , Gao Ping 
Published: August 2016

AbstractInfections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration.
Filtrating colorectal cancer associated genes by integrated analyses of global DNA methylation and hydroxymethylation in cancer and normal tissue
Authors: Li Ming , Gao Fei , Xia Yudong , Tang Yi , Zhao Wei , Jin Congcong , Luo Huijuan , Wang Junwen , Li Qingshu , Wang Yalan 
Published: August 2016

AbstractRecently, 5-hydroxymethylcytosine patterning across the tumor genome was considered as a hallmark of cancer development and progression. However, locus-specific difference of hydroxymethylation between colorectal cancer and normal tissue is unknown. In this study, we performed a newly developed method, HMST-seq, to profile 726 aberrant methylated loci and 689 aberrant hydroxymethylated loci synchronously in genome wide of colorectal cancers, majority of which presented higher methylation or lower hydroxymethylationin than in normal group. Besides, abnormal hydroxymethylated modification was more frequently occur at proximal regions close to TSSs and TSSs regions than abnormal methylation. Subsequently, we screened four genes (ALOX15, GHRHR, TFPI2 and TKTL1) with aberrant methylation and aberrant hydroxymethylation at some genome position by functional enrichment analysis as candidate genes associated with colorectal cancer. Our results may allow us to select differentially epigenetically modified target genes implicated in colorectal cancer tumorigenesis.