bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preserving self-renewal of porcine pluripotent stem cells in serum-free 3i culture condition and independent of LIF and b-FGF cytokines
Authors: Ma Yangyang , Yu Tong , Cai Yuanxing , Wang Huayan 
Published: February 2018

AbstractDerivation of bona fide porcine pluripotent stem cells is still a critical issue because porcine embryonic stem cells (ESCs) are not available yet, and most of the culture conditions to maintain porcine induced pluripotent stem cells (piPSCs) are based on conditions for mouse and human iPS cells. In this study, we generated a doxycycline-inducible porcine iPS cell line (DOX-iPSCs) and used it to screen the optimal culture condition to sustain the self-renewal of piPSCs. We found that LIF and b-FGF were required for porcine cell reprogramming, but were not essential cytokines for maintaining the self-renewal and pluripotency of piPSCs. A serum-free 3i medium, which includes three inhibitors CHIR99021, SB431542, and PD0325901, three cytokines BMP4, SCF, and IL-6, and human platelet lysates (PL), was made through serious selections. In 3i condition, the doxycycline-inducible iPSCs could be passaged for a long term without the addition of doxycycline, and the flattened morphology of intermediate state piPSCs could convert to the naïve-like morphology with the increase in endogenous pluripotent gene expressions. Additionally, pPSC cell line isolated from 5.5 days blastocysts could be sustained in 3i medium and the expression of endogenous pluripotent genes OCT4, ESRRB, and STELLA was significantly increased. Our finding directed a new reprogramming strategy by using 3i condition to maintain and convert primed piPSCs into naïve-like pluripotent state. A combination of traditional LIF/b-FGF conditions and 3i condition may help us to find out an appropriate reprogramming approach to generate the naïve state of porcine iPSCs.
LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during late mitosis
Authors: Hong Ye , Sonneville Remi , Wang Bin , Scheidt Viktor , Meier Bettina , Woglar Alexander , Demetriou Sarah , Labib Karim , Jantsch Verena , Gartner Anton 
Published: February 2018

AbstractFaithful chromosome segregation and genome maintenance requires the removal of all DNA bridges that physically link chromosomes before cells divide. Using C. elegans embryos we show that the LEM-3/Ankle1 nuclease defines a previously undescribed genome integrity mechanism by processing DNA bridges right before cells divide. LEM-3 acts at the midbody, the structure where abscission occurs at the end of cytokinesis. LEM-3 localization depends on factors needed for midbody assembly, and LEM-3 accumulation is increased and prolonged when chromatin bridges are trapped at the cleavage plane. LEM-3 locally processes chromatin bridges that arise from incomplete DNA replication, unresolved recombination intermediates, or the perturbance of chromosome structure. Proper LEM-3 midbody localization and function is regulated by AIR-2/Aurora B kinase. Strikingly, LEM-3 acts cooperatively with the BRC-1/BRCA1 homologous recombination factor to promote genome integrity. These findings provide a molecular basis for the suspected role of the LEM-3 orthologue Ankle1 in human breast cancer.
Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia
Authors: Herling Carmen D. , Abedpour Nima , Weiss Jonathan , Schmitt Anna , Jachimowicz Ron Daniel , Merkel Olaf , Cartolano Maria , Oberbeck Sebastian , Mayer Petra , Berg Valeska , Thomalla Daniel , Kutsch Nadine , Stiefelhagen Marius , Cramer Paula , Wendtner Clemens-Martin , Persigehl Thorsten , Saleh Andreas , Altmüller Janine , Nürnberg Peter , Pallasch Christian , Achter Viktor , Lang Ulrich , Eichhorst Barbara , Castiglione Roberta , Schäfer Stephan C. , Büttner Reinhard , Kreuzer Karl-Anton , Reinhardt Hans Christian , Hallek Michael , Frenzel Lukas P. , Peifer Martin 
Published: February 2018

AbstractDeciphering the evolution of cancer cells under therapeutic pressure is a crucial step to understand the mechanisms that lead to treatment resistance. To this end, we analyzed whole-exome sequencing data of eight chronic lymphocytic leukemia (CLL) patients that developed resistance upon BCL2-inhibition by venetoclax. Here, we report recurrent mutations in BTG1 (2 patients) and homozygous deletions affecting CDKN2A/B (3 patients) that developed during treatment, as well as a mutation in BRAF and a high-level focal amplification of CD274 (PD-L1) that might pinpoint molecular aberrations offering structures for further therapeutic interventions.
Author Correction: North Atlantic variability and its links to European climate over the last 3000 years
Authors: Moffa-Sánchez Paola , Hall Ian R. 
Published: February 2018

In the original version of this Article, the third sentence of the first paragraph of the “Changes in the input of polar waters into the Labrador Sea” section of the Results originally incorrectly read ‘During the spring-summer months, after the winter convection has ceased in the Labrador Sea, its northwest boundary currents (the EGC and IC) support restratification of the surface ocean through lateral transport.’ The correct version states ‘northeast’ instead of ‘northwest’. The fifth sentence of the second paragraph of the same section originally incorrectly read “In contrast, in the western section of the Nordic Seas, under the presence of warm Atlantic waters of the Norwegian Current, Nps was found to calcify deeper in the water column (100–200 m), whereas in the east under the influence of the EGC polar waters it calcified closer to the surface at a similar depth as Tq23.” The correct version states ‘eastern’ instead of ‘western’ and ‘west’ instead of ‘east’.The seventh sentence of the same paragraph originally incorrectly read “Small/large differences in Δδ18ONps-Tq indicating increased/decreased presence of warm and salty Atlantic IC waters vs. polar EGC waters in the upper water column, respectively.” The correct version starts ‘Large/small’ rather than ‘Small/large’.These errors have been corrected in both the PDF and HTML versions of the Article.
Secondary Phase Interaction at Interfaces of High-Strength Brazed Joints made using Liquid Phase Sintered Alumina Ceramics and Ag-Cu-Ti Braze Alloys
Authors: Kassam T. A. , Hari Babu N. , Ludford N. , Yan S. , Howkins A. 
Published: February 2018

AbstractAlumina-to-alumina brazed joints were formed using 96.0 and 99.7 wt.% Al2O3 ceramics using 150 µm thick Ticusil® (68.8Ag-26.7Cu-4.7 wt.% Ti) braze preforms. Brazing was conducted in a vacuum of 1 × 10−5 mbar at 850 °C for 10 minutes. Joint strengths were evaluated using four-point bend testing and were compared to the monolithic flexural strengths of standard alumina test bars according to ASTM C1161-13. Brazed joints made using 96.0 wt.% Al2O3 consistently outperformed brazed joints made using 99.7 wt.% Al2O3, despite similarities in both the flexural strengths of the standard alumina test bars and the microstructures of brazed joints. Secondary phase interaction led to the formation of Ti5Si3 reaction products at locations where the triple pocket grain boundaries of the 96.0 wt.% Al2O3 surface intersected the Ti-rich reaction layers. It is proposed that due to this interaction, brazed joints made using 96.0 wt.% Al2O3, which were relatively cost-effective to produce, achieved higher strengths than brazed joints made using 99.7 wt.% Al2O3.
Remodeling of the Candida glabrata cell wall in the gastrointestinal tract affects the gut microbiota and the immune response
Authors: Charlet Rogatien , Pruvost Youri , Tumba Gael , Istel Fabian , Poulain Daniel , Kuchler Karl , Sendid Boualem , Jawhara Samir 
Published: February 2018

AbstractThe gastrointestinal (GI) microbiota acts a natural barrier to the proliferation of opportunistic pathogens. Candida glabrata is an opportunistic yeast pathogen that has adapted to colonize all segments of the human GI tract. We observed an increase in Escherichia coli, Enterococcus faecalis, and Bacteroides vulgatus populations, and a decrease in Lactobacillus johnsonii, Bacteroides thetaiotaomicron, and Bifidobacterium animalis in mice with DSS-induced colitis. This reduction was more pronounced for L. johnsonii during C. glabrata overgrowth. In addition, C. glabrata overgrowth increased mouse mortality and inflammatory parameters, and modulated the expression of intestinal receptors and signaling pathways. The C. glabrata cell wall underwent various changes during the course of C. glabrata colonization, and showed a significant increase in chitin. C. glabrata deficient in chitin synthase-3 induced fewer inflammatory parameters than the parental strain during intestinal inflammation. Oral administration of chitin attenuated the impact of colitis, and reduced the number of aerobic bacteria and C. glabrata overgrowth, while chitinase-3-like protein-1 increased. This study provides evidence that inflammation of the gut alters the microbial balance and leads to C. glabrata cell wall remodeling through an increase in chitin, which is involved in promoting persistence of C. glabrata in the gut.
VPS4 is a dynamic component of the centrosome that regulates centrosome localization of γ-tubulin, centriolar satellite stability and ciliogenesis
Authors: Ott Carolyn , Nachmias Dikla , Adar Shai , Jarnik Michal , Sherman Shachar , Birnbaum Ramon Y. , Lippincott-Schwartz Jennifer , Elia Natalie 
Published: February 2018

AbstractThe hexameric AAA ATPase VPS4 facilitates ESCRT III filament disassembly on diverse intracellular membranes. ESCRT III components and VPS4 have been localized to the ciliary transition zone and spindle poles and reported to affect centrosome duplication and spindle pole stability. How the canonical ESCRT pathway could mediate these events is unclear. We studied the association of VPS4 with centrosomes and found that GFP-VPS4 was a dynamic component of both mother and daughter centrioles. A mutant, VPS4EQ, which can’t hydrolyze ATP, was less dynamic and accumulated at centrosomes. Centrosome localization of the VPS4EQ mutant, caused reduced γ-tubulin levels at centrosomes and consequently decreased microtubule growth and altered centrosome positioning. In addition, preventing VPS4 ATP hydrolysis nearly eliminated centriolar satellites and paused ciliogensis after formation of the ciliary vesicle. Zebrafish embryos injected with GFP-VPS4EQ mRNA were less viable, exhibited developmental defects and had fewer cilia in Kupffer’s vesicle. Surprisingly, ESCRT III proteins seldom localized to centrosomes and their depletion did not lead to these phenotypes. Our data support an ESCRT III-independent function for VPS4 at the centrosome and reveal that this evolutionary conserved AAA ATPase influences diverse centrosome functions and, as a result, global cellular architecture and development.
Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its Autoantigenicity with Pathogen Neutralization
Authors: Burbelo Peter D. , Teos Leyla Y. , Herche Jesse L. , Iadarola Michael J. , Alevizos Ilias 
Published: February 2018

AbstractRo52/TRIM21 plays a key role in antibody-dependent pathogen neutralization and is a major autoantigen in systemic lupus erythematosus, Sjögren’s syndrome (SS), and other autoimmune diseases. Here we evaluated immunoreactivity against Ro52-related molecules in SS and healthy volunteers. Although most proteins examined were not antigenic, several TRIM paralogs, including TRIM22, and TRIM38, showed sporadic immunoreactivity in SS. In contrast, the murine Ro52 ortholog with limited linear homology demonstrated high levels of autoantibodies implicating the importance of shared conformational epitopes. To further explore the autoantigencity of Ro52, deletion and point mutant analyses were employed revealing previously hidden, robust autoantibodies directed against its C-terminal immunoglobulin-binding domain. Another autoantibody, rheumatoid factor, targeting the Fc region of IgG, strongly overlapped with Ro52 seropositivity (odds ratio 14; P < 0.0001). These convergent mechanistic findings support a model whereby intracellular Ro52-bound antibody-coated pathogen complexes, released or misprocessed from infected cells, drive autoantigenicity against Ro52 and the Fc region of IgG.
Caudal autotomy as anti-predatory behaviour in Palaeozoic reptiles
Authors: LeBlanc A. R. H. , MacDougall M. J. , Haridy Y. , Scott D. , Reisz R. R. 
Published: February 2018

AbstractMany lizards can drop a portion of their tail in response to an attack by a predator, a behaviour known as caudal autotomy. The capacity for intravertebral autotomy among modern reptiles suggests that it evolved in the lepidosaur branch of reptilian evolution, because no such vertebral features are known in turtles or crocodilians. Here we present the first detailed evidence of the oldest known case of caudal autotomy, found only among members of the Early Permian captorhinids, a group of ancient reptiles that diversified extensively and gained a near global distribution before the end-Permian mass extinction event of the Palaeozoic. Histological and SEM evidence show that these early reptiles were the first amniotes that could autotomize their tails, likely as an anti-predatory behaviour. As in modern iguanid lizards, smaller captorhinids were able to drop their tails as juveniles, presumably as a mechanism to evade a predator, whereas larger individuals may have gradually lost this ability. Caudal autotomy in captorhinid reptiles highlights the antiquity of this anti-predator behaviour in a small member of a terrestrial community composed predominantly of larger amphibian and synapsid predators.
Chaotic Dynamics of Inner Ear Hair Cells
Authors: Faber Justin , Bozovic Dolores 
Published: February 2018

AbstractExperimental records of active bundle motility are used to demonstrate the presence of a low-dimensional chaotic attractor in hair cell dynamics. Dimensionality tests from dynamic systems theory are applied to estimate the number of independent variables sufficient for modelling the hair cell response. Poincaré maps are constructed to observe a quasiperiodic transition from chaos to order with increasing amplitudes of mechanical forcing. The onset of this transition is accompanied by a reduction of Kolmogorov entropy in the system and an increase in transfer entropy between the stimulus and the hair bundle, indicative of signal detection. A simple theoretical model is used to describe the observed chaotic dynamics. The model exhibits an enhancement of sensitivity to weak stimuli when the system is poised in the chaotic regime. We propose that chaos may play a role in the hair cell’s ability to detect low-amplitude sounds.
Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells
Authors: Zheng Wanglong , Wang Bingjie , Si Mengxue , Zou Hui , Song Ruilong , Gu Jianhong , Yuan Yan , Liu Xuezhong , Zhu Guoqiang , Bai Jianfa , Bian Jianchun , Liu ZongPing 
Published: February 2018

AbstractThe aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.
Angiotensin-converting enzyme inhibitor reduces scar formation by inhibiting both canonical and noncanonical TGF-β1 pathways
Authors: Fang Qing-Qing , Wang Xiao-Feng , Zhao Wan-Yi , Ding Shi-Li , Shi Bang-Hui , Xia Ying , Yang Hu , Wu Li-Hong , Li Cai-Yun , Tan Wei-Qiang 
Published: February 2018

AbstractAngiotensin-converting enzyme inhibitors (ACEIs) can improve the fibrotic processes in many internal organs. Recent studies have shown a relationship between ACEI with cutaneous scar formation, although it has not been confirmed, and the underlying mechanism is unclear. In this study, we cultured mouse NIH 3T3 fibroblasts with different concentrations of ACEI. We measured cell proliferation with a Cell Counting Kit-8 and collagen expression with a Sirius Red Collagen Detection Kit. Flow cytometry and western blotting were used to detect transforming growth factor β1 (TGF-β1) signaling. We also confirmed the potential antifibrotic activity of ACEI in a rat scar model. ACEI reduced fibroblast proliferation, suppressed collagen and TGF-β1 expression, and downregulated the phosphorylation of SMAD2/3 and TAK1, both in vitro and in vivo. A microscopic examination showed that rat scars treated with ramipril or losartan were not only narrower than in the controls, but also displayed enhanced re-epithelialization and neovascularization, and the formation of organized granulation tissue. These data indicate that ACEI inhibits scar formation by suppressing both TGF-β1/SMAD2/3 and TGF-β1/TAK1 pathways, and may have clinical utility in the future.
Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency
Authors: Nguyen Huan T. , Noguchi Satoru , Sugie Kazuma , Matsuo Yoshiyuki , Nguyen Chuyen T. H. , Koito Hitoshi , Shiojima Ichiro , Nishino Ichizo , Tsukaguchi Hiroyasu 
Published: February 2018

AbstractLysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2–deficient mice and cultured cells. LAMP-2–deficient mice at 9–24 months of age showed medial thickening with luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in Lamp2 null mice expressed more vimentin but less α-smooth muscle actin (α-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of LAMP2 in cultured human brain VSMC showed the same phenotypic transition with mitochondrial fragmentation, enhanced mitochondrial respiration, and overproduction of reactive oxygen species (ROS). These findings indicate that LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic conversion of VSMC, resulting from age-dependent accumulation of cellular waste generated by aberrant autophagy.
Iodine insertion and dispersion of refractive index in organic single crystal semiconductor
Authors: Kwon Seonho , Bae Junwan , Lee I. J. 
Published: February 2018

AbstractInsertion of halogens such as bromine or iodine affects the electronic polarizability of ions and the local field inside the medium, and thus modifies the refractive index. Acquiring precise knowledge of the dispersion of refractive index and ultimately tailoring conventional semiconductors for wide-range refractive index control have been a vital issue to resolve before realizing advanced organic optoelectronic devices. In this report, dispersions of the refractive index of a single crystal tetramethyltetraselenafulvalene [C10H12Se4] (TMTSF) are thoroughly studied from broadband interference modulations of photoluminescence (PL) spectra at various temperatures and doping levels. A large enhancement of the refractive index, more than 20% of the intrinsic value, is achieved with inclusion of a small composition of iodide ions, while the structural and optical properties remain mostly intact. Nearly temperature independent dispersion of the refractive index suggests that, unlike most polymers in which the thermal expansion coefficient dominates over the change of polarizability with temperature, the latter enhances significantly and may become more or less comparable to the thermal expansion coefficient given by 1.71 × 10−4/K, when single crystal TMTSF is doped by iodine.
Cranial shape comparison for automated objective 3D craniosynostosis surgery planning
Authors: Tolhuisen Manon L. , de Jong Guido A. , van Damme Ruud J. M. , van der Heijden Ferdinand , Delye Hans H. K. 
Published: February 2018

AbstractVirtual planning of open cranial vault reconstruction is used to simulate and define an pre-operative plan for craniosynostosis surgery. However, virtual planning techniques are subjective and dependent on the experience and preferences of the surgical team. To develop an objective automated 3D pre-operative planning technique for open cranial vault reconstructions, we used curvature maps for the shape comparison of the patient’s skull with an age-specific reference skull. We created an average skull for the age-group of 11–14 months. Also, we created an artificial test object and selected a cranial CT-scan of an 11 months old trigonocephaly patient as test case. Mesh data of skulls were created using marching cubes and raycasting. Curvature maps were computed using quadric surface fitting. The shape comparison was tested for the test object and the average skull. Finally, shape comparison was performed for the trigonocephalic skull with the average skull. Similar shapes and the area on the patient’s skull that maximally corresponded in shape with the reference shape were correctly identified. This study showed that curvature maps allow the comparison of craniosynostosis skulls with age-appropriate average skulls and a first step towards an objective user-independent pre-operative planning technique for open cranial vault reconstructions is made.