bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative NHEJ pathway proteins as components of MYCN oncogenic activity in human neural crest stem cell differentiation: implications for neuroblastoma initiation
Authors: Newman Erika A. , Chukkapalli Sahiti , Bashllari Daniela , Thomas Tina T. , Van Noord Raelene A. , Lawlor Elizabeth R. , Hoenerhoff Mark J. , Opipari Anthony W. , Opipari Valerie P. 
Published: December 2017

AbstractNeuroblastoma is a cancer of neural crest stem cell (NCSC) lineage. Signaling pathways that regulate NCSC differentiation have been implicated in neuroblastoma tumorigenesis. This is exemplified by MYCN oncogene targets that balance proliferation, differentiation, and cell death similarly in normal NCSC and in high-risk neuroblastoma. Our previous work discovered a survival mechanism by which MYCN-amplified neuroblastoma circumvents cell death by upregulating components of the error-prone non-canonical alternative nonhomologous end-joining (alt-NHEJ) DNA repair pathway. Similar to proliferating stem cells, high-risk neuroblastoma cells have enhanced DNA repair capacity, overcoming DNA damage with higher repair efficiency than somatic cells. Adequate DNA maintenance is required for lineage protection as stem cells proliferate and during tumor progression to overcome oncogene-induced replication stress. On this basis, we hypothesized that alt-NHEJ overexpression in neuroblastoma is a cancer cell survival mechanism that originates from DNA repair systems of NCSC, the presumed progenitor cell of origin. A human NCSC model was generated in which inducible MYCN triggered an immortalized phenotype capable of forming metastatic neuroectodermal tumors in mice, resembling human neuroblastoma. Critical alt-NHEJ components (DNA Ligase III, DNA Ligase I, and Poly [ADP-ribose polymerase 1]) were highly expressed in normal early NCSC, and decreased as cells became terminally differentiated. Constitutive MYCN expression maintained high alt-NHEJ protein expression, preserving the expression pattern of the immature neural phenotype. siRNA knockdown of alt-NHEJ components reversed MYCN effects on NCSC proliferation, invasion, and migration. DNA Ligase III, Ligase I, and PARP1 silencing significantly decreased neuroblastoma markers expression (TH, Phox2b, and TRKB). These results utilized the first human NCSC model of neuroblastoma to uncover an important link between MYCN and alt-NHEJ expression in developmental tumor initiation, setting precedence to investigate alt-NHEJ repair mechanics in neuroblastoma DNA maintenance.
Pyridoxine 5′-phosphate oxidase is a novel therapeutic target and regulated by the TGF-β signalling pathway in epithelial ovarian cancer
Authors: Zhang Lingyun , Zhou Daibing , Guan Wencai , Ren Weimin , Sun Wenwen , Shi Jimin , Lin Qunbo , Zhang Jinguo , Qiao Tiankui , Ye Yulong , Wu Yun , Zhang Yaning , Zuo Xulei , Connor Kristin L , Xu Guoxiong 
Published: December 2017

AbstractPyridoxine 5′-phosphate oxidase (PNPO) is an enzyme that converts pyridoxine 5′-phosphate into pyridoxal 5′-phosphate (PLP), an active form of vitamin B6 implicated in several types of cancer. However, the role of PNPO and its regulatory mechanism in epithelial ovarian cancer (EOC) are unknown. In the present study, PNPO expression in human ovarian tumour tissue and its association with the clinicopathological features of patients with EOC were examined. Further, the biological function of PNPO in EOC cells and in xenograft was evaluated. We demonstrated for the first time that PNPO was overexpressed in human EOC. Knockdown of PNPO induced EOC cell apoptosis, arrested cell cycle at G2/M phase, decreased cell proliferation, migration and invasion. Xenografts of PNPO-shRNA-expressing cells into the nude mouse attenuated tumour growth. PNPO at mRNA and protein levels in EOC cells was decreased after transforming growth factor-β1 (TGF-β1) treatment. The inhibitory effect of TGF-β1 on PNPO expression was abolished in the presence of SB-431542, a TGF-β type I receptor kinase inhibitor. Moreover, we found that TGF-β1-mediated PNPO expression was at least in part through the upregulation of miR-143-3p. These data indicate a mechanism underlying PNPO regulation by the TGF-β signalling pathway. Furthermore, PLP administration reduced PNPO expression and decreased EOC cell proliferation, suggesting a feedback loop between PLP and PNPO. Thus, our findings reveal that PNPO can serve as a novel tissue biomarker of EOC and may be a potential target for therapeutic intervention.
Copper Nanowires through Oriented Mesoporous Silica: A Step towards Protected and Parallel Atomic Switches
Authors: Ai Yong , Smida Hassiba , Ghilane Jalal , Vilà Neus , Ghanbaja Jaafar , Walcarius Alain , Lacroix Jean Christophe 
Published: December 2017

AbstractThe formation of copper atomic contacts has been investigated. Copper nanowires were grown by electrochemical deposition, in the scanning electrochemical microscopy (SECM) configuration, from a platinum microelectrode to an indium tin oxide (ITO) substrate. Self-termination leaves copper filaments between the two electrodes with an atomic point contact at the ITO electrode. Histogram analysis shows that the conductance of this contact is close to, or less than, 1 G0. Atomic contacts were also fabricated on ITO electrodes covered with vertically-aligned mesoporous silica films. Scanning Transmission Electron Microscopy images show that copper filaments occupy individual isolated nanopores. Contacts generated on bare ITO break down rapidly in sodium salicylate, whereas those generated in ITO/nanopores are unaffected; the nanopores protect the copper filaments. Finally, atomic switch behaviour was obtained using these ITO and ITO/nanopores electrodes.
Kv4.3 Modulates the Distribution of hERG
Authors: Zhao Xiao-Jing , Zhu Chao , Tian Liu-Yang , Fu Yi-Cheng , Zhang Yu , Chen Xi , Huang Yun , Li Yang 
Published: December 2017

AbstractThis study examines the interaction between hERG and Kv4.3. The functional interaction between hERG and Kv4.3, expressed in a heterologous cell line, was studied using patch clamp techniques, western blot, immunofluorescence, and co-immunoprecipitation. Co-expression of Kv4.3 with hERG increased hERG current density (tail current after a step to +10 mV: 26 ± 3 versus 56 ± 7 pA/pF, p < 0.01). Kv4.3 co-expression also increased the protein expression and promoted the membrane localization of hERG. Western blot showed Kv4.3 increased hERG expression by Hsp70. hERG and Kv4.3 co-localized and co-immunoprecipitated in cultured 293 T cells, indicating physical interactions between hERG and Kv4.3 proteins in vitro. In addition, Hsp70 interacted with hERG and Kv4.3 respectively, and formed complexes with hERG and Kv4.3. The α subunit of Ito Kv4.3 can interact with and modify the localization of the α subunit of IKr hERG, thus providing potentially novel insights into the molecular mechanism of the malignant ventricular arrhythmia in heart failure.
Earliest known lepisosteoid extends the range of anatomically modern gars to the Late Jurassic
Authors: Brito Paulo M. , Alvarado-Ortega Jésus , Meunier François J. 
Published: December 2017

AbstractLepisosteoids are known for their evolutionary conservatism, and their body plan can be traced at least as far back as the Early Cretaceous, by which point two families had diverged: Lepisosteidae, known since the Late Cretaceous and including all living species and various fossils from all continents, except Antarctica and Australia, and Obaichthyidae, restricted to the Cretaceous of northeastern Brazil and Morocco. Until now, the oldest known lepisosteoids were the obaichthyids, which show general neopterygian features lost or transformed in lepisosteids. Here we describe the earliest known lepisosteoid (Nhanulepisosteus mexicanus gen. and sp. nov.) from the Upper Jurassic (Kimmeridgian – about 157 Myr), of the Tlaxiaco Basin, Mexico. The new taxon is based on disarticulated cranial pieces, preserved three-dimensionally, as well as on scales. Nhanulepisosteus is recovered as the sister taxon of the rest of the Lepisosteidae. This extends the chronological range of lepisosteoids by about 46 Myr and of the lepisosteids by about 57 Myr, and fills a major morphological gap in current understanding the early diversification of this group.
Molecular cloning and functional characterisation of an H+-pyrophosphatase from Iris lactea
Authors: Meng Lin , Li Shanshan , Guo Jingya , Guo Qiang , Mao Peichun , Tian Xiaoxia 
Published: December 2017

AbstractTonoplast H+-pyrophosphatases (VPs) mediate vacuolar Na+ sequestration, a process important for salt tolerance of plants. The function of VP in the highly drought- and salt-tolerant perennial Iris lactea under salt stress is unclear. Here, we isolated IlVP from I. lactea and investigated its function in transgenic tobacco. IlVP was found to comprise 771 amino acid residues and showed 88% similarity with Arabidopsis AtVP1. IlVP was mainly expressed in shoots and was up-regulated by salt stress. Overexpression of IlVP enhanced growth of transgenic tobacco plants compared with wild-type (WT) plants exposed to salt stress. Transgenic plants accumulated higher quantities of Na+ and K+ in leaves, stems, and roots under salt stress, which caused higher leaf relative water content and decreased cell membrane damage compared with WT plants. Overall, IlVP encoding a tonoplast H+-pyrophosphatase can reduce Na+ toxicity in plant cells through increased sequestration of ions into vacuoles by enhanced H+-pyrophosphatase activity.
Increased plasma IL-17, IL-31, and IL-33 levels in chronic spontaneous urticaria
Authors: Lin Wei , Zhou Qiongyan , Liu Chunbo , Ying Mengxia , Xu Suling 
Published: December 2017

AbstractChronic spontaneous urticaria (CSU) is considered in a subset of patients to be an autoimmune disorder. Interleukin(IL)-17, IL-31, and IL-33 are involved in some immune response. The aim of this study was to quantify plasma IL-17, IL-31, and IL-33 levels in CSU patients and to examine their relationships with disease severity. Plasma IL-17, IL-31, and IL-33 concentration were measured in 51 CSU patients and 20 healthy subjects (HCs). Plasma IL-17 (P < 0.001), IL-31 (P < 0.001), and IL-33 (P < 0.001) concentrations were significantly higher in CSU patients when compared with those of HCs. Concerning UAS7, severe group of CSU patients had significantly higher IL-17 levels than the moderate and mild groups (P = 0.028 and 0.007, respectively), and significantly higher IL-33 concentrations than the mild group (P = 0.026). Regarding only pruritus, severe group of patients had significantly higher IL-31 levels than the mild group (P = 0.003). The IL-33 levels in the total IgE positive group were significantly higher than that of negative group (P = 0.010). Our results showed higher plasma levels of IL-17, IL-31, and IL-33 among CSU patients which may highlight a functional role of these cytokines in the pathogenesis of CSU.
Combined Effects of a Valgus Knee Brace and Lateral Wedge Insole on Walking in Patients with Medial Compartment Knee Osteoarthritis
Authors: Mirzaei Fatemeh , Arazpour Mokhtar , Baghei Roodsari Roshanak , Bahramizadeh Mahmood , Mardani Mohammad Ali 
Published: December 2017

ABSTRACT

Introduction
The use of a valgus knee brace and a lateral wedge foot orthosis in patients with knee osteoarthritis (OA) has been reported as a novel treatment strategy. The purpose of this study was to analyze the combined effect of laterally wedged inlay and knee brace on walking in volunteer subjects with medial compartment OA.

Materials and Methods
Eighteen subjects with symptomatic medial compartment knee OA participated in this study. Based on the treatment strategies, all subjects were divided into three groups: (1) lateral wedge insole, (2) valgus knee brace, and (3) both knee brace and foot orthosis. A Vicon digital motion capture system using eight cameras at a frequency of 100 Hz and two force platforms were used to capture data.

Results
In the lateral wedge group, a significant difference was observed in the knee adduction moment (KAM) with and without condition. In the valgus brace group, there was a significant difference in KAM, speed of walking, cadence, and knee joint range of motion (ROM) with and without intervention. In the valgus brace plus lateral wedge insole group, there was a significant difference in KAM and hip, knee, and ankle joints ROM.

Conclusions
The concurrent use of valgus knee brace and lateral wedge insole can produce a greater overall reduction in the KAM. The use of two types of orthoses, both separately and combined, did not improve the speed of walking, step length, and hip, knee, and ankle joints ROM in the affected side.
PICU Length of Stay: Factors Associated With Bed Utilization and Development of a Benchmarking Model
Authors: Pollack Murray M. , Holubkov Richard , Reeder Ron , Dean J. Michael , Meert Kathleen L. , Berg Robert A. , Newth Christopher J. L. , Berger John T. , Harrison Rick E. , Carcillo Joseph , Dalton Heidi , Wessel David L. , Jenkins Tammara L. , Tamburro Robert 
Published: December 2017

Objectives:
ICU length of stay is an important measure of resource use and economic performance. Our primary aims were to characterize the utilization of PICU beds and to develop a new model for PICU length of stay.

Design:
Prospective cohort. The main outcomes were factors associated with PICU length of stay and the performance of a regression model for length of stay.

Setting:
Eight PICUs.

Patients:
Randomly selected patients (newborn to 18 yr) from eight PICUs were enrolled from December 4, 2011, to April 7, 2013. Data consisted of descriptive, diagnostic, physiologic, and therapeutic information.

Interventions:
None.

Measurements and Main Results:
The mean length of stay for was 5.0 days (sd, 11.1), with a median of 2.0 days. The 50.6% of patients with length of stay less than 2 days consumed only 11.1% of the days of care, whereas the 19.6% of patients with length of stay 4.9–19 days and the 4.6% with length of stay greater than or equal to 19 days consumed 35.7% and 37.6% of the days of care, respectively. Longer length of stay was observed in younger children, those with cardiorespiratory disease, postintervention cardiac patients, and those who were sicker assessed by Pediatric Risk of Mortality scores receiving more intensive therapies. Patients in the cardiac ICU stayed longer than those in the medical ICU. The length of stay model using descriptive, diagnostic, severity, and therapeutic factors performed well (patient-level R-squared of 0.42 and institution-level R-squared of 0.76). Standardized (observed divided by expected) length of stay ratios at the individual sites ranged from 0.87 to 1.09.

Conclusions:
PICU bed utilization was dominated by a minority of patients. The 5% of patients staying the longest used almost 40% of the bed days. The multivariate length of stay model used descriptive, diagnostic, therapeutic, and severity factors and has potential applicability for internal and external benchmarking.
Alternative Fistula Risk Score for Pancreatoduodenectomy (a-FRS)
Authors: Mungroop Timothy H. , van Rijssen L. Bengt , van Klaveren David , Smits F. Jasmijn , van Woerden Victor , Linnemann Ralph J. , de Pastena Matteo , Klompmaker Sjors , Marchegiani Giovanni , Ecker Brett L. , van Dieren Susan , Bonsing Bert , Busch Olivier R. , van Dam Ronald M. , Erdmann Joris , van Eijck Casper H. , Gerhards Michael F. , van Goor Harry , van der Harst Erwin , de Hingh Ignace H. , de Jong Koert P. , Kazemier Geert , Luyer Misha , Shamali Awad , Barbaro Salvatore , Armstrong Thomas , Takhar Arjun , Hamady Zaed , Klaase Joost , Lips Daan J. , Molenaar I. Quintus , Nieuwenhuijs Vincent B. , Rupert Coen , van Santvoort Hjalmar C. , Scheepers Joris J. , van der Schelling George P. , Bassi Claudio , Vollmer Charles M. , Steyerberg Ewout W. , Abu Hilal Mohammed , Groot Koerkamp Bas , Besselink Marc G. 
Published: December 2017

Objective:
The aim of this study was to develop an alternative fistula risk score (a-FRS) for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy, without blood loss as a predictor.

Background:
Blood loss, one of the predictors of the original-FRS, was not a significant factor during 2 recent external validations.

Methods:
The a-FRS was developed in 2 databases: the Dutch Pancreatic Cancer Audit (18 centers) and the University Hospital Southampton NHS. Primary outcome was grade B/C POPF according to the 2005 International Study Group on Pancreatic Surgery (ISGPS) definition. The score was externally validated in 2 independent databases (University Hospital of Verona and University Hospital of Pennsylvania), using both 2005 and 2016 ISGPS definitions. The a-FRS was also compared with the original-FRS.

Results:
For model design, 1924 patients were included of whom 12% developed POPF. Three predictors were strongly associated with POPF: soft pancreatic texture [odds ratio (OR) 2.58, 95% confidence interval (95% CI) 1.80–3.69], small pancreatic duct diameter (per mm increase, OR: 0.68, 95% CI: 0.61–0.76), and high body mass index (BMI) (per kg/m2 increase, OR: 1.07, 95% CI: 1.04–1.11). Discrimination was adequate with an area under curve (AUC) of 0.75 (95% CI: 0.71–0.78) after internal validation, and 0.78 (0.74–0.82) after external validation. The predictive capacity of a-FRS was comparable with the original-FRS, both for the 2005 definition (AUC 0.78 vs 0.75, P = 0.03), and 2016 definition (AUC 0.72 vs 0.70, P = 0.05).

Conclusion:
The a-FRS predicts POPF after pancreatoduodenectomy based on 3 easily available variables (pancreatic texture, duct diameter, BMI) without blood loss and pathology, and was successfully validated for both the 2005 and 2016 POPF definition. The online calculator is available at www.pancreascalculator.com.
High-dimensional microbiome interactions shape host fitness
Authors: Gould Alison L. , Zhang Vivian , Lamberti Lisa , Jones Eric W. , Obadia Benjamin , Gavryushkin Alex , Korasidis Nikolaos , Carlson Jean M. , Beerenwinkel Niko , Ludington William B. 
Published: December 2017

AbstractGut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host in turn shapes the gut microbiome. Microbiomes co-evolve with their hosts and have been implicated in host speciation. However, it is unclear to what extent individual species versus community interactions within the microbiome are linked to host fitness. Here we combinatorially dissect the natural microbiome of Drosophila melanogaster and reveal that interactions between bacteria shape host fitness through life history tradeoffs. We find that the same microbial interactions that shape host fitness also shape microbiome abundances, suggesting a potential evolutionary mechanism by which microbiome communities (rather than just individual species) may be intertwined in co-selection with their hosts. Empirically, we made germ-free flies colonized with each possible combination of the five core species of fly gut bacteria. We measured the resulting bacterial community abundances and fly fitness traits including development, reproduction, and lifespan. The fly gut promoted bacterial diversity, which in turn accelerated development, reproduction, and aging: flies that reproduced more died sooner. From these measurements we calculated the impact of bacterial interactions on fly fitness by adapting the mathematics of genetic epistasis to the microbiome. Host physiology phenotypes were highly dependent on interactions between bacterial species. Higher-order interactions (involving 3, 4, and 5 species) were widely prevalent and impacted both host physiology and the maintenance of gut diversity. The parallel impacts of bacterial interactions on the microbiome and on host fitness suggest that microbiome interactions may be key drivers of evolution.SignificanceAll animals have associated microbial communities called microbiomes that can influence the physiology and fitness of their host. It is unclear to what extent individual microbial species versus ecology of the microbiome influences fitness of the host. Here we mapped all the possible interactions between individual species of bacteria with each other and with the host’s physiology. Our approach revealed that the same bacterial interactions that shape microbiome abundances also shape host fitness traits. This relationship provides a feedback that may favor the emergence of co-evolving microbiome-host units.
Study of mitotic chromatin supports a model of bookmarking by histone modifications and reveals nucleosome deposition patterns
Authors: Javasky Elisheva , Shamir Inbal , Gandhi Shashi , Egri Shawn , Sandler Oded , Rothbart Scott B. , Kaplan Noam , Jaffe Jacob D. , Goren Alon , Simon Itamar 
Published: December 2017

AbstractMitosis encompasses key molecular changes including chromatin condensation, nuclear envelope breakdown, and reduced transcription levels. Immediately after mitosis, the interphase chromatin structure is reestablished and transcription resumes. The reestablishment of the interphase chromatin is probably achieved by ‘bookmarking’,i.e., the retention of at least partial information during mitosis. Yet, while recent studies demonstrate that chromatin accessibility is generally preserved during mitosis and is only locally modulated, the exact details of the bookmarking process and its components are still unclear. To gain a deeper understanding of the mitotic bookmarking process, we merged proteomics, immunofluorescence, and ChIP-seq approaches to study the mitotic and interphase genomic organization of human cells. We focused on key histone modifications and employed HeLa-S3 cells as a model system. Generally, we observed a global concordance between the genomic organization of histone modifications in interphase and mitosis, yet the abundance of the two types of modifications we investigated was different. Whereas histone methylation patterns remain highly similar, histone acetylation patterns show a general reduction while maintaining their genomic organization. These results demonstrate that the epigenomic landscape can serve as a major component of the mitotic bookmarking process. Next, to further investigate mitosis-associated chromatin changes, we followed up on previous studies that showed that nucleosome depleted regions (NDRs) become occupied by a nucleosome during mitosis. Surprisingly, we observed that the nucleosome introduced into the NDR during mitosis encompasses a distinctive set of histone modifications, differentiating it from the surrounding nucleosomes. We show that the nucleosomes near the NDR appear to both shift into the NDR during mitosis and adopt a unique modification pattern. HDAC inhibition by the small molecule TSA reverts this pattern. These results provide evidence for a mitotic deposition and change in the modifications of the nucleosomes surrounding the NDR. Altogether, by merging multiple approaches, our study provides evidence to support a model where mitotic bookmarking is achieved by histone modifications and uncovers new insights into the deposition of nucleosomes during mitosis.