bluuebunny/crossref_metadata_2025_split huggingface dataset:
HNRNPH1 is required for rhabdomyosarcoma cell growth and survival
Authors: Li Yanfeng , Bakke Jesse , Finkelstein David , Zeng Hu , Wu Jing , Chen Taosheng 
Published: January 2018

AbstractRhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer characterized by a muscle-like phenotype. Although the average 5-y survival rate is 65% for newly diagnosed RMS, the treatment options for metastatic disease are limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in RMS tumorigenesis, we investigated its expression and effect on growth in three cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1, growth of all cell lines was reduced, most likely through a combination of apoptosis and cell cycle arrest. We then recapitulated this finding by performing in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction of tumor formation and growth. We used RNA sequencing to identify changes in gene expression after HNRNPH1 knockdown and found altered splicing of some oncogenes. Our data contribute to understanding the role of HNRNPH1 in RMS development.
Statuses of food-derived glutathione in intestine, blood, and liver of rat
Authors: Yamada Hiroaki , Ono Shinn , Wada Sayori , Aoi Wataru , Park Eun Young , Nakamura Yasushi , Sato Kenji 
Published: January 2018

AbstractOral administration of glutathione has been demonstrated to reduce exercise-induced fatigue and improve liver function, although glutathione can be synthesized in the liver. However, little is known about the underlying mechanism of this effect. To address this, the status of food-derived glutathione in the intestine, blood, and liver was examined. Glutathione-1-13C or N-acetyl-cysteine-1-13C (NAC) was orally administered to rats (50 mg/kg). Food-derived glutathione contents within tissues were estimated by subtracting endogenous glutathione-1-13C from the total glutathione-1-13C. Food-derived glutathione was present in rat intestines and livers (approximately 60 and 300 μmol/kg, respectively, 120 min after ingestion) in electrochemically reduced form, while all food-derived glutathione in the blood plasma was conjugated with proteins and low-molecular-weight thiol compounds. However, no significant amounts of NAC-derived glutathione were detected in the blood plasma. These findings indicate that food-derived glutathione is directly absorbed in its electrochemically reduced form in the intestine, is then transported in the blood in bound forms, and is finally deposited into the liver in reduced form. Therefore, upon entering the bloodstream, food-derived glutathione binds to thiol compounds and releases hydrogen atom; subsequently, it does the reverse upon incorporation into the liver, which might impact the physiological redox condition. With respect to food-derived glutathione and cysteine-containing peptides, this study provides new insights on their modes of transportation and mechanisms of action.
Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions
Authors: Cairns I. H. , Lobzin V. V. , Donea A. , Tingay S. J. , McCauley P. I. , Oberoi D. , Duffin R. T. , Reiner M. J. , Hurley-Walker N. , Kudryavtseva N. A. , Melrose D. B. , Harding J. C. , Bernardi G. , Bowman J. D. , Cappallo R. J. , Corey B. E. , Deshpande A. , Emrich D. , Goeke R. , Hazelton B. J. , Johnston-Hollitt M. , Kaplan D. L. , Kasper J. C. , Kratzenberg E. , Lonsdale C. J. , Lynch M. J. , McWhirter S. R. , Mitchell D. A. , Morales M. F. , Morgan E. , Ord S. M. , Prabu T. , Roshi A. , Shankar N. Udaya , Srivani K. S. , Subrahmanyan R. , Wayth R. B. , Waterson M. , Webster R. L. , Whitney A. R. , Williams A. , Williams C. L. 
Published: January 2018

AbstractType III solar radio bursts are the Sun’s most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5–10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.
Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain
Authors: Kobayashi Eiji , Nakano Masako , Kubota Kenta , Himuro Nobuaki , Mizoguchi Shougo , Chikenji Takako , Otani Miho , Mizue Yuka , Nagaishi Kanna , Fujimiya Mineko 
Published: January 2018

AbstractAlthough the cognitive impairment in Alzheimer’s disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.
Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour model
Authors: Yoo Su Woong , Oh Gyungseok , Safi Abdul Mohaimen , Hwang Soonjoo , Seo Young-Seok , Lee Kyung-Hwa , Kim Young L. , Chung Euiheon 
Published: January 2018

AbstractColorectal cancer is one of the leading causes of cancer-related deaths. Although several therapeutic management strategies are available at the early colon cancer stages, such as endoscopic mucosal or submucosal dissection, associated complications often include bleeding or bowel perforations. As an alternative approach, we investigated endoscopic non-ablative fractional laser (eNAFL) irradiation as a minimally invasive therapeutic modality for the treatment of early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse model and demonstrated the early-stage tumour growth delay following the eNAFL irradiation. Additionally, we evaluated the temperature changes in the eNAFL-irradiated area using numerical simulations, and induced inflammation using histological analysis. Our results indicate a minimal thermal damage confined to the irradiated spot, sparing the adjacent tissue and alteration in the tumour microenvironment. eNAFL irradiation may be clinically useful as a minimally invasive therapeutic intervention at the early stage of tumourigenesis. In future, an optimal eNAFL therapeutic dose should be determined, in order to increase the efficacy of this approach.
A dynamic allosteric pathway underlies Rad50 ABC ATPase function in DNA repair
Authors: Boswell Zachary K. , Rahman Samiur , Canny Marella D. , Latham Michael P. 
Published: January 2018

AbstractThe Mre11-Rad50 protein complex is an initial responder to sites of DNA double strand breaks. Many studies have shown that ATP binding to Rad50 causes global changes to the Mre11-Rad50 structure, which are important for DNA repair functions. Here we used methyl-based NMR spectroscopy on a series of mutants to describe a dynamic allosteric pathway within Rad50. Mutations result in changes in the side chain methyl group chemical environment that are correlated with altered nanosecond timescale dynamics. We also observe striking relationships between the magnitude of chemical shift perturbations and Rad50 and Mre11 activities. Together, these data suggest an equilibrium between a ground state and an “active” dimerization competent state of Rad50 that has locally altered structure and dynamics and is poised for ATP-induced dimerization and eventual ATP hydrolysis. Thus, this sparsely populated intermediate is critical for Mre11-Rad50-directed DNA double strand break repair.
Fingerprint analysis of Huolingshengji Formula and its neuroprotective effects in SOD1G93A mouse model of amyotrophic lateral sclerosis
Authors: Zhou Qinming , Wang Youjie , Zhang Jingjing , Shao Yaping , Li Song , Wang Yuan , Cai Huaibin , Feng Yi , Le Weidong 
Published: January 2018

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive loss of motor neurons. There are no definitive pathogenic mechanisms and effective treatments for ALS now. Traditional Chinese medicine (TCM) plays an important role in Chinese health care system. Huolingshengji Formula (HLSJ) is a TCM formula which is applied for treating flaccid syndrome. Our previous clinical study has indicated that HLSJ may have therapeutic effects in ALS patients. In the present study, we analyzed the chemical profile of HLSJ by the high-performance liquid chromatographic (HPLC) fingerprint analysis. And we investigated the therapeutic effects and neuroprotective mechanisms of HLSJ against ALS in SOD1G93A mouse model. Eleven typical peaks were identified by the fingerprint analysis of HLSJ, and the HPLC method had good precision, repeatability and stability. Consistent with our clinical studies, HLSJ significantly prolonged the lifespan, extended the disease duration, and prevented the motor neuron loss in the anterior horn of the lumbar spinal cords in SOD1G93A ALS model mice. Additionally, HLSJ alleviated the atrophy of the gastrocnemius muscles and ameliorated the apoptotic and inflammatory levels in the spinal cords of SOD1G93A mice. Collectively, our study indicated that HLSJ might be a novel candidate for the treatment of ALS.
Birth weight and body mass index z-score in childhood brain tumors: A cross-sectional study
Authors: Wang Kuan-Wen , de Souza Russell J. , Fleming Adam , Johnston Donna L. , Zelcer Shayna M. , Rassekh Shahrad Rod , Burrow Sarah , Thabane Lehana , Samaan M. Constantine 
Published: January 2018

AbstractChildren with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the medical records. Body mass index (BMI) was calculated from height and weight measures and reported as kg/m2. BMI z-scores were obtained for subjects under the age of 20 years. Multivariable linear regression was used to evaluate the relationship between birth weight and BMI and BMI z-score, adjusted for age, sex, puberty, and fat mass percentage. Higher birth weight was associated with higher BMI and BMI z-score among CBT and controls. In conclusion, birth weight is a risk factor for higher body mass during childhood in CBT, and this may help the identification of children at risk of future obesity and cardiometabolic risk.
Characterization of Conformational Ensembles of Protonated N-glycans in the Gas-Phase
Authors: Re Suyong , Watabe Shigehisa , Nishima Wataru , Muneyuki Eiro , Yamaguchi Yoshiki , MacKerell Alexander D. , Sugita Yuji 
Published: January 2018

AbstractIon mobility mass spectrometry (IM-MS) is a technique capable of investigating structural changes of biomolecules based on their collision cross section (CCS). Recent advances in IM-MS allow us to separate carbohydrate isomers with subtle conformational differences, but the relationship between CCS and atomic structure remains elusive. Here, we characterize conformational ensembles of gas-phase N-glycans under the electrospray ionization condition using molecular dynamics simulations with enhanced sampling. We show that the separation of CCSs between isomers reflects folding features of N-glycans, which are determined both by chemical compositions and protonation states. Providing a physicochemical basis of CCS for N-glycans helps not only to interpret IM-MS measurements but also to estimate CCSs of complex glycans.
Structural changes in alginate-based microspheres exposed to in vivo environment as revealed by confocal Raman microscopy
Authors: Kroneková Zuzana , Pelach Michal , Mazancová Petra , Uhelská Lucia , Treľová Dušana , Rázga Filip , Némethová Veronika , Szalai Szabolcs , Chorvát Dušan , McGarrigle James J. , Omami Mustafa , Isa Douglas , Ghani Sofia , Majková Eva , Oberholzer José , Raus Vladimír , Šiffalovič Peter , Lacík Igor 
Published: January 2018

AbstractA next-generation cure for type 1 diabetes relies on immunoprotection of insulin-producing cells, which can be achieved by their encapsulation in microspheres made of non-covalently crosslinked hydrogels. Treatment success is directly related to the microsphere structure that is characterized by the localization of the polymers constituting the hydrogel material. However, due to the lack of a suitable analytical method, it is presently unknown how the microsphere structure changesin vivo, which complicates evaluation of different encapsulation approaches. Here, confocal Raman microscopy (CRM) imaging was tailored to serve as a powerful new tool for tracking structural changes in two major encapsulation designs, alginate-based microbeads and multi-component microcapsules. CRM analyses before implantation and after explantation from a mouse model revealed complete loss of the original heterogeneous structure in the alginate microbeads, making the intentionally high initial heterogeneity a questionable design choice. On the other hand, the structural heterogeneity was conserved in the microcapsules, which indicates that this design will better retain its immunoprotective propertiesin vivo. In another application, CRM was used for quantitative mapping of the alginate concentration throughout the microbead volume. Such data provide invaluable information about the microenvironment cells would encounter upon their encapsulation in alginate microbeads.
Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil: Population Pharmacokinetic Analysis in Healthy Volunteers
Authors: Kim Jae Hyun , Han Nayoung , Kim Myeong Gyu , Yun Hwi-Yeol , Lee Sunhwa , Bae Eunjin , Kim Yon Su , Kim In-Wha , Oh Jung Mi 
Published: January 2018

AbstractThe objective of the study was to investigate the pharmacokinetic drug-drug interactions between tacrolimus (TAC) and mycophenolate mofetil (MMF) in healthy Korean male volunteers. Seventeen volunteers participated in a three-period, single-dose, and fixed sequence study. They sequentially received MMF, TAC, and the combination. Concentrations of TAC, mycophenolic acid (MPA), and its metabolites MPA 7-O-glucuronide and MPA acyl glucuronide were measured. The variants of CYP3A4, CYP3A5, SLCO1B1, SLCO1B3, ABCC2, UGT1A9, and UGT2B7 were genotyped. Drug interaction was evaluated with a non-compartmental analysis and population pharmacokinetic modelling to quantify the interaction effect. A total of 1,082 concentrations of those analytes were analysed. AUC0-inf of TAC increased by 22.1% (322.4 ± 174.1 to 393.6 ± 121.7 ng·h/mL; P < 0.05) when co-administered with MMF, whereas the pharmacokinetic parameters of MPA and its metabolites were not changed by TAC. Apparent clearance (CL/F) of TAC was 17.8 L/h [relative standard error (RSE) 11%] or 13.8 L/h (RSE 11%) without or with MMF, respectively. Interaction was explained by the exponential model. The CYP3A5 genotype was the only significant covariate. The population estimate of CL/F of TAC was 1.48-fold (RSE 16%) in CYP3A5 expressers when compared to nonexpressers. CL/F of TAC was decreased when co-administered with MMF in these subjects.
A novel mouse model carrying a human cytoplasmic dynein mutation shows motor behavior deficits consistent with Charcot-Marie-Tooth type 2O disease
Authors: Sabblah Thywill T. , Nandini Swaran , Ledray Aaron P. , Pasos Julio , Calderon Jami L. Conley , Love Rachal , King Linda E. , King Stephen J. 
Published: January 2018

AbstractCharcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which axonal degeneration causes progressive loss of motor and sensory nerve function. The loss of motor nerve function leads to distal muscle weakness and atrophy, resulting in gait problems and difficulties with walking, running, and balance. A mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset and progression of CMT2, we generated a knock-in mouse carrying the corresponding CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+ mice displayed distal muscle weakness and loss of motor coordination phenotypes consistent with those of individuals with CMT2. Analysis of the gastrocnemius of H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ) morphology including reduced size, branching, and complexity. Based on these results, the H304R/+ mouse will be an important model for uncovering functions of dynein in complex organisms, especially related to CMT onset and progression.
Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts
Authors: Murray Ebony , Hills Peter J. , Bennetts Rachel J. , Bate Sarah 
Published: January 2018

AbstractDevelopmental prosopagnosia (DP) is characterised by a severe and relatively selective deficit in face recognition, in the absence of neurological injury. Because public and professional awareness of DP is low, many adults and children are not identified for formal testing. This may partly result from the lack of appropriate screening tools that can be used by non-experts in either professional or personal settings. To address this issue, the current study sought to (a) explore when DP can first be detected in oneself and another, and (b) identify a list of the condition’s everyday behavioural manifestations. Questionnaires and interviews were administered to large samples of adult DPs, their unaffected significant others, and parents of children with the condition; and data were analysed using inductive content analysis. It was found that DPs have limited insight into their difficulties, with most only achieving realisation in adulthood. Nevertheless, the DPs’ reflections on their childhood experiences, together with the parental responses, revealed specific indicators that can potentially be used to spot the condition in early childhood. These everyday hallmark symptoms may aid the detection of individuals who would benefit from objective testing, in oneself (in adults) or another person (for both adults and children).
Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores
Authors: Grossegesse Marica , Doellinger Joerg , Fritsch Annemarie , Laue Michael , Piesker Janett , Schaade Lars , Nitsche Andreas 
Published: January 2018

AbstractThe emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown. Therefore, for the first time, we analyzed globally ubiquitination sites in CPXV mature virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral proteins among five CPXV strains revealed extensive ubiquitination of structural core proteins. Moreover, since virions contained primarily K48-linked polyubiquitin, we hypothesized that core proteins are modified accordingly. However, quantitative analysis of ubiquitinated CPXV proteins early in infection showed no proteasomal degradation of core proteins. Instead, our data indicate that the recently suggested proteasomal regulation of the uncoating factor E5 is a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating and elucidating a multitude of novel ubiquitination sites in poxvirus proteins, the present study verifies the major biological significance of ubiquitin in poxvirus infection.
Complications endodontiques de l’Ostéotomie Le Fort I. À propos d’un cas clinique
Authors: TEBBEB Nesrine , AGUIR MABROUK Najet , BHOURI Lotfi 
Published: January 2018

L’ostéotomie Le Fort I est l’une des interventions
chirurgicales orthognatique les plus fréquentes.
Cette technique est facile à réaliser, et permet
de résoudre un grand nombre de problèmes
fonctionnels et esthétiques.
Malgré tous les progrès réalisés dans
le domaine de la chirurgie orthognatique
une variété de complications a été documentée.
Le clivage osseux au cours de l’acte chirurgical
est associé à un risque particulièrement élevé
d’ischémie.
Cet article illustre un cas de nécroses
pulpaires multiples du secteur incisivo
canin et prémolaire maxillaire à la suite
d’une osteotomie Le Fort I.