bluuebunny/crossref_metadata_2025_split huggingface dataset:
An LC-MS Approach to Quantitative Measurement of Ammonia Isotopologues
Authors: Spinelli Jessica B. , Kelley Liam P. , Haigis Marcia C. 
Published: August 2017

AbstractAmmonia is a fundamental aspect of metabolism spanning all of phylogeny. Metabolomics, including metabolic tracing studies, are an integral part of elucidating the role of ammonia in these systems. However, current methods for measurement of ammonia are spectrophotometric, and cannot distinguish isotopologues of ammonia, significantly limiting metabolic tracing studies. Here, we describe a novel LC-MS-based method that quantitatively assesses both 14N-and 15N-isotopologues of ammonia in polar metabolite extracts. This assay (1) quantitatively measures the concentration of ammonia in polar metabolite isolates used for metabolomic studies, and (2) accurately determines the percent isotope abundance of 15N-ammonia in a cell lysate for 15N-isotope tracing studies. We apply this assay to quantitatively measure glutamine-derived ammonia in lung cancer cell lines with differential expression of glutaminase.
Mott Transition and Magnetism in Rare Earth Nickelates and its Fingerprint on the X-ray Scattering
Authors: Haule Kristjan , Pascut Gheorghe L. 
Published: August 2017

AbstractThe metal-insulator transition (MIT) remains among the most thoroughly studied phenomena in solid state physics, but the complexity of the phenomena, which usually involves cooperation of many degrees of freedom including orbitals, fluctuating local moments, magnetism, and the crystal structure, have resisted predictive ab-initio treatment. Here we develop ab-initio theoretical method for correlated electron materials, based on Dynamical Mean Field Theory, which can predict the change of the crystal structure across the MIT at finite temperature. This allows us to study the coupling between electronic, magnetic and orbital degrees of freedom with the crystal structure across the MIT in rare-earth nickelates. We predict the electronic free energy profile of the competing states, and the theoretical magnetic ground state configuration, which is in agreement with neutron scattering data, but is different from the magnetic models proposed before. The resonant elastic X-ray response at the K-edge, which was argued to be a probe of the charge order, is theoretically modelled within the Dynamical Mean Field Theory, including the core-hole interaction. We show that the line-shape of the measured resonant elastic X-ray response can be explained with the “site-selective” Mott scenario without real charge order on Ni sites.
Controlling Directed Protein Interaction Networks in Cancer
Authors: Kanhaiya Krishna , Czeizler Eugen , Gratie Cristian , Petre Ion 
Published: August 2017

AbstractControl theory is a well-established approach in network science, with applications in bio-medicine and cancer research. We build on recent results for structural controllability of directed networks, which identifies a set of driver nodes able to control an a-priori defined part of the network. We develop a novel and efficient approach for the (targeted) structural controllability of cancer networks and demonstrate it for the analysis of breast, pancreatic, and ovarian cancer. We build in each case a protein-protein interaction network and focus on the survivability-essential proteins specific to each cancer type. We show that these essential proteins are efficiently controllable from a relatively small computable set of driver nodes. Moreover, we adjust the method to find the driver nodes among FDA-approved drug-target nodes. We find that, while many of the drugs acting on the driver nodes are part of known cancer therapies, some of them are not used for the cancer types analyzed here; some drug-target driver nodes identified by our algorithms are not known to be used in any cancer therapy. Overall we show that a better understanding of the control dynamics of cancer through computational modelling can pave the way for new efficient therapeutic approaches and personalized medicine.
Increased incidence of cytomegalovirus coinfection in HCV-infected patients with late liver fibrosis is associated with dysregulation of JAK-STAT pathway
Authors: Ibrahim Marwa K. , Khedr Ahmed , Bader El Din Noha G. , Khairy Ahmed , El Awady Mostafa K. 
Published: August 2017

AbstractHerein, we examined the association between cytomegalovirus (CMV) coinfection and the progression of liver fibrosis in hepatitis C virus (HCV) infection, and investigated the effect of CMV coinfection on JAK-STAT pathway. CMV DNAemia was detected by PCR in DNA from controls (n = 120), and HCV patients with early (F0-F1, n = 131) and late (F2-F4, n = 179) liver fibrosis. By quantitative real time PCR (qRT-PCR), we examined the profile of 8 JAK-STAT transcripts in PBMCs RNA from 90 HCV patients (39 CMV positive and 51 CMV negative), 4 CMV mono-infected patients, and 15 controls. Our results demonstrated higher incidence of CMV in F2-F4 group than in control (OR 5.479, 95% CI 3.033–9.895, p < 0.0001) or F0-F1 groups (OR 2, 95% CI 1.238–3.181, p = 0.005). qRT-PCR showed downregulation of STAT2 (p = 0.006) and IRF7 (p = 0.02) in CMV positive group compared to CMV negative one. The downregulation of STAT2 and IRF7 was mainly in CMV positive patients with late fibrosis compared to CMV negative patients (p = 0.0007 for IRF7 and p = 0.01 for STAT2). Our results are the first to report that CMV coinfection is a possible risk factor for the progression of HCV-induced liver fibrosis, and thereby CMV screening and treatment are important for HCV patients.
HMGB1/Advanced Glycation End Products (RAGE) does not aggravate inflammation but promote endogenous neural stem cells differentiation in spinal cord injury
Authors: Wang Hongyu , Mei Xifan , Cao Yang , Liu Chang , Zhao Ziming , Guo Zhanpeng , Bi Yunlong , Shen Zhaoliang , Yuan Yajiang , Guo Yue , Song Cangwei , Bai Liangjie , Wang Yansong , Yu Deshui 
Published: August 2017

AbstractReceptor for advanced glycation end products (RAGE) signaling is involved in a series of cell functions after spinal cord injury (SCI). Our study aimed to elucidate the effects of RAGE signaling on the neuronal recovery after SCI. In vivo, rats were subjected to SCI with or without anti-RAGE antibodies micro-injected into the lesion epicenter. We detected Nestin/RAGE, SOX-2/RAGE and Nestin/MAP-2 after SCI by Western blot or immunofluorescence (IF). We found that neural stem cells (NSCs) co-expressed with RAGE were significantly activated after SCI, while stem cell markers Nestin and SOX-2 were reduced by RAGE blockade. We found that RAGE inhibition reduced nestin-positive NSCs expressing MAP-2, a mature neuron marker. RAGE blockade does not improve neurobehavior Basso, Beattie and Bresnahan (BBB) scores; however, it damaged survival of ventral neurons via Nissl staining. Through in vitro study, we found that recombinant HMGB1 administration does not lead to increased cytokines of TNF-α and IL-1β, while anti-RAGE treatment reduced cytokines of TNF-α and IL-1β induced by LPS via ELISA. Meanwhile, HMGB1 increased MAP-2 expression, which was blocked after anti-RAGE treatment. Hence, HMGB1/RAGE does not exacerbate neuronal inflammation but plays a role in promoting NSCs differentiating into mature neurons in the pathological process of SCI.
Allelic variation of the rice blast resistance gene Pid3 in cultivated rice worldwide
Authors: Lv Qiming , Huang Zhiyuan , Xu Xiao , Tang Li , Liu Hai , Wang Chunchao , Zhou Zhuangzhi , Xin Yeyun , Xing Junjie , Peng Zhirong , Li Xiaobing , Zheng Tianqing , Zhu Lihuang 
Published: August 2017

AbstractIn this study, the re-sequencing data from 3,000 rice genomes project (3 K RGP) was used to analyze the allelic variation at the rice blast resistance (R) Pid3 locus. A total of 40 haplotypes were identified based on 71 nucleotide polymorphic sites among 2621 Pid3 homozygous alleles in the 3k genomes. Pid3 alleles in most japonica rice accessions were pseudogenes due to premature stop mutations, while those in most indica rice accessions were identical to the functional haplotype Hap_6, which had a similar resistance spectrum as the previously reported Pid3 gene. By sequencing and CAPS marker analyzing the Pid3 alleles in widespread cultivars in China, we verified that Hap_6 had been widely deployed in indica rice breeding of China. Thus, we suggest that the priority for utilization of the Pid3 locus in rice breeding should be on introducing the functional Pid3 alleles into japonica rice cultivars and the functional alleles of non-Hap_6 haplotypes into indica rice cultivars for increasing genetic diversity.
Two loci single particle trajectories analysis: constructing a first passage time statistics of local chromatin exploration
Authors: Shukron Ofir , Hauer Michael , Holcman David 
Published: August 2017

AbstractStochastic single particle trajectories are used to explore the local chromatin organization. We present here a statistical analysis of the first contact time distributions between two tagged loci recorded experimentally. First, we extract the association and dissociation times from data for various genomic distances between loci, and we show that the looping time occurs in confined nanometer regions. Second, we characterize the looping time distribution for two loci in the presence of multiple DNA damages. Finally, we construct a polymer model, that accounts for the local chromatin organization before and after a double-stranded DNA break (DSB), to estimate the level of chromatin decompaction. This novel passage time statistics method allows extracting transient dynamic at scales varying from one to few hundreds of nanometers, it predicts the local changes in the number of binding molecules following DSB and can be used to characterize the local dynamic of the chromatin.
Simultaneous multi-band valley-protected topological edge states of shear vertical wave in two-dimensional phononic crystals with veins
Authors: Huo Shao-yong , Chen Jiu-jiu , Huang Hong-bo , Huang Guo-liang 
Published: August 2017

AbstractThe introduction of the concept of valley pseudospin to phononic crystals has made a remarkable topologically protected interface transport of sound, which opens a novel research area referred to as valley Hall topological insulators. Here, we demonstrate the simultaneous multi-band edge states of shear vertical waves in two-dimensional phononic crystals with veins. The multi-band edge states are topologically valley-protected and are obtained by simultaneously gapping multiple Dirac points at K (or K′) under the inversion symmetry breaking. As the relative radius of the two adjacent steel columns varies, the band diagram undergoes a topological transition which can be characterized by topological charge distributions and opposite valley Chern numbers. Subsequently, the vortex chirality of the bulk valley modes is unveiled. With numerical simulations, simultaneous multi-band valley dependent edge states and the associated valley-protected backscattering suppression around the curved waveguide are further demonstrated. Our work could become a promising platform for applications of multi-functional topological acoustic devices.
Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease
Authors: Minter Myles R. , Hinterleitner Reinhard , Meisel Marlies , Zhang Can , Leone Vanessa , Zhang Xiaoqiong , Oyler-Castrillo Paul , Zhang Xulun , Musch Mark W. , Shen Xunuo , Jabri Bana , Chang Eugene B. , Tanzi Rudolph E. , Sisodia Sangram S. 
Published: August 2017

AbstractRecent evidence suggests the commensal microbiome regulates host immunity and influences brain function; findings that have ramifications for neurodegenerative diseases. In the context of Alzheimer’s disease (AD), we previously reported that perturbations in microbial diversity induced by life-long combinatorial antibiotic (ABX) selection pressure in the APPSWE/PS1ΔE9 mouse model of amyloidosis is commensurate with reductions in amyloid-β (Aβ) plaque pathology and plaque-localised gliosis. Considering microbiota-host interactions, specifically during early post-natal development, are critical for immune- and neuro-development we now examine the impact of microbial community perturbations induced by acute ABX exposure exclusively during this period in APPSWE/PS1ΔE9 mice. We show that early post-natal (P) ABX treatment (P14-P21) results in long-term alterations of gut microbial genera (predominantly Lachnospiraceae and S24-7) and reduction in brain Aβ deposition in aged APPSWE/PS1ΔE9 mice. These mice exhibit elevated levels of blood- and brain-resident Foxp3+ T-regulatory cells and display an alteration in the inflammatory milieu of the serum and cerebrospinal fluid. Finally, we confirm that plaque-localised microglia and astrocytes are reduced in ABX-exposed mice. These findings suggest that ABX-induced microbial diversity perturbations during post-natal stages of development coincide with altered host immunity mechanisms and amyloidosis in a murine model of AD.
Tumor-infiltrating CD45RO+ Memory T Lymphocytes Predict Favorable Clinical Outcome in Solid Tumors
Authors: Hu Guoming , Wang Shimin 
Published: August 2017

AbstractThe prognostic role of tumor-infiltrating CD45RO+ memory T lymphocytes (CD45RO+ T cells) in human solid tumors remains controversial. Herein, we conducted a meta-analysis including 25 published studies with 4720 patients identified from PubMed and EBSCO to assess the prognostic impact of tumor-infiltrating CD45RO+ T cells in human solid tumors. We found that CD45RO+ T cell infiltration was significantly associated with improved overall survival (OS) and disease-free survival (DFS) in all types of solid tumors. In stratified analyses, CD45RO+ T cell infiltration significantly improved 1-year, 3-year and 5-year OS in colorectal, gastric and esophageal cancer, but only 5-year OS in hepatocellular carcinoma. And these cells were positively associated with 1-year, 3-year and 5-year DFS in hepatocellular, colorectal and esophageal cancer. In addition, high density of intratumoral CD45RO+ T cells inversely correlated with TNM stage of solid tumor. In conclusion, CD45RO+ memory T lymphocyte infiltration leads to a favorable clinical outcome in solid tumors, implicating that it is a valuable biomarker for prognostic prediction for human solid malignances.
Identification and targeting of an FGFR fusion in a pediatric thalamic “central oligodendroglioma”
Authors: Linzey Joseph R. , Marini Bernard , McFadden Kathryn , Lorenzana Adonis , Mody Rajen , Robertson Patricia L. , Koschmann Carl 
Published: August 2017

AbstractApproximately 1–5% of pediatric intracranial tumors originate in the thalamus. While great strides have been made to identify consistent molecular markers in adult oligodendrogliomas, such as the 1p/19q co-deletion, it is widely recognized that pediatric oligodendrogliomas have a vastly different molecular make-up. While pediatric thalamic or “central oligodendrogliomas” are histologically similar to peripheral pediatric oligodendrogliomas, they are behaviorally distinct and likely represent a cohesive, but entirely different entity. We describe a case of a 10-year-old girl who was diagnosed with an anaplastic glioma with features consistent with the aggressive entity often diagnosed as central or thalamic oligodendroglioma. We performed whole-exome (paired tumor and germline DNA) and transcriptome (tumor RNA) sequencing, which demonstrated an FGFR3-PHGDH fusion. We describe this fusion and our rationale for pursuing personalized, targeted therapy for the patient’s tumor that may potentially play a role in the treatment of similar cases.
Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume
Authors: Davis E G , Humphreys K L , McEwen L M , Sacchet M D , Camacho M C , MacIsaac J L , Lin D T S , Kobor M S , Gotlib I H 
Published: August 2017

AbstractNumerous studies have linked exposure to stress to adverse health outcomes through the effects of cortisol, a product of the stress response system, on cellular aging processes. Accelerated DNA methylation age is a promising epigenetic marker associated with stress and disease risk that may constitute a link from stress response to changes in neural structures. Specifically, elevated glucocorticoid signaling likely contributes to accelerating DNA methylation age, which may signify a maladaptive stress-related cascade that leads to hippocampal atrophy. We examined the relations among diurnal cortisol levels, DNA methylation age and hippocampal volume in a longitudinal study of 46 adolescent girls. We computed area under the curve from two daily cortisol collection periods, and calculated DNA methylation age using previously established methods based on a set of CpG sites associated with chronological age. We computed a residual score by partialling out chronological age; higher discrepancies reflect relatively accelerated DNA methylation age. We assessed hippocampal volume via T1-weighted images and automated volumetric segmentation. We found that greater diurnal cortisol production was associated with accelerated DNA methylation age, which in turn was associated with reduced left hippocampal volume. Finally, accelerated DNA methylation age significantly mediated the association between diurnal cortisol and left hippocampal volume. Thus, accelerated DNA methylation age may be an epigenetic marker linking hypothalamic–pituitary–adrenal axis dysregulation with neural structure. If these findings are replicated, the current study provides a method for advancing our understanding of mechanisms by which glucocorticoid signaling is associated with cellular aging and brain development.
Polarized radiative transfer modeling of warped and clumpy dusty tori
Authors: Marin F. , Schartmann M. 
Published: August 2017

Context.Active galactic nuclei (AGN) are anisotropic objects surrounded by an optically thick equatorial medium whose true geometry still defies observers.Aims.We aim to explore the optical scattering-induced polarization that emerges from clumpy and warped dusty tori to check whether they can fit the unified model predictions.Methods.We ran polarized radiative transfer simulations in a set of warped and non-warped clumpy tori to explore the differences induced by distorted dust distributions. We then included warped tori in a more complex model representative of an AGN to check, using polarimetry and imaging methods, whether warps can reproduce the expected polarization dichotomy between Seyfert-I and Seyfert-II AGN.Results.The main results from our simulations highlight that isolated warped structures imprint the polarization degree and angle with distinctive signatures at Seyfert-I orientations. Included in an AGN model, the signatures of warps are easily (but not always) washed out by multiple scattering in a clumpy environment. Imaging polarimetry may help to detect warped tori, but we prove that warps can exist in AGN circumnuclear regions without contradicting observations.Conclusions.Two warped tori with a non-significant difference in geometry in terms of photometry or spectroscopy can have entirely different signatures in polarimetry. Testing the geometry of any alternative model to the usual dusty torus using polarized radiative transfer is a necessary approach to verify or reject a hypothesis.
Medical Termination of Delayed Miscarriage: Four-Year Experience with an Outpatient Protocol
Authors: Lyra Joana , Cavaco-Gomes João , Moucho Marina , Montenegro Nuno 
Published: August 2017

Purpose To evaluate the efficacy of an outpatient protocol with vaginal misoprostol to treat delayed miscarriage.
Methods Retrospective analysis of prospectively collected data on women medically treated for missed abortion with an outpatient protocol. The inclusion criteria were: ultrasound-based diagnosis of missed abortion with less than 10 weeks; no heavy bleeding, infection, inflammatory bowel disease or misoprostol allergy; no more than 2 previous spontaneous abortions; the preference of the patient regarding the medical management. The protocol consisted of: 1) a single dose of 800 µg of misoprostol administered intravaginally at the emergency department, after which the patients were discharged home; 2) clinical and ultrasonographic evaluation 48 hours later – if the intrauterine gestational sac was still present, the application of 800 µg of vaginal misoprostol was repeated, and the patients were discharged home; 3) clinical and ultrasonography evaluation 7 days after the initiation of the protocol – if the intrauterine gestational sac was still present, surgical management was proposed. The protocol was introduced in January 2012. Every woman received oral analgesia and written general recommendations. We also gave them a paper form to be presented and filled out at each evaluation.
Results Complete miscarriage with misoprostol occurred in 340 women (90.2%). Surgery was performed in 37 (9.8%) patients, representing the global failure rate of the protocol. Miscarriage was completed after the first misoprostol administration in 208 (55.2%) women, with a success rate after the second administration of 78.1% (132/169). The average age of the women with complete resolution using misoprostol was superior to the average age of those who required surgery (33.99 years versus 31.74 years; p = 0.031). Based on the ultrasonographic findings in the first evaluation, the women diagnosed with fetal loss achieved greater success rates compared with those diagnosed with empty sac (p = 0.049).
Conclusions We conclude this is an effective and safe option in the majority of delayed miscarriage cases during the first trimester, reducing surgical procedures and their consequences.
Cerebral Microdialysis: Going Deep into Brain Biochemistry for a Better Understanding of Pathomechanisms of Acute Brain Injury
Authors: Gupta Deepak , Mazzeo Anna 
Published: August 2017

AbstractPatients with traumatic brain injury (TBI) have variable outcomes subject to intracranial hypertension, ischemia, hypotension, and various biochemical alterations. Multimodality neurointensive monitoring is standard of care for decision making in all severe TBI cases at present in most neurotrauma units. Neuromonitoring tools, such as cerebral microdialysis, may contribute to understanding the pathomechanisms of acute brain injury, provide an early warning of secondary cerebral deterioration (therapeutic window of opportunity), and help in selecting the patients most suitable to benefit from this very invasive surgical rescue therapy. Cerebral microdialysis can be used as a measure of the effect of decompressive craniectomy on neurochemistry derangement and brain energy crisis jeopardizing the injured brain. Present review discusses the cerebral microdialysis, its usefulness, and role in prognostication of severe TBIs, especially in patients post-decompressive craniectomy. The authors also discuss the current consensus guidelines on usage of cerebral microdialysis in TBI patients.