bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barcode extension for analysis and reconstruction of structures
Authors: Myhrvold Cameron , Baym Michael , Hanikel Nikita , Ong Luvena L , Gootenberg Jonathan S , Yin Peng 
Published: March 2017

AbstractCollections of DNA sequences can be rationally designed to self-assemble into predictable three-dimensional structures. The geometric and functional diversity of DNA nanostructures created to date has been enhanced by improvements in DNA synthesis and computational design. However, existing methods for structure characterization typically image the final product or laboriously determine the presence of individual, labelled strands using gel electrophoresis. Here we introduce a new method of structure characterization that uses barcode extension and next-generation DNA sequencing to quantitatively measure the incorporation of every strand into a DNA nanostructure. By quantifying the relative abundances of distinct DNA species in product and monomer bands, we can study the influence of geometry and sequence on assembly. We have tested our method using 2D and 3D DNA brick and DNA origami structures. Our method is general and should be extensible to a wide variety of DNA nanostructures.
Plasma-free amino acid profiles are predictors of cancer and diabetes development
Authors: Bi X , Henry C J 
Published: March 2017

AbstractType 2 diabetes (T2D) and cancers are two major causes of morbidity and mortality worldwide. Nowadays, there is convincing evidence of positive associations between T2D and the incidence or prognosis of a wide spectrum of cancers, for example, breast, colon, liver and pancreas. Many observational studies suggest that certain medications used to treat hyperglycemia (or T2D) may affect cancer cells directly or indirectly. The potential mechanisms of the direct T2D cancer links have been hypothesized to be hyperinsulinemia, hyperglycemia and chronic inflammation; however, the metabolic pathways that lead to T2D and cancers still remain elusive. Plasma-free amino acid (PFAA) profiles have been highlighted in their associations with the risks of developing T2D and cancers in individuals with different ethnic groups and degree of obesity. The alterations of PFAAs might be predominately caused by the metabolic shift resulted from insulin resistance. The underlying mechanisms have not been fully elucidated, in particular whether the amino acids are contributing to these diseases development in a causal manner. This review addresses the molecular and clinical associations between PFAA alterations and both T2D and cancers, and interprets possible mechanisms involved. Revealing these interactions and mechanisms may improve our understanding of the complex pathogenesis of diabetes and cancers and improve their treatment strategies.
Insomnia and somnolence in idiopathic RBD: a prospective cohort study
Authors: Postuma Ronald B. , Gagnon Jean-François , Pelletier Amelie , Montplaisir Jacques Y. 
Published: March 2017

AbstractAlthough some sleep disorders are markers of prodromal Parkinson’s disease and dementia with Lewy bodies, it is unclear whether insomnia and somnolence can predict disease. We assessed a large cohort of patients with idiopathic rapid eye movement sleep behavior disorder and age/sex matched controls, comparing the Epworth sleepiness scale, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, and polysomnographic variables. In those with repeated scales, we assessed change over time. Finally, we assessed whether sleep abnormalities predicted defined neurodegenerative disease. The 151 patients (age = 65.9, 75% male) completed sleep scales and were included. Epworth scores were similar between patients and controls (7.0+/−4.6 vs. 7.2+/−4.7, p = 0.77), and did not progress with time (change = +0.46+/−2.1, p = 0.45). Epworth scores were similar between those who developed neurodegenerative disease and those remaining disease-free (6.7+/−4.4 vs. 7.1+/−4.7, p = 0.70). Pittsburgh Index scores were higher in patients than controls (7.2+/−3.8 vs. 4.9+/−3.4, p = 0.004), mainly driven by the sleep disturbance/medication components (reflecting rapid eye movement sleep behavior disorder symptoms/treatment). Baseline Pittsburgh scores did not predict conversion to neurodegeneration, although sleep duration increased over time in those converting to neurodegenerative disease (+0.88+/−1.32 h, p = 0.014). Insomnia index scores were higher in patients than controls (10.0+/−5.5 vs. 6.35+/−4.66, p < 0.001), but declined over time (−1.43+/−5.09, p = 0.029) particularly in those converting to neurodegenerative disease. Finally, on polysomnogram, those with increased tonic rapid eye movement had higher risk of developing defined neurodegenerative disease (HR = 1.88, p = 0.039). In summary, we found that somnolence and insomnia do not predict neurodegeneration in idiopathic rapid eye movement sleep behavior disorder. As neurodegeneration progresses through prodromal stages, patients may have increasing sleep drive and duration.
Integrating personalized gene expression profiles into predictive disease-associated gene pools
Authors: Menche Jörg , Guney Emre , Sharma Amitabh , Branigan Patrick J. , Loza Matthew J. , Baribaud Frédéric , Dobrin Radu , Barabási Albert-László 
Published: March 2017

AbstractGene expression data are routinely used to identify genes thaton averageexhibit different expression levels between a case and a control group. Yet, very few of such differentially expressed genes are detectably perturbed in individual patients. Here, we develop a framework to constructpersonalizedperturbation profiles for individual subjects, identifying the set of genes that are significantly perturbed in each individual. This allows us to characterize the heterogeneity of the molecular manifestations of complex diseases by quantifying the expression-level similarities and differences among patients with the same phenotype. We show that despite the high heterogeneity of the individual perturbation profiles, patients with asthma, Parkinson and Huntington’s disease share a broadpool of sporadically disease-associated genes, and that individuals with statistically significant overlap with this pool have a 80–100% chance of being diagnosed with the disease. The developed framework opens up the possibility to apply gene expression data in the context of precision medicine, with important implications for biomarker identification, drug development, diagnosis and treatment.
Galactose and its Metabolites Deteriorate Metaphase II Mouse Oocyte Quality and Subsequent Embryo Development by Disrupting the Spindle Structure
Authors: Thakur Mili , Shaeib Faten , Khan Sana N. , Kohan-Ghadr Hamid-Reza , Jeelani Roohi , Aldhaheri Sarah R. , Gonik Bernard , Abu-Soud Husam M. 
Published: March 2017

AbstractPremature ovarian insufficiency (POI) is a frequent long-term complication of classic galactosemia. The majority of women with this disorder develop POI, however rare spontaneous pregnancies have been reported. Here, we evaluate the effect of D-galactose and its metabolites, galactitol and galactose 1-phosphate, on oocyte quality as well as embryo development to elucidate the mechanism through which these compounds mediate oocyte deterioration. Metaphase II mouse oocytes (n = 240), with and without cumulus cells (CCs), were exposed for 4 hours to D-galactose (2 μM), galactitol (11 μM) and galactose 1-phosphate (0.1 mM), (corresponding to plasma concentrations in patients on galactose-restricted diet) and compared to controls. The treated oocytes showed decreased quality as a function of significant enhancement in production of reactive oxygen species (ROS) when compared to controls. The presence of CCs offered no protection, as elevated ROS was accompanied by increased apoptosis of CCs. Our results suggested that D-galactose and its metabolites disturbed the spindle structure and chromosomal alignment, which was associated with significant decline in oocyte cleavage and blastocyst development after in-vitro fertilization. The results provide insight into prevention and treatment strategies that may be used to extend the window of fertility in these patients.
Effect of vertically oriented few-layer graphene on the wettability and interfacial reactions of the AgCuTi-SiO2f/SiO2 system
Authors: Sun Z. , Zhang L. X. , Qi J. L. , Zhang Z. H. , Hao T. D. , Feng J. C. 
Published: March 2017

AbstractWith the aim of expanding their applications, particularly when joining metals, a simple but effective method is reported whereby the surface chemical reactivity of SiO2f/SiO2 (SiO2f/SiO2 stands for silica fibre reinforced silica based composite materials and f is short for fibre) composites with vertically oriented few-layer graphene (VFG, 3–10 atomic layers of graphene vertically oriented to the substrate) can be tailored. VFG was uniformly grown on the surface of a SiO2f/SiO2 composite by using plasma enhanced chemical vapour deposition (PECVD). The wetting experiments were conducted by placing small pieces of AgCuTi alloy foil on SiO2f/SiO2 composites with and without VFG decoration. It was demonstrated that the contact angle dropped from 120° (without VFG decoration) to 50° (with VFG decoration) when the holding time was 10 min. The interfacial reaction layer in SiO2f/SiO2 composites with VFG decoration became continuous without any unfilled gaps compared with the composites without VFG decoration. High-resolution transmission electron microscopy (HRTEM) was employed to investigate the interaction between VFG and Ti from the AgCuTi alloy. The results showed that VFG possessed high chemical reactivity and could easily react with Ti even at room temperature. Finally, a mechanism of how VFG promoted the wetting of the SiO2f/SiO2 composite by the AgCuTi alloy is proposed and thoroughly discussed.
Association between the MIF-173G/C Polymorphism and Serum MIF levels with Pulmonary Tuberculosis: A Meta-analysis
Authors: Tong Xiang , Yan Zhipeng , Zhou Qilong , Liu Sitong , Han Jing , Ma Yao , Yang Xue , Fan Hong 
Published: March 2017

AbstractMany studies have indicated thatMacrophage migration inhibitory factor (MIF)-173G/Cgene polymorphisms are associated with susceptibility to pulmonary tuberculosis (PTB). Additionally, some studies have suggested that there are higher levels of serum MIF in patients with PTB than the controls. However, the results of these studies were underpowered. The current study aimed to precisely evaluate the association between theMIF-173G/Cpolymorphism and serum MIF concentrations with PTB. Therefore, a systematic literature search was preformed to identify studies involving the indicated association. Eleven articles (1316 cases and 1272 controls) were included in the study. The results indicated that theMIF-173G/Cpolymorphism was significantly associated with PTB susceptibility, especially in Asians. Interestingly, the results further detected that circulating MIF levels were significantly higher in patients with PTB than in healthy controls, but this was only the case among Asians. Moreover, the statistical significance was also similar to that of the high quality group. The present study indicated that theMIF-173G/Cpolymorphism may contribute to the development of PTB. Furthermore, significantly higher serum MIF levels were observed in PTB patients than in controls, which further indicated that the MIF may play an important role in PTB progression, particularly in Asians.
Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials
Authors: Qian Li Jun , Gao Yao , Zhang Yan Mei , Chu Ming , Yao Jing , Xu Di 
Published: March 2017

AbstractProprotein convertase subtilisin/kexin9 monoclonal antibodies (PCSK9-mAb) have been studied intensively to identify their effect in lowering levels of low density lipoprotein cholesterol (LDL-C). However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases. Efficacy outcomes included parameter changes from baseline in LDL-C and other lipid levels. Therapeutic safety were evaluated by rates of common adverse events. A total of 15 studies encompassing 4,288 patients with at least 8 weeks duration were selected. Overall, the therapeutic efficacy was achieved with significant reduction in LDL-C, TC, TG, Lp(a), Apo-B versus placebo. The decline in familial hypercholesterolemia patients (−53.28%, 95% CI: −59.88 to −46.68%) was even more obvious than that in statin-intolerant patients (−34.95%, 95% CI: −41.46 to −28.45%). No obvious safety difference was found out in the rates of common and serious adverse events. To conclude, PCSK9-mAb contributes to the decreased level of LDL-C and other lipids in familial hypercholesterolemia and statin-intolerant patients with satisfactory safety and tolerability.
ELF5-Mediated AR Activation Regulates Prostate Cancer Progression
Authors: Li Kai , Guo Yongmin , Yang Xiong , Zhang Zhihong , Zhang Changwen , Xu Yong 
Published: March 2017

AbstractThe transcription factor E74-like factor 5 (ELF5) is a potent antioncogene that can prevent epithelial-mesenchymal transition (EMT) and metastasis in prostate cancer (PCa). However, little is known how it suppress the tumor growth and if it can interact with androgen receptor (AR). In this study, we find that the ELF5 is frequently expressed in AR activated PCa cells, where it binds to AR acting as a physiological partner and negatively regulates its transcriptional activity. In addition, the interaction between ELF5 and AR is androgen-dependent. Downregulation of ELF5 by shRNA increases the expression of AR-response genes and the progression of PCa. Moreover, ELF5 is a AR-dependent gene that its expression can be induced by androgen and suppressed by antiandrogen treatment. Notably, forced reduction of ELF5 in LNCaP cells facilitates the binding of AR to ARE in ELF5 gene and enabling its transcription, so that low level ELF5 can turn up its own expression by the negative feedback loop.
Worldwide circulation of HSV-2 × HSV-1 recombinant strains
Authors: Koelle David M. , Norberg Peter , Fitzgibbon Matthew P. , Russell Ronnie M. , Greninger Alex L. , Huang Meei-Li , Stensland Larry , Jing Lichen , Magaret Amalia S. , Diem Kurt , Selke Stacy , Xie Hong , Celum Connie , Lingappa Jairam R. , Jerome Keith R. , Wald Anna , Johnston Christine 
Published: March 2017

AbstractHomo sapiens harbor two distinct, medically significant species of simplexviruses, herpes simplex virus (HSV)-1 and HSV-2, with estimated divergence 6–8 million years ago (MYA). Unexpectedly, we found that circulating HSV-2 strains can contain HSV-1 DNA segments in three distinct genes. Using over 150 genital swabs from North and South America and Africa, we detected recombinants worldwide. Common, widely distributed gene UL39 genotypes are parsimoniously explained by an initial >457 basepair (bp) HSV-1 × HSV-2 crossover followed by back-recombination to HSV-2. Blocks of >244 and >539 bp of HSV-1 DNA within genes UL29 and UL30, respectively, have reached near fixation, with a minority of strains retaining sequences we posit as ancestral HSV-2. Our data add to previous in vitro and animal work, implying that in vivo cellular co-infection with HSV-1 and HSV-2 yields viable interspecies recombinants in the natural human host.
A Dual Pathogenic Mechanism Links Tau Acetylation to Sporadic Tauopathy
Authors: Trzeciakiewicz Hanna , Tseng Jui-Heng , Wander Connor M. , Madden Victoria , Tripathy Ashutosh , Yuan Chao-Xing , Cohen Todd J. 
Published: March 2017

AbstractTau acetylation has recently emerged as a dominant post-translational modification (PTM) in Alzheimer’s disease (AD) and related tauopathies. Mass spectrometry studies indicate that tau acetylation sites cluster within the microtubule (MT)-binding region (MTBR), suggesting acetylation could regulate both normal and pathological tau functions. Here, we combined biochemical and cell-based approaches to uncover a dual pathogenic mechanism mediated by tau acetylation. We show that acetylation specifically at residues K280/K281 impairs tau-mediated MT stabilization, and enhances the formation of fibrillar tau aggregates, highlighting both loss and gain of tau function. Full-length acetylation-mimic tau showed increased propensity to undergo seed-dependent aggregation, revealing a potential role for tau acetylation in the propagation of tau pathology. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds. Our study identifies a potential “two-hit” mechanism in which tau acetylation disengages tau from MTs and also promotes tau aggregation. Thus, therapeutic approaches to limit tau K280/K281 acetylation could simultaneously restore MT stability and ameliorate tau pathology in AD and related tauopathies.
MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies
Authors: Yin Kaifeng , Lin Wenting , Guo Jing , Sugiyama Toshihiro , Snead Malcolm L. , Hacia Joseph G. , Paine Michael L. 
Published: March 2017

AbstractAmelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.
CRISPR/Cas9-generated p47phox-deficient cell line for Chronic Granulomatous Disease gene therapy vector development
Authors: Wrona Dominik , Siler Ulrich , Reichenbach Janine 
Published: March 2017

AbstractDevelopment of gene therapy vectors requires cellular models reflecting the genetic background of a disease thus allowing for robust preclinical vector testing. For human p47phox-deficient chronic granulomatous disease (CGD) vector testing we generated a cellular model using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 to introduce a GT-dinucleotide deletion (ΔGT) mutation in p47phox encoding NCF1 gene in the human acute myeloid leukemia PLB-985 cell line. CGD is a group of hereditary immunodeficiencies characterized by impaired respiratory burst activity in phagocytes due to a defective phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In Western countries autosomal-recessive p47phox-subunit deficiency represents the second largest CGD patient cohort with unique genetics, as the vast majority of p47phox CGD patients carries ΔGT deletion in exon two of the NCF1 gene. The established PLB-985 NCF1 ΔGT cell line reflects the most frequent form of p47phox-deficient CGD genetically and functionally. It can be differentiated to granulocytes efficiently, what creates an attractive alternative to currently used iPSC models for rapid testing of novel gene therapy approaches.
Correlating Oxygen Evolution Catalysts Activity and Electronic Structure by a High-Throughput Investigation of Ni1-y-zFeyCrzOx
Authors: Schwanke Christoph , Stein Helge Sören , Xi Lifei , Sliozberg Kirill , Schuhmann Wolfgang , Ludwig Alfred , Lange Kathrin M. 
Published: March 2017

AbstractHigh-throughput characterization by soft X-ray absorption spectroscopy (XAS) and electrochemical characterization is used to establish a correlation between electronic structure and catalytic activity of oxygen evolution reaction (OER) catalysts. As a model system a quasi-ternary materials library of Ni1-y-zFeyCrzOx was synthesized by combinatorial reactive magnetron sputtering, characterized by XAS, and an automated scanning droplet cell. The presence of Cr was found to increase the OER activity in the investigated compositional range. The electronic structure of NiII and CrIII remains unchanged over the investigated composition spread. At the Fe L-edge a linear combination of two spectra was observed. These spectra were assigned to FeIII in Oh symmetry and FeIII in Td symmetry. The ratio of FeIII Oh to FeIII Td increases with the amount of Cr and a correlation between the presence of the FeIII Oh and a high OER activity is found.
Novel computational method for predicting polytherapy switching strategies to overcome tumor heterogeneity and evolution
Authors: Jonsson Vanessa D. , Blakely Collin M. , Lin Luping , Asthana Saurabh , Matni Nikolai , Olivas Victor , Pazarentzos Evangelos , Gubens Matthew A. , Bastian Boris C. , Taylor Barry S. , Doyle John C. , Bivona Trever G. 
Published: March 2017

AbstractThe success of targeted cancer therapy is limited by drug resistance that can result from tumor genetic heterogeneity. The current approach to address resistance typically involves initiating a new treatment after clinical/radiographic disease progression, ultimately resulting in futility in most patients. Towards a potential alternative solution, we developed a novel computational framework that uses human cancer profiling data to systematically identify dynamic, pre-emptive, and sometimes non-intuitive treatment strategies that can better control tumors in real-time. By studying lung adenocarcinoma clinical specimens and preclinical models, our computational analyses revealed that the best anti-cancer strategies addressed existing resistant subpopulations as they emerged dynamically during treatment. In some cases, the best computed treatment strategy used unconventional therapy switching while the bulk tumor was responding, a prediction we confirmed in vitro. The new framework presented here could guide the principled implementation of dynamic molecular monitoring and treatment strategies to improve cancer control.