bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Cancer Computational Analysis Reveals Metastasis-Associated Variant of Desmoplastic Reaction Involving INHBA and THBS2
Authors: Kim Hoon , Watkinson John , Varadan Vinay , Anastassiou Dimitris 
Published: July 2019

AbstractDespite extensive research, the details of the metastasis-associated biological mechanisms are largely unknown. Here, we analyze data from multiple cancers using a novel computational method identifying sets of genes whose coordinated overexpression indicates the presence of a particular phenotype. We conclude that there is one shared “core” metastasis-associated gene expression signature corresponding to a specific variant of desmoplastic reaction, present in a large subset of samples that have exceeded a threshold of invasive transition specific to each cancer, indicating that the biological mechanism is triggered at that point. For example this threshold is reached at stage IIIc in ovarian cancer and at stage II in colorectal cancer. It has several features, such as coordinated expression of particular collagens, mainly COL11A1 and other genes, mainly THBS2 and INHBA. The universally prominent presence of INHBA in all cancers strongly suggests a biological mechanism centered on activin A induced TGF-β signaling, because activin A is a member of the TGF-β superfamily consisting of an INHBA homodimer. It is accompanied by the expression of several transcription factors related to epithelial-mesenchymal transition, but not of SNAI1, and expression of E-cadherin is not downregulated. It is reversible, as evidenced by its absence in many matched metastasized samples, but its presence indicates that metastasis has occurred. Therefore, these results can be used for developing high-specificity biomarkers, as well as potential multi-cancer metastasis-inhibiting therapeutics targeting the corresponding biological mechanism.
Vestibular stimulation reduces unrealistic optimism
Authors: Tamagni Corinne , Palla Antonella , Krummenacher Peter , Vitacco Deborah , Huberle Elisabeth , Straumann Dominik , Hegemann Stefan , McKay Ryan , Brugger Peter 
Published: July 2019

AbstractUnrealistic optimism (UO) refers to the tendency of healthy people to underestimate their risk of future misfortune. Just as left-ear caloric irrigation attenuates anosognosia (denial of manifest illness) in clinical patients, we found that it also reduces UO about future health risks in healthy individuals. This finding demonstrates asymmetric hemispheric involvement in emotion regulation and self-evaluation, and suggests that a similar neuropsychological process underpins anosognosia and healthy optimism.
Living unicellular eukaryote Tetrahymena pyriformis as a model for study of mitochondrial energetics in mammalian cells under conditions of reduced oxidative metabolism.
Authors: Mokhova Elena 
Published: July 2019

AbstractSome “animal-like” protozoa are used instead of mammalian cells in diverse investigations. Tetrahymena pyriformis cells in stationary phase of growth and washed from oxidative substrates (T.pyriformis) function under conditions of reduced oxidative metabolism. To elucidate if T.pyriformis can be applied as a model for mitochondrial energetics study in mammalian cells during hibernation, the features of T.pyriformis mitochondria were compared with that of liver mitochondria isolated from hibernating animals; the published earlier data were used. Based on the respiration recording and observation of Mito Tracker Red fluorescence in living T.pyriformis we tentatively concluded that the mitochondrial electrical membrane potential, Δψ, is low, and that the most part of the proton motive force is stored as the difference of pH between the sides of inner mitochondrial membrane. A sharp decrease of the maximal uncoupler-stimulated respiration rates was observed in the liver mitochondria isolated from hibernating animals. These and other data are explained by hypothesis that remodeling the liver mitochondria to a condense configuration is prerequisite for reduction of the oxidative metabolism. The rearrangement possibly resembles the apoptosis with the initial Δψ decrease induced by the respiratory activity suppression; the process has been earlier studied by E. Gotlieb and coauthors. The data suggest that T.pyriformis are suitable to study of some aspects of mitochondrial role in cellular adaptation to metabolic depression; that the evolutionary ancient mechanisms are conserved in a modified form in the ciliate and mammalian cells.
Computational Prediction and Analysis of the NAPP - DR6 Interaction: Implications for Alzheimer&apos;s Research
Authors: Audie Josheph , Ponomarev Sergei 
Published: July 2019

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder that involves a devastating clinical course and lacks an effective treatment. A biochemical model for neuronal development that might have implications for AD, recently proposed by Nikolaev and co-workers, hinges on a novel protein-protein interaction between the death cell receptor six (DR6) ectodomain and an N-terminal fragment of amyloid precursor protein (NAPP). The model provides a coherent and satisfying framework for better understanding AD pathophysiology. Moreover, the DR6-NAPP interaction offers a tempting target for novel pharmacological intervention. Given all of this, we constructed a structural model of the DR6-NAPP interaction using the neurotrophin p75 receptor as a template. Importantly, crucial steps in the modeling pipeline were independently validated using the p75 receptor. The final docked model shows excellent agreement with a variety of biophysical and theoretical data sets. Particularly worth noting is the excellent observed agreement between the theoretically calculated DR6-NAPP binding free energy and the corresponding experimental quantity. In brief, the balance of the evidence suggests that the DR6-NAPP model proposed here should prove useful in future studies, modeling work and efforts aimed at structure-based drug design.
CDAO-Store: A New Vision in Data Integration
Authors: Chisham Brandon , Le Trung , Pontelli Enrico , Son Tran , Wright Ben 
Published: July 2019

AbstractThe Comparative Data Analysis Ontology (CDAO) 1 is an ontology developed, as part of the EvoInfo2 and EvoIO3 groups supported by NESCent4, to provide semantics to the descriptions of data and transformations commonly found in the domain of phylogenetic inference. The core concepts of the ontology enables the description of phylogenetic trees and associated character data matrices.
Diffusion Approximations for Demographic Inference: DaDi
Authors: Gutenkunst Ryan , Hernandez Ryan , Williamson Scott , Bustamante Carlos 
Published: July 2019

AbstractModels of demographic history (population sizes, migration rates, and divergence times) inferred from genetic data complement archeology and serve as null models in genome scans for selection. Most current inference methods are computationally limited to considering simple models or non-recombining data. We introduce a method based on a diffusion approximation to the joint frequency spectrum of genetic variation between populations. Our implementation, DaDi, can model up to three interacting populations and scales well to genome-wide data. We have applied DaDi to human data from Africa, Europe, and East Asia, building the most complex statistically well-characterized model of human migration out of Africa to date.
Waist Circumference predicting Cardiovascular Disease in Korean Men and Women
Authors: Jee Sun Ha , Park Sat Byul 
Published: July 2019

Abstract
Objective:
Obesity and cardiovascular disease (CVD) are closely related and have become increasingly prevalent in Korea. Asians are more prone to obesity-related co-morbidities than Caucasians, even at lower body mass index (BMI) and/or smaller waist circumference (WC) values. Nevertheless, little is known regarding the association of WC with the risk of CVD in non-Caucasian populations. The authors conducted a prospective cohort study of WC and the risk of CVD in the Korean Heart Study.

Methods:
We examined the association of WC to CVD incidence among 53,026 Korean adults (30,152 men, 22,874 women) with no history of CVD and/or cancer. During a mean follow-up of 8.6 years, 2,722 incident cases of atherosclerotic cardiovascular disease (ASCVD) including 1,383 cases of ischemic heart disease (IHD) and 1,012 cases of stroke were documented. Results: Average WC at baseline was 84.0&177;8.2 cm in men and 75.2&177;8.9 cm in women. After adjustment for age and BMI, WC was significantly associated with cardiovascular risk factors (P &lt;.001). In men, a WC of &8805;91 cm was associated with an ASCVD hazard ratio (HR) of 1.62 (95% confidence interval (CI): 1.25, 2.10) and an IHD HR of 1.70 (95% CI: 1.19, 2.42) in comparison with a WC of &lt;78 cm even after further adjustment for BMI and traditional risk factors (P for trend = 0.0118, 0.0139 respectively). In women, the progressive associations of WC with ASCVD, IHD and stroke were observed. These associations were however attenuated after further adjustment for BMI and traditional risk factors. The multivariable HRs for ASCVD, IHD, and stroke increased with higher WC in both men and women.

Conclusions:
Central obesity significantly and independently contributes to cardiovascular outcomes in Korean men and women.
The Inhibitory Fc[gamma] Receptor is Unnecessary for IVIG Efficacy
Authors: Leontyev Danila , Katsman Yulia , Ma Xue-Zhong , Branch Donald 
Published: July 2019

AbstractIntravenous gamma globulin (IVIG) is used as an effective therapy for many different autoimmune and inflammatory diseases. The current paradigm for the mechanism underpinning anti-inflammatory effects links IVIG administration to increased expression and activity of the inhibitory Fc[gamma] receptor (Fc[gamma]RIIB) on splenic macrophages. This hypothesis has been disputed in the literature. Here we show that IVIG administered in the context of passive antibody-mediated thrombocytopenia to be therapeutically efficacious in both splenectomized and unmanipulated Balb/c mice despite no upregulation of Fc[gamma]RIIB mRNA in the spleen. Moreover, IVIG effectively ameliorated immune thrombocytopenia (ITP) in Fc[gamma]RIIB-deficient Balb/c mice, but not in Fc[gamma]RIIB-/- or Fc[gamma]RIIB+/+ control mice with a C57BL6/129S background. Our results demonstrate that Fc[gamma]RIIB is not relevant to the beneficial effects of IVIG. We anticipate that investigators will now shift their research focus away from Fc[gamma]RIIB and seek out other possible mechanism(s) to explain the plethora of diseases and conditions treatable with IVIG.
The Gramene Genetic Diversity Module: a resource for genotype-phenotype association analysis in grass species
Authors: Chen Charles , DeClerck Genevieve , Casstevens Terry , Youens-Clark Ken , Zhang Jon , Ware Doreen , Jaiswal Pankaj , McCouch Susan , Buckler Edward 
Published: July 2019

AbstractThe Genetic Diversity module of the Gramene database ("http://www.gramene.org/diversity":http://www.gramene.org/diversity) is specifically designed to handle data from high-throughput sequencing and array-based genotyping plateforms. Empowered by the Genomic Diversity and Phenotype Data Model, Gramene Genetic Diversity module provides live database connectivities of RFLP, SSR and SNP allele data, information about QTL, passport data for wild and cultivated germplasm from rice, maize, wheat, and Arabidopsis, and quantitative phenotypic data for some of these accessions. Large datasets of SNP variation are searchable via genomic positions of interest by SNP Query tool on a sequenced genome; and, trait associations, patterns of linkage disequilibrium and diversity can be evaluated using TASSEL. The Gramene database is updated twice a year, with the most recent release (Build 31) completed in May 2010.
Solving the protein folding problems
Authors: Bywater Robert 
Published: July 2019

AbstractThe protein folding problem persists in being the major unsolved problem in biophysics and molecular biology. The most immediate obstacle to its solution is said to be the immense combinatorial difficulty of finding the global minimum energy structure, due to the galactic number of possible rotamer states for the polypeptide backbone and its sidechains, the so-called Levinthal paradox1. Much attention has been paid to the topography of the free energy surface that the folding polypeptide has to negotiate in order to find this minimum and the notion of a funnel-shaped topography has been proposed2. While this has achieved wide acceptance, providing insight into the possible shape of the free energy surface, it still does not solve the problem. In this work it is suggested that, in order to proceed further with this line of enquiry, it would be useful to focus on not one but, rather, two of the free energy minima accessible to the folding polypeptide. These two minima are considered to represent the active and inactive, or resting, states of the protein. There is experimental evidence for this model and a well populated database of structures that is analysed in detail in this work.
Single gene-based distinction of individual microbial genomes from a mixed population of microbial cells
Authors: Tamminen Manu , Virta Marko 
Published: July 2019

Abstract
Background:
Recent progress in environmental microbiology has revealed vast populations of microbes in any given habitat that cannot be detected by conventional culturing strategies. The use of sensitive genetic detection methods such as CARD-FISH and in situ PCR have been limited by the cell wall permeabilization requirement that cannot be performed similarly on all cell types without lysing some and leaving some unpermeabilized. Furthermore, the detection of low copy targets such as genes present in single copies in the microbial genomes, has remained problematic.

Methodology/Principal Findings:
We describe an emulsion-based procedure to trap individual microbial cells into picoliter-volume polyacrylamide droplets that provide a support for genetic material and therefore allow degradation of cellular material to expose the individual genomes. The polyacrylamide droplets are subsequently converted into picoliter-scale reactors for genome amplification. The amplified genomes are labelled based on the presence of a target gene and differentiated from those that do not contain the gene by flow cytometry. Using the Escherichia coli strains XL1 and MC1061, which differ with respect to the presence (XL1) or absence (MC1061) of a single copy of a tetracycline resistance gene per genome, we demonstrate that XL1 genomes present at 0.01% of MC1061 genomes can be differentiated using this method. Using a spiked sediment microbial sample, we demonstrate that the method is applicable to complex environmental microbial communities as a target gene-based screen for individual microbes.

Conclusions/Significance:
The genomic support for complete cell degradation allows an exposure of individual genomes of environmental bacteria. The genome exposure followed by genome amplification and labelling combines the benefits of in situ-PCR and FISH methods and permits the detection cells with single copy chromosomal targets in complex mixtures of microbial cells. The method could be optimized for fluorescence-activated cell sorting to enrich genetic material of interest from complex environmental samples.
From Blood Oxygenation Level Dependent (BOLD) signals to brain temperature maps
Authors: Sotero Roberto C , Iturria-Medina Yasser 
Published: July 2019

AbstractA theoretical framework is presented for converting Blood Oxygenation Level Dependent (BOLD) images to temperature maps, based on the idea that disproportional local changes in cerebral blood flow (CBF) as compared with cerebral metabolic rate of oxygen consumption (CMRO2) during functional brain activity, lead to both brain temperature changes and the BOLD effect. Using an oxygen limitation model and a BOLD signal model we obtain a transcendental equation relating CBF and CMRO2 changes with the corresponding BOLD signal, which is solved in terms of the Lambert W function. Inserting this result in the dynamic bio-heat equation describing the rate of temperature changes in the brain, we obtain a non autonomous ordinary differential equation that depends on the BOLD response, which is solved numerically for each brain voxel. In order to test the method, temperature maps obtained from a real BOLD dataset are calculated showing temperature variations in the range: (-0.15, 0.1) which is consistent with experimental results. The method could find potential clinical uses as it is an improvement over conventional methods which require invasive probes and can record only few locations simultaneously. Interestingly, the statistical analysis revealed that significant temperature variations are more localized than BOLD activations. This seems to exclude the use of temperature maps for mapping neuronal activity as areas where it is well known that electrical activity occurs (such as V5 bilaterally) are not activated in the obtained maps. But it also opens questions about the nature of the information processing and the underlying vascular network in visual areas that give rise to this result.
Host Genetics and Viral Diversity: Report from a Global HIV Vaccine Enterprise Working Group
Authors: McMichael Andrew , McCutchan Francine , Working Group convened by the Globa the 
Published: July 2019

AbstractThe Global HIV Vaccine Enterprise convened a workshop in September 2009 to discuss human and viral genetic variation and its impact on future directions for HIV vaccine research and development. The formidable challenges presented by virus and host genetic variability are interrelated and complicate vaccine development. HIV vaccine researchers need to develop innovative approaches that will facilitate addressing these questions in novel ways.
Inactivation of the Retinoblastoma Protein by Mutant B-Raf in Malignant Melanoma
Authors: Kusano Eiji , Murata Satoru , Ohtsuki Mamitaro , Furukawa Yusuke , Kobayashi Yukiko , Kobayashi Takahisa , Kikuchi Jiro , Wada Taeko , Futaki Ken 
Published: July 2019

AbstractAlthough activating mutations of B-Raf are the most common genetic abnormalities in human melanomas, the mechanism by which mutant B-Raf transforms melanocytes is poorly understood. Here we show that the retinoblastoma tumor suppressor protein (pRB) is a direct target of B-Raf and is inactivated by phosphorylation in melanomas carrying B-Raf mutations. In contrast, pRB is undetectable in melanomas with wild-type B-Raf. Mutant B-Raf directly interacts with pRB and induces its phosphorylation at serine-249 and threonine-252 (S249/T252). Inhibition of B-Raf activity results in dephosphorylation of pRB at S249/T252 along with other sites in melanoma cells. S249/T252 are phosphorylated earlier than other sites during cell cycle entry of normal melanocytes. Blocking B-Raf activation precluded S249/T252 phosphorylation in mitogen-stimulated melanocytes, which was accompanied by the impaired phosphorylation of pRB at other sites. B-Raf enhanced CDK2-mediated pRB phosphorylation in an in vitro kinase assay. These results suggest that B-Raf is an initiating RB kinase, which triggers inactivation of pRB at the earliest step in the cell cycle entry of normal melanocytes, and its activating mutations cause deregulated growth, leading to the development of melanoma.
A theory for the tissue specificity of BRCA1/2 related and other hereditary cancers
Authors: Friedenson Bernard 
Published: July 2019

AbstractWomen who inherit a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. All these suggestions share the assumption that some disabled function of normal tumor suppressor genes leads to a tissue specific cancer response. Here the idea is proposed and tested that major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to an inflammatory process or to a carcinogen such as during digestion, metabolism or elimination. An innate genomic deficit in a tumor suppressor gene impairs normal responses to these extrinsic challenges and exacerbates the susceptibility to disease in organ targets. This hypothesis also fits data for several tumor suppressors beyond BRCA1/2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.
Membrane repair against H. pylori promotes cancer cell proliferation
Authors: Lin Li-Ling , Huang Hsuan-Cheng , Ogihara Satoshi , Wang Jin-Town , Chen Chiung-Nien , Juan Hsueh-Fen 
Published: July 2019

AbstractMembrane repair is a universal response against physical and biological insults and enables cell survival. Helicobacter pylori is one of the most common human pathogens and the first formally recognized bacterial carcinogen associated with gastric cancer. However, little is known about host membrane repair in the context of H. pylori infection. Here we show that H. pylori disrupts the host plasma membrane and induces Ca2+ influx, which triggers the translocation of annexin family members A1 and A4 to the plasma membrane. This in turn activates a membrane repair response through the recruitment of lysosomal membranes and the induction of downstream signaling transduction pathways that promote cell survival and proliferation. Based on our data, we propose a new model by which H. pylori infection activates annexin A1 and A4 for membrane repair and how annexin A4 over-expression induced signaling promotes cell proliferation. Continual activation of this membrane repair response signaling cascade may cause abnormal cellular states leading to carcinogenesis. This study links H. pylori infection to membrane repair, providing insight into potential mechanisms of carcinogenesis resulting from membrane damage.
Universal fractal scaling of self-organized networks
Authors: Laurienti Paul , Joyce Karen , Telesford Qawi , Burdette Jonathan , Hayasaka Satoru 
Published: July 2019

AbstractThere is an abundance of literature on complex networks describing a variety of relationships among units in social, biological, and technological systems. Such networks, consisting of interconnected nodes, are often self-organized, naturally emerging without any overarching designs on topological structure yet enabling efficient interactions among nodes. Here we show that the number of nodes and the density of connections in such self-organized networks exhibit a power law relationship. We examined the size and connection density of 46 self-organizing networks of various biological, social, and technological origins, and found that the size-density relationship follows a fractal relationship spanning over 6 orders of magnitude. This finding indicates that there is an optimal connection density in self-organized networks following fractal scaling regardless of their sizes.