bluuebunny/crossref_metadata_2025_split huggingface dataset:
2-Aminoadipic acid (2-AAA) as a potential biomarker for insulin resistance in childhood obesity
Authors: Lee Hyo Jung , Jang Han Byul , Kim Won-Ho , Park Keon Jae , Kim Kwang Youl , Park Sang Ick , Lee Hye- Ja 
Published: September 2019

AbstractInsulin resistance is an important clinical feature of metabolic syndrome, which includes obesity and type 2 diabetes. Increased adipose energy storage in obesity promote insulin resistance and other metabolic adverse effects. To identify a new link between adipocyte and insulin resistance, we performed targeted metabolite profiling of differentiated adipocytes and studied the association between adipogenic metabolites and insulin resistance. We found a correlation between 2-aminoadipic acid (2-AAA) and adipogenic differentiation. Also, circulatory 2-AAA was positively associated with obesity-related factors (fat mass, fat percent, waist circumference, BMI, BMI z-score, triglycerides, insulin, and HOMA-IR) at baseline and after 2 years in the children cohort study. Of these factors, increased BMI z-score and HOMA-IR were the primary independent factors associated with higher 2-AAA levels, and the baseline 2-AAA level was an indicator of the BMI z-score after 2 years. To validate the relationship between 2-AAA and obesity-related factors, we analyzed changes in 2-AAA levels following obesity intervention programs in two independent studies. In both studies, changes in 2-AAA levels during the intervention period were positively correlated with changes in the BMI z-score and HOMA-IR after adjusting for confounders. Moreover, the 2-AAA levels were increased in cell and mouse models of obesity-related insulin resistance. Excess 2-AAA levels led to impaired insulin signaling in insulin-sensitive cells (liver, skeletal muscle and adipose cells) and caused abnormal gluconeogenesis. Our results demonstrate that 2-AAA is associated with adipogenesis and insulin resistance. In this regard, 2-AAA could be a potential biomarker of obesity and obesity-related metabolic disorders.
Spidroins and Silk Fibers of Aquatic Spiders
Authors: Correa-Garhwal Sandra M. , Clarke Thomas H. , Janssen Marc , Crevecoeur Luc , McQuillan Bryce N. , Simpson Angela H. , Vink Cor J. , Hayashi Cheryl Y. 
Published: September 2019

AbstractSpiders are commonly found in terrestrial environments and many rely heavily on their silks for fitness related tasks such as reproduction and dispersal. Although rare, a few species occupy aquatic or semi-aquatic habitats and for them, silk-related specializations are also essential to survive in aquatic environments. Most spider silks studied to date are from cob-web and orb-web weaving species, leaving the silks from many other terrestrial spiders as well as water-associated spiders largely undescribed. Here, we characterize silks from three Dictynoidea species: the aquatic spiders Argyroneta aquatica and Desis marina as well as the terrestrial Badumna longinqua. From silk gland RNA-Seq libraries, we report a total of 47 different homologs of the spidroin (spider fibroin) gene family. Some of these 47 spidroins correspond to known spidroin types (aciniform, ampullate, cribellar, pyriform, and tubuliform), while other spidroins represent novel branches of the spidroin gene family. We also report a hydrophobic amino acid motif (GV) that, to date, is found only in the spidroins of aquatic and semi-aquatic spiders. Comparison of spider silk sequences to the silks from other water-associated arthropods, shows that there is a diversity of strategies to function in aquatic environments.
Longitudinal decline in lung function: a community-based cohort study in Korea
Authors: Leem Ah Young , Park Boram , Kim Young Sam , Chang Joon , Won Sungho , Jung Ji Ye 
Published: September 2019

AbstractProgressive decline in lung function is the hallmark of chronic obstructive pulmonary disease (COPD). We aimed to assess the rate of decline in forced expiratory volume in 1 second (FEV1) in patients from a community cohort database in Korea. 5,865 subjects aged 40–69 years from the Ansung-Ansan cohort database I–III (2001–2006) were included in this study. We assessed the annual rate of decline in FEV1 over time in relation to smoking status, patient sex, and presence or absence of pre-bronchodilator airflow limitation using a generalized additive mixed model. The mean follow-up duration was 3.8 years. The annual mean decline in FEV1 in the entire cohort was significantly more rapid for men than women (31.3 mL vs 27.0 mL, P = 0.003). Among men without pre-bronchodilator airflow limitation, annual mean declines in FEV1 were 31.5, 35.5, and 40.1 mL for never smokers, former smokers (P = 0.09 vs. never smokers), and current smokers (P < 0.001 vs. never smokers), respectively; and 23.4, 19.7, and 33.9 mL, respectively, for men with pre-bronchodilator airflow limitation. Thus, among Korean males, smoking accelerates lung function decline over time whereas smoking cessation slows the rate of FEV1 decline regardless of pre-bronchodilator airflow limitation. This underscores the importance of smoking cessation in Koreans.
Social dominance hierarchy type and rank contribute to phenotypic variation within cages of laboratory mice
Authors: Varholick Justin A. , Pontiggia Alice , Murphy Eimear , Daniele Vanessa , Palme Rupert , Voelkl Bernhard , Würbel Hanno , Bailoo Jeremy D. 
Published: September 2019

AbstractA tacit assumption in laboratory animal research is that animals housed within the same cage or pen are phenotypically more similar than animals from different cages or pens, due to their shared housing environment. This assumption drives experimental design, randomization schemes, and statistical analysis plans, while neglecting social context. Here, we examined whether a domain of social context—social dominance—accounted for more phenotypic variation in mice than cage-identity. First, we determined that cages of mice could be categorized into one of three dominance hierarchies with varying degrees of dominance behavior between cage-mates, and low levels of agonistic behavior in the home-cage. Most groups formed dynamic hierarchies with unclear ranks, contrasting with recent accounts of stable transitive hierarchies in groups of mice. Next, we measured some phenotypic traits, and found that social dominance (i.e. dominance hierarchy type and degree of dominance behavior) consistently accounted for some phenotypic variation in all outcome measures, while cage-identity accounted for phenotypic variation in some measures but virtually no variation in others. These findings highlight the importance of considering biologically relevant factors, such as social dominance, in experimental designs and statistical plans.
Emergence of consistent intra-individual locomotor patterns during zebrafish development
Authors: Fitzgerald Jennifer A. , Kirla Krishna Tulasi , Zinner Carl P. , vom Berg Colette M. 
Published: September 2019

AbstractThe analysis of larval zebrafish locomotor behavior has emerged as a powerful indicator of perturbations in the nervous system and is used in many fields of research, including neuroscience, toxicology and drug discovery. The behavior of larval zebrafish however, is highly variable, resulting in the use of large numbers of animals and the inability to detect small effects. In this study, we analyzed whether individual locomotor behavior is stable over development and whether behavioral parameters correlate with physiological and morphological features, with the aim of better understanding the variability and predictability of larval locomotor behavior. Our results reveal that locomotor activity of an individual larva remains consistent throughout a given day and is predictable throughout larval development, especially during dark phases, under which larvae demonstrate light-searching behaviors and increased activity. The larvae’s response to startle-stimuli was found to be unpredictable, with no correlation found between response strength and locomotor activity. Furthermore, locomotor activity was not associated with physiological or morphological features of a larva (resting heart rate, body length, size of the swim bladder). Overall, our findings highlight the areas of intra-individual consistency, which could be used to improve the sensitivity of assays using zebrafish locomotor activity as an endpoint.
Machine learning for comprehensive forecasting of Alzheimer’s Disease progression
Authors: Fisher Charles K. , Smith Aaron M. , Walsh Jonathan R. ,   Coalition Against Major Diseases, Simon Adam J. , Edgar Chris , Jack Clifford R. , Holtzman David , Russell David , Hill Derek , Grosset Donald , Wood Fred , Vanderstichele Hugo , Morris John , Blennow Kaj , Marek Ken , Shaw Leslie M , Albert Marilyn , Weiner Michael , Fox Nick , Aisen Paul , Cole Patricia E. , Petersen Ronald , Sherer Todd , Kubick Wayne ,   Abbott, Alliance for Aging Research, Alzheimer’s Association, Alzheimer’s Foundation of America, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Critical Path Institute, CHDI Foundation, Inc., Eli Lilly and Company, F. Hoffmann-La Roche Ltd, Forest Research Institute, Genentech, Inc., GlaxoSmithKline, Johnson & Johnson, National Health Council, Novartis Pharmaceuticals Corporation, Parkinson’s Action Network, Parkinson’s Disease Foundation, Pfizer, Inc., sanofi-aventis. Collaborating Organiza
Published: September 2019

AbstractMost approaches to machine learning from electronic health data can only predict a single endpoint. The ability to simultaneously simulate dozens of patient characteristics is a crucial step towards personalized medicine for Alzheimer’s Disease. Here, we use an unsupervised machine learning model called a Conditional Restricted Boltzmann Machine (CRBM) to simulate detailed patient trajectories. We use data comprising 18-month trajectories of 44 clinical variables from 1909 patients with Mild Cognitive Impairment or Alzheimer’s Disease to train a model for personalized forecasting of disease progression. We simulate synthetic patient data including the evolution of each sub-component of cognitive exams, laboratory tests, and their associations with baseline clinical characteristics. Synthetic patient data generated by the CRBM accurately reflect the means, standard deviations, and correlations of each variable over time to the extent that synthetic data cannot be distinguished from actual data by a logistic regression. Moreover, our unsupervised model predicts changes in total ADAS-Cog scores with the same accuracy as specifically trained supervised models, additionally capturing the correlation structure in the components of ADAS-Cog, and identifies sub-components associated with word recall as predictive of progression.
Refinements of LC-MS/MS Spectral Counting Statistics Improve Quantification of Low Abundance Proteins
Authors: Lee Ha Yun , Kim Eunhee G. , Jung Hye Ryeon , Jung Jin Woo , Kim Han Byeol , Cho Jin Won , Kim Kristine M. , Yi Eugene C. 
Published: September 2019

AbstractMass spectrometry-based spectral count has been a common choice of label-free proteome quantification due to the simplicity for the sample preparation and data generation. The discriminatory nature of spectral count in the MS data-dependent acquisition, however, inherently introduces the spectral count variation for low-abundance proteins in multiplicative LC-MS/MS analysis, which hampers sensitive proteome quantification. As many low-abundance proteins play important roles in cellular processes, deducing low-abundance proteins in a quantitatively reliable manner greatly expands the depth of biological insights. Here, we implemented the Moment Adjusted Imputation error model in the spectral count refinement as a post PLGEM-STN for improving sensitivity for quantitation of low-abundance proteins by reducing spectral count variability. The statistical framework, automated spectral count refinement by integrating the two statistical tools, was tested with LC-MS/MS datasets of MDA-MB468 breast cancer cells grown under normal and glucose deprivation conditions. We identified about 30% more quantifiable proteins that were found to be low-abundance proteins, which were initially filtered out by the PLGEM-STN analysis. This newly developed statistical framework provides a reliable abundance measurement of low-abundance proteins in the spectral count-based label-free proteome quantification and enabled us to detect low-abundance proteins that could be functionally important in cellular processes.
An association study of severity of intellectual disability with peripheral biomarkers of disabled children in a rehabilitation home, Kolkata, India
Authors: Sengupta Aaveri , Das Ujjal , Manna Krishnendu , Biswas Sushobhan , Datta Siddhartha , Khan Amitava , Bhattacharya Tuhin , Saha Samrat , Mitra Tapashi , Mukherjee Swapan , Sadhu Anup K. , Paul Suhrita , Ghosh Saurabh , Sharma Rakhi Dey , Dey Sanjit 
Published: September 2019

AbstractThe current investigation has identified the biomarkers associated with severity of disability and correlation among plethora of systemic, cellular and molecular parameters of intellectual disability (ID) in a rehabilitation home. The background of study lies with the recent clinical evidences which identified complications in ID. Various indicators from blood and peripheral system serve as potential surrogates for disability related changes in brain functions. ID subjects (Male, age 10 ± 5 yrs, N = 45) were classified as mild, moderate and severe according to the severity of disability using standard psychometric analysis. Clinical parameters including stress biomarkers, neurotransmitters, RBC morphology, expressions of inflammatory proteins and neurotrophic factor were estimated from PBMC, RBC and serum. The lipid peroxidation of PBMC and RBC membranes, levels of serum glutamate, serotonin, homocysteine, ROS, lactate and LDH-A expression increased significantly with severity of ID whereas changes in RBC membrane β-actin, serum BDNF, TNF-α and IL-6 was found non-significant. Structural abnormalities of RBC were more in severely disabled children compared to mildly affected ones. The oxidative stress remained a crucial factor with severity of disability. This is confirmed not only by RBC alterations but also with other cellular dysregulations. The present article extends unique insights of how severity of disability is correlated with various clinical, cellular and molecular markers of blood. This unique study primarily focuses on the strong predictors of severity of disability and their associations via brain-blood axis.
Organogermanium suppresses cell death due to oxidative stress in normal human dermal fibroblasts
Authors: Takeda Tomoya , Doiyama Sota , Azumi Junya , Shimada Yasuhiro , Tokuji Yoshihiko , Yamaguchi Hiroaki , Nagata Kosuke , Sakamoto Naoya , Aso Hisashi , Nakamura Takashi 
Published: September 2019

AbstractReactive oxygen species (ROS) are very harmful to dermal cells, and it is thus important to develop cosmetics that protect the skin from ROS and other stimuli. Repagermanium is a synthetic water-soluble organogermanium polymer, and in this study, we attempted to visualize the incorporation of germanium into normal human dermal fibroblasts (NHDFs) using isotope microscopy. In addition, the content of 3-(trihydroxygermyl)propanoic acid (THGP), a hydrolyzed monomer of repagermanium, in NHDFs was determined through liquid chromatography mass spectrometry (LC-MS/MS), and the dose-dependent incorporation of THGP was confirmed. We then evaluated the preventive effects of THGP against ROS-induced NHDF death and confirmed the observed preventive effects through gene profiling and expression analysis. The addition of 0.59–5.9 mM THGP reduced cell death resulting from ROS damage caused by the reaction between xanthine oxidase and hypoxanthine and the direct addition of H2O2. Furthermore, this study provides the first demonstration that the effect of THGP was not due to the direct scavenging of ROS, which indicates that the mechanism of THGP differs from that of general antioxidants, such as ascorbic acid. The gene profiling and expression analysis showed that THGP suppressed the expression of the nuclear receptor subfamily 4 group A member 2 (NR4A2) gene, which is related to cell death, and the interleukin 6 (IL6) and chemokine (C-X-C motif) ligand 2 (CXCL2) genes, which are related to the inflammatory response. Furthermore, the production of IL6 induced by H2O2 was suppressed by the THGP treatment. Our data suggest that the preventive effect of THGP against ROS-induced cell death is not due to antioxidant enzymes or ROS scavenging.
The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response
Authors: Castro-Muñoz Leonardo Josué , Manzo-Merino Joaquín , Muñoz-Bello J. Omar , Olmedo-Nieva Leslie , Cedro-Tanda Alberto , Alfaro-Ruiz Luis Alberto , Hidalgo-Miranda Alfredo , Madrid-Marina Vicente , Lizano Marcela 
Published: September 2019

AbstractThe Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.
Evaluation of the functional effects of genetic variants‒missense and nonsense SNPs, indels and copy number variations‒in the gene encoding human deoxyribonuclease I potentially implicated in autoimmunity
Authors: Ueki Misuzu , Kimura-Kataoka Kaori , Fujihara Junko , Iida Reiko , Kawai Yasuyuki , Kusaka Akari , Sasaki Takamitsu , Takeshita Haruo , Yasuda Toshihiro 
Published: September 2019

AbstractGenetic variants, such as single nucleotide polymorphisms (SNPs), in the deoxyribonuclease I (DNase I) gene which remarkably reduce or abolish the activity are assumed to be substantially responsible for the genetic backgrounds determining susceptibility to autoimmune dysfunction. Here, we evaluated many genetic variants, including missense and nonsense SNPs, and indel (inframe) variants in the gene, potentially implicated in autoimmune diseases as functional variants resulting in altered activity levels. Eighteen missense and 7 nonsense SNPs, and 9 indel (inframe) variants were found to result in loss of function and disappearance of DNase I activity. Furthermore, considering the positions in the DNase I protein corresponding to the various nonsense SNPs, all of the other nonsense SNPs and frameshift variants registered in the Ensembl database (https://asia.ensembl.org) appear likely to exert a pathogenetic effect through loss of the activity. Accordingly, a total of 60 genetic variants in the DNase 1 gene (DNASE1) inducing abolishment or marked reduction of the DNase I activity could be identified as genetic risk factors for autoimmunity, irrespective of how sparsely they were distributed in the population. It was noteworthy that SNP p.Gln244Arg, reportedly associated with autoimmunity and reducing the activity to about half of that of the wild type, and SNP p.Arg107Gly, abolishing the activity completely, were distributed worldwide and in African populations at the polymorphic level, respectively. On the other hand, with regard to copy number variations in DNASE1 where loss of copy leads to a reduction of the in vivo enzyme activity, only 2 diploid copy numbers were distributed in Japanese and German populations, demonstrating no loss of copy. These exhaustive data for genetic variants in DNASE1 resulting in loss or marked reduction of the DNase I activity are highly informative when considering genetic predisposition leading to autoimmune dysfunction.
Effect of expression alteration in flanking genes on phenotypes of St8sia2-deficient mice
Authors: Ikegami Keisuke , Saigoh Kazumasa , Fujioka Atsuko , Nagano Mamoru , Kitajima Ken , Sato Chihiro , Masubuchi Satoru , Kusunoki Susumu , Shigeyoshi Yasufumi 
Published: September 2019

AbstractST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) synthesizes polysialic acid (PSA), which is essential for brain development. Although previous studies reported that St8sia2-deficient mice that have a mixed 129 and C57BL/6 (B6) genetic background showed mild and variable phenotypes, the reasons for this remain unknown. We hypothesized that this phenotypic difference is caused by diversity in the expression or function of flanking genes of St8sia2. A genomic polymorphism and gene expression analysis in the flanking region revealed reduced expression of insulin-like growth factor 1 receptor (Igf1r) on the B6 background than on that of the 129 strain. This observation, along with the finding that administration of an IGF1R agonist during pregnancy increased litter size, suggests that the decreased expression of Igf1r associated with ST8SIA2 deficiency caused lethality. This study demonstrates the importance of gene expression level in the flanking regions of a targeted null allele having an effect on phenotype.
Shape Effect on the Refractive Index Sensitivity at Localized Surface Plasmon Resonance Inflection Points of Single Gold Nanocubes with Vertices
Authors: Jeon Hui Bin , Tsalu Philippe Vuka , Ha Ji Won 
Published: September 2019

AbstractPlasmonic gold nanoparticles with sharp tips and vertices, such as gold bipyramids (AuBPs) and gold nanocubes (AuNCs), have been widely used for high-sensitivity localized surface plasmon resonance (LSPR) sensing. However, conventional LSPR sensors based on frequency shifts have a major disadvantage: the asymmetry and broadening of LSPR peaks because of instrumental, environmental, and chemical noises that limit the precise determination of shift positions. Herein, we demonstrated an alternative method to improve the efficiency of the sensors by focusing on homogeneous LSPR scattering inflection points (IFs) of single gold nanoparticles with a single resonant mode. In addition, we investigated the effect of the shape and vertices of AuNCs on the refractive index (RI) sensitivity of homogeneous LSPR IFs by comparing with gold nanospheres (AuNSs) of similar size. The results show that for both AuNCs and AuNSs, tracking homogeneous LSPR IFs allows for higher RI sensitivity than tracking the frequency shifts of the LSPR peaks. Furthermore, single AuNCs with vertices exhibited higher RI sensitivity than single AuNSs of similar size in the homogeneous LSPR IFs. Therefore, we provided a deeper insight into the RI sensitivity of homogeneous LSPR IFs of AuNCs with vertices for their use in LSPR-based biosensors.