bluuebunny/crossref_metadata_2025 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

Insulin 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

Spiders 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

Progressive 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

A 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

The 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

Most 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

Mass 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

The 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

Reactive 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

The 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

Genetic 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

ST8 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

Plasmonic 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.
The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8
Authors: Venegas Francisco A. , Köllisch Gabriele , Mark Kerstin , Diederich Wibke E. , Kaufmann Andreas , Bauer Stefan , Chavarría Max , Araya Juan J. , García-Piñeres Alfonso J.
Published: September 2019

Violacein, an indole-derived, purple-colored natural pigment isolated fromChromobacterium violaceumhas shown multiple biological activities. In this work, we studied the effect of violacein in different immune cell lines, namely THP-1, MonoMac 6, ANA-1, Raw 264.7 cells, as well as in human peripheral blood mononuclear cells (PBMCs). A stimulation of TNF-α production was observed in murine macrophages (ANA-1 and Raw 264.7), and in PBMCs, IL-6 and IL-1β secretion was detected. We obtained evidence of the molecular mechanism of activation by determining the mRNA expression pattern upon treatment with violacein in Raw 264.7 cells. Incubation with violacein caused activation of pathways related with an immune and inflammatory response. Our data utilizing TLR-transfected HEK-293 cells indicate that violacein activates the human TLR8 (hTLR8) receptor signaling pathway and not human TLR7 (hTLR7). Furthermore, we found that the immunostimulatory effect of violacein in PBMCs could be suppressed by the specific hTLR8 antagonist, CU-CPT9a. Finally, we studied the interaction of hTLR8 with violaceinin silicoand obtained evidence that violacein could bind to hTLR8 in a similar fashion to imidazoquinoline compounds. Therefore, our results indicate that violacein may have some potential in contributing to future immune therapy strategies.
Light-induced changes of the subretinal space of the temporal retina observed via optical coherence tomography
Authors: Messner Alina , Werkmeister René M. , Seidel Gerald , Stegmann Hannes , Schmetterer Leopold , Aranha dos Santos Valentin
Published: September 2019

Photoreceptor function is impaired in many retinal diseases like age-related macular degeneration. Currently, assessment of the photoreceptor function for the early diagnosis and monitoring of these diseases is either subjective, as in visual field testing, requires contact with the eye, like in electroretinography, or relies on research prototypes with acquisition speeds unattained by conventional imaging systems. We developed an objective, noncontact method to monitor photoreceptor function using a standard optical coherence tomography system. This method can be used with various white light sources for stimulation. The technique was applied in five volunteers and detected a decrease of volume of the subretinal space associated with light adaptation processes of the retina.
Antimicrobial activity and mechanism of action of a novel peptide present in the ecdysis process of centipede Scolopendra subspinipes subspinipes
Authors: Chaparro-Aguirre Elisa , Segura-Ramírez Paula J. , Alves Flavio L. , Riske Karin A. , Miranda Antonio , Silva Júnior Pedro I.
Published: September 2019

One of the most important cellular events in arthropods is the moulting of the cuticle (ecdysis). This process allows them to grow until they reach sexual maturity. Nevertheless, during this stage, the animals are highly exposed to pathogens. Consequently, it can be assumed that arthropods counter with an efficient anti-infective strategy that facilitates their survival during ecdysis. Herein, we characterized a novel antimicrobial peptide called Pinipesin, present in the exuviae extract of the centipede Scolopendra subspinipes subspinipes. The antimicrobial activity of Pinipesin was tested. The haemolytic activity of the peptide was evaluated and its possible mechanism of action was investigated. Identification was carried out by mass spectrometry analysis. Pinipesin displayed potent antimicrobial effects against different microorganisms and showed low haemolytic effects against human erythrocytes at high concentrations. It has a monoisotopic mass of 1213.57 Da, its sequence exhibited high similarity with some cuticular proteins, and it might act intracellularly by interfering with protein synthesis. Our data suggest that Pinipesin might be part of a prophylactic immune response during the ecdysis process of centipedes. Therefore, it is a promising candidate for the development of non-conventional antibiotics that could help fight infectious diseases and represents an exciting discovery for this taxon.
Radiochemical examination of transthyretin (TTR) brain penetration assisted by iododiflunisal, a TTR tetramer stabilizer and a new candidate drug for AD
Authors: Rios Xabier , Gómez-Vallejo Vanessa , Martín Abraham , Cossío Unai , Morcillo Miguel Ángel , Alemi Mobina , Cardoso Isabel , Quintana Jordi , Jiménez-Barbero Jesús , Cotrina Ellen Y. , Valencia Gregorio , Arsequell Gemma , Llop Jordi
Published: September 2019

It is well settled that the amyloidogenic properties of the plasma protein transporter transthyretin (TTR) can be modulated by compounds that stabilize its native tetrameric conformation. TTR is also present in cerebrospinal fluid where it can bind to Aβ-peptides and prevent Aβ aggregation. We have previously shown that treatment of Alzheimer’s Disease (AD) model mice with iododiflunisal (IDIF), a TTR tetramer stabilizing compound, prevents AD pathologies. This evidence positioned IDIF as a new lead drug for AD. In dissecting the mechanism of action of IDIF, we disclose here different labeling strategies for the preparation of 131I-labeled IDIF and 131I- and 124I-labeled TTR, which have been further used for the preparation of IDIF-TTR complexes labeled either on the compound or the protein. The biodistribution of all labeled species after intravenous administration has been investigated in mice using ex vivo and in vivo techniques. Our results confirm the capacity of TTR to cross the blood brain barrier (BBB) and suggest that the formation of TTR-IDIF complexes enhances BBB permeability of both IDIF and TTR. The increased TTR and IDIF brain concentrations may result in higher Aβ-peptide sequestration capacity with the subsequent inhibition of AD symptoms as we have previously observed in mice.
Cooperation in an Assortative Matching Prisoners Dilemma Experiment with Pro-Social Dummies
Authors: Yang Chun-Lei , Yue Ching-Syang Jack
Published: September 2019

Assortative matching (AM) can be theoretically an effective means to facilitate cooperation. We designed a controlled lab experiment with three treatments on multi-round prisoner’s dilemma. With matching based on weighted history (WH) as surrogate for AM, we show that adding pro-social dummies to the WH treatment may significantly improve cooperation, compared to both the random matching and the WH treatment. In society where assortative matching is effective and promoted by the underlying culture, institutional promotion of virtue role models can be interpreted as generating additional pro-social dummies, so as to move the initial state of cooperators into the basin of attraction for a highly cooperative polymorphic equilibrium.
Upregulation of the chromatin remodeler HELLS is mediated by YAP1 in Sonic Hedgehog Medulloblastoma
Authors: Robinson M. Hope , Maximov Victor , Lallani Shoeb , Farooq Hamza , Taylor Michael D. , Read Renee D. , Kenney Anna Marie
Published: September 2019

Medulloblastoma is a malignant pediatric tumor that arises from neural progenitors in the cerebellum. Despite a five-year survival rate of ~70%, nearly all patients incur adverse side effects from current treatment strategies that drastically impact quality of life. Roughly one-third of medulloblastoma are driven by aberrant activation of the Sonic Hedgehog (SHH) signaling pathway. However, the scarcity of genetic mutations in medulloblastoma has led to investigation of other mechanisms contributing to cancer pathogenicity including epigenetic regulation of gene expression. Here, we show that Helicase, Lymphoid Specific (HELLS), a chromatin remodeler with epigenetic functions including DNA methylation and histone modification, is induced by Sonic Hedgehog (SHH) in SHH-dependent cerebellar progenitor cells and the developing murine cerebella. HELLS is also up-regulated in mouse and human SHH medulloblastoma. Others have shown that HELLS activity generally results in a repressive chromatin state. Our results demonstrate that increased expression of HELLS in our experimental systems is regulated by the oncogenic transcriptional regulator YAP1 downstream of Smoothened, the positive transducer of SHH signaling. Elucidation of HELLS as one of the downstream effectors of the SHH pathway may lead to novel targets for precision therapeutics with the promise of better outcomes for SHH medulloblastoma patients.
Glucagon-like peptide 1 and Glucagon-like peptide 2 in relation to osteoporosis in non-diabetic postmenopausal women
Authors: Montes Castillo María Cristina , Martínez Ramírez María José , Soriano Arroyo Rubén , Prieto Gomez Isabel , Segarra Robles Ana Belén , Garrido-Martínez Macarena , Santiago-Fernández Piedad , Delgado Rodríguez Miguel
Published: September 2019

Osteoporosis results from an imbalance in bone remodeling, which is known to follow a circadian rhythm determined by a functional relationship between intestine and bone tissue. Specific intestinal peptides have been identified as mediators. Glucagon-like peptide 1 and glucagon-like peptide 2, have been associated with bone health. Our main objective was to determine whether postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2 and dipeptidyl-peptidase 4 activity, are associated with osteoporosis in non-diabetic postmenopausal women. We studied non-diabetic postmenopausal women with osteoporosis diagnosed by dual-energy X-ray absorptiometry (cases, n = 43) and age-matched (±1 yr) controls without osteoporosis or a history of osteoporotic fracture (n = 43). We measured postprandial plasma levels of glucagon-like peptide 1, glucagon-like peptide 2, and dipeptidyl-peptidase 4 activity, bone mineral density, and baseline levels of bone remodeling markers and analyzed the food intake using a food-frequency questionnaire. Postprandial glucagon-like peptide 1 values were lower (p < 0.001) in cases, μ (SEM) = 116.25 (2.68), than in controls, μ (SEM) = 126.79 (2.68). Glucagon-like peptide 1 was associated with reduced osteoporosis risk in the crude logistic regression analysis [OR (95% CI) = 0.724 (0.53–0.97), p = 0.031] and adjusted analysis [OR = 0.603 (0.38–0.94), p = 0.027]. We found no association of glucagon-like peptide 2, or dipeptidyl-peptidase 4 activity with osteoporosis. Postprandial glucagon-like peptide 1 levels are related to osteoporosis and osteoporosis risk in non-diabetic postmenopausal women. Further studies are required to verify these findings.
Oxidative stress-dependent and -independent death of glioblastoma cells induced by non-thermal plasma-exposed solutions
Authors: Tanaka Hiromasa , Mizuno Masaaki , Katsumata Yuko , Ishikawa Kenji , Kondo Hiroki , Hashizume Hiroshi , Okazaki Yasumasa , Toyokuni Shinya , Nakamura Kae , Yoshikawa Nobuhisa , Kajiyama Hiroaki , Kikkawa Fumitaka , Hori Masaru
Published: September 2019

Non-thermal atmospheric pressure plasma has been widely used for preclinical studies in areas such as wound healing, blood coagulation, and cancer therapy. We previously developed plasma-activated medium (PAM) and plasma-activated Ringer’s lactate solutions (PAL) for cancer treatments. Many in vitro and in vivo experiments demonstrated that both PAM and PAL exhibit anti-tumor effects in several types of cancer cells such as ovarian, gastric, and pancreatic cancer cells as well as glioblastoma cells. However, interestingly, PAM induces more intracellular reactive oxygen species in glioblastoma cells than PAL. To investigate the differences in intracellular molecular mechanisms of the effects of PAM and PAL in glioblastoma cells, we measured gene expression levels of antioxidant genes such as CAT, SOD2, and GPX1. Microarray and quantitative real-time PCR analyses revealed that PAM elevated stress-inducible genes that induce apoptosis such as GADD45α signaling molecules. PAL suppressed genes downstream of the survival and proliferation signaling network such as YAP/TEAD signaling molecules. These data reveal that PAM and PAL induce apoptosis in glioblastoma cells by different intracellular molecular mechanisms.
PCR-based Sepsis@Quick test is superior in comparison with blood culture for identification of sepsis-causative pathogens
Authors: Trung Ngo Tat , Thau Nguyen Sy , Bang Mai Hong , Song Le Huu
Published: September 2019

Sepsis is an acute, often fatal syndrome that requires early diagnosis and proper treatment. Blood culture (BC) is the gold standard for the identification of pathogens, however it has marked limitations, including that it is time-consuming (delaying treatment) and can only detect microbes that readily grow under culture conditions. Alternatively, non-culture-based methodologies like polymerase chain reaction (PCR) are faster but also have limitations; e.g., the reaction is often inhibited by the abundance of human DNA and thus can only detect limited known target pathogens. In our previous publication, we have demonstrated a proof-of-concept of a simple pre-analytical tool to remove human DNA from patients’ blood specimens, hence allowing downstream PCRs to detect rare bacterial genetic materials. In the current study, we reported a better performance of a novel prototype diagnosis kit named Sepsis@Quick that combines human DNA removal step with real-time PCRs compared to blood-culture for identifying sepsis causative bacteria. Our data showed that Sepsis@Quick is superior to blood culture in which the novel diagnostic kit could identify more pathogens and even polymicrobial infection, faster and less influenced by the empirical administration of broad spectrum antibiotic therapy (single administration or combination of cephalosporin III and fluoroquinolon). Additionally, for the first time, we demonstrated that positive results achieved by Sepsis@Quick are significantly associated with a reduction of sepsis-related mortality.
Preparation of β-CD-DPPE-Dox Nanomedicine and Its’ Application as the Anticancer and Antitumor Drug
Authors: Yan Miaomiao , Cai Anran , Li Jing , Xin Meixiu , Liu Mingying , Wang Chunhua , Wei Guangcheng
Published: September 2019

β-CD-DPPE molecule was synthesized through the conjugation of β-CD-NH2 and the DPPE molecule, and its’ water-solubility was more excellent than the traditional phospholipid molecule. The spherical micelles was formed by β-CD-DPPE molecule in aqueous solution, and the β-CD-DPPE-Dox nanomedicine can be prepared through loading Dox (Doxorubicin) into the micelles, and the Dox loading ratio was about 82.3 ± 7.27%. At the same time the Dox release behavior from the nanomedicine was sustained-release and pH controlled release, and the release test in vitro showed that the release rate of the Dox at the lower pH was faster than that of normal pH (pH = 7.4), which indicated that the rate of release in the tumor microenvironment is faster than in the normal tissue. Biological test showed that the micelles was low cytotoxicity, and the cytotoxicity of β-CD-DPPE-Dox nanomedicine was lower than the Dox under the same Dox concentration, and the β-CD-DPPE-Dox nanomedicine could effectively induce cancer cell apoptosis and inhibit the tumor growth.
Subphenotypes of Cardiac Arrest Patients Admitted to Intensive Care Unit: a latent profile analysis of a large critical care database
Authors: Zhang Zhongheng , Yao Min , Ho Kwok M. , Hong Yucai
Published: September 2019

Cardiac arrest (CA) may occur due to a variety of causes with heterogeneity in their clinical presentation and outcomes. This study aimed to identify clinical patterns or subphenotypes of CA patients admitted to the intensive care unit (ICU). The clinical and laboratory data of CA patients in a large electronic healthcare database were analyzed by latent profile analysis (LPA) to identify whether subphenotypes existed. Multivariable Logistic regression was used to assess whether mortality outcome was different between subphenotypes. A total of 1,352 CA patients fulfilled the eligibility criteria were included. The LPA identified three distinct subphenotypes: Profile 1 (13%) was characterized by evidence of significant neurological injury (low GCS). Profile 2 (15%) was characterized by multiple organ dysfunction with evidence of coagulopathy (prolonged aPTT and INR, decreased platelet count), hepatic injury (high bilirubin), circulatory shock (low mean blood pressure and elevated serum lactate); Profile 3 was the largest proportion (72%) of all CA patients without substantial derangement in major organ function. Profile 2 was associated with a significantly higher risk of death (OR: 2.09; 95% CI: 1.30 to 3.38) whilst the mortality rates of Profiles 3 was not significantly different from Profile 1 in multivariable model. LPA using routinely collected clinical data could identify three distinct subphenotypes of CA; those with multiple organ failure were associated with a significantly higher risk of mortality than other subphenotypes. LPA profiling may help researchers to identify the most appropriate subphenotypes of CA patients for testing effectiveness of a new intervention in a clinical trial.
Effect of porosity enhancing agents on the electrochemical performance of high-energy ultracapacitor electrodes derived from peanut shell waste
Authors: Sylla N. F. , Ndiaye N. M. , Ngom B. D. , Momodu D. , Madito M. J. , Mutuma B. K. , Manyala N.
Published: September 2019

In this study, the synthesis of porous activated carbon nanostructures from peanut (Arachis hypogea) shell waste (PSW) was described using different porosity enhancing agents (PEA) at various mass concentrations via a two-step process. The textural properties obtained were depicted with relatively high specific surface area values of 1457 m2 g−1, 1625 m2 g−1 and 2547 m2 g−1 for KHCO3, K2CO3 and KOH respectively at a mass concentration of 1 to 4 which were complemented by the presence of a blend of micropores, mesopores and macropores. The structural analyses confirmed the successful transformation of the carbon-containing waste into an amorphous and disordered carbonaceous material. The electrochemical performance of the material electrodes was tested in a 2.5 M KNO3 aqueous electrolyte depicted its ability to operate reversibly in both negative and positive potential ranges of 0.90 V. The activated carbon obtained from the carbonized CPSW:PEA with a mass ratio of 1:4 yielded the best electrode performance for all featured PEAs. The porous carbons obtained using KOH activation displayed a higher specific capacitance and the lower equivalent series resistance as compared to others. The remarkable performance further corroborated the findings linked to the textural and structural properties of the material. The assembled device operated in a neutral electrolyte (2.5 M KNO3) at a cell potential of 1.80 V, yielded a ca. 224.3 F g−1 specific capacitance at a specific current of 1 A g−1 with a corresponding specific energy of 25.2 Wh kg−1 and 0.9 kW kg−1 of specific power. This device energy was retained at 17.7 Wh kg−1 when the specific current was quadrupled signifying an excellent supercapacitive retention with a corresponding specific power of 3.6 kW kg−1. These results suggested that peanut shell waste derived activated carbons are promising candidates for high-performance supercapacitors.
Author Correction: Environmentally Optimal, Nutritionally Sound, Protein and Energy Conserving Plant Based Alternatives to U.S. Meat
Authors: Eshel Gidon , Stainier Paul , Shepon Alon , Swaminathan Akshay
Published: September 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Measurements of electrically tunable refractive index of MoS2 monolayer and its usage in optical modulators
Authors: Kravets Vasyl G. , Wu Fan , Auton Gregory H. , Yu Tongcheng , Imaizumi Shinji , Grigorenko Alexander N.
Published: September 2019

Two-dimensional materials hold a great promise for developing extremely fast, compact and inexpensive optoelectronic devices. A molybdenum disulphide (MoS2) monolayer is an important example which shows strong, stable and gate tunable optical response even at room temperature near excitonic transitions. However, optical properties of a MoS2monolayer are not documented well. Here, we investigate the electric field effect on optical properties of a MoS2 monolayer and extract the dependence of MoS2 optical constants on gating voltage. The field effect is utilised to achieve ~10% visible light modulation for a hybrid electro-optical waveguide modulator based on MoS2. A suggested hybrid nanostructure consists of a CMOS compatible Si3N4 dielectric waveguide sandwiched between a thin gold film and a MoS2 monolayer which enables a selective enhancement of polarised electro-absorption in a narrow window of angles of incidence and a narrow wavelength range near MoS2 exciton binding energies. The possibility to modulate visible light with 2D materials and the robust nature of light modulation by MoS2 could be useful for creation of reliable ultra-compact electro-optical hybrid visible-light modulators.
A chemical titration method for quantification of carbenes in Mo- or W-containing catalysts for metathesis of ethylene with 2-butenes: verification and application potential
Authors: Otroshchenko Tatiana , Reinsdorf Ole , Linke David , Kondratenko Evgenii V.
Published: September 2019

We introduce and experimentally validate a simple titration method for quantifying the number of carbenes acting as active sites in the metathesis of ethylene with 2-butenes over Mo- or W-containing catalysts.
Magnetic anisotropy in trigonal planar Fe(ii) bis(trimethylsilyl)amido complexes of the type [Fe{N(SiMe3)2}2L]—experiment and theory
Authors: Bodenstein Tilmann , Eichhöfer Andreas
Published: September 2019

The paper presents a combined experimental and theoretical study of the influence of the type of neutral ligand L on the electronic and magnetic properties of trigonal planar iron(ii) bis(trimethylsilyl)amido complexes [Fe(N(SiMe3)2L].
Phosphine-free ruthenium NCN-ligand complexes and their use in catalytic CO2 hydrogenation
Authors: Sung Molly M. H. , Prokopchuk Demyan E. , Morris Robert H.
Published: September 2019

A ruthenium hydride with a fluxional NHC ligand catalyses the hydrogenation of carbon dioxide.
The role of neutral Rh(PONOP)H, free NMe2H, boronium and ammonium salts in the dehydrocoupling of dimethylamine-borane using the cationic pincer [Rh(PONOP)(η2-H2)]+ catalyst
Authors: Spearing-Ewyn E. Anastasia K. , Beattie Nicholas A. , Colebatch Annie L. , Martinez-Martinez Antonio J. , Docker Andrew , Boyd Timothy M. , Baillie Gregg , Reed Rachel , Macgregor Stuart A. , Weller Andrew S.
Published: September 2019

Cationic σ-dihydrogen, σ-amine-borane and neutral hydride complexes, based upon {Rh(PONOP)}, are all shown play a role in the dehydrocoupling of H3B·NMe2H. Movement between the three is promoted by free amine, NMe2H.
Correction: Rapid, versatile and sensitive method for the quantification of radium in environmental samples through cationic extraction and inductively coupled plasma mass spectrometry
Authors: Dalencourt Claire , Michaud Annie , Habibi Azza , Leblanc Alexa , Larivière Dominic
Published: September 2019

Correction for ‘Rapid, versatile and sensitive method for the quantification of radium in environmental samples through cationic extraction and inductively coupled plasma mass spectrometry’ by Claire Dalencourt et al., J. Anal. At. Spectrom., 2018, 33, 1031–1040.
The nanoGRAVUR framework to group (nano)materials for their occupational, consumer, environmental risks based on a harmonized set of material properties, applied to 34 case studies
Authors: Wohlleben Wendel , Hellack Bryan , Nickel Carmen , Herrchen Monika , Hund-Rinke Kerstin , Kettler Katja , Riebeling Christian , Haase Andrea , Funk Birgit , Kühnel Dana , Göhler Daniel , Stintz Michael , Schumacher Christian , Wiemann Martin , Keller Johannes , Landsiedel Robert , Broßell Dirk , Pitzko Sabine , Kuhlbusch Thomas A. J.
Published: September 2019

Grouping can replace animal testing to demonstrate the safe use of nanomaterials, but previously case studies were missing.
Structural characterization of ginseng cyclopeptides and detection of capability to induce apoptosis in gastrointestinal cancer cells
Authors: Liu Zhuo , Fu Junhao , Xiao Shengwei , Wang Dongxin
Published: September 2019

Gastrointestinal tumors are the most frequently diagnosed malignancy and the second highest contributor to cancer mortality.
Development of a fused imidazo[1,2-a]pyridine based fluorescent probe for Fe3+ and Hg2+ in aqueous media and HeLa cells
Authors: Srivastava Suman , Thakur Neha , Singh Ashutosh , Shukla Poonam , Maikhuri Vipin Kumar , Garg Neha , Prasad Ashok , Pandey Rampal
Published: September 2019

A new fluorescent sensor 5 having fused imidazopyridine scaffold has been synthesized via cascade cyclization. It exhibits highly sensitive and selective detection of Fe3+ (‘turn-on’) and Hg2+ (‘turn-off’) in vitro and in HeLa cells.