bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opsin gene expression regulated by testosterone level in a sexually dimorphic lizard
Authors: Tseng Wen-Hsuan , Lin Jhan-Wei , Lou Chen-Han , Lee Ko-Huan , Wu Leang-Shin , Wang Tzi-Yuan , Wang Feng-Yu , Irschick Duncan J. , Lin Si-Min 
Published: October 2018

AbstractExpression of nuptial color is usually energetically costly, and is therefore regarded as an ‘honest signal’ to reflect mate quality. In order to choose a mate with high quality, both sexes may benefit from the ability to precisely evaluate their mates through optimizing visual systems which is in turn partially regulated by opsin gene modification. However, how terrestrial vertebrates regulate their color vision sensitivity is poorly studied. The green-spotted grass lizard Takydromus viridipunctatus is a sexually dimorphic lizard in which males exhibit prominent green lateral colors in the breeding season. In order to clarify relationships among male coloration, female preference, and chromatic visual sensitivity, we conducted testosterone manipulation with mate choice experiments, and evaluated the change of opsin gene expression from different testosterone treatments and different seasons. The results indicated that males with testosterone supplementation showed a significant increase in nuptial color coverage, and were preferred by females in mate choice experiments. By using quantitative PCR (qPCR), we also found that higher levels of testosterone may lead to an increase in rhodopsin-like 2 (rh2) and a decrease in long-wavelength sensitive (lws) gene expression in males, a pattern which was also observed in wild males undergoing maturation as they approached the breeding season. In contrast, females showed the opposite pattern, with increased lws and decreased rh2 expression in the breeding season. We suggest this alteration may facilitate the ability of male lizards to more effectively evaluate color cues, and also may provide females with the ability to more effectively evaluate the brightness of potential mates. Our findings suggest that both sexes of this chromatically dimorphic lizard regulate their opsin expression seasonally, which might play an important role in the evolution of nuptial coloration.
Drug survival of biologics in treating psoriasis: a meta-analysis of real-world evidence
Authors: Lin Pei-Tzu , Wang Shu-Hui , Chi Ching-Chi 
Published: October 2018

AbstractDrug survival of biologics represents their real-world effectiveness and safety. We conducted a meta-analysis of real-world evidence on the drug survival of biologics in treating psoriasis. We searched the PubMed, CENTRAL, and EMBASE databases from inception to 7th October 2017 for studies reporting the annual drug survival for at least 1 year. Two authors independently screened and selected relevant studies, and assessed their risk of bias. A third author was available for arbitrating discrepancies. We conducted a random-effects model meta-analysis to obtain the respective pooled drug survival from year 1 to 4. We conducted subgroup analysis on biologic-naïve subjects, discontinuation for loss of efficacy and adverse effects. We included 37 studies with 32,631 subjects. The drug survival for all biologics decreased with time, dropping from 66% at year 1 to 41% at year 4 for etanercept, from 69% to 47% for adalimumab, from 61% to 42% for infliximab, and from 82% to 56% for ustekinumab. Ustekinumab was associated with the highest drug survival in all and biologic-naïve subjects. Etanercept was associated with the lowest drug survival and was most commonly discontinued for loss of efficacy. Infliximab was most frequently associated with discontinuation for adverse effects. Clinicians may use this study as a reference in treating psoriasis.
Intravital imaging with two-photon microscopy reveals cellular dynamics in the ischeamia-reperfused rat heart
Authors: Matsuura Ryohei , Miyagawa Shigeru , Fukushima Satsuki , Goto Takasumi , Harada Akima , Shimozaki Yuri , Yamaki Kazumasa , Sanami Sho , Kikuta Junichi , Ishii Masaru , Sawa Yoshiki 
Published: October 2018

AbstractRecent advances in intravital microscopy have provided insight into dynamic biological events at the cellular level in both healthy and pathological tissue. However, real-time in vivo cellular imaging of the beating heart has not been fully established, mainly due to the difficulty of obtaining clear images through cycles of cardiac and respiratory motion. Here we report the successful recording of clear in vivo moving images of the beating rat heart by two-photon microscopy facilitated by cardiothoracic surgery and a novel cardiac stabiliser. Subcellular dynamics of the major cardiac components including the myocardium and its subcellular structures (i.e., nuclei and myofibrils) and mitochondrial distribution in cardiac myocytes were visualised for 4–5 h in green fluorescent protein-expressing transgenic Lewis rats at 15 frames/s. We also observed ischaemia/reperfusion (I/R) injury-induced suppression of the contraction/relaxation cycle and the consequent increase in cell permeability and leukocyte accumulation in cardiac tissue. I/R injury was induced in other transgenic mouse lines to further clarify the biological events in cardiac tissue. This imaging system can serve as an alternative modality for real time monitoring in animal models and cardiological drug screening, and can contribute to the development of more effective treatments for cardiac diseases.
Genetic and functional diversity of double-stranded DNA viruses in a tropical monsoonal estuary, India
Authors: Jasna Vijayan , Parvathi Ammini , Dash Abhinandita 
Published: October 2018

AbstractThe present study illustrates the genetic diversity of four uncultured viral communities from the surface waters of Cochin Estuary (CE), India. Viral diversity inferred using Illumina HiSeq paired-end sequencing using a linker-amplified shotgun library (LASL) revealed different double-stranded DNA (dsDNA) viral communities. The water samples were collected from four stations PR1, PR2, PR3, and PR4, during the pre-monsoon (PRM) season. Analysis of virus families indicated that the Myoviridae was the most common viral community in the CE followed by Siphoviridae and Podoviridae. There were significant (p < 0.05) spatial variations in the relative abundance of dominant families in response to the salinity regimes. The relative abundance of Myoviridae and Podoviridae were high in the euryhaline region and Siphoviridae in the mesohaline region of the estuary. The predominant phage type in CE was phages that infected Synechococcus. The viral proteins were found to be involved in major functional activities such as ATP binding, DNA binding, and DNA replication. The study highlights the genetic diversity of dsDNA viral communities and their functional protein predictions from a highly productive estuarine system. Further, the metavirome data generated in this study will enhance the repertoire of publicly available dataset and advance our understanding of estuarine viral ecology.
Mutations of FAM111B gene are not associated with Systemic Sclerosis
Authors: Gcelu A. , Deshpande G. , Shaboodien G. , Spracklen T. F. , Kalla A. , Tikly M. , Mayosi B. M. , Hodkinson B 
Published: October 2018

AbstractSystemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (FAM111B) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established FAM111B as a candidate gene for SSc. Patients and Methods: Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in FAM111B. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B. Results: Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two FAM111B genetic variants. The c.917 A > G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988 C > T variant (rs35732637) occurred in three SSc patients and 42/243 (17.3%) of healthy controls, and is a known polymorphism. Conclusion: One rare variant was found in a patient with SSc but has no functional or structural impact on the FAM111B gene. In this cohort, FAM111B gene mutations are not associated with SSc.
Long-ranged Protein-glycan Interactions Stabilize von Willebrand Factor A2 Domain from Mechanical Unfolding
Authors: Dong Chuqiao , Lee Jumin , Kim Seonghoon , Lai Whitney , Webb Edmund B. , Oztekin Alparslan , Zhang X. Frank , Im Wonpil 
Published: October 2018

Abstractvon Willebrand Factor (vWF) is a large multimeric protein that binds to platelets and collagen in blood clotting. vWF A2 domain hosts a proteolytic site for ADAMTS13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) to regulate the size of vWF multimers. This regulation process is highly sensitive to force conditions and protein-glycan interactions as the process occurs in flowing blood. There are two sites on A2 domain (N1515 and N1574) bearing various N-linked glycan structures. In this study, we used molecular dynamics (MD) simulation to study the force-induced unfolding of A2 domain with and without a single N-linked glycan type on each site. The sequential pullout of β-strands was used to represent a characteristic unfolding sequence of A2. This unfolding sequence varied due to protein-glycan interactions. The force-extension and total energy-extension profiles also show differences in magnitude but similar characteristic shapes between the systems with and without glycans. Systems with N-linked glycans encountered higher energy barriers for full unfolding and even for unfolding up to the point of ADAMTS13 cleavage site exposure. Interestingly, there is not much difference observed for A2 domain structure itself with and without glycans from standard MD simulations, suggesting roles of N-glycans in A2 unfolding through long-ranged protein-glycan interactions.
Quantitative study of 18F-(+)DTBZ image: comparison of PET template-based and MRI based image analysis
Authors: Jung Lung Hsu , Weng Yi-Hsin , Wen Ming-Ching , Hsiao Ing-Tsung , Lin Kun-Ju 
Published: October 2018

Abstract[18F]9-fluoropropyl-(+)-dihydrotetrabenazine (18F-(+)DTBZ) is a recently developed PET tracer to investigate the vesicular monoamine transporter type 2 (VMAT2) activity in measuring dopaminergic degeneration in vivo and monitoring the severity of Parkinson’s disease (PD). However, manual drawing of the striatal regions is time consuming and prone to human bias. In the current study, we developed an automated method to quantify the signals of the striatum on 18F-(+)DTBZ images. 39 patients with PD and 26 controls were enrolled. Traditional brain magnetic resonance imaging (MRI) and 18F-(+)DTBZ PET were acquired. Both indirect normalization of native PET images to the standard space through individual brain MRI and directly coregistration of native images to the transporter-specific PET template in standard space were performed. Specific uptake ratios (SURs) in 10 predefined regions were used as indicators of VMAT2 activities to correlate with motor severity. Our results showed patients with PD had significant lower SURs in the bilateral putamina, caudates and globus pallidi than controls. SURs in the caudate and putamen were significantly correlated with motor severity. The contralateral putaminal region performed best in discriminating between PD patients and controls. Finally, the results from the application of the 18F-(+)DTBZ PET template were comparable to those derived from the traditional MRI based method. Thus, 18F-(+)DTBZ PET imaging holds the potential to effectively differentiate PD patients from controls. The 18F-(+)DTBZ PET template-based method for automated quantification of presynaptic VMAT2 transporter density is easier to implement and may facilitate efficient, robust and user-independent image analysis.
A neural network based model effectively predicts enhancers from clinical ATAC-seq samples
Authors: Thibodeau Asa , Uyar Asli , Khetan Shubham , Stitzel Michael L. , Ucar Duygu 
Published: October 2018

AbstractEnhancers are cis-acting sequences that regulate transcription rates of their target genes in a cell-specific manner and harbor disease-associated sequence variants in cognate cell types. Many complex diseases are associated with enhancer malfunction, necessitating the discovery and study of enhancers from clinical samples. Assay for Transposase Accessible Chromatin (ATAC-seq) technology can interrogate chromatin accessibility from small cell numbers and facilitate studying enhancers in pathologies. However, on average, ~35% of open chromatin regions (OCRs) from ATAC-seq samples map to enhancers. We developed a neural network-based model, Predicting Enhancers from ATAC-Seq data (PEAS), to effectively infer enhancers from clinical ATAC-seq samples by extracting ATAC-seq data features and integrating these with sequence-related features (e.g., GC ratio). PEAS recapitulated ChromHMM-defined enhancers in CD14+ monocytes, CD4+ T cells, GM12878, peripheral blood mononuclear cells, and pancreatic islets. PEAS models trained on these 5 cell types effectively predicted enhancers in four cell types that are not used in model training (EndoC-βH1, naïve CD8+ T, MCF7, and K562 cells). Finally, PEAS inferred individual-specific enhancers from 19 islet ATAC-seq samples and revealed variability in enhancer activity across individuals, including those driven by genetic differences. PEAS is an easy-to-use tool developed to study enhancers in pathologies by taking advantage of the increasing number of clinical epigenomes.
Opposite Carcinogenic Effects of Circadian Clock Gene BMAL1
Authors: Korkmaz Tuba , Aygenli Fatih , Emisoglu Handan , Ozcelik Gozde , Canturk Asena , Yilmaz Secil , Ozturk Nuri 
Published: October 2018

AbstractThe circadian clock confers daily rhythmicity on many biochemical and physiological functions and its disruption is associated with increased risks of developing obesity, diabetes, heart disease and cancer. Although, there are studies on the role of Bmal1 in carcinogenesis using germline, conditional or tissue-specific knockouts, it is still not well understood how BMAL1 gene affects cancer-related biological events at the molecular level. We, therefore, took an in vitro approach to understand the contribution of BMAL1 in this molecular mechanism using human breast epithelial cell lines by knocking out BMAL1 gene with CRISPR technology. We preferred epithelial cells over fibroblasts as the most of cancers originate from epithelial cells. After obtaining BMAL1 knockouts by targeting the gene at two different sites from non-tumorigenic MCF10A and invasive tumorigenic MDA-MB-231 cells, we analysed apoptosis and invasion properties of the cell lines as representative events in tumor development. BMAL1 disruption sensitized both cell lines to a bulky-DNA adduct forming agent (cisplatin) and a double-strand break-inducing agent (doxorubicin), while it enhanced the invasive properties of MDA-MB-231 cells. These results show that the disruption of clock genes may have opposing carcinogenic effects.
Standardized phytotherapic extracts rescue anomalous locomotion and electrophysiological responses of TDP-43 Drosophila melanogaster model of ALS
Authors: Maccioni Riccardo , Setzu Maria Dolores , Talani Giuseppe , Solari Paolo , Kasture Ameya , Sucic Sonja , Porru Simona , Muroni Patrizia , Sanna Enrico , Kasture Sanjay , Acquas Elio , Liscia Anna 
Published: October 2018

AbstractFindings from studies using animal models expressing amyotrophic lateral sclerosis (ALS) mutations in RNA-binding proteins, such as Transactive Response DNA-binding protein-43 (TDP-43), indicate that this protein, which is involved in multiple functions, including transcriptional regulation and pre-mRNA splicing, represents a key candidate in ALS development. This study focuses on characterizing, in a Drosophila genetic model of ALS (TDP-43), the effects of Mucuna pruriens (Mpe) and Withania somnifera (Wse). Electrophysiological and behavioural data in TDP-43 mutant flies revealed anomalous locomotion (i.e. impaired climbing with unexpected hyperactivity) and sleep dysregulation. These features, in agreement with previous findings with a different ALS model, were at least partially, rescued by treatment with Mpe and Wse. In addition, electrophysiological recordings from dorsal longitudinal muscle fibers and behavioral observations of TDP-43 flies exposed to the volatile anaesthetics, diethyl ether or chloroform, showed paradoxical responses, which were normalized upon Mpe or Wse treatment. Hence, given the involvement of some potassium channels in the effects of anaesthetics, our results also hint toward a possible dysregulation of some potassium channels in the ALS-TDP-43 Drosophila model, that might shed new light on future therapeutic strategies pertaining to ALS.
Association of domain-specific physical activity and cardiorespiratory fitness with all-cause and cause-specific mortality in two population-based cohort studies
Authors: Bahls Martin , Groß Stefan , Baumeister Sebastian E. , Völzke Henry , Gläser Sven , Ewert Ralf , Markus Marcello R. P. , Medenwald Daniel , Kluttig Alexander , Felix Stephan B. , Dörr Marcus 
Published: October 2018

AbstractPhysical activity (PA) reduces the risk for mortality. Whether the beneficial effects of PA are domain specific is unclear. We associated leisure time (LTPA), sports (SPA) and work (WPA) related PA and cardiorespiratory fitness (CRF) with all-cause mortality in two German population-based cohorts. We used data of the Study of Health in Pomerania (SHIP, n = 2,935, median age 53; 48% male) and the Cardiovascular Disease, Living and Ageing in Halle study (CARLA, n = 1,776, median age 64 and 54% male). Mortality was determined after a median follow-up of 8.2 years in SHIP (n = 332) and 11.5 years in CARLA (n = 409). LTPA (SHIP: hazard ratio [HR] per standard deviation [SD] 0.82 95%-CI 0.73 to 0.91 and CARLA: HR per SD 0.70: 95%-CI 0.59 to 0.82) and SPA (SHIP: HR per SD 0.80 95%-CI 0.71 to 0.91 and CARLA: HR per SD 0.70 95%-CI 0.60 to 0.82) but not WPA were inversely associated with all-cause mortality. In a subsample CRF was inversely related to mortality and positively to LTPA and sports SPA. No association was found for WPA. Our results may suggest that the inverse association between PA and mortality are partly influenced by higher CRF.
Chronic p27Kip1 Induction by Dexamethasone Causes Senescence Phenotype and Permanent Cell Cycle Blockade in Lung Adenocarcinoma Cells Over-expressing Glucocorticoid Receptor
Authors: Patki Mugdha , McFall Thomas , Rosati Rayna , Huang Yanfang , Malysa Agnes , Polin Lisa , Fielder Abigail , Wilson Mike R. , Lonardo Fulvio , Back Jessica , Li Jing , Matherly Larry H. , Bepler Gerold , Ratnam Manohar 
Published: October 2018

AbstractDexamethasone (Dex), co-administered to lung adenocarcinoma patients with pemetrexed chemotherapy, protects against pemetrexed cytotoxicity by inducing reversible G1 arrest, reflected by the effect of Dex on FLT-PET images of patient tumors. However, perioperative Dex treatment increases survival but the mechanism is unknown. In cells with glucocorticoid receptor-α (GR) expression corresponding to higher clinical tumor levels, Dex-induced growth arrest was followed by marked cell expansion, beta-galactosidase expression and Ki67 negativity, despite variable p53 and K-RAS status. Dex induced a transient early surge in p21Cip1. However, a progressive, irreversible loss of clonogenic growth, whose time of onset was dependent on GR level and Dex dose, was independent of p21Cip1and caused by gradual accumulation of p27Kip1 due to transcriptional activation of p27Kip1 by Dex. This effect was independent of canonical pathways of senescence or p27Kip1 regulation. The in vitro observations were reflected by growth suppression and P27Kip1 induction in GR-overexpressing tumor xenografts compared with isogenic low-GR tumors. Extended Dex treatment induces irreversible cell cycle blockade and a senescence phenotype through chronic activation of the p27Kip1 gene in GR overexpressing lung tumor cell populations and hence could improve outcome of surgery/pemetrexed chemotherapy and sensitize tumors to immunotherapy.
Determination of extended substrate specificity of the MALT1 as a strategy for the design of potent substrates and activity-based probes
Authors: Kasperkiewicz Paulina , Kołt Sonia , Janiszewski Tomasz , Groborz Katarzyna , Poręba Marcin , Snipas Scott J. , Salvesen Guy S. , Drąg Marcin 
Published: October 2018

AbstractMucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) belongs to the CD clan of cysteine proteases. MALT1 is a unique enzyme among this clan because it recognizes the basic amino acid arginine in the P1 pocket. Previous studies carried out with natural amino acids revealed the substrate specificity of the P4-P1 pockets of MALT1 but have provided only limited information about the catalytic preferences of this enzyme. In this study, we exploited Hybrid Combinatorial Substrate Library and Internally Quenched Fluorescence substrate technologies to interrogate the extended substrate specificity profile of the S5-S2’ active site pockets using unnatural amino acids. This strategy resulted in the design of a peptide-based fluorogenic substrate, which exhibited significant activity toward MALT1. Subsequently, the substrate sequence was further utilized to develop potent, irreversible activity-based probes.
Origin of radiation resistance in multi-principal element alloys
Authors: Do Hyeon-Seok , Lee Byeong-Joo 
Published: October 2018

AbstractUsing molecular dynamics simulations, we characterized the generation and evolution of radiation-induced point defects in the CoCrFeMnNi high-entropy alloy (HEA), to compare it with pure Ni and pure Fe. The generation of primary point defects was investigated by a cascade simulation at 773 K and the evolution of point defect clusters by a defect evolution simulation using 1 at% defect-containing samples. The numbers of residual defects after cascade and surviving defects after evolution in the CoCrFeMnNi HEA are smaller than those in pure Ni and pure Fe. The defect clusters appearing in the CoCrFeMnNi HEA after the defect evolution are unstable because of the alloy complexity. The origin of the slower radiation damage accumulation and the higher radiation damage tolerance in the CoCrFeMnNi HEA is discussed.