bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genes involved in thoracic exoskeleton formation during the pupal-to-adult molt in a social insect model, Apis mellifera
Authors: Soares Michelle Prioli Miranda , Barchuk Angel Roberto , Simões Ana Carolina Quirino , dos Santos Cristino Alexandre , de Paula Freitas Flávia Cristina , Canhos Luísa Lange , Bitondi Márcia Maria Gentile 
Published: August 2013

AbstractBackgroundThe insect exoskeleton provides shape, waterproofing, and locomotionviaattached somatic muscles. The exoskeleton is renewed during molting, a process regulated by ecdysteroid hormones. The holometabolous pupa transforms into an adult during the imaginal molt, when the epidermis synthe3sizes the definitive exoskeleton that then differentiates progressively. An important issue in insect development concerns how the exoskeletal regions are constructed to provide their morphological, physiological and mechanical functions. We used whole-genome oligonucleotide microarrays to screen for genes involved in exoskeletal formation in the honeybee thoracic dorsum. Our analysis included three sampling times during the pupal-to-adult molt, i.e., before, during and after the ecdysteroid-induced apolysis that triggers synthesis of the adult exoskeleton.ResultsGene ontology annotation based on orthologous relationships withDrosophila melanogastergenes placed the honeybee differentially expressed genes (DEGs) into distinct categories of Biological Process and Molecular Function, depending on developmental time, revealing the functional elements required for adult exoskeleton formation. Of the 1,253 unique DEGs, 547 were upregulated in the thoracic dorsum after apolysis, suggesting induction by the ecdysteroid pulse. The upregulated gene set included 20 of the 47 cuticular protein (CP) genes that were previously identified in the honeybee genome, and three novel putative CP genes that do not belong to a known CP family.In situhybridization showed that two of the novel genes were abundantly expressed in the epidermis during adult exoskeleton formation, strongly implicating them as genuine CP genes. Conserved sequence motifs identified the CP genes as members of the CPR, Tweedle, Apidermin, CPF, CPLCP1 and Analogous-to-Peritrophins families. Furthermore, 28 of the 36 muscle-related DEGs were upregulated during thede novoformation of striated fibers attached to the exoskeleton. A search forcis-regulatory motifs in the 5′-untranslated region of the DEGs revealed potential binding sites for known transcription factors. Construction of a regulatory network showed that various upregulated CP- and muscle-related genes (15 and 21 genes, respectively) share common elements, suggesting co-regulation during thoracic exoskeleton formation.ConclusionsThese findings help reveal molecular aspects of rigid thoracic exoskeleton formation during the ecdysteroid-coordinated pupal-to-adult molt in the honeybee.
Genome-wide modeling of complex phenotypes in Caenorhabditis elegans and Drosophila melanogaster
Authors: De Supriyo , Zhang Yongqing , Wolkow Catherine A , Zou Sige , Goldberg Ilya , Becker Kevin G 
Published: August 2013

Abstract

Background
The genetic and molecular basis for many intermediate and end stage phenotypes in model systems such as C. elegans and D. melanogaster has long been known to involve pleiotropic effects and complex multigenic interactions. Gene sets are groups of genes that contribute to multiple biological or molecular phenomena. They have been used in the analysis of large molecular datasets such as microarray data, Next Generation sequencing, and other genomic datasets to reveal pleiotropic and multigenic contributions to phenotypic outcomes. Many model systems lack species specific organized phenotype based gene sets to enable high throughput analysis of large molecular datasets.

Results and discussion
Here, we describe two novel collections of gene sets in C. elegans and D. melanogaster that are based exclusively on genetically determined phenotypes and use a controlled phenotypic ontology. We use these collections to build genome-wide models of thousands of defined phenotypes in both model species. In addition, we demonstrate the utility of these gene sets in systems analysis and in analysis of gene expression-based molecular datasets and show how they are useful in analysis of genomic datasets connecting multigenic gene inputs to complex phenotypes.

Conclusions
Phenotypic based gene sets in both C. elegans and D. melanogaster are developed, characterized, and shown to be useful in the analysis of large scale species-specific genomic datasets. These phenotypic gene set collections will contribute to the understanding of complex phenotypic outcomes in these model systems.
The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide
Authors: Kapetanovic Ronan , Fairbairn Lynsey , Downing Alison , Beraldi Dario , Sester David P , Freeman Tom C , Tuggle Christopher K , Archibald Alan L , Hume David A 
Published: August 2013

Abstract

Background
The draft genome of the domestic pig (Sus scrofa) has recently been published permitting refined analysis of the transcriptome. Pig breeds have been reported to differ in their resistance to infectious disease. In this study we examine whether there are corresponding differences in gene expression in innate immune cells

Results
We demonstrate that macrophages can be harvested from three different compartments of the pig (lungs, blood and bone-marrow), cryopreserved and subsequently recovered and differentiated in CSF-1. We have performed surface marker analysis and gene expression profiling on macrophages from these compartments, comparing twenty-five animals from five different breeds and their response to lipopolysaccharide. The results provide a clear distinction between alveolar macrophages (AM) and monocyte-derived (MDM) and bone-marrow-derived macrophages (BMDM). In particular, the lung macrophages express the growth factor, FLT1 and its ligand, VEGFA at high levels, suggesting a distinct pathway of growth regulation. Relatively few genes showed breed-specific differential expression, notably CXCR2 and CD302 in alveolar macrophages. In contrast, there was substantial inter-individual variation between pigs within breeds, mostly affecting genes annotated as being involved in immune responses.

Conclusions
Pig macrophages more closely resemble human, than mouse, in their set of macrophage-expressed and LPS-inducible genes. Future research will address whether inter-individual variation in macrophage gene expression is heritable, and might form the basis for selective breeding for disease resistance.
Endogenous retroviruses and multiple sclerosis–new pieces to the puzzle
Authors: Nissen Kari K , Laska Magdalena J , Hansen Bettina , Terkelsen Thorkild , Villesen Palle , Bahrami Shervin , Petersen Thor , Pedersen Finn S , Nexø Bjørn A 
Published: August 2013

Abstract
The possibility that retroviruses play a role in multiple sclerosis (MS) has long been considered; accumulating findings suggest this to be most likely in the form of human endogenous retroviruses (HERVs). A genetic test series of fifty endogenous retroviral loci for association with MS in Danes showed SNP markers near a specific endogenous retroviral locus, HERV-Fc1 located on the X-chromosome, to be positive. Bout Onset MS was associated with the HERV-Fc1 locus, while a rarer form, Primary Progressive MS, was not. Moreover, HERV-Fc1 Gag RNA in plasma was increased 4-fold in patients with recent history of attacks, relative to patients in a stable state and to healthy controls.
Finally, genetic variations in restriction genes for retroviruses influence the risk of MS, providing further support for a role of retroviral elements in disease.
We speculate that endogenous retroviruses may activate the innate immune system in a variety of ways, involving the host proteins, TRIMs, TLRs, TREXs and STING. Observations in HIV-positive patients suggest that antiretroviral drugs can curb MS. Thus, these new findings regarding the etiology and pathogenesis of MS, suggest alternative ways to challenge autoimmune diseases.
EURO-WABB: an EU rare diseases registry for Wolfram syndrome, Alström syndrome and Bardet-Biedl syndrome
Authors: Farmer Amy , Aymé Ségolène , de Heredia Miguel Lopez , Maffei Pietro , McCafferty Susan , Młynarski Wojciech , Nunes Virginia , Parkinson Kay , Paquis-Flucklinger Véronique , Rohayem Julia , Sinnott Richard , Tillmann Vallo , Tranebjærg Lisbeth , Barrett Timothy G 
Published: August 2013

AbstractBackgroundWolfram, Alström and Bardet-Biedl (WABB) syndromes are rare diseases with overlapping features of multiple sensory and metabolic impairments, including diabetes mellitus, which have caused diagnostic confusion. There are as yet no specific treatments available, little or no access to well characterized cohorts of patients, and limited information on the natural history of the diseases. We aim to establish a Europe-wide registry for these diseases to inform patient care and research.MethodsEURO-WABB is an international multicenter large-scale observational study capturing longitudinal clinical and outcome data for patients with WABB diagnoses. Three hundred participants will be recruited over 3 years from different sites throughout Europe. Comprehensive clinical, genetic and patient experience data will be collated into an anonymized disease registry. Data collection will be web-based, and forms part of the project’s Virtual Research and Information Environment (VRIE). Participants who haven’t undergone genetic diagnostic testing for their condition will be able to do so via the project.ConclusionsThe registry data will be used to increase the understanding of the natural history of WABB diseases, to serve as an evidence base for clinical management, and to aid the identification of opportunities for intervention to stop or delay the progress of the disease. The detailed clinical characterisation will allow inclusion of patients into studies of novel treatment interventions, including targeted interventions in small scale open label studies; and enrolment into multi-national clinical trials. The registry will also support wider access to genetic testing, and encourage international collaborations for patient benefit.
Ssanghwa-tang, an oriental herbal cocktail, exerts anti-melanogenic activity by suppression of the p38 MAPK and PKA signaling pathways in B16F10 cells
Authors: Kim Aeyung , Yim Nam-Hui , Im Minju , Jung Young Pil , Liang Chun , Cho Won-Kyung , Ma Jin Yeul 
Published: August 2013

Abstract

Background
Ssanghwa-tang (SHT) is a widely used medication for the treatment of fatigue, pain, inflammation, hypothermia, erectile dysfunction, cancer, and osteoporosis in Asia, however, role of SHT on the melanin synthesis has not been checked previously. Thus, the present study was designed to determine the effect of SHT on α-melanocyte stimulating hormone (α-MSH)-induced melanogensis and its mechanisms of action in murine B16F10 melanoma cells.

Method
Cellular melanin content and tyrosinase activity in murine B16F10 melanoma cells were determined after α-MSH stimulation with or without pre-treatment of SHT at the concentration of 250 and 500 μg/ml. Expression level of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, microphthalmia-associated transcription factor (MITF), and activation of c-AMP-dependent protein kinase (PKA), c-AMP-related element binding protein (CREB), and mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis.

Results
SHT significantly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of MITF, tyrosinase, and TRP-1. In addition, SHT remarkably suppressed tyrosinase, CRE, and MITF luciferase reporter activity in a resting state as well as in α-MSH-stimulating condition. Phosphorylation of p38 MAPK by α-MSH stimulation was efficiently blocked by SHT pre-treatment. Moreover, SHT as an herbal cocktail showed synergistic anti-melanogenic effect compared with that of each single constituent herb.

Conclusion
SHT efficiently inhibited c-AMP-induced melanin synthesis in B16F10 cells via suppression of PKA and p38 MAPK signaling pathways and subsequently decreased the level of CREB phosphorylation, MITF, and melanogenic enzymes. These results indicate that SHT may be useful as herbal medicine for treating hyperpigmentation and cosmetics as a skin-whitening agent.
Glycolipid metabolic status of overweight/obese adolescents aged 9- to 15-year-old and the BMI-SDS/BMI cut-off value of predicting dyslipidemiain boys, Shanghai, China: a cross-sectional study
Authors: Gong Chun-dan , Wu Qiao-ling , Chen Zheng , Zhang Dan , Zhao Zheng-yan , Peng Yong-mei 
Published: August 2013

AbstractBackgroundThe prevalence of adolescents’ obesity and overweight has dramatically elevated in China. Obese children were likely to insulin resistance and dyslipidemia, which are risk factors of cardiovascular diseases. However there was no cut-off point of anthropometric values to predict the risk factors in Chinese adolescents. The present study was to investigate glycolipid metabolism status of adolescents in Shanghai and to explore the correlations between body mass index standard deviation score (BMI-SDS) and metabolic indices, determine the best cut-off value of BMI-SDS to predict dyslipidemia.MethodsFifteen schools in Shanghai’s two districts were chosen by cluster sampling and primary screening was done in children aged 9-15 years old. After screening of bodyweight and height, overweight and obese adolescents and age-matched children with normal body weight were randomly recruited in the study. Anthropometric measurements, biochemical measurements of glycolipid profiles were done. SPSS19.0 was used to analyze the data. Receiver operating characteristic (ROC) curves were made and the best cut-off values of BMI-SDS to predict dyslipidemia were determined while the Youden indices were maximum.ResultsFive hundred and thirty-eight adolescents were enrolled in this research, among which 283 have normal bodyweight, 115 were overweight and 140 were obese. No significant differences of the ages among 3 groups were found. There were significant differences of WC-SDS (p<0.001), triacylglycerol (p<0.05), high and low density lipoprotein cholesterol (p<0.01), fasting insulin (p<0.01) and C-peptide (p<0.001) among 3 groups. Significant difference of fasting glucose was only found between normal weight and overweight group. Significant difference of total cholesterol was found between obese and normal weight group. There was no significant difference of glycated hemoglobin among 3 groups. The same tendency was found in boys but not in girls. Only HDL-C reduced and TG increased while BMI elevated in girls. The best cut-off value of BMI-SDS was 1.22 to predict dyslipidemia in boys. The BMI cut-off was 21.67 in boys.ConclusionOverweight and obese youths had reduced insulin sensitivity and high prevalence of dyslipidemia. When BMI-SDS elevated up to 1.22 and BMI was higher than 21.67 in boys, dyslipidemia may happen.
GRK2 blockade with βARKct is essential for cardiac β2-adrenergic receptor signaling towards increased contractility
Authors: Salazar Norma C , Vallejos Ximena , Siryk Ashley , Rengo Giuseppe , Cannavo Alessandro , Liccardo Daniela , De Lucia Claudio , Gao Erhe , Leosco Dario , Koch Walter J , Lymperopoulos Anastasios 
Published: August 2013

AbstractBackgroundβ1- and β2–adrenergic receptors (ARs) play distinct roles in the heart, e.g. β1AR is pro-contractile and pro-apoptotic but β2AR anti-apoptotic and only weakly pro-contractile. G protein coupled receptor kinase (GRK)-2 desensitizes and opposes βAR pro-contractile signaling by phosphorylating the receptor and inducing beta-arrestin (βarr) binding. We posited herein that GRK2 blockade might enhance the pro-contractile signaling of the β2AR subtype in the heart. We tested the effects of cardiac-targeted GRK2 inhibition in vivo exclusively on β2AR signaling under normal conditions and in heart failure (HF).ResultsWe crossed β1AR knockout (B1KO) mice with cardiac-specific transgenic mice expressing the βARKct, a known GRK2 inhibitor, and studied the offspring under normal conditions and in post-myocardial infarction (MI). βARKct expression in vivo proved essential for β2AR-dependent contractile function, as β2AR stimulation with isoproterenol fails to increase contractility in either healthy or post-MI B1KO mice and it only does so in the presence of βARKct. The main underlying mechanism for this is blockade of the interaction of phosphodiesterase (PDE) type 4D with the cardiac β2AR, which is normally mediated by the actions of GRK2 and βarrs on the receptor. The molecular “brake” that PDE4D poses on β2AR signaling to contractility stimulation is thus “released”. Regarding the other beneficial functions of cardiac β2AR, βARKct increased overall survival of the post-MI B1KO mice progressing to HF, via a decrease in cardiac apoptosis and an increase in wound healing-associated inflammation early (at 24 hrs) post-MI. However, these effects disappear by 4 weeks post-MI, and, in their place, upregulation of the other major GRK in the heart, GRK5, is observed.ConclusionsGRK2 inhibition in vivo with βARKct is absolutely essential for cardiac β2AR pro-contractile signaling and function. In addition, β2AR anti-apoptotic signaling in post-MI HF is augmented by βARKct, although this effect is short-lived.
Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy
Authors: Zhao Hongjuan , Thong Alan , Nolley Rosalie , Reese Stephen W , Santos Jennifer , Ingels Alexandre , Peehl Donna M 
Published: August 2013

Abstract

Background
Effective eradication of high-risk primary prostate cancer (HRPCa) could significantly decrease mortality from prostate cancer. However, the discovery of curative therapies for HRPCa is hampered by the lack of authentic preclinical models.

Methods
We improved upon tumorgraft models that have been shown to predict drug response in other cancer types by implanting thin, precision-cut slices of HRPCa under the renal capsule of immunodeficient mice. Tissue slice grafts (TSGs) from 6 cases of HRPCa were established in mice. Following androgen deprivation by castration, TSGs were recovered and the presence and phenotype of cancer cells were evaluated.

Results
High-grade cancer in TSGs generated from HRPCa displayed characteristic Gleason patterns and biomarker expression. Response to androgen deprivation therapy (ADT) was as in humans, with some cases exhibiting complete pathologic regression and others showing resistance to castration. As in humans, ADT decreased cell proliferation and prostate-specific antigen expression in TSGs. Adverse pathological features of parent HRPCa were associated with lack of regression of cancer in corresponding TSGs after ADT. Castration-resistant cancer cells remaining in TSGs showed upregulated expression of androgen receptor target genes, as occurs in castration-resistant prostate cancer (CRPC) in humans. Finally, a rare subset of castration-resistant cancer cells in TSGs underwent epithelial-mesenchymal transition, a process also observed in CRPC in humans.

Conclusions
Our study demonstrates the feasibility of generating TSGs from multiple patients and of generating a relatively large number of TSGs from the same HRPCa specimen with similar cell composition and histology among control and experimental samples in an in vivo setting. The authentic response of TSGs to ADT, which has been extensively characterized in humans, suggests that TSGs can serve as a surrogate model for clinical trials to achieve rapid and less expensive screening of therapeutics for HRPCa and primary CRPC.
Charge storage characteristics of Au nanocrystal memory improved by the oxygen vacancy-reduced HfO2 blocking layer
Authors: Tang Ruifan , Huang Kai , Lai Hongkai , Li Cheng , Wu Zhiming , Kang Junyong 
Published: August 2013

Abstract
This study characterizes the charge storage characteristics of metal/HfO2/Au nanocrystals (NCs)/SiO2/Si and significantly improves memory performance and retention time by annealing the HfO2 blocking layer in O2 ambient at 400°C. Experimental evidence shows that the underlying mechanism can be effectively applied to reduce oxygen vacancy and suppress unwanted electron trap-assisted tunneling. A memory window of 1 V at an applied sweeping voltage of ±2 V is also shown. The low program/erase voltage (±2 V) and the promising retention performances indicate the potential application of NCs in low-voltage, non-volatile memory devices.
Carrier frequency offset estimation method for 2 × 1 MISO TDS-OFDM systems
Authors: Oh Jong Gyu , Heo Jun , Kim Joon Tae 
Published: August 2013

Abstract
In time-domain synchronous (TDS)-orthogonal frequency division multiplexing (OFDM) systems, a pseudo noise (PN) sequence is inserted instead of the cyclic prefix. The PN sequence is used not only as a guard interval but also as a training sequence for channel estimation and synchronization in the time domain. Recently, research studies on 2 × 1 multi input-single output (MISO) TDS-OFDM systems have been conducted, and different PN sequences (which are orthogonal to one another or cyclically shifted) are transmitted at each transmit antenna for channel estimation, which are modulated by binary phase shift keying in the same phase angle. However, when the absolute phase difference among the transmitted PN sequences is π, a PN sequence cancellation problem occurs, making the estimation of an accurate carrier frequency offset (CFO) difficult. In this paper, a CFO estimation method with the aid of PN sequences for 2 × 1 MISO TDS-OFDM systems is proposed. In the proposed method, the phase of the PN sequences at each antenna is rotated differently and transmitted to prevent a PN sequence-canceling problem. In addition, a CFO estimation scheme using channel state information is proposed to estimate an accurate CFO in time-varying channels. We show by computer simulations that the mean square error performance of the proposed method over an additive white Gaussian noise environment and time-varying Rayleigh channel is higher than that of the conventional method.