bluuebunny/crossref_metadata_2025_split huggingface dataset:
The duration of gastrin treatment affects global gene expression and molecular responses involved in ER stress and anti-apoptosis
Authors: Selvik Linn-Karina M , Fjeldbo Christina S , Flatberg Arnar , Steigedal Tonje S , Misund Kristine , Anderssen Endre , Doseth Berit , Langaas Mette , Tripathi Sushil , Beisvag Vidar , Lægreid Astrid , Thommesen Liv , Bruland Torunn 
Published: June 2013

Abstract

Background
How cells decipher the duration of an external signal into different transcriptional outcomes is poorly understood. The hormone gastrin can promote a variety of cellular responses including proliferation, differentiation, migration and anti-apoptosis. While gastrin in normal concentrations has important physiological functions in the gastrointestine, prolonged high levels of gastrin (hypergastrinemia) is related to pathophysiological processes.

Results
We have used genome-wide microarray time series analysis and molecular studies to identify genes that are affected by the duration of gastrin treatment in adenocarcinoma cells. Among 403 genes differentially regulated in transiently (gastrin removed after 1 h) versus sustained (gastrin present for 14 h) treated cells, 259 genes upregulated by sustained gastrin treatment compared to untreated controls were expressed at lower levels in the transient mode. The difference was subtle for early genes like Junb and c-Fos, but substantial for delayed and late genes. Inhibition of protein synthesis by cycloheximide was used to distinguish between primary and secondary gastrin regulated genes. The majority of gastrin upregulated genes lower expressed in transiently treated cells were primary genes induced independently of de novo protein synthesis. This indicates that the duration effect of gastrin treatment is mainly mediated via post-translational signalling events, while a smaller fraction of the differentially expressed genes are regulated downstream of primary transcriptional events. Indeed, sustained gastrin treatment specifically induced prolonged ERK1/2 activation and elevated levels of the AP-1 subunit protein JUNB. Enrichment analyses of the differentially expressed genes suggested that endoplasmic reticulum (ER) stress and survival is affected by the duration of gastrin treatment. Sustained treatment exerted an anti-apoptotic effect on serum starvation-induced apoptosis via a PKC-dependent mechanism. In accordance with this, only sustained treatment induced anti-apoptotic genes like Clu, Selm and Mcl1, while the pro-apoptotic gene Casp2 was more highly expressed in transiently treated cells. Knockdown studies showed that JUNB is involved in sustained gastrin induced expression of the UPR/ER stress related genes Atf4, Herpud1 and Chac1.

Conclusion
The duration of gastrin treatment affects both intracellular signalling mechanisms and gene expression, and ERK1/2 and AP-1 seem to play a role in converting different durations of gastrin treatment into distinct cellular responses.
Genetic variability of mutans streptococci revealed by wide whole-genome sequencing
Authors: Song Lifu , Wang Wei , Conrads Georg , Rheinberg Anke , Sztajer Helena , Reck Michael , Wagner-Döbler Irene , Zeng An-Ping 
Published: June 2013

Abstract

Background
Mutans streptococci are a group of bacteria significantly contributing to tooth decay. Their genetic variability is however still not well understood.

Results
Genomes of 6 clinical S. mutans isolates of different origins, one isolate of S. sobrinus (DSM 20742) and one isolate of S. ratti (DSM 20564) were sequenced and comparatively analyzed. Genome alignment revealed a mosaic-like structure of genome arrangement. Genes related to pathogenicity are found to have high variations among the strains, whereas genes for oxidative stress resistance are well conserved, indicating the importance of this trait in the dental biofilm community. Analysis of genome-scale metabolic networks revealed significant differences in 42 pathways. A striking dissimilarity is the unique presence of two lactate oxidases in S. sobrinus DSM 20742, probably indicating an unusual capability of this strain in producing H2O2 and expanding its ecological niche. In addition, lactate oxidases may form with other enzymes a novel energetic pathway in S. sobrinus DSM 20742 that can remedy its deficiency in citrate utilization pathway.
Using 67 S. mutans genomes currently available including the strains sequenced in this study, we estimates the theoretical core genome size of S. mutans, and performed modeling of S. mutans pan-genome by applying different fitting models. An “open” pan-genome was inferred.

Conclusions
The comparative genome analyses revealed diversities in the mutans streptococci group, especially with respect to the virulence related genes and metabolic pathways. The results are helpful for better understanding the evolution and adaptive mechanisms of these oral pathogen microorganisms and for combating them.
Comparative genomic analysis of six bacteria belonging to the genus Novosphingobium: insights into marine adaptation, cell-cell signaling and bioremediation
Authors: Gan Han Ming , Hudson André O , Rahman Ahmad Yamin Abdul , Chan Kok Gan , Savka Michael A 
Published: June 2013

Abstract

Background
Bacteria belonging to the genus Novosphingobium are known to be metabolically versatile and occupy different ecological niches. In the absence of genomic data and/or analysis, knowledge of the bacteria that belong to this genus is currently limited to biochemical characteristics. In this study, we analyzed the whole genome sequencing data of six bacteria in the Novosphingobium genus and provide evidence to show the presence of genes that are associated with salt tolerance, cell-cell signaling and aromatic compound biodegradation phenotypes. Additionally, we show the taxonomic relationship between the sequenced bacteria based on phylogenomic analysis, average amino acid identity (AAI) and genomic signatures.

Results
The taxonomic clustering of Novosphingobium strains is generally influenced by their isolation source. AAI and genomic signature provide strong support the classification of Novosphingobium sp. PP1Y as Novosphingobium pentaromaticivorans PP1Y. The identification and subsequent functional annotation of the unique core genome in the marine Novosphingobium bacteria show that ectoine synthesis may be the main contributing factor in salt water adaptation. Genes coding for the synthesis and receptor of the cell-cell signaling molecules, of the N-acyl-homoserine lactones (AHL) class are identified. Notably, a solo luxR homolog was found in strain PP1Y that may have been recently acquired via horizontal gene transfer as evident by the presence of multiple mobile elements upstream of the gene. Additionally, phylogenetic tree analysis and sequence comparison with functionally validated aromatic ring hydroxylating dioxygenases (ARDO) revealed the presence of several ARDOs (oxygenase) in Novosphingobium bacteria with the majority of them belonging to the Groups II and III of the enzyme.

Conclusions
The combination of prior knowledge on the distinctive phenotypes of Novosphingobium strains and meta-analysis of their whole genomes enables the identification of several genes that are relevant in industrial applications and bioremediation. The results from such targeted but comprehensive comparative genomics analysis have the potential to contribute to the understanding of adaptation, cell-cell communication and bioremediation properties of bacteria belonging to the genus Novosphingobium.
Enriched environment and masticatory activity rehabilitation recover spatial memory decline in aged mice
Authors: Mendes Fabíola de Carvalho Chaves de Sique , de Almeida Marina Negrão Frota , Felício André Pinheiro Gurgel , Fadel Ana Carla , Silva Diego de Jesus , Borralho Thaíssa Gomes , da Silva Rodrigo Perez , Bento-Torres João , Vasconcelos Pedro Fernando da Costa , Perry Victor Hugh , Ramos Edson Marcos Leal Soares , Picanço-Diniz Cristovam Wanderley , Sosthenes Marcia Consentino Kronka 
Published: June 2013

Abstract

Background
To measure the impact of masticatory reduction on learning and memory, previous studies have produced experimental masticatory reduction by modified diet or molar removal. Here we induced spatial learning impairment in mice by reducing masticatory activity and then tested the effect of a combination of environmental enrichment and masticatory rehabilitation in recovering spatial learning at adulthood and in later life. For 6 months (6M) or 18 months (18M), we fed three groups of mice from postnatal day 21 respectively with a hard diet (HD) of pellets; pellets followed by a powdered, soft diet (HD/SD, divided into equal periods); or pellets followed by powder, followed by pellets again (HD/SD/HD, divided into equal periods). To mimic sedentary or active lifestyles, half of the animals from each group were raised from weaning in standard cages (impoverished environment; IE) and the other half in enriched cages (enriched environment; EE). To evaluate spatial learning, we used the Morris water maze.

Results
IE6M-HD/SD mice showed lower learning rates compared with control (IE6M-HD) or masticatory rehabilitated (IE6MHD/SD/HD) animals. Similarly, EE-HD/SD mice independent of age showed lower performance than controls (EE-HD) or rehabilitated mice (EE-HD/SD/HD). However, combined rehabilitation and EE in aged mice improved learning rate up to control levels. Learning rates did not correlate with swim speed.

Conclusions
Reduction in masticatory activity imposed on mice previously fed a hard diet (HD/SD) impaired spatial learning in the Morris water maze. In adults, masticatory rehabilitation recovered spatial abilities in both sedentary and active mice, and rehabilitation of masticatory activity combined with EE recovered these losses in aged mice.
Perception of quality of care among residents of public nursing-homes in Spain: a grounded theory study
Authors: Rodríguez-Martín Beatriz , Martínez-Andrés María , Cervera-Monteagudo Beatriz , Notario-Pacheco Blanca , Martínez-Vizcaíno Vicente 
Published: June 2013

Abstract

Background
The quality of care in nursing homes is weakly defined, and has traditionally focused on quantify nursing homes outputs and on comparison of nursing homes’ resources. Rarely the point of view of clients has been taken into account. The aim of this study was to ascertain what means “quality of care” for residents of nursing homes.

Methods
Grounded theory was used to design and analyze a qualitative study based on in-depth interviews with a theoretical sampling including 20 persons aged over 65 years with no cognitive impairment and eight proxy informants of residents with cognitive impairment, institutionalized at a public nursing home in Spain.

Results
Our analysis revealed that participants perceived the quality of care in two ways, as aspects related to the persons providing care and as institutional aspects of the care’s process. All participants agreed that aspects related to the persons providing care was a pillar of quality, something that, in turn, embodied a series of emotional and technical professional competences. Regarding the institutional aspects of the care’s process, participants laid emphasis on round-the-clock access to health care services and on professional’s job stability.

Conclusions
This paper includes perspectives of the nursing homes residents, which are largely absent. Incorporating residents’ standpoints as a complement to traditional institutional criteria would furnish health providers and funding agencies with key information when it came to designing action plans and interventions aimed at achieving excellence in health care.
Functional characterisation of human cells harbouring a novel t(2p;7p) translocation involving TNS3 and EXOC6Bgenes
Authors: Ludwig Desiree , Carter Jessica , Smith James R , Borsani Giuseppe , Barlati Sergio , Hafizi Sassan 
Published: June 2013

AbstractBackgroundTensin3 is an intracellular cytoskeleton-regulating protein, the loss of which is associated with increased cell motility, as has been observed in some human cancers. A novel chromosomal translocation, t(2;7)(p13;p12), present in a patient with a complex syndromic phenotype, directly involves Tensin3 (TNS3) andEXOC6Bgenes. This translocation could impair the expression of Tensin3 and ExoC6B proteins, and potentially produce two novel fusion transcripts. In the present study, we have investigated the expression and phenotypic features of these potential products in cultured cells from the proband.MethodsSkin fibroblasts isolated from the proband as well as an age-matched control were grown in cell culture. Cells were used for quantitative RT-PCR, western blot and immunofluorescent confocal microscopy, which determined Tensin3 gene and protein expression. Phase-contrast and confocal microscopy additionally revealed cellular phenotype differences. A scratch wound assay monitored by live cell imaging measured cellular migration rates.ResultsThe levels of Tensin3 at both mRNA and protein levels were lower in proband cells versus control fibroblasts. Proband cells displayed broader and shorter morphologies versus control fibroblasts, and immunofluorescent staining revealed additional Tensin3 expression along cytoskeletal filaments and the cell periphery only in control fibroblasts. In addition, proband fibroblasts showed a significantly higher migration rate than control cells over 24 h.ConclusionsThe phenotypic changes observed in proband cells may arise fromTNS3haploinsufficiency, causing partial loss of full-length Tensin3 protein. These results further expose a role for Tensin3 in cytoskeletal organisation and cell motility and may also help to explain the syndromic features observed in the patient.
Induction of chromosome instability and stomach cancer by altering the expression pattern of mitotic checkpoint genes in mice exposed to areca-nut
Authors: Kurkalang Sillarine , Banerjee Atanu , Ghoshal Nitin , Dkhar Hughbert , Chatterjee Anupam 
Published: June 2013

Abstract

Background
There are strong indications for a causal association between areca-nut consumption and cancers. In Meghalaya, India, the variety of areca-nut is used as raw and unprocessed form whose chemical composition and pharmacological actions have been reported. Yet we know little on the initial pathway involved in areca-nut associated carcinogenesis since it is difficult to assess its effects on genetic alterations without interference of other compounding factors. Therefore, present study was undertaken in mice to verify the ability of raw areca-nut (RAN) to induce cancer and to monitor the expression of certain genes involved in carcinogenesis. This study was not intended to isolate any active ingredients from the RAN and to look its action.

Methods
Three groups of mice (n = 25 in each) were taken and used at different time-points for different experimental analysis. The other three groups of mice (n = 15 in each) were considered for tumor induction studies. In each set, two groups were administered RAN-extract ad libitum in drinking water with or without lime. The expression of certain genes was assessed by conventional RT-PCR and immunoblotting. The mice were given the whole RAN-extract with and without lime in order to mimic the human consumption style of RAN.

Results
Histological preparation of stomach tissue revealed that RAN induced stomach cancer. A gradual increase in the frequency of precocious anaphase and aneuploid cells was observed in the bone marrow cells with a greater increment following RAN + lime administeration. Levels of p53, Bax, Securin and p65 in esophageal and stomach cells were elevated during early days of RAN exposure while those of different mitotic checkpoint proteins were downregulated. Apoptotic cell death was detected in non-cancerous stomach cells but not in tumor cells which showed overexpression of Bax and absence of PARP.

Conclusion
Present study suggested (a) RAN induces stomach cancer, however, presence of lime promoted higher cell transformation and thereby developed cancer earlier, (b) perturbations in components of the chromosome segregation machinery could be involved in the initial process of carcinogenicity and (c) the importance of precocious anaphase as a screening marker for identification of mitotic checkpoint defects during early days.
Immunomodulatory activity of polysaccharides isolated from Clerodendrum splendens: Beneficial effects in experimental autoimmune encephalomyelitis
Authors: Kouakou Koffi , Schepetkin Igor A , Jun SangMu , Kirpotina Liliya N , Yapi Ahoua , Khramova Daria S , Pascual David W , Ovodov Yury S , Jutila Mark A , Quinn Mark T 
Published: June 2013

AbstractBackgroundExtracts of leaves fromClerodendrumhave been used for centuries to treat a variety of medicinal problems in tropical Africa. However, little is known about the high-molecular weight active components conferring therapeutic properties to these extracts.MethodsPolysaccharides from the leaves ofClerodendrum splendenswere extracted and fractionated by ion exchange and size-exclusion chromatography. Molecular weight determination, sugar analysis, degree of methyl esterification, and other chemical characterization of the fractions were performed. Immunomodulatory activity of the fractions was evaluated by determining their ability to induce monocyte/macrophage nitric oxide (NO), cytokine production, and mitogen-activated protein kinase (MAPK) phosphorylation. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice, and severity of EAE was monitored in mice treated with intraperitoneal (i.p.) injections of the most active polysaccharide fraction. Lymph nodes (LN) and spleen were harvested, and levels of cytokines in supernatants from LN cells and splenocytes challenged with myelin oligodendrocyte glycoprotein peptide were determined.ResultsFractions containing type II arabinogalactan had potent immunomodulatory activity. Specifically, the high-molecular weight sub-fractionCSP-AU1(average of 38.5 kDa) induced NO and cytokine [interleukin (IL)-1α, -1β, -6, -10, tumor necrosis factor (TNF; designated previously as TNF-α), and granulocyte macrophage-colony stimulating factor (GM-CSF)] production by human peripheral blood mononuclear cells (PBMCs) and monocyte/macrophages.CSP-AU1-induced secretion of TNF was prevented by Toll-like receptor 4 (TLR4) antagonist LPS-RS, indicating a role for TLR4 signaling. Treatment withCSP-AU1also induced phosphorylation of a number of MAPKs in human PBMC and activated AP-1/NF-κB.In vivotreatment of mice withCSP-AU1andCSP-NU1resulted in increased serum IL-6, IL-10, TNF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α/CCL3, and MIP-1β/CCL4.CSP-AU1treatment of mice with EAE (50 mg/kg,i.p., daily, 13 days) resulted in significantly reduced disease severity in this experimental model of multiple sclerosis. Levels of IL-13, TNF, interferon (IFN)-γ, IL-17, and GM-CSF were also significantly decreased, whereas transforming growth factor (TGF)-β was increased in LN cells fromCSP-AU1-treated EAE mice.ConclusionsPolysaccharideCSP-AU1is a potent natural innate immunomodulator with a broad spectrum of agonist activityin vitroand immunosupressive properties after chronic administrationin vivo.
Production of hydroxycinnamoyl anthranilates from glucose in Escherichia coli
Authors: Eudes Aymerick , Juminaga Darmawi , Baidoo Edward E K , Collins F William , Keasling Jay D , Loqué Dominique 
Published: June 2013

Abstract

Background
Oats contain hydroxycinnamoyl anthranilates, also named avenanthramides (Avn), which have beneficial health properties because of their antioxidant, anti-inflammatory, and antiproliferative effects. The microbial production of hydroxycinnamoyl anthranilates is an eco-friendly alternative to chemical synthesis or purification from plant sources. We recently demonstrated in yeast (Saccharomyces cerevisiae) that coexpression of 4-coumarate: CoA ligase (4CL) from Arabidopsis thaliana and hydroxycinnamoyl/benzoyl-CoA/anthranilate N-hydroxycinnamoyl/benzoyltransferase (HCBT) from Dianthus caryophyllus enabled the biological production of several cinnamoyl anthranilates upon feeding with anthranilate and various cinnamates. Using engineering strategies to overproduce anthranilate and hydroxycinnamates, we describe here an entire pathway for the microbial synthesis of two Avns from glucose in Escherichia coli.

Results
We first showed that coexpression of HCBT and Nt4CL1 from tobacco in the E. coli anthranilate-accumulating strain W3110 trpD9923 allowed the production of Avn D [N-(4′-hydroxycinnamoyl)-anthranilic acid] and Avn F [N-(3′,4′-dihydroxycinnamoyl)-anthranilic acid] upon feeding with p-coumarate and caffeate, respectively. Moreover, additional expression in this strain of a tyrosine ammonia-lyase from Rhodotorula glutinis (Rg TAL) led to the conversion of endogenous tyrosine into p-coumarate and resulted in the production of Avn D from glucose. Second, a 135-fold improvement in Avn D titer was achieved by boosting tyrosine production using two plasmids that express the eleven genes necessary for tyrosine synthesis from erythrose 4-phosphate and phosphoenolpyruvate. Finally, expression of either the p-coumarate 3-hydroxylase Sam5 from Saccharothrix espanensis or the hydroxylase complex HpaBC from E. coli resulted in the endogenous production of caffeate and biosynthesis of Avn F.

Conclusion
We established a biosynthetic pathway for the microbial production of valuable hydroxycinnamoyl anthranilates from an inexpensive carbon source. The proposed pathway will serve as a platform for further engineering toward economical and sustainable bioproduction of these pharmaceuticals and other related aromatic compounds.
Hierarchical level features based trainable segmentation for electron microscopy images
Authors: Wang Shuangling , Cao Guibao , Wei Benzheng , Yin Yilong , Yang Gongping , Li Chunming 
Published: June 2013

Abstract

Background
The neuronal electron microscopy images segmentation is the basic and key step to efficiently build the 3D brain structure and connectivity for a better understanding of central neural system. However, due to the visual complex appearance of neuronal structures, it is challenging to automatically segment membranes from the EM images.

Methods
In this paper, we present a fast, efficient segmentation method for neuronal EM images that utilizes hierarchical level features based on supervised learning. Hierarchical level features are designed by combining pixel and superpixel information to describe the EM image. For pixels in a superpixel have similar characteristics, only part of them is automatically selected and used to reduce information redundancy. To each selected pixel, 34 dimensional features are extracted by traditional way. Each superpixel itself is viewed as a unit to extract 35 dimensional features with statistical method. Also, 3 dimensional context level features among multi superpixels are extracted. Above three kinds of features are combined as a feature vector, namely, hierarchical level features to use for segmentation. Random forest is used as classifier and is trained with hierarchical level features to perform segmentation.

Results
In small sample condition and with low-dimensional features, the effectiveness of our method is verified on the data set of ISBI2012 EM Segmentation Challenge, and its rand error, warping error and pixel error attain to 0.106308715, 0.001200104 and 0.079132453, respectively.

Conclusions
Comparing to pixel level or superpixel level features, hierarchical level features have better discrimination ability and the proposed method is promising for membrane segmentation.