bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acidic pH shock induces the expressions of a wide range of stress-response genes
Authors: Kim Yoon Jung , Moon Myung Hee , Song Jae Yang , Smith Colin P , Hong Soon-Kwang , Chang Yong Keun 
Published: December 2008

Abstract

Background
Environmental signals usually enhance secondary metabolite production in Streptomycetes by initiating complex signal transduction system. It is known that different sigma factors respond to different types of stresses, respectively in Streptomyces strains, which have a number of unique signal transduction mechanisms depending on the types of environmental shock. In this study, we wanted to know how a pH shock would affect the expression of various sigma factors and shock-related proteins in S. coelicolor A3(2).

Results
According to the results of transcriptional and proteomic analyses, the major number of sigma factor genes were upregulated by an acidic pH shock. Well-studied sigma factor genes of sigH (heat shock), sigR (oxidative stress), sigB (osmotic shock), and hrdD that play a major role in the secondary metabolism, were all strongly upregulated by the pH shock. A number of heat shock proteins including the DnaK family and chaperones such as GroEL2 were also observed to be upregulated by the pH shock, while their repressor of hspR was strongly downregulated. Oxidative stress-related proteins such as thioredoxin, catalase, superoxide dismutase, peroxidase, and osmotic shock-related protein such as vesicle synthases were also upregulated in overall.

Conclusion
From these observations, an acidic pH shock was considered to be one of the strongest stresses to influence a wide range of sigma factors and shock-related proteins including general stress response proteins. The upregulation of the sigma factors and shock proteins already found to be related to actinorhodin biosynthesis was considered to have contributed to enhanced actinorhodin productivity by mediating the pH shock signal to regulators or biosynthesis genes for actinorhodin production.
Microarray-based estimation of SNP allele-frequency in pooled DNA using the Langmuir kinetic model
Authors: Yin Bin-Cheng , Li Honghua , Ye Bang-Ce 
Published: December 2008

Abstract

Background
High throughput genotyping of single nucleotide polymorphisms (SNPs) for genome-wide association requires technologies for generating millions of genotypes with relative ease but also at a reasonable cost and with high accuracy. In this work, we have developed a theoretical approach to estimate allele frequency in pooled DNA samples, based on the physical principles of DNA immobilization and hybridization on solid surface using the Langmuir kinetic model and quantitative analysis of the allelic signals.

Results
This method can successfully distinguish allele frequencies differing by 0.01 in the actual pool of clinical samples, and detect alleles with a frequency as low as 2%. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and actual frequencies having an r2 = 0.9992. These results demonstrated that this method could allow the accurate estimation of absolute allele frequencies in pooled samples of DNA in a feasible and inexpensive way.

Conclusion
We conclude that this novel strategy for quantitative analysis of the ratio of SNP allelic sequences in DNA pools is an inexpensive and feasible alternative for detecting polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans.
Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts
Authors: Lovas Agnes , Radke Dörte , Albrecht Daniela , Yilmaz Z Buket , Möller Ulrich , Habenicht Andreas JR , Weih Falk 
Published: December 2008

AbstractBackgroundLymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described, the classical inhibitor of NF-κB α (IκBα)-regulated and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-κB heterodimers, respectively.ResultsUsing microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryonic fibroblasts (MEFs) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that were regulated by RelA and/or RelB. The majority of LTβR-regulated genes required the presence of both RelA and RelB, revealing significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, LTβR activation inhibited expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (pparg), suggesting that LTβR signaling may interfere with adipogenic differentiation.ConclusionMicroarray analysis of LTβR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB.
Lipopolysaccharide (LPS) potentiates hydrogen peroxide toxicity in T98G astrocytoma cells by suppression of anti-oxidative and growth factor gene expression
Authors: Yue Gang , Shi Guanfang , Azaro Marco A , Yang Qifeng , Hu Guohong , Luo Minjie , Yin Kingsley , Nagele Robert G , Fine Daniel H , Yang Jin-Ming , Li Honghua 
Published: December 2008

AbstractBackgroundLipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria with proved role in pathogenesis of sepsis. Brain injury was observed with both patients dead from sepsis and animal septic models. However,in vitroadministration of LPS has not shown obvious cell damage to astrocytes and other relative cell lines while it does cause endothelial cell deathin vitro. These observations make it difficult to understand the role of LPS in brain parenchymal injury.ResultsTo test the hypothesis that LPS may cause biological changes in astrocytes and make the cells to become vulnerable to reactive oxygen species, a recently developed highly sensitive and highly specific system for large-scale gene expression profiling was used to examine the gene expression profile of a group of 1,135 selected genes in a cell line, T98G, a derivative of human glioblastoma of astrocytic origin. By pre-treating T98G cells with different dose of LPS, it was found that LPS treatment caused a broad alteration in gene expression profile, but did not cause obvious cell death. However, after short exposure to H2O2, cell death was dramatically increased in the LPS pretreated samples. Interestingly, cell death was highly correlated with down-regulated expression of antioxidant genes such as cytochrome b561, glutathione s-transferase a4 and protein kinase C-epsilon. On the other hand, expression of genes encoding growth factors was significantly suppressed. These changes indicate that LPS treatment may suppress the anti-oxidative machinery, decrease the viability of the T98G cells and make the cells more sensitive to H2O2stress.ConclusionThese results provide very meaningful clue for further exploring and understanding the mechanism underlying astrocyte injury in sepsisin vivo, and insight for why LPS could cause astrocyte injuryin vivo, but notin vitro. It will also shed light on the therapeutic strategy of sepsis.
Buffering by gene duplicates: an analysis of molecular correlates and evolutionary conservation
Authors: Hannay Kevin , Marcotte Edward M , Vogel Christine 
Published: December 2008

Abstract

Background
One mechanism to account for robustness against gene knockouts or knockdowns is through buffering by gene duplicates, but the extent and general correlates of this process in organisms is still a matter of debate. To reveal general trends of this process, we provide a comprehensive comparison of gene essentiality, duplication and buffering by duplicates across seven bacteria (Mycoplasma genitalium, Bacillus subtilis, Helicobacter pylori, Haemophilus influenzae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Escherichia coli), and four eukaryotes (Saccharomyces cerevisiae (yeast), Caenorhabditis elegans (worm), Drosophila melanogaster (fly), Mus musculus (mouse)).

Results
In nine of the eleven organisms, duplicates significantly increase chances of survival upon gene deletion (P-value ≤ 0.05), but only by up to 13%. Given that duplicates make up to 80% of eukaryotic genomes, the small contribution is surprising and points to dominant roles of other buffering processes, such as alternative metabolic pathways. The buffering capacity of duplicates appears to be independent of the degree of gene essentiality and tends to be higher for genes with high expression levels. For example, buffering capacity increases to 23% amongst highly expressed genes in E. coli. Sequence similarity and the number of duplicates per gene are weak predictors of the duplicate's buffering capacity. In a case study we show that buffering gene duplicates in yeast and worm are somewhat more similar in their functions than non-buffering duplicates and have increased transcriptional and translational activity.

Conclusion
In sum, the extent of gene essentiality and buffering by duplicates is not conserved across organisms and does not correlate with the organisms' apparent complexity. This heterogeneity goes beyond what would be expected from differences in experimental approaches alone. Buffering by duplicates contributes to robustness in several organisms, but to a small extent – and the relatively large amount of buffering by duplicates observed in yeast and worm may be largely specific to these organisms. Thus, the only common factor of buffering by duplicates between different organisms may be the by-product of duplicate retention due to demands of high dosage.
Environmental rRNA inventories miss over half of protistan diversity
Authors: Jeon Sunok , Bunge John , Leslin Chesley , Stoeck Thorsten , Hong Sunhee , Epstein Slava S 
Published: December 2008

Abstract

Background
The main tool to discover novel microbial eukaryotes is the rRNA approach. This approach has important biases, including PCR discrimination against certain rRNA gene species, which makes molecular inventories skewed relative to the source communities. The degree of this bias has not been quantified, and it remains unclear whether species missed from clone libraries could be recovered by increasing sequencing efforts, or whether they cannot be detected in principle. Here we attempt to discriminate between these possibilities by statistically analysing four protistan inventories obtained using different general eukaryotic PCR primers.

Results
We show that each PCR primer set-specific clone library is not a sample from the community diversity but rather from a fraction of this diversity. Therefore, even sequencing such clone libraries to saturation would only recover that fraction, which, according to the parametric models, varies between 17 ± 4% to 49 ± 10%, depending on the set of primers. The pooled data is thus qualitatively richer than individual libraries, even if normalized to the same sequencing effort.

Conclusion
The use of a single pair of primers leads to significant underestimation of the true community richness at all levels of taxonomic hierarchy. The majority of available protistan rRNA gene surveys likely sampled less than half of the target diversity, and might have completely missed the rest. The use of multiple PCR primers reduces this bias but does not necessarily eliminate it.
Association between Ngb polymorphisms and ischemic stroke in the Southern Chinese Han population
Authors: Lin Yi , Fang Ling , Xue Xie-Hua , Murong Shen-Xing , Wang Ning , Wu Zhi-Ying 
Published: December 2008

Abstract

Background

Neuroglobin (Ngb), one of novel members of the globin superfamily, is expressed predominantly in brain neurons, and appears to modulate hypoxic-ischemic insults. The mechanisms underlying Ngb-mediated neuronal protection are still unclear. For it is one of the candidate protective factors for ischemic stroke, we conducted a case-control study to clarify the association of Ngb polymorphisms with ischemic stroke in the Southern Chinese Han population.

Methods
355 cases and 158 controls were recruited. With brain imaging, cases were subdivided into large-artery atherosclerosis (LVD) and small-vessel occlusion (SVD) stroke. PCR amplified all the four exons of Ngb and flanking intron sequence for each exon. Genotyping for Ngb was achieved by direct sequencing and mismatched PCR-RFLP. Polymorphisms were studied both individually and as haplotypes in each group and subgroup which subdivided according to gender or age.

Results
Two intronic polymorphisms 89+104 c>t and 322-110 (6a)>5a were identified. The allele frequency of 89+104 t was decreased in stroke cases. The protective effect seems to be more pronounced in subgroups of female patients and age > 60 years. Also, we have confirmed decreased LDL-C level and reduced hypertension and hypercholesterolemia in 89+104 t allele carriers. In contrast, the 322-110 (6a)>5a genotype distribution was similar between cases and controls. However, the haplotype 89+104 c>t/322-110 (6a)>5a was related with LVD and SVD stroke. The haplotype c-5a was more frequent in both LVD and SVD groups while t-6a was more frequent in controls.

Conclusion
Ngb polymorphism 89+104 t had protective effects on LVD and SVD in the Southern Chinese Han population. A "hitchhiking" effect was observed for the 89+104 t/322-110 (6a) genotype combination especially for LVD.
Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples
Authors: Ribeiro Franclim Ricardo , Meireles Ana Margarida , Rocha Ana Sofia , Teixeira Manuel Rodrigues 
Published: December 2008

Abstract

Background
Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.

Methods
We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.

Results
The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.

Conclusion
We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.
Gambling problems in the family – A stratified probability sample study of prevalence and reported consequences
Authors: Wenzel Hanne Gro , Øren Anita , Bakken Inger Johanne 
Published: December 2008

Abstract

Background
Prior studies on the impact of problem gambling in the family mainly include help-seeking populations with small numbers of participants. The objective of the present stratified probability sample study was to explore the epidemiology of problem gambling in the family in the general population.

Methods
Men and women 16–74 years-old randomly selected from the Norwegian national population database received an invitation to participate in this postal questionnaire study. The response rate was 36.1% (3,483/9,638). Given the lack of validated criteria, two survey questions ("Have you ever noticed that a close relative spent more and more money on gambling?" and "Have you ever experienced that a close relative lied to you about how much he/she gambles?") were extrapolated from the Lie/Bet Screen for pathological gambling. Respondents answering "yes" to both questions were defined as Concerned Significant Others (CSOs).

Results
Overall, 2.0% of the study population was defined as CSOs. Young age, female gender, and divorced marital status were factors positively associated with being a CSO. CSOs often reported to have experienced conflicts in the family related to gambling, worsening of the family's financial situation, and impaired mental and physical health.

Conclusion
Problematic gambling behaviour not only affects the gambling individual but also has a strong impact on the quality of life of family members.
A Plasmodium yoelii soluble factor inhibits the phenotypic maturation of dendritic cells
Authors: Orengo Jamie M , Wong Kurt A , Ocaña-Morgner Carlos , Rodriguez Ana 
Published: December 2008

AbstractBackgroundInfection with the protozoan parasitePlasmodiumis the cause of malaria.Plasmodiuminfects host erythrocytes causing the pathology of the disease.Plasmodium-infected erythrocytes can modulate the maturation of dendritic cells (DCs) and alter their capacity to activate T cells.MethodsMice infected withPlasmodium yoeliiand isolatedP. yoelii-infected erythrocytes were used to study their effect on the maturation of mouse dendritic cells.ResultsDCs are not able to mature in response to LPS injection during the late stage ofP. yoeliiinfection in mice, indicating impaired functionality of these cellsin vivo.P. yoelii-infected erythrocytes inhibit the maturation of DCsin vitroin a dose-dependent manner, which is consistent with the inhibition found during late infection when parasite burden is highest. The inhibition of DC maturation and the cytokine secretion profile of DCs are modulated by soluble factors released byP. yoelii-infected erythrocytes. A small, heat-stable, non-hydrophobic molecule ofP. yoelii-infected erythrocytes rapidly inhibits the LPS induced phenotypic maturation of DCs in a reversible manner.ConclusionThese findings add evidence to the malaria associated immune suppressionin vivoandin vitroand provide insight into the nature and mechanism of thePlasmodiumfactor(s) responsible for altering DC functions.
Prolyl isomerase Pin1 is highly expressed in Her2-positive breast cancer and regulates erbB2 protein stability
Authors: Lam Prudence B , Burga Laura N , Wu Bryan P , Hofstatter Erin W , Lu Kun Ping , Wulf Gerburg M 
Published: December 2008

AbstractOverexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself.MethodsImmunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence.ResultsSixty-four samples (28.7%) stained positive for Her2 (IHC 3+), and 54% (122/223) of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5%) were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL.ConclusionPin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.
A paraneoplastic manifestation of metastatic breast cancer responding to endocrine therapy: a case report
Authors: Wood Joanna P , Haynes Andrew P , Cheung KL 
Published: December 2008

Abstract

Background
Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.

Case presentation
We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms.

Conclusion
This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause.
It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.