bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prion subcellular fractionation reveals infectivity spectrum, with a high titre-low PrPreslevel disparity
Authors: Lewis Victoria , Haigh Cathryn L , Masters Colin L , Hill Andrew F , Lawson Victoria A , Collins Steven J 
Published: April 2012

Abstract

Background
Prion disease transmission and pathogenesis are linked to misfolded, typically protease resistant (PrPres) conformers of the normal cellular prion protein (PrPC), with the former posited to be the principal constituent of the infectious 'prion'. Unexplained discrepancies observed between detectable PrPres and infectivity levels exemplify the complexity in deciphering the exact biophysical nature of prions and those host cell factors, if any, which contribute to transmission efficiency. In order to improve our understanding of these important issues, this study utilized a bioassay validated cell culture model of prion infection to investigate discordance between PrPres levels and infectivity titres at a subcellular resolution.

Findings
Subcellular fractions enriched in lipid rafts or endoplasmic reticulum/mitochondrial marker proteins were equally highly efficient at prion transmission, despite lipid raft fractions containing up to eight times the levels of detectable PrPres. Brain homogenate infectivity was not differentially enhanced by subcellular fraction-specific co-factors, and proteinase K pre-treatment of selected fractions modestly, but equally reduced infectivity. Only lipid raft associated infectivity was enhanced by sonication.

Conclusions
This study authenticates a subcellular disparity in PrPres and infectivity levels, and eliminates simultaneous divergence of prion strains as the explanation for this phenomenon. On balance, the results align best with the concept that transmission efficiency is influenced more by intrinsic characteristics of the infectious prion, rather than cellular microenvironment conditions or absolute PrPres levels.
Anti-proliferative effects of Salacia reticulata leaves hot-water extract on interleukin-1β-activated cells derived from the synovium of rheumatoid arthritis model mice
Authors: Sekiguchi Yuusuke , Mano Hiroshi , Nakatani Sachie , Shimizu Jun , Kobata Kenji , Wada Masahiro 
Published: April 2012

Abstract

Background

Salacia reticulata (SR) is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL) to inhibit in vitro the interleukin-1β (IL-1β)-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice.

Findings
Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC), liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and protease digestion.
The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 μg/mL. Treatment with a low dose (25 μg dry matter per millilitre) of the extract inhibited IL-1β-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP) genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1β-activated cell proliferation.

Conclusions
We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1β-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins.
Effects of vitamin D supplementation on the bone specific biomarkers in HIV infected individuals under treatment with efavirenz
Authors: Etminani-Esfahani Maryam , Khalili Hossein , Jafari Sirous , Abdollahi Alireza , Dashti-Khavidaki Simin 
Published: April 2012

Abstract

Background
It was reported that antiretroviral drugs such as efavirenz can increase the catabolism of vitamin D in HIV infected individuals. We have not found any study that evaluated effects of vitamin D supplementation on the bone specific biomarkers in HIV positive patients under treatment with antiretroviral regimen containing efavirenz.

Findings
Vitamin D deficiency was detected in 88.4 % of included patients. Baseline osteocalcin, but not collagen telopeptidase, serum levels were lower than normal range in all of these individuals. Both bone biomarkers’ concentrations increased significantly (p < 0.001 for both of them) after supplementation of vitamin D and it was more predominant for osteocalcin.
Vitamin D deficiency was detected in 88.4 % of included patients. Baseline osteocalcin, but not collagen telopeptidase, serum levels were lower than normal range in all of these individuals. Both bone biomarkers’ concentrations increased significantly (p < 0.001 for both of them) after supplementation of vitamin D and it was more predominant for osteocalcin.

Conclusion
In the HIV-infected patients under treatment with efavirenz, vitamin D deficiency is prevalent. After supplementation with single dose of 300,000 IU vitamin D in this population, the activation of osteoblasts and osteoclasts stimulates bone formation and resorption respectively with favorable bone formation without any adverse event. Significant percent of HIV infected individuals are vitamin d deficient that could benefit from vitamin D supplementation.
Barrel cortical neurons and astrocytes coordinately respond to an increased whisker stimulus frequency
Authors: Zhao Jun , Wang Dangui , Wang Jin-Hui 
Published: April 2012

Abstract

Background
Nerve cells program the brain codes to manage well-organized cognitions and behaviors. It remains unclear how a population of neurons and astrocytes work coordinately to encode their spatial and temporal activity patterns in response to frequency and intensity signals from sensory inputs.

Results
With two-photon imaging and electrophysiology to record cellular functions in the barrel cortex in vivo, we analyzed the activity patterns of neurons and astrocytes in response to whisker stimuli with increasing frequency, an environmental stimulus pattern that rodents experience in the accelerated motion. Compared to the resting state, whisker stimulation caused barrel neurons and astrocytes to be activated more synchronously. An increased stimulus frequency up-regulated the activity strength of neurons and astrocytes as well as coordinated their interaction. The coordination among the barrel neurons and astrocytes was fulfilled by increasing their functional connections.

Conclusions
Our study reveals that the nerve cells in the barrel cortex encode frequency messages in whisker tactile inputs through setting their activity coordination.
Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity
Authors: Wang Min , Li Shupeng , Zhang Hongyu , Pei Lin , Zou Shengwei , Lee Frank JS , Wang Yu Tian , Liu Fang 
Published: April 2012

Abstract
Over-activation of AMPARs (α−amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors) is implicated in excitotoxic neuronal death associated with acute brain insults, such as ischemic stroke. However, the specific molecular mechanism by which AMPARs, especially the calcium-impermeable AMPARs, induce neuronal death remains poorly understood. Here we report the identification of a previously unrecognized molecular pathway involving a direct protein-protein interaction that underlies GluR2-containing AMPAR-mediated excitotoxicity. Agonist stimulation of AMPARs promotes GluR2/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) complex formation and subsequent internalization. Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia.
Clinical significance of stanniocalcin-1 detected in peripheral blood and bone marrow of esophageal squamous cell carcinoma patients
Authors: Song Haizhu , Xu Biao , Yi Jun 
Published: April 2012

Abstract

Background
Stanniocalcin-1 (STC-1) is a potential marker of disseminated tumor cells (DTCs). The aim of this study was to examine STC-1 expression in peripheral blood (PB) and bone marrow (BM) of esophageal squamous cell carcinoma (ESCC) patients, and to evaluate its clinical significance.

Methods
A total of 85 ESCC patients treated with radical resection were enrolled in this study. Immunohistochemistry was used to detect STC-1 protein expression in ESCC tissues. Nested RT-PCR was used to detect STC-1 mRNA expression in PB and BM.

Results
There were 71 cases (83.5%) showed a higher level of STC-1 protein expression in tumor tissues than in adjacent normal tissues (P < 0.001). Furthermore, the frequencies of STC-1 mRNA expression detected in PB and BM were 37.6% (32/85) and 21.2% (18/85), respectively, and together increased sensitivity to 48.2% (41/85), which was much higher than that in patients with benign esophageal disease (5.0%, 2/40, P < 0.001). In addition, STC-1 mRNA expression either in PB or BM was correlated with lymph metastasis, advanced stage and adverse 2-year progression free survival (PFS). In a multivariate analysis using the Cox proportional hazard model, STC-1 expression in PB and/or BM was an independent unfavorable prognostic factor for ESCC, apart from lymph metastasis and clinical stage.

Conclusions
STC-1 mRNA expression is a reliable marker for detection of DTCs in PB and BM of ESCC patients, and STC-1-positive DTCs may be a promising tool for diagnosis and prognosis assessment in ESCC.
Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma: efficacy and safety
Authors: Ma Yue , Xu Ying-Chun , Tang Lei , Zhang Zan , Wang Jian , Wang Hong-Xia 
Published: April 2012

Abstract

Purpose
To evaluate the efficacy of cytokine-induced killer (CIK) cell therapy in the treatment of hepatocellular carcinoma.

Materials and methods
Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells".

Results
The analysis showed significant survival benefit (one-year survival, p < 0.001; two-year survival, p < 0.001; median overall survival, p < 0.001) in favor of CIK-based therapy. Comparison of CIK group versus non-CIK group resulted in a significantly prolonged progression-free survival (PFS) (p < 0.01). A favored disease control rate (DCR) and overall response rate (ORR) were also observed in patients receiving CIK cell therapy (p < 0.01). Meanwhile, patients in the CIK group showed better quality of life (QoL), diminished HBV-DNA content and AFP level (p < 0.01). Comparing T-lymphocyte subsets in peripheral blood, the analysis showed the ratio of CD3+, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p < 0.01).

Conclusions
CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.
Examination of PHB Depolymerases in Ralstonia eutropha: Further Elucidation of the Roles of Enzymes in PHB Homeostasis
Authors: Brigham Christopher J , Reimer Esther N , Rha ChoKyun , Sinskey Anthony J 
Published: April 2012

Abstract
Polyhydroxyalkanoates (PHA) are biodegradable polymers that are attractive materials for use in tissue engineering and medical device manufacturing. Ralstonia eutropha is regarded as the model organism for PHA biosynthesis. We examined the effects of PHA depolymerase (PhaZ) expression on PHA homeostasis in R. eutropha strains. In order to analyze the impact of PhaZs on R. eutropha granule architecture, we performed electron microscopy on several phaZ knockout strains and the wild type strain grown under PHA production conditions. Analysis of the acquired micrographs was based on stereology: the ratio of granule area and cell area was determined, along with total granule count per full-size cell image. Cells bearing a phaZ2 knockout mutation alone or in conjunction with a phaZ1 mutation were found to have a high granule volume per cell volume and a higher granule count compared to wild type. A phaZ quadruple knockout strain appeared to have a low granule volume per cell volume and a low granule count per cell. Cells bearing a phaZ3 knockout were found to have a higher granule count than the wild type, whereas granule volume per cell volume was similar. Accordingly, we hypothesize that PhaZs have not only an impact on PHA degradation but also on the 3-dimensional granule architecture. Based on our data, PhaZ2 is postulated to affect granule density. This work increased our knowledge about PHA depolymerases in R. eutropha, including enzymes that had previously been uncharacterized.
Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA)
Authors: Too Chun Lai , Yahya Abqariyah , Murad Shahnaz , Dhaliwal Jasbir Singh , Larsson Per Tobias , Muhamad Nor Asiah , Abdullah Nor Aini , Mustafa Amal Nasir , Klareskog Lars , Alfredsson Lars , Padyukov Leonid , Bengtsson Camilla ,   MyEIRA study group
Published: April 2012

Abstract
Introduction
Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent.

Methods
A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated.

Results
In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA.

Conclusions
The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.
CIP2A is a target of bortezomib in human triple negative breast cancer cells
Authors: Tseng Ling-Ming , Liu Chun-Yu , Chang Kung-Chi , Chu Pei-Yi , Shiau Chung-Wai , Chen Kuen-Feng 
Published: April 2012

Abstract
Introduction
Triple negative breast cancer (TNBC) is very aggressive and currently has no specific therapeutic targets, such as hormone receptors or human epidermal growth factor receptor type 2 (HER2); therefore, prognosis is poor. Bortezomib, a proteasome inhibitor, may exert efficacy in TNBC through its multiple cellular effects. Here, we tested the efficacy of bortezomib and examined the drug mechanism in breast cancer cells.

Methods
Five breast cancer cell lines: TNBC HCC-1937, MDA-MB-231, and MDA-MB-468; HER2-overexpressing MDA-MB-453; and estrogen receptor positive MCF-7 were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western Blot. Signal transduction pathways in cells were assessed by Western Blot. Gene silencing was done by small interfering RNA (siRNA). In vivo efficacy of bortezomib was tested in nude mice with breast cancer xenografts. Immunohistochemical study was performed on tumor tissues from patients with TNBC.

Results
Bortezomib induced significant apoptosis, which was independent of its proteasome inhibition, in the three TNBC cell lines, but not in MDA-MB-453 or MCF-7 cells. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A), a cellular inhibitor of protein phosphatase 2A (PP2A), mediated the apoptotic effect of bortezomib. We showed that bortezomib inhibited CIP2A in association with p-Akt downregulation in a dose- and time-dependent manner in all sensitive TNBC cells, whereas no alterations in CIP2A expression and p-Akt were noted in bortezomib-resistant cells. Overexpression of CIP2A upregulated p-Akt and protected MDA-MB-231 and MDA-MB-468 cells from bortezomib-induced apoptosis, whereas silencing CIP2A by siRNA overcame the resistance to bortezomib-induced apoptosis in MCF-7 cells. In addition, bortezomib downregulated CIP2A mRNA but did not affect the degradation of CIP2A protein. Furthermore, bortezomib exerted in vivo antitumor activity in HCC-1937 xenografted tumors, but not in MCF-7 tumors. Bortezomib downregulated CIP2A expression in the HCC-1937 tumors but not in the MCF-7 tumors. Importantly, CIP2A expression is readily detectable in tumor samples from TNBC patients.

Conclusions
CIP2A is a major determinant mediating bortezomib-induced apoptosis in TNBC cells. CIP2A may thus be a potential therapeutic target in TNBC.
Global mRNA decay analysis at single nucleotide resolution reveals segmental and positional degradation patterns in a Gram-positive bacterium
Authors: Kristoffersen Simen M , Haase Chad , Weil M Ryan , Passalacqua Karla D , Niazi Faheem , Hutchison Stephen K , Desany Brian , Kolstø Anne-Brit , Tourasse Nicolas J , Read Timothy D , Økstad Ole Andreas 
Published: April 2012

Abstract
Background
Recent years have shown a marked increase in the use of next-generation sequencing technologies for quantification of gene expression (RNA sequencing, RNA-Seq). The expression level of a gene is a function of both its rate of transcription and RNA decay, and the influence of mRNA decay rates on gene expression in genome-wide studies of Gram-positive bacteria is under-investigated.

Results
In this work, we employed RNA-Seq in a genome-wide determination of mRNA half-lives in the Gram-positive bacterium Bacillus cereus. By utilizing a newly developed normalization protocol, RNA-Seq was used successfully to determine global mRNA decay rates at the single nucleotide level. The analysis revealed positional degradation patterns, with mRNAs being degraded from both ends of the molecule, indicating that both 5' to 3' and 3' to 5' directions of RNA decay are present in B. cereus. Other operons showed segmental degradation patterns where specific ORFs within polycistrons were degraded at variable rates, underlining the importance of RNA processing in gene regulation. We determined the half-lives for more than 2,700 ORFs in B. cereus ATCC 10987, ranging from less than one minute to more than fifteen minutes, and showed that mRNA decay rate correlates globally with mRNA expression level, GC content, and functional class of the ORF.

Conclusions
To our knowledge, this study presents the first global analysis of mRNA decay in a bacterium at single nucleotide resolution. We provide a proof of principle for using RNA-Seq in bacterial mRNA decay analysis, revealing RNA processing patterns at the single nucleotide level.
Detection and characterization of small focal hepatic lesions (≤2.5 cm in diameter): a comparison of diffusion-weighted images before and after administration of gadoxetic acid disodium at 3.0T
Authors: Song Kyoung Doo , Kim Young Kon , Lee Won Jae , Lee Min Woo , Park Min Jung , Hwang Jiyoung , Lee Mi Hee 
Published: April 2012

Background As diffusion-weighted imaging (DWI) is routinely incorporated into the standard clinical protocol, it is clinically relevant to determine whether DWI after gadoxetic acid is comparable to pre-contrast DWI, with regard to the detection and characterization of focal liver lesions. Purpose To compare DWI before and after administration of gadoxetic acid in the detection and characterization of small (≤2.5 cm) focal hepatic lesions. Material and Methods One hundred and fifty-eight patients with 237 focal hepatic lesions (≤2.5 cm) (124 HCCs, 50 metastases, 2 cholangiocarcinomas, 43 hemangiomas, and 18 cysts) were included. DWIs were obtained before and after administration of gadoxetic acid. Non-breath-hold DWI was performed with b values of 0, 100, and 800 s/mm2. Signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and apparent diffusion coefficients (ADCs) of the liver and lesion were calculated. Lesion detection with each DWI was evaluated with alternative free-response receiver-operating characteristic analysis by two observers. The sensitivity of the characterization of focal hepatic lesions as solid (malignancy) or non-solid (benignity) with each DWI was calculated using a five-point confidence scale. Inter-observer agreement regarding lesion detection and characterization was evaluated using kappa statistics. Results SNRs of the liver on post-contrast DWI were significantly lower than on unenhanced DWI at b = 800 s/mm2 ( P < 0.05). SNRs, CNRs, and ADCs of focal hepatic lesions were not significantly different between two DWIs ( P > 0.05). The diagnostic accuracy (Az) for lesion detection and the sensitivity for lesion characterization did not show significant difference between two DWIs ( P > 0.05). With regard to the detection and characterization of focal hepatic lesions, the kappa values for two DWIs indicated good and excellent inter-observer agreement, respectively. Conclusion Gadoxetic acid-enhanced DWI showed comparable diagnostic capability to unenhanced DWI for the detection and characterization of small focal hepatic lesions.