bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gadolinium Containing Photochromic Micelles as Potential Magnetic Resonance Imaging Traceable Drug Carriers
Authors: Heta Yushi , Kumaki Kentaro , Hifumi Hiroki , Citterio Daniel , Tanimoto Akihiro , Suzuki Koji 
Published: February 2012

AbstractNovel photochromic amphipathic molecules, KMR‐AZn (Gd‐DTPA‐AZCn), composed of hydrophilic Gd‐DTPA and hydrophobic alkylated azobenzene were prepared. In aqueous environment, KMR‐AZn indicated self‐assembly. The resulting aggregates were demonstrated to be able to include a hydrophobic drug substitute (hydrophobic fluorescent dye) into the internal core, and to release the included compound upon photoirradiation within 10 min through the influence of azobenzene photoisomerization. This micellar MRI contrast agent exhibited three‐ to four‐fold higher r1 relaxivity (r1 = 14.5–16.5 mm−1 s−1, 0.47 T at 40°C) than the widely applied small molecule contrast agent Gd‐DTPA (Magnevist®r1 = 4.1 mm−1 s−1, 0.47 T at 40°C). This dual functionality of encapsulated compound release and increased MR imaging contrast indicates that KMR‐AZn is a potential candidate for application as a lipid‐based MRI‐traceable drug carrier.
Theoretical Study of Absorption and Fluorescence Spectra of Firefly Luciferin in Aqueous Solutions
Authors: Hiyama Miyabi , Akiyama Hidefumi , Yamada Kenta , Koga Nobuaki 
Published: February 2012

AbstractThe absorption and fluorescence spectra of firefly luciferin, which is an analog of oxyluciferin, are investigated by performing the density functional theory (DFT) calculations, especially focusing on the experimentally unassigned peaks. Time‐dependent DFT calculations are performed for the excited states of firefly luciferin and its conjugate acids and bases. We find that (1) the peaks in the experimental absorption spectra correspond to the excited states of not only (6′O−, 4COO−) and (6′OH, 4COO−), but also (6′OH, 4COOH) and (6′OH, 3H+, 4COOH); (2) the peaks in the experimental fluorescence spectra correspond to the excited states of not only (6′O−, 4COO−), but also (6′OH, 4COO−), (6′O−, 4COOH), (6′OH, 4COOH) and (6′OH, 3H+, 4COOH); (3) the unassigned peak near 400 nm in the experimental absorption spectra at pH 1 is assigned to the absorption from the equilibrium ground state to the first excited state of (6′OH, 3H+, 4COOH); and (4) the unassigned peak at 610 nm in the experimental fluorescence spectra corresponds to the transition from the equilibrium first excited state to the ground state of (6′OH, 4COO−).
Presence of a Large β(1-3)Glucan Linked to Chitin at the Saccharomyces cerevisiae Mother-Bud Neck Suggests Involvement in Localized Growth Control
Authors: Cabib Enrico , Blanco Noelia , Arroyo Javier 
Published: February 2012

ABSTRACT

Previous results suggested that the chitin ring present at the yeast mother-bud neck, which is linked specifically to the nonreducing ends of β(1-3)glucan, may help to suppress cell wall growth at the neck by competing with β(1-6)glucan and thereby with mannoproteins for their attachment to the same sites. Here we explored whether the linkage of chitin to β(1-3)glucan may also prevent the remodeling of this polysaccharide that would be necessary for cell wall growth. By a novel mild procedure, β(1-3)glucan was isolated from cell walls, solubilized by carboxymethylation, and fractionated by size exclusion chromatography, giving rise to a very high-molecular-weight peak and to highly polydisperse material. The latter material, soluble in alkali, may correspond to glucan being remodeled, whereas the large-size fraction would be the final cross-linked structural product. In fact, the β(1-3)glucan of buds, where growth occurs, is solubilized by alkali. A
gas1
mutant with an expected defect in glucan elongation showed a large increase in the polydisperse fraction. By a procedure involving sodium hydroxide treatment, carboxymethylation, fractionation by affinity chromatography on wheat germ agglutinin-agarose, and fractionation by size chromatography on Sephacryl columns, it was shown that the β(1-3)glucan attached to chitin consists mostly of high-molecular-weight material. Therefore, it appears that linkage to chitin results in a polysaccharide that cannot be further remodeled and does not contribute to growth at the neck. In the course of these experiments, the new finding was made that part of the chitin forms a noncovalent complex with β(1-3)glucan.
Role of the NiFe Hydrogenase Hya in Oxidative Stress Defense in Geobacter sulfurreducens
Authors: Tremblay Pier-Luc , Lovley Derek R. 
Published: February 2012

ABSTRACT

Geobacter sulfurreducens
, an Fe(III)-reducing deltaproteobacterium found in anoxic subsurface environments, contains 4 NiFe hydrogenases. Hyb, a periplasmically oriented membrane-bound NiFe hydrogenase, is essential for hydrogen-dependent growth. The functions of the three other hydrogenases are unknown. We show here that the other periplasmically oriented membrane-bound NiFe hydrogenase, Hya, is necessary for growth after exposure to oxidative stress when hydrogen or a highly limiting concentration of acetate is the electron source. The beneficial impact of Hya on growth was dependent on the presence of H
2
in the atmosphere. Moreover, the Hya-deficient strain was more sensitive to the presence of superoxide or hydrogen peroxide. Hya was also required to safeguard Hyb hydrogen oxidation activity after exposure to O
2
. Overexpression studies demonstrated that Hya was more resistant to oxidative stress than Hyb. Overexpression of Hya also resulted in the creation of a recombinant strain better fitted for exposure to oxidative stress than wild-type
G. sulfurreducens
. These results demonstrate that one of the physiological roles of the O
2
-resistant Hya is to participate in the oxidative stress defense of
G. sulfurreducens
.
Repression of Salmonella entericaphoPExpression by Small Molecules from Physiological Bile
Authors: Antunes L. Caetano M. , Wang Melody , Andersen Sarah K. , Ferreira Rosana B. R. , Kappelhoff Reinhild , Han Jun , Borchers Christoph H. , Finlay B. Brett 
Published: February 2012

ABSTRACTInfection withSalmonella entericaserovar Typhi in humans causes the life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice withSalmonella entericaserovar Typhimurium. Using this murine model, we previously characterized the interactions betweenSalmonellaTyphimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed thatSalmonellaTyphimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions betweenSalmonellaand the gallbladder environment, we compared the transcriptomes ofSalmonellacultures grown in LB broth or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect ofSalmonellainteractions with bile through the identification of the global regulatorphoPas a bile-responsive gene. Repression ofphoPexpression could also be achieved using physiological, but not commercial, bovine bile. The biological activity does not involve PhoPQ sensing of a bile component and is not caused by bile acids, the most abundant organic components of bile. Bioactivity-guided purification allowed the identification of a subset of small molecules from bile that can elicit full activity; however, a single compound withphoPinhibitory activity could not be isolated, suggesting that multiple molecules may act in synergy to achieve this effect. Due to the critical role ofphoPinSalmonellavirulence, further studies in this area will likely reveal aspects of the interaction betweenSalmonellaand bile that are relevant to disease.
GntR-Type Transcriptional Regulator PckR Negatively Regulates the Expression of Phosphoenolpyruvate Carboxykinase in Corynebacterium glutamicum
Authors: Hyeon Jeong Eun , Kang Dae Hee , Kim Young In , You Seung Kyou , Han Sung Ok 
Published: February 2012

ABSTRACT

The
pck
(
cg3169
) gene of
Corynebacterium glutamicum
encodes a phosphoenolpyruvate carboxykinase (PEPCK). Here, a candidate transcriptional regulator that binds to the promoter region of
pck
was detected using a DNA affinity purification approach. An isolated protein was identified to be PckR (Cg0196), a GntR family transcriptional regulator which consists of 253 amino acids with a mass of 27 kDa as measured by peptide mass fingerprinting. The results of electrophoretic mobility shift assays verified that PckR specifically binds to the
pck
promoter. The putative regulator binding region extended from position −44 to −27 (an 18-bp sequence) relative to the transcriptional start point of the
pck
gene. We measured the expression of
pck
in a
pckR
deletion mutant by using quantitative real-time reverse transcription-PCR. The expression level of
pck
in the
pckR
mutant was 7.6 times higher than that in wild-type cells grown in glucose. Comparative DNA microarray hybridizations and bioinformatic searches revealed the gene composition of the transcriptional regulon of
C. glutamicum
. Based on these results, PckR seemed to play an important role in the regulation of PEPCK in
C. glutamicum
grown in glucose. In particular, these assays revealed that PckR acts as a repressor of
pck
expression during glucose metabolism.
A Stress-Inducible Quorum-Sensing Peptide Mediates the Formation of Persister Cells with Noninherited Multidrug Tolerance
Authors: Leung Vincent , Lévesque Céline M. 
Published: February 2012

ABSTRACT

Within a given microbial population, a small subpopulation known as dormant persister cells exists. This persistence property ensures the survival of the population as a whole in the presence of lethal factors. Although persisters are highly important in antibiotic therapy, the mechanism for persistence is still not thoroughly understood. We show here that the cariogenic organism
Streptococcus mutans
forms persister cells showing noninherited multidrug tolerance. We demonstrated that the ectopic expression of the type II toxin-antitoxin systems, MazEF and RelBE, caused an increase in the number of persisters. In a search for additional persistence genes, an expression library was constructed, and several clones exhibiting a significant difference in persister formation after prolonged antibiotic treatment were selected. The candidate persister genes include genes involved in transcription/replication, sugar metabolism, cell wall synthesis, and energy metabolism, clearly pointing to redundant pathways for persister formation. We have previously reported that the
S. mutans
quorum-sensing peptide, CSP pheromone, was a stress-inducible alarmone capable of conveying sophisticated messages in the bacterial population. In this study, we demonstrate the involvement of the intraspecies quorum-sensing system during the formation of stress-induced multidrug-tolerant persisters. To the best of our knowledge, this is the first study reporting the induction of bacterial persistence using a quorum-sensing regulatory system.
A VapBC Toxin-Antitoxin Module Is a Posttranscriptional Regulator of Metabolic Flux in Mycobacteria
Authors: McKenzie Joanna L. , Robson Jennifer , Berney Michael , Smith Tony C. , Ruthe Alaine , Gardner Paul P. , Arcus Vickery L. , Cook Gregory M. 
Published: February 2012

ABSTRACT

The largest family of toxin-antitoxin (TA) modules are encoded by the
vapBC
operons, but their roles in bacterial physiology remain enigmatic. Microarray analysis in
Mycobacterium smegmatis
overexpressing VapC/VapBC revealed a high percentage of downregulated genes with annotated roles in carbon transport and metabolism, suggesting that VapC was targeting specific metabolic mRNA transcripts. To validate this hypothesis, purified VapC was used to identify the RNA cleavage site
in vitro
. VapC had RNase activity that was sequence specific, cleaving single-stranded RNA substrates at AUAU and AUAA
in vitro
and
in vivo
(
viz
., MSMEG_2121 to MSMEG_2124). A bioinformatic analysis of these regions suggested that an RNA hairpin 3′ of the AUA(U/A) motif is also required for efficient cleavage. VapC-mediated regulation
in vivo
was demonstrated by showing that MSMEG_2124 (
dhaF
) and MSMEG_2121 (
dhaM
) were upregulated in a Δ
vapBC
mutant growing on glycerol. The Δ
vapBC
mutant had a specific rate of glycerol consumption that was 2.4-fold higher than that of the wild type during exponential growth. This increased rate of glycerol consumption was not used for generating bacterial biomass, suggesting that metabolism by the Δ
vapBC
mutant was uncoupled from growth. These data suggest a model in which VapC regulates the rate of glycerol utilization to match the anabolic demands of the cell, allowing for fine-tuning of the catabolic rate at a posttranscriptional level.
Acupuncture Combined with Curcumin Attenuates Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats
Authors: Zhang Feng , Ma Jin , Lu Yin , Ni Guang-Xia , Ni Chun-Yan , Zhang Xue-Jiao , Zhang Xiao-Ping , Kong De-Song , Wang Ai-Yun , Chen Wen-Xing , Zheng Shi-Zhong 
Published: February 2012

Background Increasingly, studies demonstrate the effectiveness of acupuncture therapy against liver fibrosis. Curcumin is a natural product with antifibrotic effects, but has poor pharmacokinetic profiles. This study aimed to evaluate whether acupuncture combined with curcumin could more potently attenuate liver fibrosis in chemical intoxicated rats. Methods 60 Sprague–Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination therapy groups. During the establishment of fibrosis using carbon tetrachloride (CCl4), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, pathological indexes and histology for hepatic injury and fibrogenesis were detected. The expression of extracellular matrix (ECM) components was also determined. Results Acupuncture combined with curcumin potently protected the liver from CCl4-induced injury and fibrogenesis, as indicated by reduced levels of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, hyaluronic acid, laminin and procollagen III. Combined use also led to significant liver histological improvements. Furthermore, combined use effectively inhibited ECM expression such as α-smooth muscle actin, fibronectin and α1(1) collagen. Conclusions Acupuncture treatment could significantly enhance the antifibrotic efficacy of curcumin on CCl4-induced hepatic fibrosis in rats in vivo, suggesting that a combination of acupuncture with curcumin may be exploited for the prevention of hepatic fibrosis.
Quality of medical care and excess mortality in psychiatric patients—a nationwide register-based study in Sweden
Authors: Björkenstam Emma , Ljung Rickard , Burström Bo , Mittendorfer-Rutz Ellenor , Hallqvist Johan , Weitoft Gunilla Ringbäck 
Published: February 2012

ObjectiveTo assess overall and cause-specific mortality and the quality of somatic care among psychiatric patients.DesignA register-based cohort study.SettingAll individuals aged 20–79 years in Sweden in 2005.ParticipantsIn total 6 294 339 individuals.Primary outcome measureThe individuals were followed for mortality in 2006 and 2007, generating 72 187 deaths. Psychiatric patients were grouped according to their diagnosis in the National Patient Register. Mortality risk of psychiatric patients was compared with that of non-psychiatric patients. Estimates of RR of mortality were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Psychiatric patients were compared with non-psychiatric patients for three healthcare quality indicators: the proportion of avoidable hospitalisations, case death rate after myocardial infarction and statin use among diabetic patients.ResultsCompared with individuals with no episodes of treatment for mental disorder, psychiatric patients had a substantially increased risk of all studied causes of death as well as death from conditions considered amenable to intervention by the health service, that is, avoidable mortality. The highest mortality was found among those with another mental disorder, predominantly substance abuse (for women, an IRR of 4.7 (95% CI 4.3 to 5.0) and for men, an IRR of 4.8 (95% CI 4.6 to 5.0)). The analysis of quality of somatic care revealed lower levels of healthcare quality for psychiatric patients, signalling failures in public health and medical care.ConclusionThis study shows a marked increase in excess mortality, suggesting a lower quality of somatic healthcare in psychiatric patients.
A New Biomarker That Predicts Colonic Neoplasia Outcome in Patients with Hyperplastic Colonic Polyps
Authors: Do Catherine , Bertrand Claudine , Palasse Julien , Delisle Marie-Bernadette , Shulkes Arthur , Cohen-Jonathan-Moyal Elizabeth , Ferrand Audrey , Seva Catherine 
Published: February 2012

AbstractThe most frequently occurring lesions in the colon are the hyperplastic polyps. Hyperplastic polyps have long been considered as lesions with no malignant potential and colonoscopy for these patients is not recommended. However, recent works suggest that hyperplastic polyps may represent precursor lesions of some sporadic colorectal cancers. Until now, no biomarker allows to identify the subset of hyperplastic polyps that may have a malignant potential. Because the hormone precursor progastrin has been involved in colon carcinogenesis, we investigated whether its expression in hyperplastic polyps predicts the occurrence of colonic neoplasm after resection of hyperplastic polyps. We retrospectively analyzed progastrin expression in hyperplastic polyps from 74 patients without history of colorectal pathology. In our study, 41% of patients presenting an initial hyperplastic polyp subsequently developed adenomatous polyps, recognized as precursor lesions for colorectal adenocarcinomas. Progastrin was overexpressed in the hyperplastic polyps in 40% of the patients. We showed a significant association between progastrin overexpression and shortened neoplasm-free survival (P = 0.001). Patients with high overexpression of progastrin had a 5-year neoplasm-free survival rate of 38% as compared with 100% for the patients with low progastrin expression. In addition, we established a predictive test on the basis of progastrin staining and patients' age that predicts occurrence of neoplasm after developing a first hyperplastic polyp with a sensitivity of 100% [95% confidence interval (CI), 79%–100%] and a specificity of 74% (51%–90%). We show that progastrin expression evaluation in hyperplastic polyps is an efficient prognostic tool to determine patients with higher risk of metachronous neoplasms who could benefit from an adapted follow-up. Cancer Prev Res; 5(4); 675–84. ©2012 AACR.
Suppression of Tumor Invasion and Metastasis by Concurrent Inhibition of c-Met and VEGF Signaling in Pancreatic Neuroendocrine Tumors
Authors: Sennino Barbara , Ishiguro-Oonuma Toshina , Wei Ying , Naylor Ryan M. , Williamson Casey W. , Bhagwandin Vikash , Tabruyn Sebastien P. , You Weon-Kyoo , Chapman Harold A. , Christensen James G. , Aftab Dana T. , McDonald Donald M. 
Published: February 2012

Abstract
Invasion and metastasis increase after the inhibition of VEGF signaling in some preclinical tumor models. In the present study we asked whether selective VEGF inhibition is sufficient to increase invasion and metastasis and whether selective c-Met inhibition is sufficient to block this effect. Treatment of pancreatic neuroendocrine tumors in RIP-Tag2 mice with a neutralizing anti-VEGF antibody reduced tumor burden but increased tumor hypoxia, hypoxia-inducible factor-1α, and c-Met activation and also increased invasion and metastasis. However, invasion and metastasis were reduced by concurrent inhibition of c-Met by PF-04217903 or PF-02341066 (crizotinib). A similar benefit was found in orthotopic Panc-1 pancreatic carcinomas treated with sunitinib plus PF-04217903 and in RIP-Tag2 tumors treated with XL184 (cabozantinib), which simultaneously blocks VEGF and c-Met signaling. These findings document that invasion and metastasis are promoted by selective inhibition of VEGF signaling and can be reduced by the concurrent inhibition of c-Met.
Significance: This report examines the mechanism of increased tumor aggressiveness after anti-VEGF therapy and presents evidence for roles of vascular pruning, hypoxia, and c-Met activation. The results show that simultaneous inhibition of c-Met and VEGF signaling not only slows tumor growth but also reduces invasion and metastasis. Cancer Discovery; 2(3); 270–87. ©2012 AACR.
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Reduced Cx43 Expression Triggers Increased Fibrosis Due to Enhanced Fibroblast Activity
Authors: Jansen John A. , van Veen Toon A.B. , de Jong Sanne , van der Nagel Roel , van Stuijvenberg Leonie , Driessen Helen , Labzowski Ronald , Oefner Carolin M. , Bosch Astrid A. , Nguyen Tri Q. , Goldschmeding Roel , Vos Marc A. , de Bakker Jacques M.T. , van Rijen Harold V.M. 
Published: February 2012

Background—
Arrhythmogenic ventricular remodeling is hallmarked by both reduced gap junction expression and increased collagen deposition. We hypothesized that reduced connexin43 (Cx43) expression is responsible for enhanced fibrosis in the remodeled heart, resulting in an arrhythmogenic substrate. Therefore, we investigated the effect of normal or reduced Cx43 expression on the formation of fibrosis in a physiological (aging) and pathophysiological (transverse aortic constriction [TAC]) mouse model.

Methods and Results—

The Cx43
fl/fl
and Cx43
CreER(T)/fl
mice were aged 18 to 21 months or, at the age of 3 months, either TAC or sham operated and euthanized after 16 weeks. Epicardial activation mapping of the right and left ventricles was performed on Langendorff perfused hearts. Sustained ventricular arrhythmias were induced in 0 of 11 aged Cx43
fl/fl
and 10 of 15 Cx43
Cre-ER(T)/fl
mice (
P
<0.01). Cx43 expression was reduced by half in aged Cx43
CreER(T)/fl
compared with aged Cx43
fl/fl
mice, whereas collagen deposition was significantly increased from 1.1±0.2% to 7.4±1.3%. Aged Cx43
CreER(T)/fl
mice with arrhythmias had significantly higher levels of fibrosis and conduction heterogeneity than aged Cx43
CreER(T)/fl
mice without arrhythmias. The TAC operation significantly increased fibrosis in control compared with sham (4.0±1.2% versus 0.4±0.06%), but this increase was significantly higher in Cx43
CreER(T)/fl
mice (10.8±1.4%). Discoidin domain receptor 2 expression was unchanged, but procollagen peptide I and III expression and collagen type 1α2 mRNA levels were higher in TAC–operated Cx43HZ mice.

Conclusions—
Reduced cellular coupling results in more excessive collagen deposition during aging or pressure overload in mice due to enhanced fibroblast activity, leading to increased conduction in homogeneity and proarrhythmia.