bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of conserved aromatic amino acids in the discoidin domain of Paenibacillus β-1,3-glucanase
Authors: Cheng Yueh-Mei , Hsieh Feng-Chia , Meng Menghsiao 
Published: November 2009

Abstract
The 190-kDa Paenibacillus β-1,3-glucanase (LamA) contains a catalytic module of the glycoside hydrolase family 16 (GH16) and several auxiliary domains. Of these, a discoidin domain (DS domain), present in both eukaryotic and prokaryotic proteins with a wide variety of functions, exists at the carboxyl-terminus. To better understand the bacterial DS domain in terms of its structure and function, this domain alone was expressed in Escherichia coli and characterized. The results indicate that the DS domain binds various polysaccharides and enhances the biological activity of the GH16 module on composite substrates. We also investigated the importance of several conserved aromatic residues in the domain's stability and substrate-binding affinity. Both were affected by mutations of these residues; however, the effect on protein stability was more notable. In particular, the forces contributed by a sandwiched triad (W1688, R1756, and W1729) were critical for the presumable β-sandwich fold.
Hepcidin is elevated in mice injected with Mycoplasma arthritidis
Authors: Koening Curry L , Mu Hong-Hua , Van Schelt Adam , Lo Eric , Ward Diane M , Kaplan Jerry , De Domenico Ivana 
Published: November 2009

Abstract

Mycoplasma arthritidis causes arthritis in specific mouse strains. M. arthritidis mitogen (MAM), a superantigen produced by M. arthritidis, activates T cells by forming a complex between the major histocompatability complex II on antigen presenting cells and the T cell receptor on CD4+ T lymphocytes. The MAM superantigen is also known to interact with Toll-like receptors (TLR) 2 and 4. Hepcidin, an iron regulator protein, is upregulated by TLR4, IL-6, and IL-1. In this study, we evaluated serum hepcidin, transferrin saturation, ferritin, IL-6, IL-1, and hemoglobin levels in M. arthritidis injected C3H/HeJ (TLR2+/+, TLR4-/-) mice and C3H/HeSnJ (TLR2+/+, TLR4+/+) mice over a 21 day period. C3H/HeJ mice have a defective TLR4 and an inability to produce IL-6. We also measured arthritis severity in these mice and the amount of hepcidin transcripts produced by the liver and spleen. C3H/HeJ mice developed a more severe arthritis than that of C3H/HeSnJ mice. Both mice had an increase in serum hepcidin within three days after infection. Hepcidin levels were greater in C3H/HeJ mice despite a nonfunctioning TLR4 and low serum levels of IL-6. Splenic hepcidin production in C3H/HeJ mice was delayed compared to C3H/HeSnJ mice. Unlike C3H/HeSnJ mice, C3H/HeJ mice did not develop a significant rise in serum IL-6 levels but did develop a significant increase in IL-1β during the first ten days after injection. Both mice had an increase in serum ferritin but a decrease in serum transferrin saturation. In conclusion, serum hepcidin regulation in C3H/HeJ mice does not appear to be solely dependent upon TLR4 or IL-6.
Genetic diversity and phylogeography of Seewis virus in the Eurasian common shrew in Finland and Hungary
Authors: Kang Hae Ji , Arai Satoru , Hope Andrew G , Song Jin-Won , Cook Joseph A , Yanagihara Richard 
Published: November 2009

Abstract
Recent identification of a newfound hantavirus, designated Seewis virus (SWSV), in the Eurasian common shrew (Sorex araneus), captured in Switzerland, corroborates decades-old reports of hantaviral antigens in this shrew species from Russia. To ascertain the spatial or geographic variation of SWSV, archival liver tissues from 88 Eurasian common shrews, trapped in Finland in 1982 and in Hungary during 1997, 1999 and 2000, were analyzed for hantavirus RNAs by reverse transcription-polymerase chain reaction. SWSV RNAs were detected in 12 of 22 (54.5%) and 13 of 66 (19.7%) Eurasian common shrews from Finland and Hungary, respectively. Phylogenetic analyses of S- and L-segment sequences of SWSV strains, using maximum likelihood and Bayesian methods, revealed geographic-specific genetic variation, similar to the phylogeography of rodent-borne hantaviruses, suggesting long-standing hantavirus-host co-evolutionary adaptation.
A randomised controlled comparison of early post-pyloric versus early gastric feeding to meet nutritional targets in ventilated intensive care patients
Authors: White Hayden , Sosnowski Kellie , Tran Khoa , Reeves Annelli , Jones Mark 
Published: November 2009

Abstract
Introduction
To compare outcomes from early post-pyloric to gastric feeding in ventilated, critically ill patients in a medical intensive care unit (ICU).

Methods
Prospective randomized study. Ventilated patients were randomly assigned to receive enteral feed via a nasogastric or a post-pyloric tube. Post-pyloric tubes were inserted by the bedside nurse and placement was confirmed radiographically.

Results
A total of 104 patients were enrolled, 54 in the gastric group and 50 in the post-pyloric group. Bedside post-pyloric tube insertion was successful in 80% of patients. Patients who failed post-pyloric insertion were fed via the nasogastric route, but were analysed on an intent-to treat basis. A per protocol analysis was also performed. Baseline characteristics were similar for all except Acute Physiology and Chronic Health Evaluation II (APACHE II) score, which was higher in the post-pyloric group. There was no difference in length of stay or ventilator days. The gastric group was quicker to initiate feed 4.3 hours (2.9 - 6.5 hours) as compared to post-pyloric group 6.6 hours (4.5 - 13.0 hours) (P = 0.0002). The time to reach target feeds from admission was also faster in gastric group: 8.7 hours (7.6 - 13.0 hours) compared to 12.3 hours (8.9 - 17.5 hours). The average daily energy and protein deficit were lower in gastric group 73 Kcal (2 - 288 Kcal) and 3.5 g (0 - 15 g) compared to 167 Kcal (70 - 411 Kcal) and 6.5 g (2.8 - 17.3 g) respectively but was only statistically significant for the average energy deficit (P = 0.035). This difference disappeared in the per protocol analysis. Complication rates were similar.

Conclusions
Early post-pyloric feeding offers no advantage over early gastric feeding in terms of overall nutrition received and complications

Trial Registration
Clinical Trial: anzctr.org.au:ACTRN12606000367549
Expression of Ankyrin Repeat and Suppressor of Cytokine Signaling Box Protein 4 (Asb-4) in Proopiomelanocortin Neurons of the Arcuate Nucleus of Mice Produces a Hyperphagic, Lean Phenotype
Authors: Li Ji-Yao , Chai Biao-Xin , Zhang Weizhen , Wang Hui , Mulholland Michael W. 
Published: November 2009

Abstract
Ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 (Asb-4) is specifically expressed in the energy homeostasis-related brain areas and colocalizes with proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC). Injection of insulin into the third ventricle of the rat brain increased Asb-4 mRNA expression in the paraventricular nucleus but not in the ARC of the hypothalamus, whereas injection of leptin (ip) increased Asb-4 expression in both mouse paraventricular nucleus and ARC. A transgenic mouse in which Myc-tagged Asb-4 is specifically expressed in POMC neurons of the ARC was made and used to study the effects of Asb-4 on ingestive behavior and metabolic rate. Animals with overexpression of Asb-4 in POMC neurons demonstrated an increase in food intake. However, POMC-Asb-4 transgenic animals gained significantly less weight from 6–30 wk of age. The POMC-Asb-4 mice had reduced fat mass and increased lean mass and lower levels of blood leptin. The transgenic animals were resistant to high-fat diet-induced obesity. Transgenic mice had significantly higher rates of oxygen consumption and carbon dioxide production than wild-type mice during both light and dark periods. The locomotive activity of transgenic mice was increased. The overexpression of Asb-4 in POMC neurons increased POMC mRNA expression in the ARC. The transgenic animals had no observed effect on peripheral glucose metabolism and the activity of the autonomic nervous system. These results indicate that Asb-4 is a key regulatory protein in the central nervous system, involved in the control of feeding behavior and metabolic rate.
Functional Effects of Polymorphisms in the Human Gene Encoding 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1): A Sequence Variant at the Translation Start of 11β-HSD1 Alters Enzyme Levels
Authors: Malavasi Elise L. V. , Kelly Val , Nath Nikita , Gambineri Alessandra , Dakin Rachel S. , Pagotto Uberto , Pasquali Renato , Walker Brian R. , Chapman Karen E. 
Published: November 2009

AbstractRegeneration of active glucocorticoids within liver and adipose tissue by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be of pathophysiological importance in obesity and metabolic syndrome and is a therapeutic target in type 2 diabetes. Polymorphisms in HSD11B1, the gene encoding 11β-HSD1, have been associated with metabolic phenotype in humans, including type 2 diabetes and hypertension. Here, we have tested the functional consequences of two single nucleotide polymorphisms located in contexts that potentially affect tissue levels of 11β-HSD1. We report no effect of allelic variation at rs846910, a polymorphism within the 5′-flanking region of the gene on HSD11B1 promoter activity in vitro. However, compared with the common G allele, the A allele of rs13306421, a polymorphism located two nucleotides 5′ to the translation initiation site, gave higher 11β-HSD1 expression and activity in vitro and was translated at higher levels in in vitro translation reactions, possibly associated with a lower frequency of “leaky scanning.” These data suggest that this polymorphism may have direct functional consequences on levels of 11β-HSD1 enzyme activity in vivo. However, the rs13306421 A sequence variant originally reported in other ethnic groups may be of low prevalence because it was not detected in a population of 600 European Caucasian women.
Molecular Mechanism of the Inhibition of Estradiol-Induced Endometrial Epithelial Cell Proliferation by Clomiphene Citrate
Authors: Amita Mitsuyoshi , Takahashi Toshifumi , Tsutsumi Seiji , Ohta Tsuyoshi , Takata Keiko , Henmi Noriko , Hara Shuichiro , Igarashi Hideki , Takahashi Kazuhiro , Kurachi Hirohisa 
Published: November 2009

AbstractWe examined the molecular mechanisms of the antiestrogenic effects of clomiphene citrate (CC) in the endometrium using two types of cell lines, Ishikawa and EM-E6/E7/hTERT cells. CC or ICI182780 inhibited 17β-estradiol (E2)-induced endometrial cell proliferation and transcriptional activation of the estrogen response element (ERE) gene. We directly visualized the ligand-estrogen receptor (ER)α interaction using green fluorescent protein (GFP)-tagged ERα in a single living cell. Whereas E2 changed the nuclear localization of GFP-ERα to a punctate distribution within 5 min, CC or ICI182780 changed the slower and less mobilization of GFP-ERα compared with E2. Pretreatment with CC or ICI182780 partly prevented the E2-induced nuclear redistribution of GFP-ERα. Fluorescence recovery after photobleaching revealed that GFP-ERα mobility treated with E2 was more rapid than that treated by CC or ICI182780. As coactivator recruitment to the ER is essential for ER-dependent transcription, we examined the interaction between ERα and steroid receptor coactivator-1 (SRC-1). The complex formation between ERα and SRC-1 was significantly increased by E2 but was prevented in the presence of CC or ICI182780 by coimmunoprecipitation. Moreover, the E2-induced colocalization of GFP-ERα and SRC-1 was prevented in the presence of CC or ICI182780 according to an immunofluorescence assay. We also observed that the reduction of SRC-1 using small interfering RNA for SRC-1 resulted in the inhibition of E2-induced cell proliferation and transcriptional activation of the ERE gene. Collectively, these results suggest that CC may inhibit E2-induced endometrial epithelial cell proliferation and ERE transactivation by inhibiting the recruitment of SRC-1 to ERα.
Naturally Occurring Glucokinase Mutations Are Associated with Defects in Posttranslational S-Nitrosylation
Authors: Ding Shi-Ying , Tribble Nicholas D. , Kraft Catherine A. , Markwardt Michele , Gloyn Anna L. , Rizzo Mark A. 
Published: November 2009

Abstract
Posttranslational activation of glucokinase (GCK) through S-nitrosylation has been recently observed in the insulin-secreting pancreatic β-cell; however, the function of this molecular mechanism in regulating the physiology of insulin secretion is not well understood. To more fully understand the function of posttranslational regulation of GCK, we examined two naturally occurring GCK mutations that map to residues proximal to the S-nitrosylated cysteine and cause mild fasting hyperglycemia (maturity-onset diabetes of the young; subtype glucokinase). The kinetics of recombinantly generated GCK-R369P and GCK-V367M were assessed in vitro. The GCK-R369P protein has greatly reduced catalytic activity (relative activity index 0.05 vs. 1.00 for wild type), whereas the GCK-V367M has near normal kinetics (relative activity index 1.26 vs. 1.00 for wild type). Quantitative imaging and biochemical assays were used to assess the effect of these mutants on the metabolic response to glucose, GCK activation, and S-nitrosylation of GCK in βTC3 insulinoma cells. Expression of either mutant in βTC3 cells did not affect the metabolic response to 5 mm glucose. However, expression of either mutant blocked the effects of insulin on glucose-stimulated nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate reduction, suggesting defects in posttranslational regulation of GCK. Each of these mutations blocked GCK activation, and prevented posttranslational cysteine S-nitrosylation. Our findings link defects in hormone-regulated GCK S-nitrosylation to hyperglycemia and support a role for posttranslational regulation of GCK S-nitrosylation as a vital regulatory mechanism for glucose-stimulated insulin secretion.
Elastic energy storage in the mantis shrimp's fast predatory strike
Authors: Zack T. I. , Claverie T. , Patek S. N. 
Published: November 2009

SUMMARYStorage of elastic energy is key to increasing the power output of many biological systems. Mantis shrimp (Stomatopoda) must store considerable elastic energy prior to their rapid raptorial strikes; however, little is known about the dynamics and location of elastic energy storage structures in this system. We used computed tomography (CT) to visualize the mineralization patterns in Gonodactylaceus falcatus and high speed videography of Odontodactylus scyllarus to observe the dynamics of spring loading. Using a materials testing apparatus, we measured the force and work required to contract the elastic structures in G. falcatus. There was a positive linear correlation between contraction force and contraction distance; alternative model tests further supported the use of a linear model. Therefore, we modeled the system as a Hookean spring. The force required to fully compress the spring was positively correlated with body mass and appendage size, but the spring constant did not scale with body size, suggesting a possible role of muscle constraints in the scaling of this system. One hypothesized elastic storage structure, the saddle, only contributed approximately 11% of the total measured force, thus suggesting that primary site of elastic energy storage is in the mineralized ventral bars found in the merus segment of the raptorial appendages. Furthermore, the intact system exhibited 81% resilience and severing the saddle resulted in a non-significant reduction to 77% resilience. The remarkable shapes and mineralization patterns that characterize the mantis shrimp's raptorial appendage further reveal a highly integrated mechanical power amplification system based on exoskeletal elastic energy storage.
The peptide hormone pQDLDHVFLRFamide (crustacean myosuppressin) modulates theHomarus americanuscardiac neuromuscular system at multiple sites
Authors: Stevens J. S. , Cashman C. R. , Smith C. M. , Beale K. M. , Towle D. W. , Christie A. E. , Dickinson P. S. 
Published: November 2009

SUMMARYpQDLDHVFLRFamide is a highly conserved crustacean neuropeptide with a structure that places it within the myosuppressin subfamily of the FMRFamide-like peptides. Despite its apparent ubiquitous conservation in decapod crustaceans, the paracrine and/or endocrine roles played by pQDLDHVFLRFamide remain largely unknown. We have examined the actions of this peptide on the cardiac neuromuscular system of the American lobster Homarus americanus using four preparations: the intact animal, the heart in vitro, the isolated cardiac ganglion (CG), and a stimulated heart muscle preparation. In the intact animal, injection of myosuppressin caused a decrease in heartbeat frequency. Perfusion of the in vitro heart with pQDLDHVFLRFamide elicited a decrease in the frequency and an increase in the amplitude of heart contractions. In the isolated CG, myosuppressin induced a hyperpolarization of the resting membrane potential of cardiac motor neurons and a decrease in the cycle frequency of their bursting. In the stimulated heart muscle preparation, pQDLDHVFLRFamide increased the amplitude of the induced contractions, suggesting that myosuppressin modulates not only the CG, but also peripheral sites. For at least the in vitro heart and the isolated CG, the effects of myosuppressin were dose-dependent (10−9 to 10−6 mol l−1 tested), with threshold concentrations (10−8−10−7 mol l−1) consistent with the peptide serving as a circulating hormone. Although cycle frequency, a parameter directly determined by the CG, consistently decreased when pQDLDHVFLRFamide was applied to all preparation types, the magnitudes of this decrease differed, suggesting the possibility that, because myosuppressin modulates the CG and the periphery, it also alters peripheral feedback to the CG.
Daptomycin Versus Other Antimicrobial Agents for the Treatment of Skin and Soft Tissue Infections: A Meta-Analysis
Authors: Bliziotis loannis A , Plessa Eleni , Peppas George , Falagas Matthew E 
Published: November 2009

BACKGROUND Skin and soft tissue infections (SSTIs) are common in everyday clinical practice. Daptomycin has been shown to achieve very good concentrations in skin and soft tissues. OBJECTIVE To compare the effectiveness and toxicity of daptomycin with that of other antimicrobials for the treatment of SSTIs. METHODS PubMed, Scopus, and the Cochrane Central Register of Controlled Trials were searched for articles published up to March 2009. Comparative studies in which daptomycin was used in the intervention group were included in this meta-analysis. The primary outcome of interest was clinical success; secondary outcomes were microbiologic success, clinical success in subsets with complicated SSTIs (cSSTIs) or infections due to methicillin-resistant Staphylococcus aureus; (MRSA), clinical success of daptomycin-versus vancomycin-treated patients, time to clinical cure, treatment-related adverse events, withdrawal from treatment due to toxicity, all-cause mortality, and development of resistance. RESULTS Four studies were included in the analysis (3 were randomized controlled trials [RCTs]). Vancomycin and semisynthetic penicillins were used in the comparator arm. Three studies reported on patients with cSSTIs. The intention-to-treat (ITT) population was 1557 patients. No statistically significant difference between daptomycin and comparators was found regarding clinical success in clinically evaluable (OR 0.89; 95% CI 0.63 to 1.25 in the 3 RCTs and OR 1.34; 95% CI 0.38 to 4.66 with all 4 studies included), ITT, MRSA-infected patients, and those with cSSTIs. Two studies reported that significantly fewer patients with cSSTIs required prolonged treatment in the daptomycin arm and that clinical cure was faster than with comparators. No difference between the compared regimens was found in other outcomes. CONCLUSIONS Daptomycin is effective and safe for the treatment of SSTIs. Studies evaluating the optimal duration of daptomycin therapy for cSSTIs, comparing daptomycin with new agents, and focusing on proven MRSA SSTIs will be helpful for the further evaluation of the drug.
Psychotropic Medication Changes, Polypharmacy, and the Risk of Early Readmission in Suicidal Adolescent Inpatients
Authors: Fontanella Cynthia A , Bridge Jeffrey A , Campo John V 
Published: November 2009

Background: Adolescents with acute suicidal ideation and attempts are frequently treated with psychotropic medications in psychiatric hospitals. However, little is known about whether pharmacologic interventions used to stabilize suicidal adolescents within inpatient settings are effective in reducing early readmission. Objective: To examine whether psychotropic medication changes and polypharmacy are associated with 30-day readmission rates for suicidal adolescents. Methods: We conducted a retrospective cohort study of 318 Medicaid-enrolled adolescents admitted for suicidal behaviors to 3 major inpatient psychiatric hospitals in Maryland. Comprehensive data on patient demographics, clinical factors, service history, and inpatient treatment practices were collected from hospital medical records. Medications prescribed prior to admission and during the hospital stay were matched and compared with regard to drug, dosage, and frequency of administration to identify the different types of medication changes. Multivariate Cox proportional hazard analysis was used to examine the association of medication changes and polypharmacy with readmission. Results: At least one medication change was made in 78% of suicidal adolescent inpatients, typically the addition of an antidepressant, mood stabilizer, or antipsychotic. At discharge, nearly one quarter (23%) of youths were prescribed 3 or more medications from different drug classes. Controlling for demographic and clinical factors, the addition of an antidepressant was associated with an 85% lower risk of readmission (HR 0.15; 95% CI 0.03 to 0.68). However, the use of 3 or more medications from different drug classes was associated with a 2.6 times higher risk of readmission (95% CI 1.03 to 6.52). Conclusions: In this sample of suicidal adolescents, antidepressant treatment was associated with a lower risk of readmission and polypharmacy was associated with a higher risk of readmission. Study findings highlight the need for quality improvement efforts that optimize pharmacologic treatment and physician decision making.