bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Expression of the Normal Cellular Isoform of Prion Protein in Inclusion‐Body Myositis, Inflammatory Myopathies and Denervation Atrophy
Authors: Zanusso Gianluigi , Vattemi Gaetano , Ferrari Sergio , Tabaton Massimo , Pecini Elisa , Cavallaro Tiziana , Tomelleri Giuliano , Filosto Massimiliano , Tonin Paola , Nardelli Ettore , Rizzuto Nicola , Monaco Salvatore 
Published: July 2010

The cellular isoform of the prion protein (PrPc) is a glycosylphosphatidylinositol‐anchored glycoprotein, normally expressed in neural and non‐neural tissues, including skeletal muscle. In transmissible spongiform encephalopathies, or prion diseases, PrPc, which is soluble in nondenaturing detergent and sensitive to proteinase K (PK)‐treatment, represents the molecular substrate for the production of a detergent‐insoluble and PK‐resistant isoform, termed PrPSc.In human prion diseases, PrPSc accumulation occurs only in brain tissues, with the exception of new variant Creutzfeldt‐Jakob disease, where PrPSc is also detected in lymphoid tissues.Increased amounts of prion protein expression and deposition have been described in pathological muscle fibers of two human muscle disorders, called sporadic inclusion‐body myositis (s‐IBM) and hereditary inclusion‐body myopathy, but it is unknown whether accumulated prion protein reflects normal PrPc or PrPSc.We investigated the biochemical characteristics of prion protein in normal human muscle, s‐IBM, other inflammatory myopathies and denervation atrophy.We report that 1) both the glycoform profile and size of the normal muscle PrPc are different from those of human brain PrPc; 2) in addition to s‐IBM, increased PrPc expression is seen in polymyositis, dermatomyositis and neurogenic muscle atrophy, but PrPc glycoforms are unchanged; 3) only the normal PrPc isoform, and not PrPSc, is detected in s‐IBM. The present results exclude that s‐IBM is a prion disease.
Prevalence of HSV‐1 LAT in Human Trigeminal, Geniculate, and Vestibular Ganglia and Its Implication for Cranial Nerve Syndromes
Authors: Theil Diethilde , Arbusow Viktor , Derfuss Tobias , Strupp Michael , Pfeiffer Matthias , Mascolo Andrea , Brandt Thomas 
Published: July 2010

Herpes simplex virus type 1 (HSV‐1) enters sensory neurons and can remain latent there until reactivation. During latency restricted HSV‐1 gene expression takes place in the form of latency‐associated transcripts (LAT). LAT has been demonstrated to be important not only for latency but also for reactivation, which may cause cranial nerve disorders.Tissue sections of the trigeminal ganglia (TG), geniculate ganglia (GG), and the vestibular ganglia (VG) from seven subjects were examined for the presence of LAT using the in situ hybridization technique. LAT was found on both sides in all TG (100%), on both sides of five subjects (70%) in the GG, and in none of the VG. Using a second more sensitive detection method (RT‐PCR), we found LAT in the VG of seven of ten other persons (70%).This is the first study to demonstrate viral latency in the VG, a finding that supports the hypothesis that vestibular neuritis is caused by HSV‐1 reactivation. The distribution of LAT in the cranial nerve ganglia indicates that primary infection occurs in the TG and GG and subsequently spreads along the faciovestibular anastomosis to the VG.
Ability of Selected Lactic Acid Bacteria to Ferment a Pearl Millet–Soybean Slurry to Produce Gruels for Complementary Foods for Young Children
Authors: Songré‐Ouattara Laurencia T. , Mouquet‐Rivier Claire , Humblot Christèle , Rochette Isabelle , Diawara Bréhima , Guyot Jean‐Pierre 
Published: July 2010

Abstract:  To assess the ability of lactic acid bacteria to improve some nutritional characteristics of the pearl millet–soybean slurry to prepare complementary foods for young children in African countries, inoculation was performed using strains previously selected for their ability to hydrolyse starch, phytate, or α‐galactooligosaccharides (α‐GOS). For the sake of comparison with the action of a natural microflora, fermentation was also performed by back slopping inoculation, that is, with a sample obtained from spontaneously fermented traditional pearl millet slurry obtained from a small scale processing unit in Burkina Faso (Ouagadougou). Starter cultures thrived on the slurry as shown by counts on MRS agar, TTGE fingerprints, and fermentation patterns. The fermentation of precooked slurries inoculated by back slopping or with mixed cultures containing the amylolytic strain Lb. plantarum A6 enabled partial starch hydrolysis. Corresponding gruels had a suitable consistency for young child feeding at high dry matter content, and a high energy density: 88.7 ± 4.2 and 75.8 ± 5.1 kcal/100 g of sweetened gruel, for the gruels inoculated by back slopping or with Lb. plantarum A6, respectively. Unexpectedly, no decrease in phytates was observed in any of the experiments, suggesting the presence of one or more inhibitory compounds in soybean. Furthermore, preprocessing conditions before fermentation affect the carbohydrate composition of slurry and have a more profound effect than fermentation on the reduction of the α‐GOS content.Practical Application:  This research aims to investigate the capacity of selected lactic acid bacteria to produce in a bioprocess high energy density and nutritious gruels for complementary feeding of young children from an African cereal (pearl millet) mixed with soybean.
Addition of Soluble Soybean Polysaccharides to Dairy Products as a Source of Dietary Fiber
Authors: Chen Wenpu , Duizer Lisa , Corredig Milena , Goff H. Douglas 
Published: July 2010

Abstract:  Increasing consumption of dietary fiber in food leads to many important health benefits: for example, reduction in blood cholesterol, reduced risk of diabetes, and improved laxation. Water soluble soybean polysaccharide (SSPS) is a dietary fiber extracted and refined from okara, a byproduct of soy manufacturing. It was incorporated into 3 categories of dairy‐based products, thickened milkshake‐style beverages, puddings, and low‐fat ice cream, to the maximum amount without over‐texturing the food. Rheological measurements and sensory tests were used to develop desirable SSPS‐fortified products. From the rheological data, 4% SSPS‐fortified dairy beverages and 4% SSPS ‐fortified puddings were in the range of commercial products. From sensory analyses, 4% SSPS‐fortified dairy beverage with 0.015%κ−carrageenan, 4% SSPS‐fortified pudding with 0.1%κ−carrageenan, and 2% SSPS‐fortified low‐fat ice cream gained the highest scores in consumer hedonic rating. Panelists also indicated their willingness to consume those products if they were available commercially.Practical Application:  Since the dietary fiber intake of many people is below their suggested adequate intake values, strategies to successfully fortify foods with fiber may help alleviate this gap. We have developed 3 dairy products, a beverage, a pudding, and a low‐fat ice cream, that have been fortified with soluble soybean polysaccharide at levels of 4%, 4%, and 2%, respectively. These products were within acceptable ranges of rheological parameters and other physical stability measurements and were judged to be acceptable by sensory analyses.
Small‐molecule elicitation of microbial secondary metabolites
Authors: Pettit Robin K. 
Published: July 2010

SummaryMicrobial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the biosynthetic potential of many strains is much greater than that observed by fermentation. Prodding the expression of such silent (cryptic) pathways will allow us to maximize the chemical diversity available from microorganisms. Cryptic metabolic pathways can be accessed in the laboratory using molecular or cultivation‐based approaches. A targeted approach related to cultivation‐based methods is the application of small‐molecule elicitors to specifically affect transcription of secondary metabolite gene clusters. With the isolation of the novel secondary metabolites lunalides A and B, oxylipins, cladochromes F and G, nygerone A, chaetoglobosin‐542, ‐540 and ‐510, sphaerolone, dihydrosphaerolone, mutolide and pestalone, and the enhanced production of known secondary metabolites like penicillin and bacitracin, chemical elicitation is proving to be an effective way to augment natural product libraries.
In VivoEfficacy of Simulated Human Dosing Regimens of Prolonged-Infusion Doripenem against Carbapenemase- ProducingKlebsiella pneumoniae
Authors: Bulik Catharine C. , Nicolau David P. 
Published: July 2010

ABSTRACTCarbapenemase-producingKlebsiella pneumoniae(KPC) bacteria are rapidly becoming one of the most detrimental drug-resistant Gram-negative pathogens. Doripenem is the newest FDA-approved carbapenem that has the greatestin vitropotency against a wide range of Gram-negative organisms, including multidrug-resistant organisms. Previous work in an animal model has shown efficacy againstPseudomonas aeruginosawith MICs above the current breakpoints of susceptibility. The purpose of this study is to evaluate the efficacy of 1-g and 2-g dose prolonged infusions of doripenem against KPC isolates in both an immunocompetent and neutropenic murine thigh model. Seven clinical KPC isolates (broth microdilution [BMD] MIC range, 4 to 32 μg/ml; Etest MIC range, 3 to >32 μg/ml) were used. After infection, groups of mice were administered doripenem doses previously shown to simulate the exposures observed in humans after the administration of 1 or 2 g every 8 h as a 4-h infusion. In immunocompromised mice, 1- and 2-g doses of doripenem achieved bacteriostasis against isolates with MICs up to and including 8 μg/ml and 16 μg/ml, respectively. In immunocompetent animals, statistically significant reductions in the number of CFU were observed with overall decreases of approximately 1 log (P< 0.05). While carbapenemase-producingKlebsiella pneumoniaecontinues to decrease our meager supply of active agents, the ability of doripenem to produce CFU reductions in the presence of white blood cells (WBCs) using humanized exposures suggests the potential utility of this agent in combination against this increasingly problematic pathogen.
An Ertapenem-Resistant Extended-Spectrum-β-Lactamase-Producing
Klebsiella pneumoniae
Clone Carries a Novel OmpK36 Porin Variant
Authors: García-Fernández Aurora , Miriagou Vivi , Papagiannitsis Costas C. , Giordano Alessandra , Venditti Mario , Mancini Carlo , Carattoli Alessandra 
Published: July 2010

ABSTRACT

Carbapenem-resistant
Klebsiella pneumoniae
caused an outbreak in a hospital in Rome, Italy. The clinical isolates were tested by antimicrobial susceptibility testing, pulsed-field gel electrophoresis, multilocus sequence typing, plasmid typing, and β-lactamase identification. The OmpK35 and OmpK36 porins were analyzed by SDS-PAGE, and their genes were amplified and sequenced. Complementation experiments were performed using a recombinant unrelated
ompK36
gene. An ertapenem-resistant and imipenem- and meropenem-susceptible clone was identified and assigned to the sequence type 37 lineage by MLST; it carried SHV-12 and CTX-M-15 ESBLs, did not produce the OmpK35 due to a nonsense mutation, and expressed a novel OmpK36 variant (OmpK36V). This variant showed two additional amino acids located within the L3 internal loop, one of the highly conserved domains of the protein. Two isolates of the same clone also exhibited resistance to imipenem and meropenem, due to the loss of OmpK36 expression by a nonsense mutation occurring in the
ompK36V
variant gene. These were the first carbapenem-resistant
K. pneumoniae
isolates identified within the hospital. Screening for the
ompK36V
gene of unrelated
K. pneumoniae
isolates derived from patients from 2006 to 2009 demonstrated the high frequency of this gene variant as well as its association with ertapenem resistance, reduced susceptibility to meropenem, and susceptibility to imipenem.
Lersivirine, a Nonnucleoside Reverse Transcriptase Inhibitor with Activity against Drug-Resistant Human Immunodeficiency Virus Type 1
Authors: Corbau Romuald , Mori Julie , Phillips Chris , Fishburn Lesley , Martin Alex , Mowbray Charles , Panton Wendy , Smith-Burchnell Caroline , Thornberry Adele , Ringrose Heather , Knöchel Thorsten , Irving Steve , Westby Mike , Wood Anthony , Perros Manos 
Published: July 2010

ABSTRACTThe nonnucleoside reverse transcriptase inhibitors (NNRTIs) are key components of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus type 1 (HIV-1). A major problem with the first approved NNRTIs was the emergence of mutations in the HIV-1 reverse transcriptase (RT), in particular K103N and Y181C, which led to resistance to the entire class. We adopted an iterative strategy to synthesize and test small molecule inhibitors from a chemical series of pyrazoles against wild-type (wt) RT and the most prevalent NNRTI-resistant mutants. The emerging candidate, lersivirine (UK-453,061), binds the RT enzyme in a novel way (resulting in a unique resistance profile), inhibits over 60% of viruses bearing key RT mutations, with 50% effective concentrations (EC50s) within 10-fold of those for wt viruses, and has excellent selectivity against a range of human targets. Altogether lersivirine is a highly potent and selective NNRTI, with excellent efficacy against NNRTI-resistant viruses.
Short Cationic Antimicrobial Peptides Interact with ATP
Authors: Hilpert Kai , McLeod Brett , Yu Jessie , Elliott Melissa R. , Rautenbach Marina , Ruden Serge , Bürck Jochen , Muhle-Goll Claudia , Ulrich Anne S. , Keller Sandro , Hancock Robert E. W. 
Published: July 2010

ABSTRACT
The mode of action of short, nonhelical antimicrobial peptides is still not well understood. Here we show that these peptides interact with ATP and directly inhibit the actions of certain ATP-dependent enzymes, such as firefly luciferase, DnaK, and DNA polymerase. α-Helical and planar or circular antimicrobial peptides did not show such interaction with ATP.
Silver Coordination Polymers for Prevention of Implant Infection: Thiol Interaction, Impact on Respiratory Chain Enzymes, and Hydroxyl Radical Induction
Authors: Gordon Oliver , Vig Slenters Tünde , Brunetto Priscilla S. , Villaruz Amer E. , Sturdevant Daniel E. , Otto Michael , Landmann Regine , Fromm Katharina M. 
Published: July 2010

ABSTRACT

Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti-infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on
in vitro
-grown biofilms and prevented murine S
taphylococcus epidermidis
implant infection
in vivo
with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of
S. epidermidis
at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact.
End-of-life decisions as bedside rationing. An ethical analysis of life support restrictions in an Indian neonatal unit
Authors: Miljeteig I , Johansson K A , Sayeed S A , Norheim O F 
Published: July 2010

IntroductionHundreds of thousands of premature neonates born in low-income countries are implicitly denied treatment each year. Studies from India show that treatment is rationed even for neonates born at 32 gestational age weeks (GAW), and multiple external factors influence treatment decisions. Is withholding of life-saving treatment for children born between 28 and 32 GAW acceptable from an ethical perspective?MethodA seven-step impartial ethical analysis, including outcome analysis of four accepted priority criteria: severity of disease, treatment effect, cost effectiveness and evidence for neonates born at 28 and 32 GAW.ResultsThe ethical analysis sketches out two possibilities: (a) It is not ethically permissible to limit treatment to neonates below 32 GAW when assigning high weight to health maximisation and overall health equality. Neonates below 32 GAW score high on severity of disease and efficiency and cost-effectiveness of treatment if one gives full weight to early years of a newborn life. It is in the child's best interest to be treated. (b) It can be considered ethically permissible if high weight is assigned to reducing inequality of welfare and maximising overall welfare and/or not granting full weight to early years of newborns is considered acceptable. From an equity-motivated health and welfare perspective, we would not accept (b), as it relies on accepting the lack of proper welfare policies for the poor and disabled in India.ConclusionExplicit priority processes in India for financing neonatal care are needed. If premature neonates are perceived as worth less than other patient groups, the reasons should be explored among a broad range of stakeholders.
An epigenetic chromatin remodeling role for NFATc1 in transcriptional regulation of growth and survival genes in diffuse large B-cell lymphomas
Authors: Pham Lan V. , Tamayo Archito T. , Li Changping , Bueso-Ramos Carlos , Ford Richard J. 
Published: July 2010

Abstract
The nuclear factor of activated T cells (NFAT) family of transcription factors functions as integrators of multiple signaling pathways by binding to chromatin in combination with other transcription factors and coactivators to regulate genes central for cell growth and survival in hematopoietic cells. Recent experimental evidence has implicated the calcineurin/NFAT signaling pathway in the pathogenesis of various malignancies, including diffuse large B-cell lymphoma (DLBCL). However, the molecular mechanism(s) underlying NFATc1 regulation of genes controlling lymphoma cell growth and survival is still unclear. In this study, we demonstrate that the transcription factor NFATc1 regulates gene expression in DLBCL cells through a chromatin remodeling mechanism that involves recruitment of the SWItch/Sucrose NonFermentable chromatin remodeling complex ATPase enzyme SMARCA4 (also known as Brahma-related gene 1) to NFATc1 targeted gene promoters. The NFATc1/Brahma-related gene 1 complex induces promoter DNase I hypersensitive sites and recruits other transcription factors to the active chromatin site to regulate gene transcription. Targeting NFATc1 with specific small hairpin RNA inhibits DNase I hypersensitive site formation and down-regulates target gene expression. Our data support a novel epigenetic control mechanism for the transcriptional regulation of growth and survival genes by NFATc1 in the pathophysiology of DLBCL and suggests that targeting NFATc1 could potentially have therapeutic value.
Ceftriaxone-induced up-regulation of cortical and striatal GLT1 in the R6/2 model of Huntington's disease
Authors: Sari Youssef , Prieto Anne L , Barton Scott J , Miller Benjamin R , Rebec George V 
Published: July 2010

Abstract

Background
Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by cortico-striatal dysfunction and loss of glutamate uptake. At 7 weeks of age, R6/2 mice, which model an aggressive form of juvenile HD, show a glutamate-uptake deficit in striatum that can be reversed by treatment with ceftriaxone, a β-lactam antibiotic that increases GLT1 expression. Only at advanced ages (> 11 weeks), however, do R6/2 mice show an actual loss of striatal GLT1. Here, we tested whether ceftriaxone can reverse the decline in GLT1 expression that occurs in older R6/2s.

Results
Western blots were used to assess GLT1 expression in both striatum and cerebral cortex in R6/2 and corresponding wild-type (WT) mice at 9 and 13 weeks of age. Mice were euthanized for immunoblotting 24 hr after five consecutive days of once daily injections (ip) of ceftriaxone (200 mg/kg) or saline vehicle. Despite a significant GLT1 reduction in saline-treated R6/2 mice relative to WT at 13, but not 9, weeks of age, ceftriaxone treatment increased cortical and striatal GLT1 expression relative to saline in all tested mice.

Conclusions
The ability of ceftriaxone to up-regulate GLT1 in R6/2 mice at an age when GLT1 expression is significantly reduced suggests that the mechanism for increasing GLT1 expression is still functional. Thus, ceftriaxone could be effective in modulating glutamate transmission even in late-stage HD.
CIG-DB: the database for human or mouse immunoglobulin and T cell receptor genes available for cancer studies
Authors: Nakamura Yoji , Komiyama Tomoyoshi , Furue Motoki , Gojobori Takashi , Akiyama Yasuto 
Published: July 2010

AbstractBackgroundImmunoglobulin (IG or antibody) and the T-cell receptor (TR) are pivotal proteins in the immune system of higher organisms. In cancer immunotherapy, the immune responses mediated by tumor-epitope-binding IG or TR play important roles in anticancer effects. Although there are public databases specific for immunological genes, their contents have not been associated with clinical studies. Therefore, we developed an integrated database of IG/TR data reported in cancer studies (the Cancer-related Immunological Gene Database [CIG-DB]).DescriptionThis database is designed as a platform to explore public human and murine IG/TR genes sequenced in cancer studies. A total of 38,308 annotation entries for IG/TR proteins were collected from GenBank/DDBJ/EMBL and the Protein Data Bank, and 2,740 non-redundant corresponding MEDLINE references were appended. Next, we filtered the MEDLINE texts by MeSH terms, titles, and abstracts containing keywords related to cancer. After we performed a manual check, we classified the protein entries into two groups: 611 on cancer therapy (Group I) and 1,470 on hematological tumors (Group II). Thus, a total of 2,081 cancer-related IG and TR entries were tabularized. To effectively classify future entries, we developed a computational method based on text mining and canonical discriminant analysis by parsing MeSH/title/abstract words. We performed a leave-one-out cross validation for the method, which showed high accuracy rates: 94.6% for IG references and 94.7% for TR references. We also collected 920 epitope sequences bound with IG/TR. The CIG-DB is equipped with search engines for amino acid sequences and MEDLINE references, sequence analysis tools, and a 3D viewer. This database is accessible without charge or registration athttp://www.scchr-cigdb.jp/, and the search results are freely downloadable.ConclusionsThe CIG-DB serves as a bridge between immunological gene data and cancer studies, presenting annotation on IG, TR, and their epitopes. This database contains IG and TR data classified into two cancer-related groups and is able to automatically classify accumulating entries into these groups. The entries in Group I are particularly crucial for cancer immunotherapy, providing supportive information for genetic engineering of novel antibody medicines, tumor-specific TR, and peptide vaccines.