bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Unusual Bovine Spongiform Encephalopathy Cases Detected in Great Britain
Authors: Stack M. , Focosi‐Snyman R. , Cawthraw S. , Davis L. , Jenkins R. , Thorne L. , Chaplin M. , Everitt S. , Saunders G. , Terry L. 
Published: May 2009

SummaryBovine spongiform encephalopathy (BSE) was first identified in Great Britain (GB) in 1986 and was subsequently detected in many other countries, world‐wide. A decade after the start of the bovine epidemic, the first cases of new variant Creutzfeldt‐Jakob disease (vCJD) in humans were linked to probable ingestion of BSE infected tissue, highlighting a new zoonotic disease. An abnormal protease‐resistant protein (PrPres) in a diseased subject, derived from a post‐translational change of a normal host cellular membrane protein (PrPc), is a reliable disease marker for the whole group of neurodegenerative transmissible spongiform encepalopathies (TSEs). Immunology‐based techniques, such as Western immunoblotting, have previously indicated that BSE cases all give a uniform molecular profile for PrPres. Periodic lesion profiling of the spongiform change throughout different brain regions of infected mice and cattle has also indicated a single agent for BSE. However, in 2001 rapid testing for PrPres was introduced for the active surveillance of ruminants within Europe, and approximately 40 BSE cases have now been recognized that differ in their molecular profiles from those typically found. These unusual BSE cases have been detected in several European countries, and in Japan and the USA. At present, the cases appear as two distinct types based on the molecular mass (Mm) of the unglycosylated PrPres protein band relative to that of classical BSE. One type is of a higher Mm (H‐type) and the other shows a lower Mm (L‐type). Transmission studies in mice have shown that both H‐type and L‐type BSE have biological characteristics that are different from those of the classical BSE agent. This study describes the prion protein (PRNP) genotype and molecular profiles of the first two cases of H‐type BSE detected in GB in comparison with those obtained for classical BSE, scrapie in sheep from GB and a control H‐type BSE case from France.
The Quest for More Efficient Industrial Engines: A Review of Current Industrial Engine Development and Applications
Authors: Cullen Barry , McGovern Jim 
Published: May 2009

Abstract
This paper addresses the need for efficiency gains in the modern industrial engine as utilized in combined heat and power (CHP) generation and other distributed generation situations. Power generation is discussed in terms of reciprocating-engine-based plant operating on Otto type thermodynamic cycles. The current state of the technology and the research being conducted is examined. Internal combustion engine performance improvement in the industrial engine sector focuses on improvements in the combustion characteristics of the plant, with emphasis on areas such as piston design, valve timing, and supercharging. Maximum brake-thermal efficiencies, in percentage terms, are currently in the 40s. In CHP generation, most of the energy not utilized for mechanical power is recovered as heat from various engine systems, such as jacket water and exhaust, and utilized for space or process heating. In other distributed generation situations, this energy is not utilized in this manner and is lost to the surroundings. While second law analysis would provide a more meaningful interpretation of the efficiency defect, this approach is still not the norm. Distributed generation benefits directly from efficiency improvements; the more efficient use of primary energy leads to reduced fuel costs. Combined heat and power generation is, however, more sensitive to the matching between the plant and its energy sinks, as its successful implementation is dictated by the ability of a site to fully utilize the heat and electrical power produced by the plant. At present, the energy balance of such engines typically dictates that heat is produced in greater quantity than electrical power, the ratio being of the order of 1.1–1.5:1. Due to this production imbalance, it is accepted that in order to be economically feasible, thermal and electrical demand should be coincident and also all heat and power should be utilized. This has traditionally led to certain sectors being deemed unsuitable for CHP use. Some current research is aimed at tipping the production balance of these engines in favor of electrical power production; however, performance gains in this regard are slow. This paper concludes with some brief commentary on current industrial engine developments and applications.
Mapping barleyDsinsertions using wheat deletion lines reveals high insertion frequencies in gene-rich regions with high to moderate recombination rates
Authors: Randhawa Harpinder S. , Singh Jaswinder , Lemaux Peggy G. , Gill Kulvinder S. 
Published: May 2009

Gene distribution is highly uneven in the large genomes of barley and wheat; however, location, order, and gene density of gene-containing regions are very similar between the two genomes. Flanking sequences from 35 unique, single-copy, barley Ds insertion events were physically mapped using wheat nullisomic-tetrasomic, ditelosomic, and deletion lines. Of the 35 sequences, 23 (66%) detected 34 loci mapping on all 7 homoeologous wheat groups. Seven sequences were not mapped owing to lack of polymorphism and the remaining 5 (14%) were barley-specific. All 34 loci physically mapped to the previously identified gene-rich regions (GRRs) of wheat, making the contained genes candidates for targeted mutagenesis by remobilization. Transpositions occurred preferentially into GRRs with higher recombination rates. The GRRs containing 17 of the 23 Ds insertions accounted for 60%–89% of the respective arm’s recombination. The remaining 6 (17%) insertions mapped to GRRs with <15% of the arm’s recombination. Overall, kb/cM estimates for the Ds-containing GRRs were twofold higher than those for regions without insertions. These results suggest that all genes may be targeted by transposon-based gene cloning, although the transposition frequency for genes present in recombination-poor regions is significantly less than that present in highly recombinogenic regions.
Generation and characterization of the antibacterial activity of a novel hybrid antimicrobial peptide comprising functional domains from different insect cecropins
Authors: Plunkett Richard M. , Murray Stuart I. , Lowenberger Carl A. 
Published: May 2009

The search for new antimicrobial compounds involves finding novel sources of chemotherapeutic compounds or manipulating and combining structures from existing molecules. Small antimicrobial peptides (AMPs) are components of innate immune defenses characterized in greatest detail in insect-derived AMPs. We have generated hybrid AMPs (hAMPs) by combining functional motifs from different insect AMPs as a proof of principle that we can generate molecules with lower minimum inhibitory concentrations, and with different activity and target specificity than either parent molecule. A two-helix, cecropin-like hAMP was created by linking the N-terminal α helix of cecropin A from Aedes aegypti to the C-terminal α helix of cecropin A1 from Drosophila melanogaster . This molecule exhibits antibacterial activity at sub-micromolar concentrations with a target specificity that differs from either parent molecule. Antibacterial activity of the hybrid molecule was found to be greater against Gram-negative than Gram-positive bacteria. No hemolysis was observed in sheep red blood cells exposed to concentrations up to 50 µmol/L, suggesting the peptide is not detrimental to eukaryotic cells.
Subinhibitory concentrations of fluconazole increase the intracellular sodium content in both fluconazole-resistant and -sensitive Candida albicans strains
Authors: Kolecka Anna , Krauke Yannick , Bujdakova Helena , Sychrova Hana 
Published: May 2009

Fluconazole-sensitive (SC 5314) and -resistant (clinical isolate 1173) Candida albicans strains were compared in terms of their osmotolerance and tolerance to toxic sodium cations. The two strains did not differ in their tolerance to high osmotic pressure in general but exhibited distinct sensitivities to sodium cations. Although the fluconazole-resistant 1173 strain contained, under all conditions tested, significantly lower intracellular amounts of Na+, it was much more sodium sensitive than the SC 5314 strain. The addition of subinhibitory concentrations of fluconazole to media supplemented with NaCl significantly influenced the growth of both strains and resulted in substantially elevated intracellular sodium concentrations compared with growth in medium containing NaCl but no fluconazole.
Bacterial diversity of soil samples from the western Himalayas, India
Authors: Gangwar Pooja , Alam Syed Imteyaz , Bansod Sunita , Singh Lokendra 
Published: May 2009

High-altitude cold habitats of the Himalayas are little explored with respect to bacterial diversity. Diverse bacterial species and phylotypes obtained by culture-dependent and culture-independent approaches are reported here. Phylogenetic analysis and modulation of bacterial diversity with altitude and available organic carbon content are also described. Psychrophilic and psychrotolerant bacteria dominated the Himalayan habitats, accounting for 60% of the cultivated strains. Isolates produced one or more (up to five) hydrolytic enzymes, lipase being the one secreted by most strains (62%). Partial 16S rRNA gene sequences were obtained for 99 bacterial strains and 74 clones obtained from soil samples from the western Himalayas. Forty-five percent of cultured bacterial strains belonged to the Proteobacteria group with 39% belonging to γ-Proteobacteria. Firmicutes was the second most abundant class with 32% of the total isolates followed by Actinobacteria (16%) and Bacteroidetes (6%). Most of the strains belonged to the genus Bacillus (30%) followed by Pseudomonas (24%) and Arthrobacter (12%). In culture-independent studies, phylotypes belonging to the Proteobacteria were dominant (73%) with the majority being β-Proteobacteria (31%). The bacterial diversity exhibited an altitude gradient with a gradual decline in the number of genera with increase in altitude. The isolates exhibited close phylogenetic affinities to bacteria from other cold habitats.
Property law and Imperial and British titles: the Dukes of Marlborough and the Principality of Mindelheim
Authors: Cox Noel 
Published: May 2009

AbstractThe title of prince of the Holy Roman Empire was conferred in 1704 upon all the children heirs and lawful descendants, male and female, of John Churchill, the first duke of Marlborough. The title of prince of Mindelheim was granted in 1705 to all male descendants and daughters of the first duke. But following the Treaty of Utrecht in 1713 and the Treaty of Rastatt in 1714 the principality passed to Bavaria. The right of the dukes of Marlborough to use the style and title was thus lost, and any residual rights would have expired in 1722 on the death of the duke, as they could not pass to a daughter (unlike his British titles). Despite this it is still common practice to describe the Duke of Marlborough as a Prince of the Holy Roman Empire and Prince of Mindelheim. This paper considers the differences in the treatment of the descent of the British and imperial titles.
Cell-nonautonomous function of Id1 in the hematopoietic progenitor cell niche
Authors: Suh Hyung Chan , Ji Ming , Gooya John , Lee Michael , Klarmann Kimberly D. , Keller Jonathan R. 
Published: May 2009

AbstractDevelopment of hematopoietic stem cells (HSCs) and their immediate progeny is maintained by the interaction with cells in the microenvironment. We found that hematopoiesis was dysregulated in Id1−/− mice. Although the frequency of HSCs in Id1−/− bone marrow was increased, their total numbers remained unchanged as the result of decreased bone marrow cellularity. In addition, the ability of Id1−/− HSCs to self-renew was normal, suggesting Id1 does not affect HSC function. Id1−/− progenitors showed increased cycling in vivo but not in vitro, suggesting cell nonautonomous mechanisms for the increased cycling. Id1−/− HSCs developed normally when transplanted into Id1+/+ mice, whereas the development of Id1+/+ HSCs was impaired in Id1−/− recipients undergoing transplantation and reproduced the hematologic features of Id1−/− mice, indicating that the Id1−/− microenvironment cannot support normal hematopoietic development. Id1−/− stromal cells showed altered production of cytokines in vitro, and cytokine levels were deregulated in vivo, which could account for the Id1−/− hematopoietic phenotypes. Thus, Id1 is required for regulating the hematopoietic progenitor cell niche but is dispensable for maintaining HSCs.
An in vivo chemical library screen in Xenopus tadpoles reveals novel pathways involved in angiogenesis and lymphangiogenesis
Authors: Kälin Roland E. , Bänziger-Tobler Nadja E. , Detmar Michael , Brändli André W. 
Published: May 2009

AbstractAngiogenesis and lymphangiogenesis are essential for organogenesis but also play important roles in tissue regeneration, chronic inflammation, and tumor progression. Here we applied in vivo forward chemical genetics to identify novel compounds and biologic mechanisms involved in (lymph)angiogenesis in Xenopus tadpoles. A novel 2-step screening strategy involving a simple phenotypic read-out (edema formation or larval lethality) followed by semiautomated in situ hybridization was devised and used to screen an annotated chemical library of 1280 bioactive compounds. We identified 32 active compounds interfering with blood vascular and/or lymphatic development in Xenopus. Selected compounds were also tested for activities in a variety of endothelial in vitro assays. Finally, in a proof-of-principle study, the adenosine A1 receptor antagonist 7-chloro-4-hydroxy-2-phenyl-1,8-naphthyridine, an inhibitor of blood vascular and lymphatic development in Xenopus, was shown to act also as a potent antagonist of VEGFA-induced adult neovascularization in mice. Taken together, the present chemical library screening strategy in Xenopus tadpoles represents a rapid and highly efficient approach to identify novel pathways involved in (lymph)angiogenesis. In addition, the recovered compounds represent a rich resource for in-depth analysis, and their drug-like features will facilitate further evaluation in preclinical models of inflammation and cancer metastasis.
Epoxyeicosatrienoates are the dominant eicosanoids in human lungs upon microbial challenge
Authors: Kiss L. , Schütte H. , Padberg W. , Weissmann N. , Mayer K. , Gessler T. , Voswinckel R. , Seeger W. , Grimminger F. 
Published: May 2009

Lipoxygenase, cyclo-oxygenase and cytochrome P450 (CYP) products of arachidonic acid (AA) are implicated in pulmonary vasoregulation. The CYP-mediated epoxyeicosatrienoates (EETs) have been described previously as the predominant eicosanoids in human lungs upon stimulation with the Ca2+ionophore A23187. In this study, we challenged perfused human lungs with two microbial agents:Escherichia colihaemolysin (ECH) and formyl-methionyl-leucyl-phenylalanine (fMLP).Both stimuli elicited pronounced generation of leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostanoids (PTs) and EETs/dihydroxyeicosatrienoic acids (DHETs), as assessed by liquid chromatography–mass spectrometry, paralleled by pulmonary artery pressor response and lung oedema formation. The maximum buffer concentrations of EETs/DHETs surpassed those of LTs plus HETEs and PTs by a factor of four (ECH) or three (AA/fMLP). Dual 5-lipoxygenase/cyclo-oxygenase inhibition caused pronounced reduction of AA/fMLP-induced LT/PT synthesis and oedema formation but only limited attenuation of pulmonary vasoconstriction, while inhibition of CYP epoxygenase clearly attenuated AA/fMLP-induced EET/DHET synthesis and vasoconstriction but not oedema formation, suggesting a major contribution of LTs/PTs to vascular leakage and of EETs/DHETs to pressor response.Consequently, generation of EETs/DHETs is greater than that of LTs plus HETEs and PTs inex vivoperfused human lungs upon microbial challenge suggesting a substantial contribution of these mediators to inflammatory–infectious pulmonary injury.
Tbx1 and Brn4regulate retinoic acid metabolic genes during cochlear morphogenesis
Authors: Braunstein Evan M , Monks Dennis C , Aggarwal Vimla S , Arnold Jelena S , Morrow Bernice E 
Published: May 2009

Abstract

Background
In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. Tbx1, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. Tbx1 is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of Tbx1 in the POM, we have conditionally inactivated Tbx1 in the mesoderm while keeping expression in the otic vesicle intact.

Results
Conditional mutants (TCre-KO) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that Tbx1 expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4
-;Tbx1
+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. Cyp26a1 expression was altered in the TCre-KO, while Cyp26c1 showed reduced expression in both TCre-KO and Brn4
-;Tbx1
+/- embryos.

Conclusion
These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.
Gene expression in lungs of mice lacking the 5-hydroxytryptamine transporter gene
Authors: Crona Daniel , Harral Julie , Adnot Serge , Eddahibi Saadia , West James 
Published: May 2009

AbstractBackgroundWhile modulation of the serotonin transporter (5HTT) has shown to be a risk factor for pulmonary arterial hypertension for almost 40 years, there is a lack of in vivo data about the broad molecular effects of pulmonary inhibition of 5HTT. Previous studies have suggested effects on inflammation, proliferation, and vasoconstriction. The goal of this study was to determine which of these were supported by alterations in gene expression in serotonin transporter knockout mice.MethodsEight week old normoxic mice with a 5-HTT knock-out (5HTT-/-) and their heterozygote(5HTT+/-) or wild-type(5HTT+/+) littermates had right ventricular systolic pressure(RVSP) assessed, lungs collected for RNA, pooled, and used in duplicate in Affymetrix array analysis. Representative genes were confirmed by quantitative RT-PCR and western blot.ResultsRVSP was normal in all groups. Only 124 genes were reliably changed between 5HTT-/- and 5HTT+/+ mice. More than half of these were either involved in inflammatory response or muscle function and organization; in addition, some matrix, heme oxygenase, developmental, and energy metabolism genes showed altered expression. Quantitative RT-PCR for examples from each major group confirmed changes seen by array, with an intermediate level in 5HTT +/- mice.ConclusionThese results for the first time show the in vivo effects of 5HTT knockout in lungs, and show that many of the downstream mechanisms suggested by cell culture and ex vivo experiments are also operational in vivo. This suggests that the effect of 5HTT on pulmonary vascular function arises from its impact on several systems, including vasoreactivity, proliferation, and immune function.
Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells
Authors: Akide-Ndunge Oscar Bate , Tambini Elisa , Giribaldi Giuliana , McMillan Paul J , Müller Sylke , Arese Paolo , Turrini Francesco 
Published: May 2009

Abstract

Background

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy.

Methods
Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp 60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane.

Results
In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of antioxidant enzymes was also increased in oxidatively-stressed trophozoites.

Conclusion
Results indicated that mRNA expression of parasite antioxidant enzymes and HSPs was co-ordinated and stage-dependent. Secondly, both systems were redox-responsive and showed remarkably increased and co-ordinated expression in oxidatively-stressed parasites and in parasites growing in antioxidant blunted G6PD-deficient RBCs. Lastly, as important anti-malarials either increase oxidant stress or impair antioxidant defense, results may encourage the inclusion of anti-HSP molecules in anti-malarial combined drugs.
Can abuse deterrent formulations make a difference? Expectation and speculation
Authors: Budman Simon H , Grimes Serrano Jill M , Butler Stephen F 
Published: May 2009

AbstractIt is critical that issues surrounding the abuse and misuse of prescription opioids be balanced with the need for these medications for the treatment of pain. One way to decrease the abuse of prescription opioid medications is to develop abuse deterrent formulations (or ADFs) that in some way prevent drug abusers from extracting out the active ingredient in order to employ alternate routes of administration, such as injection, snorting, and smoking. Several factors including the pharmacokinetic profile of the drug, the features of the drug formulation that make it attractive or unattractive for abuse, the type of drug abuser, the progression of one's addiction pathway, and one's social environment may all play a role in the abuse of prescription opioids and what methods are used to abuse these drugs. This paper will examine these factors in order to understand how they affect the abuse of prescription opioids and routes of administration, and how the development of ADFs may alter these patterns.