julilili42/papers huggingface dataset:
sae is essential for expression of the staphylococcal adhesins Eap and Emp
2005-06-01

Eap and Emp are two Staphylococcus aureus adhesins initially described as extracellular matrix binding proteins. Eap has since emerged as being important in adherence to and invasion of eukaryotic cells, as well as being described as an immunomodulator and virulence factor in chronic infections. This paper describes the mapping of the transcription start point of the eap and emp promoters. Moreover, using reporter-gene assays and real-time PCR in defined regulatory mutants, environmental conditions and global regulators affecting expression of eap and emp were investigated. Marked differences were found in expression of eap and emp between strain Newman and the 8325 derivatives SH1000 and 8325-4. Moreover, both genes were repressed in the presence of glucose. Analysis of expression of both genes in various regulatory mutants revealed that sarA and agr were involved in their regulation, but the data suggested that there were additional regulators of both genes. In a sae mutant, expression of both genes was severely repressed. sae expression was also reduced in the presence of glucose, suggesting that repression of eap and emp in glucose-containing medium may, in part, be a consequence of a decrease in expression of sae .
Comprehensive language mapping in children, using functional magnetic resonance imaging: what??s missing counts
2005-06-01

Noninvasive language mapping is a frequently used application of functional magnetic resonance imaging. The examination of children, however, poses both practical and technical challenges. To this effect, we have developed two new paradigms mainly requiring passive listening to stories from which several key words were removed. Results were compared with a standard active verb-generation task, particularly with regard to hemispheric dominance in frontal brain areas. Fifteen healthy children (seven boys, eight girls, 6-14 years) were scanned. Distinct frontal activation was seen in our new tasks, which was stronger when the tasks were analyzed specifically with regard to the missing words. This confirms the hypothesis that the removal of these words is the key in inducing frontal activation. Frontal lateralization was consistent and strong in all three paradigms. Additionally, receptive language areas are also mapped by our new tasks. We conclude that our two new, child-friendly functional magnetic resonance imaging paradigms are useful in determining hemispheric dominance for language in children too young or too impaired to execute an active task. They also allow robust mapping of receptive language areas.
Patterns of molecular and morphological differentiation in Fagus (Fagaceae): phylogenetic implications
2005-06-01

To study phylogenetic relationships among species of Fagus , the internal transcribed spacer regions ITS1 and ITS2 of the nuclear ribosomal DNA and morphological data were analyzed. Both molecular and morphologically based phylogenies suggest that Eurasian species of Fagus subgenus Fagus are basal to the North American Fagus grandifolia . The subgenus Fagus is a paraphyletic group basal to three East Asian species forming the subgenus Engleriana . Due to a considerably large amount of DNA polymorphism, relationships among basal species of Fagus could not be entirely resolved when analyzing ITS sequences with standard methods. Morphological trees helped to resolve more clearly relationships within the subgenus Fagus . The East Asian F. hayatae is suggested to be basal to the rest of the genus. This hypothesis is further supported by distinctive patterns of nucleotide variability found for ITS regions, allowing for basic and derived types to be distinguished. The high degree of ITS polymorphism within Fagus can be explained by (1) the complex evolutionary behavior of this marker, (2) the stenoecious ecological characteristic of Fagus with respect to its continuous geographic range throughout much of the Cenozoic, and (3) the absence of major radiations into further habitats as occurred in other Fagaceae.
Cooperative Cytotoxicity of Proteasome Inhibitors and Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand in Chemoresistant Bcl-2-Overexpressing Cells
2005-06-01

Abstract Purpose: Bcl-2 overexpression is frequently detected in lymphoid malignancies, being associated with poor prognosis and reduced response to therapy. Here, we evaluated whether Bcl-2 overexpression affects the cytotoxic activity of proteasome inhibitors taken alone or in association with conventional anticancer drugs or tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Experimental Design: Jurkat cells engineered to overexpress Bcl-2 were treated with proteasome inhibitors (MG132, epoxomicin, and bortezomib), anticancer drugs (etoposide and doxorubicin), TRAIL, or combinations of these compounds. Cell death and loss of mitochondrial transmembrane potential were detected by flow cytometry. Cytosolic relocalization of cytochrome c and SMAC/Diablo, caspase cleavage, and Bcl-2 and Mcl-1 levels were determined by immunoblotting. Nuclear factor-κB inhibition was done by retroviral transduction with a dominant-negative mutant of IκBα. Results: Bcl-2 overexpression results in significant inhibition of apoptosis in response to proteasome inhibitors, antiblastics, and TRAIL. Addition of TRAIL to proteasome inhibitors results in a synergistic cytotoxic effect in Bcl-2-overexpressing cells, whereas this result is not reproduced by the combination of proteasome inhibitors with antiblastic drugs. Importantly, proteasome inhibitors plus TRAIL induce mitochondrial dysfunction irrespective of up-regulated Bcl-2. Bcl-2 cleavage to a fragment with putative proapoptotic activity and elimination of antiapoptotic Mcl-1 may both play a role in proteasome inhibitors-TRAIL cooperation. Conversely, nuclear factor-κB inhibition by proteasome inhibitors is per se insufficient to explain the observed synergy. Conclusions: Combined proteasome inhibitors and TRAIL overcome the apoptotic threshold raised by Bcl-2 and may prove useful in the treatment of chemoresistant malignancies with up-regulated Bcl-2.
Sorption of HOC in soils with carbonaceous contamination: Influence of organic‐matter composition
2005-06-01

Abstract Detailed information about structure and composition of organic sorbents is required to understand their impact on sorption capacity and sorption kinetic of organic pollutants. Therefore, the chemical composition of organic material from 18 geosorbents was investigated by solid‐state 13 C nuclear‐magnetic‐resonance (NMR) spectroscopy. Structural parameters such as aromaticity, polarity, and alkyl‐C content were related to the Freundlich sorption exponent ( 1 / n ) and the sorption coefficient . The geosorbents included three natural and four combusted coals (carbonaceous material), three Histosols, five mineral soils from Germany containing inputs of technogenic carbonaceous material, derived from industrial activities, and four non‐contaminated mineral soils from Germany. Equilibrium sorption was measured for five hydrophobic organic compounds and analyzed with the solubility‐normalized Freundlich sorption isotherm. With increasing maturation degree, the proportion of polar constituents decreases from the natural soils to the coals. In contrast to the non‐polluted mineral soils, the soils with technogenic input are characterized by high aromaticity and low polarity. A positive correlation between sorption coefficient and aromaticity was found. The Freundlich exponent ( 1 / n ) is negatively correlated with the aromaticity, denoting an increase of adsorption processes with increasing aromaticity. Likewise, the contribution of partitioning decreases. This sorption mechanism predominates only if the organic matter in the samples contains a high proportion of polar compounds.
Superconducting Quantum Interference Filters Operated in Commercial Miniature Cryocoolers
2005-06-01

Superconducting Quantum Interference Filters (SQIF's) are multi-loop arrays of Josephson junctions possessing unconventional grating structures. The flux-to-voltage transfer function of SQIF's is unique and has a single delta-peak like characteristics at zero applied magnetic field. The fault tolerance of SQIF's allows them to be realized in standard high-temperature grain boundary Josephson junction technology. We have successfully designed high-temperature YBCO SQIF's with voltage swings of more than 3 mV and a rather large dynamical range. This large dynamical range allows high-Tc SQIF's to be operated in commercial miniature cryocoolers at 50 K-80 K without any significant problems. Typical parasitic oscillations which are induced by the 55 Hz driven compressor of the cryocooler do not degrade the performance of SQIF's. Even if SQIF's are operated fully unshielded no significant degradation of the performance has been observed.
Comparison of Different Methods for Enhancing the Dissolution Rate of Poorly Soluble Drugs: Case of Griseofulvin
2005-06-01

An improvement of the bioavailability of poorly soluble drugs by enhancing their dissolution rate is one of the challenging topics in drug development. Griseofulvin, an antifugal drug with poor solubility and dissolution behavior, was used as an example to demonstrate and evaluate the efficiency of three different methods proposed for this purpose: micronization by milling and by precipitation from supercritical fluids and adsorption on a carrier (silica aerogel).
Human Adaptive Immune System Rag2−/−γc−/− Mice
2005-06-01

A bstract : Although many biologic principles are conserved in mice and humans, species‐specific differences exist, for example, in susceptibility and response to pathogens, that often do not allow direct implementation of findings in experimental mice to humans. Research in humans, however, for ethical and practical reasons, is largely restricted to in vitro assays that lack components and the complexity of a living organism. To nevertheless study the human hematopoietic and immune system in vivo , xenotransplantation assays have been developed that substitute human components to small animals. Here, we summarize our recent findings that transplantation of human cord blood CD34 + cells to newborn Rag2 −/− γ c −/− mice leads to de novo development of major functional components of the human adaptive immune system. These human adaptive immune system Rag2 −/− γ c −/− (huAIS‐RG) mice can now be used as a technically straightforward preclinical model to evaluate in vivo human adaptive immune system development as well as immune responses, for example, to vaccines or live infectious pathogens.
NovG, a DNA-binding protein acting as a positive regulator of novobiocin biosynthesis
2005-06-01

The biosynthetic gene cluster of the aminocoumarin antibiotic novobiocin contains two putative regulatory genes, i.e. novE and novG . The predicted gene product of novG shows a putative helix–turn–helix DNA-binding motif and shares sequence similarity with StrR, a well-studied pathway-specific transcriptional activator of streptomycin biosynthesis. Here functional proof is provided, by genetic and biochemical approaches, for the role of NovG as a positive regulator of novobiocin biosynthesis. The entire novobiocin cluster of the producer organism Streptomyces spheroides was expressed in the heterologous host Streptomyces coelicolor M512, and additional strains were produced which lacked the novG gene within the heterologously expressed cluster. These Δ novG strains produced only 2 % of the novobiocin formed by the S. coelicolor M512 strains carrying the intact novobiocin cluster. The production could be restored by introducing an intact copy of novG into the mutant. The presence of novG on a multicopy plasmid in the strain containing the intact cluster led to almost threefold overproduction of the antibiotic, suggesting that novobiocin biosynthesis is limited by the availability of NovG protein. Furthermore, purified N-terminal His 6 -tagged NovG showed specific DNA-binding activity for the novG – novH and the cloG – cloY intergenic regions of the novobiocin and clorobiocin biosynthetic gene clusters, respectively. By comparing the DNA sequences of the fragments binding NovG, conserved inverted repeats were identified in both fragments, similar to those identified as the binding sites for StrR. The consensus sequence for the StrR and the putative NovG binding sites was GTTCRACTG(N) 11 CRGTYGAAC. Therefore, NovG and StrR apparently belong to the same family of DNA-binding regulatory proteins.
Multiple reflectance interference spectroscopy measurements made in parallel for binding studies
2005-06-01

Reflectometric interference spectroscopy (RIfS) for the direct optical detection of biomolecular interaction has gained increasing interest in recent years compared to fluorophore based assays. The method has been established in the last decade as a robust and simple optical tool to perform such binding studies taking advantage of low temperature dependence and its capability of time-resolved monitoring of binding processes. Therefore various single-channel setups are given in review. In addition, the capability of parallel measurements and miniaturisation is discussed. The different properties of the setups are presented and the theoretical background is outlined. Many applications are given for this method in comparison to other direct optical detection methods; concentrating on a number of applications that have not yet been published. The capability of using this method in the area of high throughput screening of libraries and the application to combinatorial chemistry is demonstrated.
Mycorrhiza Formation Enhances Adaptive Response of Hybrid Poplar to Drought
2005-06-01

A bstract : Mycorrhized and nonmycorrhized plants of hybrid poplar ( Populus tremula L. × Populus tremuloides Mich) were cultivated in petri dishes until the amount of water became limiting (detected by a decrease of photosynthetic yield). RNA was isolated from both main and fine roots and used for analysis of water channel (aquaporin) gene expression by semiquantitative RT‐PCR. For three of five investigated aquaporin genes, expression did not differ between mycorrhized and nonmycorrhized plants. However, expression of the two other aquaporin genes was more pronounced in fine roots of mycorrhized plants, indicating that the root‐fungus symbiosis may improve the water transport capacity under conditions of reduced water availability.
Superconducting Quantum Interference Filters as Absolute Magnetic Field Sensors
2005-06-01

We propose Superconducting Quantum Interference Filters (SQIFs) as high sensitive magnetic field detectors. The SQIF is made of high critical temperature grain boundary Josephson junctions, and it is surrounded by an on chip superconducting pick-up loop which enhances the magnetic field sensitivity of about 10 times with respect to the same SQIF without pick-up loop. The devices are operated in Stirling microcoolers, at a temperature of about 70 K. In the presence of an applied magnetic field B, SQIFs show the typical magnetic field dependent voltage response V(B), which is sharp delta-like dip in the vicinity of zero magnetic field. When the SQIF is cooled with magnetic shield, and then the shield is removed, the presence of the ambient magnetic field induces a shift of the dip position from B/sub 0/ /spl ap/ 0 to a value B /spl ap/ B/sub 1/, which is about the average value of the Earth magnetic field, at our latitude. The low hysteresis observed in the sequence of experiments makes SQIFs suitable for high precision measurements of the absolute magnetic field. Typical magnetic flux noise spectra of SQIFs show a white noise level of about 0.6 /spl mu/T//spl radic/Hz. Comparative measurements of the direct spectra with the spectra measured by using noise reduction techniques reveal a significant decrease of the 1/f noise levels. The experimental results are discussed in view of potential applications of high critical temperature SQIFs in magnetometry.
Carnivorous plant chemistry
2005-06-01

Abstract Phytochemical data are contrasted with phylogenetic relationships of carnivorous plants. Naphthoquinone profiles of a representative set of Nepenthes species are evaluated in comparison with previously published chemical data for Nepenthales (containing four distinct carnivorous plant families). The iridoids sarracenin and aucubin are identified as valuable chemical markers of Sarraceniaceae and Scrophulariales, respectively. The latter order (that contains the carnivorous Lentibulariaceae and Byblidaceae) is also characterized by the common occurrence of the phenylethanoid caffeic acid glycoside acteoside. No taxonomically relevant metabolite is known from Cephalotaceae so far.
HD10: Investigating reduction of combined modality treatment intensity in early stage Hodgkin’s lymphoma. Interim analysis of a randomized trial of the German Hodgkin Study Group (GHSG)
2005-06-01

6506 Background: Early stage Hodgkin's lymphoma (HL) in stages I-II without risk factors currently is successfully treated with combined modality of chemotherapy (usually ABVD) followed by involved field irradiation (IF) in most study groups, reaching complete remission rates higher than 90%. In the HD10 trial the GHSG investigated if the number of ABVD cycles as well as IF-radiotherapy (RT) dose could be safely reduced. Methods: 1131 patients (pts) with early stage disease (stage I,II without risk factors) were randomized between 4 cycles vs. 2 cycles of ABVD and 30 Gy IF vs. 20 Gy IF in a 2x2 factorial design between 5/1998 and 5/2002. Primary endpoint was freedom from treatment failure (FFTF). Results: The second interim analysis conducted in August 2003 comprised of 847 pts (75%) that were well balanced between treatments arms concerning baseline characteristics. Complete remission rates were high with 98.4% of all pts while progressive disease or no change was observed in 0.9% of cases. Relapse rate was 2.5%, thirteen patients died during the study (1.5%). The most common WHO grade 3/4 toxicity during CT was leukopenia with 19% (4xABVD: 22%, 2xABVD: 15%). RT was well tolerated with dysphagia in 2.3%. So far ten secondary neoplasias were reported: 1AML, 4 NHL and 5 solid tumors. FFTF after a median observation time of two years was 96.6% with no statistical differences between CT of 4xABVD vs. 2xABVD or RT of 30Gy IF vs. 20Gy IF. Overall survival was 98.5% without any statistical differences in CT and RT comparisons either. Conclusions: Further analysis will show if these promising interim results will allow to reduce further therapy intensity in combined modality treatment of early stage HL both in terms of the composition of drugs (ABVD->AV in HD13) as well as RT dose. No significant financial relationships to disclose.
Effects of propofol on N -methyl-D-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons
2005-06-01

The threshold concentration for significant effects of propofol on the NMDA-induced increase of intraneuronal calcium turned out to be in the upper limit of propofol concentrations that are considered to be clinically relevant. However, in the presence of high propofol concentrations, inhibition of NMDA receptor-mediated calcium increase might contribute to neuroprotective effects observed with propofol.
An acyl-CoA dehydrogenase is involved in the formation of the Δcis3 double bond in the acyl residue of the lipopeptide antibiotic friulimicin in Actinoplanes friuliensis
2005-06-01

The lipopeptide antibiotic friulimicin, produced by Actinoplanes friuliensis , is an effective drug against Gram-positive bacteria, such as methicillin-resistant Staphylococcus epidermidis and Staphylococcus aureus strains. Friulimicin consists of a cyclic peptide core of ten amino acids and an acyl residue linked to an exocyclic amino acid. The acyl residue is essential for antibiotic activity, varies in length from C13 to C15, and carries a characteristic double bond at position Δ cis 3. Sequencing of a DNA fragment adjacent to a previously described fragment encoding some of the friulimicin biosynthetic genes revealed several genes whose gene products resemble enzymes of lipid metabolism. One of these genes, lipB , encodes an acyl-CoA dehydrogenase homologue. To elucidate the function of the LipB protein, a lipB insertion mutant was generated and the friulimicin derivative (FR242) produced by the mutant was purified. FR242 had antibiotic activity lower than friulimicin in a bioassay. Gas chromatography showed that the acyl residue of wild-type friulimicin contains a double bond, whereas a saturated bond was present in FR242. These results were confirmed by the heterologous expression of lipB in Streptomyces lividans T7, which led to the production of unsaturated fatty acids not found in the S. lividans T7 parent strain. These results indicate that the acyl-CoA dehydrogenase LipB is involved in the introduction of the unusual Δ cis 3 double bond into the acyl residue of friulimicin.
Adenylyl cyclase Rv0386 from Mycobacterium tuberculosis H37Rv uses a novel mode for substrate selection
2005-06-01

Class III adenylyl cyclases usually possess six highly conserved catalytic residues. Deviations in these canonical amino acids are observed in several putative adenylyl cyclase genes as apparent in several bacterial genomes. This suggests that a variety of catalytic mechanisms may actually exist. The gene Rv0386 from Mycobacterium tuberculosis codes for an adenylyl cyclase catalytic domain fused to an AAA‐ATPase and a helix‐turn‐helix DNA‐binding domain. In Rv0386, the standard substrate, adenine‐defining lysine‐aspartate couple is replaced by glutamine‐asparagine. The recombinant adenylyl cyclase domain was active with a V max of 8 nmol cAMP·mg −1 ·min −1 . Unusual for adenylyl cyclases, Rv0386 displayed 20% guanylyl cyclase side‐activity with GTP as a substrate. Mutation of the glutamine‐asparagine pair either to alanine residues or to the canonical lysine‐aspartate consensus abolished activity. This argues for a novel mechanism of substrate selection which depends on two noncanonical residues. Data from individual and coordinated point mutations suggest a model for purine definition based on an amide switch related to that previously identified in cyclic nucleotide phosphodiesterases.
Role of Glucoxidation and Lipid Oxidation in the Development of Atherosclerosis
2005-06-01

A bstract : Previous data have indicated that modification of proteins/lipids by glucoxidation and/or lipid oxidation may initiate/propagate the formation of atherosclerotic plaques. Although the biomarker carboxymethyllysine (CML) has been detected in these lesions, the origin of the reactive oxygen species (ROS) leading to its formation and the source of its carbon backbone are unknown. As presented here, the stimulation of cultured monocytes by phorbol‐12‐myristate‐13‐acetate (TPA), an activator of protein kinase C that can mimic the effects of high glucose, angiotensin II, and other physiological stimuli, leads to cellular ROS generation and concomitant formation of intracellular CML. Inhibitors of ROS‐generating cellular systems such as NO synthase, xanthine oxidase, or cytochrome P450 oxidase had no effect on CML formation. Likewise, in cells with inactive NAD(P)H oxidase no reduced CML formation was found. In cells exhibiting a high glycolysis rate, CML formation was unaffected. Because we found rapid CML formation in the presence of unsaturated fatty acids, it appears that lipid oxidation is quantitatively more important. In vivo studies revealed strong intracellular CML staining in areas of histiocytic/monocytic infiltration or proliferation, mostly associated with atheroma formation. Corresponding CML staining patterns were found in healing wounds of different ages, indicating that formation of atherosclerosis is a chronic wound repair associated with a low‐grade inflammatory reaction. In summary, CML is formed concomitantly with oxidative stress in activated monocytes and can be regarded as a biomarker for a low‐grade inflammatory tissue reaction in the atherosclerotic plaque. Its formation via lipid oxidation may be involved in the development of atherosclerosis.