julilili42/papers huggingface dataset:
2009-01-13

In addition a new group of glycoside hydrolase inhibitors isolated from ac-A literature survey on the structures tinomycetes is discussed in detail, with and specificities of enzyme inhibitors special reference to detection, producisolated from microorganisms is presen-tion, pharmacological effects and structed, with special emphasis on protease ture of the inhibitors.An integral part inhibitors and inhibitors of adrenaline in the chain of a-1,4-linked D-glucopymetabolism.ranose units is a core structure consistingDieses Dokument wurde zum persönlichen Gebrauch heruntergeladen.Vervielfältigung nur mit Zustimmung des Verlages.
2009-01-13

The isoquinoline alkaloids and their biosynthetic relatives include many compounds which show important physiological properties in animals: dopamine, mescaline, morphine, papaverine, and narcotine are pertinent examples.The biosynthetic routes to the members of this family start from the essen-tial aminoacids tyiosine or phenflalanine.Decarboxylation gives a phenethylamine building block (C,-C,) which then combines with an additional building block to form an isoquinoline ring.This stage of the general biosynthetic scheme is illustrated by the biosynthesis of the cactus alkaloid anhalonidine.Many important classes of alkaloid are produced by further transformation of simple isoquinoline systems.In Skeletal Structures of Simple Tetrahydroisoquinoline Alkaloids Scheme
HESS observations ofγ-ray bursts in 2003–2007
2009-01-14

Aims. Very-high-energy (VHE; 100 GeV) -rays are expected from -ray bursts (GRBs) in some scenarios. Exploring this photon energy regime is necessary for understanding the energetics and properties of GRBs.&#13;\\nMethods. GRBs have been one of the prime targets for the HESS experiment, which makes use of four Imaging Atmospheric Cherenkov Telescopes (IACTs) to detect VHE -rays. Dedicated observations of 32 GRB positions were made in the years 2003-2007 and a search for VHE -ray counterparts of these GRBs was made. Depending on the visibility and observing conditions, the observations mostly start minutes to hours after the burst and typically last two hours.&#13;\\nResults. Results from observations of 22 GRB positions are presented. Evidence of a VHE signal was found neither in observations of any individual GRBs nor from stacking data from subsets of GRBs with higher expected VHE flux according to a model-independent ranking scheme. Upper limits for the VHE -ray flux from the GRB positions were derived. For those GRBs with measured redshifts, differential upper limits at the energy threshold after correcting for absorption due to extra-galactic background light are also presented
INTEGRAL observation of hard X-ray variability of the TeV binary LS 5039/RX J1826.2-1450
2009-01-14

LS 5039/RX J1826.2-1450 is one of the few High Mass X-ray binary systems from which radio and high energy TeV emission has been observed. Moreover, variability of the TeV emission with orbital period was detected. We investigate the hard X-ray (25 - 200keV) spectral and timing properties of the source with the monitoring IBIS/ISGRI instrument on-board the INTEGRAL satellite. We present the analysis of INTEGRAL observations for a total of about 3 Msec exposure time, including both public data and data from the Key Programme. We search for flux and spectral variability related to the orbital phase. The source is observed to emit from 25 up to 200 keV and the emission is concentrated around inferior conjunction. Orbital variability in the hard X-ray band is detected and established to be in phase with the orbitally modulated TeV emission observed with H.E.S.S. For this energy range we determine an average flux for the inferior conjunction phase interval of erg cm s , and a flux upper limit for the superior conjunction phase interval of erg cm s (90% conf. level respectively). The spectrum for the inferior conjunction phase interval follows a power law with an index (90% conf. level).
Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians
2009-01-14

The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations.
Toll-Like Receptor Engagement Enhances the Immunosuppressive Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells by Inducing Indoleamine-2,3-dioxygenase-1 via Interferon-β and Protein Kinase R
2009-01-15

Abstract Mesenchymal stem cells (MSC) display unique suppressive properties on T-cell immunity, thus representing an attractive vehicle for the treatment of conditions associated with harmful T-cell responses such as organ-specific autoimmunity and graft-versus-host disease. Toll-like receptors (TLR) are primarily expressed on antigen-presenting cells and recognize conserved pathogen-derived components. Ligation of TLR activates multiple innate and adaptive immune response pathways to eliminate and protect against invading pathogens. In this work, we show that TLR expressed on human bone marrow-derived MSC enhanced the immunosuppressive phenotype of MSC. Immunosuppression mediated by TLR was dependent on the production of immunosuppressive kynurenines by the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase-1 (IDO1). Induction of IDO1 by TLR involved an autocrine interferon (IFN)-β signaling loop, which was dependent on protein kinase R (PKR), but independent of IFN-γ. These data define a new role for TLR in MSC immunobiology, which is to augment the immunosuppressive properties of MSC in the absence of IFN-γ rather than inducing proinflammatory immune response pathways. PKR and IFN-β play a central, previously unidentified role in orchestrating the production of immunosuppressive kynurenines by MSC. Disclosure of potential conflicts of interest is found at the end of this article.
Reversal of P-glycoprotein–Mediated Multidrug Resistance by the Murine Double Minute 2 Antagonist Nutlin-3
2009-01-15

Abstract Murine double minute 2 (MDM2) negatively regulates the activity of the tumor suppressor protein p53. Nutlin-3 is a MDM2 inhibitor under preclinical investigation as nongenotoxic activator of the p53 pathway for cancer therapy. Here, nutlin-3 was evaluated for its activity alone or in combination with established chemotherapeutic drugs for antitumor action in chemosensitive and chemoresistant neuroblastoma and rhabdomyosarcoma cell lines. Effects of nutlin-3 single treatment were much more pronounced in p53 wild-type cell lines (IC50s &amp;lt;3 μmol/L) than in p53-mutated cell lines (IC50s &amp;gt;17 μmol/L). In sharp contrast to the expectations, nutlin-3 concentrations that did not affect viability of p53-mutated cell lines strongly increased the efficacy of vincristine in p53-mutated, P-glycoprotein (P-gp)–overexpressing cell lines (decrease in IC50s 92- to 3,434-fold). Similar results were obtained for other P-gp substrates. Moreover, nutlin-3 reduced efflux of rhodamine 123 and other fluorescence dyes that are effluxed by P-gp. Investigation of Madin-Darby canine kidney (MDCK) II cells stably transfected with plasmids encoding for P-gp (MDCKII MDR1) or multidrug resistance protein 1 (MRP-1, MDCKII MRP1) revealed that nutlin-3 not only interferes with P-gp but also affects MRP-1–mediated efflux. Kinetic studies and investigation of P-gp-ATPase activity showed that nutlin-3 is likely to act as a P-gp transport substrate. Examination of the nutlin-3 enantiomers nutlin-3a and nutlin-3b revealed that, in contrast to MDM2-inhibitory activity that is limited to nutlin-3a, both enantiomers similarly interfere with P-gp–mediated drug efflux. In conclusion, nutlin-3–induced inhibition of P-gp and MRP-1 was discovered as a novel anticancer mechanism of the substance in this report. [Cancer Res 2009;69(2):416–21]
Phylogenetic analysis of the triterpene cyclase protein family in prokaryotes and eukaryotes suggests bidirectional lateral gene transfer
2009-01-15

Summary Functional constraints to modifications in triterpene cyclase amino acid sequences make them good candidates for evolutionary studies on the phylogenetic relatedness of these enzymes in prokaryotes as well as in eukaryotes. In this study, we used a set of identified triterpene cyclases, a group of mainly bacterial squalene cyclases and a group of predominantly eukaryotic oxidosqualene cyclases, as seed sequences to identify 5288 putative triterpene cyclase homologues in publicly available databases. The Cluster Analysis of Sequences software was used to detect groups of sequences with increased pairwise sequence similarity. The sequences fall into two main clusters, a bacterial and a eukaryotic. The conserved, informative regions of a multiple sequence alignment of the family were used to construct a neighbour‐joining phylogenetic tree using the AsaturA and maximum likelihood phylogenetic tree using the PhyML software. Both analyses showed that most of the triterpene cyclase sequences were similarly grouped to the accepted taxonomic relationships of the organism the sequences originated from, supporting the idea of vertical transfer of cyclase genes from parent to offspring as the main evolutionary driving force in this protein family. However, a small group of sequences from three bacterial species ( Stigmatella , Gemmata and Methylococcus ) grouped with an otherwise purely eukaryotic cluster of oxidosqualene cyclases, while a small group of sequences from seven fungal species and a sequence from the fern Adiantum grouped consistently with a cluster of otherwise purely bacterial squalene cyclases. This suggests that lateral gene transfer may have taken place, entailing a transfer of oxidosqualene cyclases from eukaryotes to bacteria and a transfer of squalene cyclase from bacteria to an ancestor of the group of Pezizomycotina fungi.
Ichthyoses – Part 2: Congenital ichthyoses
2009-01-15

Summary Congenital ichthyoses are a group of genetic disorders with defective cornification, clinically characterized by scaling of the skin. Additionally, distinctive cutaneous inflammation can often be observed. For most of the patients these diseases lead to a significant restriction in quality of life. The diagnostic hallmarks are discussed. The diagnostic criteria include clinical and histological findings, often enhanced or confirmed by specialized tests. Because many of the congenital ichthyoses are extremely rare, their accurate diagnosis is often carried out in specialized centers. After discussing the vulgar ichthyoses as well as the diagnostic and therapeutic options in part one, in this second part we review congenital ichthyoses both with and without associated symptoms, focusing on the common genetic changes and their clinical phenotype. Specific therapies are still not available for most of these disorders. The use of different topical agents (e. g. urea, retinoids and salicylic acid) and baths followed by mechanical keratolysis (sometimes in combination with systemic retinoids) reduce skin symptoms. Patients with uncommon congenital ichthyoses often benefit from interdisciplinary management which involves specialized dermatological centers.
Ichthyoses – Part 1: Differential diagnosis of vulgar ichthyoses and therapeutic options
2009-01-15

Summary Ichthyoses are a group of genetic disorders with defective cornification, clinically characterized by scaling of the skin. Additionally, distinctive cutaneous inflammation can often be observed. For most of the patients these diseases lead to a significant restriction in quality of life. The diagnostic criteria include clinical and histological findings, often confirmed by specialized tests. Because many of the ichthyoses are extremely rare, their accurate diagnosis is often carried out in specialized centers. We summarize isolated vulgar and congenital ichthyoses both with and without associated symptoms and focus on the common genetic changes and their clinical phenotype. Specific therapies are still not available for most of these genetic disorders. The use of different topical agents (e. g. urea, retinoids and salicylic acid) and baths followed by mechanical keratolysis (sometimes in combination with systemic retinoids) reduce symptoms. Patients with uncommon congenital ichthyoses often benefit from interdisciplinary management which involves specialized dermatological centers. In this first part of the paper the vulgar ichthyoses as well as the diagnostic and therapeutic options are discussed. The second part focuses on the congenital ichthyoses and their differential diagnosis.
Law of large numbers and large deviations for dependent risks
2009-01-15

We analyse the mathematical structure of models for large risk portfolios, especially for credit risk models. These risk portfolios are modelled using a multivariate mixture model for the dependence structure between the risks. The dependence structures are characterized by latent variables Θ, which play the role of systematic risks. We show that, depending on the choice of the distribution of Θ, there are different asymptotic behaviours for the aggregated risk portfolio, namely law of large numbers/central limit theorem behaviour and large deviation behaviour.
Frequent non-reciprocal exchange in microsatellite-containing-DNA-regions of vertebrates
2009-01-15

Microsatellites are DNA-fragments containing short repetitive motifs with 2-10 bp. They are highly variable in most species and distributed throughout the whole genome. It is broadly accepted that their high degree of variability is closely associated with mispairing of DNA-strands during the replication phase, termed slippage, although recombination is also observed. The aim of this study is to demonstrate evidence that non-reciprocal recombination processes changing the total genomic structure are common in microsatellites and flanking regions. We sequenced DNA fragments from birds in which microsatellites are located, and analyzed the structure of the microsatellites and their flanking regions. Additionally, other data and those from literature of three microsatellite regions of primates coding for the Ataxin-2, the Huntingtin and the TATA-box binding protein were analyzed. The structures of seven avian and three primate microsatellites support the hypothesis that non-reciprocal recombination is a common process that may also contribute considerably to the variation at microsatellite loci. We conclude that results of population genetic studies that are analyzed statistically with methods based on stepwise mutation models should be interpreted with caution if no detailed information on the allelic variation of microsatellites is available.
Effective thalamic deep brain stimulation for neuropathic tremor in a patient with severe demyelinating neuropathy
2009-01-16

Postural and action tremor in peripheral neuropathy is characteristic of Roussy-Levy syndrome. A patient with a severe demyelinating neuropathy and disabling neuropathic tremor successfully treated by deep brain stimulation (DBS) is reported. Disease onset was at age 63 years with sensory symptoms and slight action tremor. Within the following 9 years a severe, drug resistant, postural and action tremor developed rendering the patient unable to feed himself. At age 72 years the patient was treated by bilateral DBS of the ventral intermediate thalamic nucleus, with a useful 30% reduction in tremor. The clinical benefit of the stimulation remained stable over a 1 year postoperative observation period.
The Commonly Performed Nerve Sparing Total Prostatectomy Does Not Acknowledge the Actual Nerve Courses
2009-01-16

Common nerve sparing total prostatectomy provides the possibility to preserve around 55% of all periprostatic nerve fibers focused on the posterolateral location, especially at the apex (80% to 90% nerve sparing). However, it does not consider the actual course of the nerve fibers. To further improve the clinical outcome the actual nerve courses must be considered to preserve the nerve continuum. These findings suggest modification of the nerve sparing technique.
Polyphosphates from Mycobacterium bovis– potent inhibitors of class III adenylate cyclases
2009-01-16

cAMP generation in bacteria is often stimulated by sudden, but lasting, changes in extracellular conditions, whereas intracellular cAMP concentrations quickly settle at new levels. As bacteria lack G‐proteins, it is unknown how bacterial adenylate cyclase (AC) activities are modulated. Mycobacterium tuberculosis has 15 class III AC genes; therefore, we examined whether mycobacteria contain a factor that may regulate AC activities. We identified mycobacterial polyphosphates with a mean chain length of 72 residues as highly potent inhibitors of dimeric class IIIa, class IIIb and class IIIc ACs from M. tuberculosis and other bacteria. The identity of the inhibitor was established by phosphatase degradation, 31 P‐NMR, acid or base hydrolysis, PAGE and comparisons with commercial standards, and functional substitution by several polyphosphates. The data indicate that each AC dimer occupies 8–15 phosphate residues on a polyphosphate strand. Other polyionic polymers such as polyglutamate, polylysine and hyaluronic acid do not affect cyclase activity. Notably, the structurally unrelated class I AC Cya from Escherichia coli is unaffected. Bacterial polyphosphate metabolism is generally viewed in the context of stress‐related regulatory networks. Thus, regulation of bacterial class III ACs by polyphosphates could be a component of the bacterial stress response.
Metallothioneins and Related Chelators
2009-01-19

This title is not available to purchase from Royal Society of Chemistry. Please visit www.bioinorganic-chemistry.org/mils for title information. These sulfur-rich chelators, being important in metal ion homeostasis, find increasing attention. MILS-5, written by 30 internationally recognized experts, focuses on this hot topic. The reader is supported by about 20 tables, more than 80 illustrations and nearly 2000 references. This book is an essential resource for scientists working in a wide range of disciplines from environmental toxicology and inorganic biochemistry all the way through to physiology and medicine.
Entry of Substances Into Perilymph Through the Bone of the Otic Capsule After Intratympanic Applications in Guinea Pigs
2009-01-19

Gentamicin and TMPA can enter perilymph of guinea pigs through the RWM and simultaneously through the bony otic capsule. Drug distribution along the cochlea after intratympanic applications will therefore be dramatically different in rodents and humans. Results obtained from intratympanic drug treatments of animals, in which the bulla is filled with solution and contacts the bony capsule of the cochlea, do not provide a good model for the situation in humans.
Costs of the detection of metastases and follow-up examinations in cutaneous melanoma
2009-01-19

At present, no universally accepted recommendations exist for cutaneous melanoma follow-up. Various surveillance strategies, some associated with significant cost, others of uncertain value, are routinely used. This study aimed to evaluate of the costs incurred for varied surveillance strategies practiced in Europe and the USA. One thousand nine hundred and sixty-nine cutaneous melanoma patients with stage I-III disease attending the Department of Dermatology, University of Tuebingen for follow-up between 1996 and 1998 participated in the study. Routine surveillance consisted of cutaneous examination, lymph node and abdomen sonography, chest radiograph (CR) and blood tests. The costs incurred were based upon the 2004 German official scale for medical reimbursement and the 2004 Medicare fee reimbursement schedule (USA). The total charges were based on the number of recurrences detected per stage. Recurrences were detected in 1.5% of patients with stage I, 18.0% in stage II, and 68.6% in stage III. Physical examination was the most effective method, detecting 50.0% of recurrences. Lymph node sonography was effective in stage II-III, detecting 13.2% of recurrences; CR and abdominal sonography, detecting 4.5 and 3.4% of recurrences, were deemed beneficial in stage III. Blood tests detected 1.4% of recurrences and were deemed to be ineffective. Computed tomography scans were valuable in clarifying ambiguous findings and helping to detect 22.5% of recurrences (1.9% in stage I, 1.9% in stage II, and 18.6% in stage III). A risk-adapted surveillance strategy for stage I-II including thorough history, physical examination and lymph node sonography but omitting CR, blood work and abdomen sonography, seems appropriate and cost effective.
Metallothioneins in Yeast and Fungi
2009-01-19

Small cysteine-rich proteins sharing most if not all of the general features used to define the metallothionein (MT) superfamily are found in yeast and fungi. Unlike MTs from mammalian sources, most of the known yeast and fungal MTs are Cu(I) rather than Zn(II) or Cd(II) binding proteins. The sequences of fungal MTs reported so far are quite diverse, in such a way that fungal MTs are assigned to six different families. Family 8 contains the MTs with the highest similarity to the N-terminal domains of mammalian MTs. The best characterized member of this family is isolated from the ascomycete Neurospora crassa. It represents a copper-induced polypeptide of only about 25 amino acid residues and harbors a single cluster made up of six Cu(I) that are bound to its seven cysteine residues. The MTs assigned to families 9 and 10 are MT-1 and MT-2 found in the human pathogenic yeast Candida glabrata. The regulation of these proteins employing a copper sensitive transcription factor shares the same principle as were described for the MTs found in Saccharomyces cerevisiae, Cu-MT and Crs5, that are assigned to families 12 and 13. S. cerevisiae Cu-MT is the only MT, of which the structure including its Cu(I)8-thiolate core has been revealed. It should be emphasized that this is the largest known Cu cluster in biological systems. Besides the presentation of these well studied aspects, the open questions of Cd(II) and Zn(II) binding in yeasts and fungi are addressed and future directions of the MT research are discussed.