julilili42/papers huggingface dataset:
Expression of Adiponectin Receptor mRNA in Human Skeletal Muscle Cells Is Related to In Vivo Parameters of Glucose and Lipid Metabolism
2004-09-01

The adiponectin receptors, AdipoR1 and AdipoR2, are thought to transmit the insulin-sensitizing, anti-inflammatory, and atheroprotective effects of adiponectin. In this study, we examined whether AdipoR mRNA expression in human myotubes correlates with in vivo measures of insulin sensitivity. Myotubes from 40 metabolically characterized donors expressed 1.8-fold more AdipoR1 than AdipoR2 mRNA (588 ± 35 vs. 321 ± 39 fg/μg total RNA). Moreover, the expression levels of both receptors correlated with each other (r = 0.45, P &amp;lt; 0.01). AdipoR1 mRNA expression was positively correlated with in vivo insulin and C-peptide concentrations, first-phase insulin secretion, and plasma triglyceride and cholesterol concentrations before and after adjustment for sex, age, waist-to-hip ratio, and body fat. Expression of AdipoR2 mRNA clearly associated only with plasma triglyceride concentrations. In multivariate linear regression models, mRNA expression of AdipoR1, but not AdipoR2, was a determinant of first-phase insulin secretion independent of insulin sensitivity and body fat. Finally, insulin did not directly modify myotube AdipoR1 mRNA expression in vitro. In conclusion, we provide evidence that myotube mRNA levels of both receptors are associated with distinct metabolic functions but not with insulin sensitivity. AdipoR1, but not AdipoR2, expression correlated with insulin secretion. The molecular nature of this link between muscle and β-cells needs to be further clarified.
Genetics of Parkinson's disease.
2004-09-01

The etiology of most cases of Parkinson's disease (PD) remains unknown. In recent years, however, research has successfully focused on genetic factors contributing to the degeneration of dopaminergic neurons. Causative mutations have been identified in several monogenically inherited forms of the disease. Although these genetic forms of PD are usually rare, the gene discoveries are likely to identify molecular pathways that are also relevant in the sporadic disorder. These studies have led to the identification of (i) the central role of α-synuclein aggregation, secondary to either point mutations or an amplification of the α-synuclein gene; and (ii) the relevance of defects in the proteasomal protein degradation pathway in the molecular pathogenesis of recessive parkin-linked forms of PD. The recent discoveries of two additional recessive forms associated with mutations in the genes DJ-1 and PINK1 have brought the mitochondrial energy metabolism and the cell's defence against toxic free radicals into the focus of research.
Polymorphonuclear leukocytes (PMNs) induce protective Th1-type cytokine epithelial responses in an in vitro model of oral candidosis
2004-09-01

The immune response and the anticandidal activity of keratinocytes and polymorphonuclear leukocytes (PMNs) play a key role in host defence against localized Candida albicans infection. An established model of oral candidosis based on reconstituted human oral epithelium (RHE) was supplemented with PMNs to study the effect of these immune cells during experimental oral candidosis. Infection of RHE with C. albicans induced a strong expression of the chemokine interleukin-8 (IL-8) and the cytokine granulocyte-macrophages colony-stimulating factor (GM-CSF), and a moderate stimulation of interleukin-1 α (IL-1 α ), interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), interferon γ (IFN- γ ) and tumour necrosis factor α (TNF- α ) by keratinocytes. This immune response was associated with chemoattraction of PMNs to the site of infection, whereas uninfected RHE failed to induce cytokine expression or to attract PMNs. Growth of the pathogen and tissue damage of C. albicans -infected RHE were significantly reduced when PMNs were applied to the apical epithelial surface or when PMNs migrated through a perforated basal polycarbonate filter of the model. Notably, protection against epithelial tissue damage was also observed when PMNs were placed on the basal side of non-perforated filters, which prevented PMN migration into the RHE. Addition of PMNs enhanced a Th1-type immune response (IFN- γ , TNF- α ), down-regulated the expression of the Th2-type cytokine interleukin-10 (IL-10), and was associated with protection against Candida -induced tissue damage. This PMN-supplemented model of oral candidosis mimics the in vivo situation, and provides a promising tool for studying the immunological interactions between keratinocytes and C. albicans , as well as the influence of PMNs on C. albicans pathogenesis.
Biosynthesis of Chloro-β-Hydroxytyrosine, a Nonproteinogenic Amino Acid of the Peptidic Backbone of Glycopeptide Antibiotics
2004-09-01

ABSTRACT The role of the putative P450 monooxygenase OxyD and the chlorination time point in the biosynthesis of the glycopeptide antibiotic balhimycin produced by Amycolatopsis balhimycina were analyzed. The oxyD gene is located directly downstream of the bhp (perhydrolase) and bpsD (nonribosomal peptide synthetase D) genes, which are involved in the synthesis of the balhimycin building block β-hydroxytyrosine (β-HT). Reverse transcriptase experiments revealed that bhp , bpsD , and oxyD form an operon. oxyD was inactivated by an in-frame deletion, and the resulting mutant was unable to produce an active compound. Balhimycin production could be restored (i) by complementation with an oxyD gene, (ii) in cross-feeding studies using A. balhimycina JR1 (a null mutant with a block in the biosynthesis pathway of the building blocks hydroxy- and dihydroxyphenylglycine) as an excretor of the missing precursor, and (iii) by supplementation of β-HT in the growth medium. These data demonstrated an essential role of OxyD in the formation pathway of this amino acid. Liquid chromatography-electrospray ionization-mass spectrometry analysis indicated the biosynthesis of completely chlorinated balhimycin by the oxyD mutant when culture filtrates were supplemented with nonchlorinated β-HT. In contrast, supplementation with 3-chloro-β-HT did not restore balhimycin production. These results indicated that the chlorination time point was later than the stage of free β-HT, most likely during heptapeptide synthesis.
The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism
2004-09-01

Rho-like GTPases such as RhoA, Rac1 and Cdc42 are key regulators of actin-dependent cell functions including cell morphology, adhesion and migration. Tiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, is an important regulator of cell shape and invasiveness in epithelial cells and fibroblasts. Overexpression of Tiam1 in metastatic melanoma cells converted the constitutive mesenchymal phenotype into an epithelial-like phenotype. This included the induction of stringent cell-cell contacts mediated by the Ig-like receptor ALCAM (activated leukocyte cell adhesion molecule) and actin redistribution to cell-cell junctions. This phenotypic switch was dependent on increased Rac but not Rho activity, and on the redistribution and adhesive function of ALCAM, whereas cadherins were not involved. Although cell proliferation was significantly enhanced, the gain of cell-cell junctions strongly counteracted cell motility and invasion as shown for two- and three-dimensional collagen assays as well as invasion into human skin reconstructs. The reverse transition from mesenchymal invasive to a resident epithelial-like phenotype implicates a role for Tiam1/Rac signaling in the control of cell-cell contacts through a novel ALCAM-mediated mechanism.
A new Xinjiangchelyid turtle (Testudines, Eucryptodira) from the Jurassic Qigu Formation of the southern Junggar Basin, Xinjiang, north‐west China
2004-09-01

A new eucryptodiran turtle, Xinjiangchelys qiguensis sp. nov. from the Upper Jurassic (Oxfordian — ?Kimmeridgian) Qigu Formation of the southern Junggar Basin (north‐west China) is described. The type material consists of a partial skeleton, including the complete carapace, plastron, nearly all cervical vertebrae, both scapulae, the pelvis and one ulna. It is clearly identifiable as a basal eucryptodire since it lacks the mesoplastron. It is distinguished from other species of Xinjiangchelys by several autapomorphies of the carapace and plastron, such as the first and fifth vertebrals extending on the peripherals, the plastron with three pairs of gulars, and an intergular which does not contact the hyoplastron. In the postcranium, the scapula with a long acromial and a small scapular process, the pelvis with a short ilial shaft and the elongated cervical vertebrae are characteristic. A new phylogenetic analysis of the in‐group phylogeny of the Xinjiangchelyidae is proposed and discussed, resulting in a new classification of the family. Xinjiangchelys ( Toxocheloides ) narynensis is regarded as a nomen dubium . Shartegemys is referred to Xinjiangchelys , whereas the holotypes of ‘ Plesiochelys ’ chungkingensis and ‘ P ’. latimarginalis are excluded from the genus Xinjiangchelys but included in the Xinjiangchelyidae.
Muscle Type Dependent Increase in Intramyocellular Lipids during Prolonged Fasting of Human Subjects: A Proton MRS Study
2004-09-01

The amount of intramyocellular lipids in skeletal muscle was assessed by proton magnetic resonance spectroscopy during a voluntary fasting period of 120 h in four healthy lean volunteers. The aim of the study was to determine whether muscular lipid uptake in the presence of high plasma lipid levels, or lipid oxidation due to lacking glycogen as a source of energy in musculature, are the dominant effects on intramyocellular lipid levels under fasting conditions in various muscle types. Intramyocellular lipids were quantified in the tibialis anterior (mixed type I and type II fibers, predominantly type II) and the soleus muscle (predominantly type I fibers) before and after 24 h, 72 h, and 120 h of fasting. An extreme increase in intramyocellular lipids to levels of 369 % (median) was found in the tibialis anterior muscle compared to baseline value (intramyocellular lipid level prior to fasting, set to 100 %; p = 0.02). The soleus muscle with clearly higher baseline content of intramyocellular lipids (2 - 4-fold compared to tibialis anterior) revealed slightly delayed and less pronounced uptake of intramyocellular lipids during fasting to 152 % (median) after 120 h (p = 0.02). The absolute increment in intramyocellular lipids (in terms of ratios between lipid and creatine signals) was also higher in tibialis anterior than in soleus (not statistically significant). These findings indicate augmentation of the intramyocellular lipid pool during long-term elevation of plasma FFA in the presence of low plasma insulin concentrations in both muscles investigated. The rate of muscular lipid oxidation during fasting is clearly lower than the increased uptake of FFA by myocytes.
Hearing Lips: Gamma-band Activity During Audiovisual Speech Perception
2004-09-01

Auditory pattern changes have been shown to elicit increases in magnetoencephalographic gamma-band activity (GBA) over left inferior frontal cortex, forming part of the putative auditory ventral "what" processing stream. The present study employed a McGurk-type paradigm to assess whether GBA would be associated with subjectively perceived changes even when auditory stimuli remain unchanged. Magnetoencephalograms were recorded in 16 human subjects during audiovisual mismatch perception. Both infrequent visual (auditory /ta/ + visual /pa/) and acoustic deviants (auditory/pa/ + visual /ta/) were compared with frequent audiovisual standards (auditory /ta/ and visual /ta/). Statistical probability mapping revealed spectral amplitude increases at approximately 75 and approximately 78 Hz to visual deviants. GBA to visual deviants peaked 160 ms after auditory stimulus onset over posterior parietal cortex, at 270 ms over occipital areas and at 320 ms over left inferior frontal cortex. The latter GBA enhancement was consistent with the increase observed previously to pure acoustic mismatch, supporting a role of left inferior frontal cortex for the representation of perceived auditory pattern change. The preceding gamma-band changes over posterior areas may reflect processing of incongruent lip movements in visual motion areas and back-projections to earlier visual cortex.
The youngest African clymeniids (Ammonoidea, Late Devonian) – failed survivors of the Hangenberg Event
2004-09-01

A co-occurrence of the clymeniid Postclymenia evoluta Schmidt, 1924 and the goniatite Acutimitoceras hilarum Korn, 2002 is reported from the Anti-Atlas of Morocco. Both species occur in the same limestone horizon within the Acutimitoceras prorsum Zone, that has yielded an exclusive conodont fauna of the Upper praesulcata Zone (latest Devonian, above the Hangenberg Black Shale). This record is firm evidence that some clymeniids survived the global Hangenberg Event, but soon later became extinct without descendants.
Terminal nerve and vision
2004-09-01

Abstract The vertebrate retina receives efferent input from different parts of the central nervous system. Efferent fibers are thought to influence retinal information processing but their functional role is not well understood. One of the best‐described retinopetal fiber systems in teleost retinae belongs to the terminal nerve complex. Gonadotropin‐releasing hormone (GnRH) and molluscan cardioexcitatory tetrapeptide (FMRFamide)‐containing fibers from the ganglion of the terminal nerve form a dense fiber plexus in the retina at the border of the inner nuclear and inner plexiform layer. Peptide‐containing fibers surround and contact perikarya of dopaminergic interplexiform cells in teleost retina. In vitro experiments demonstrated that exogenously supplied GnRH mediates dopaminergic effects on the membrane potential and on the morphology of dendritic tips (spinules) of cone horizontal cells. These effects can be specifically blocked by GnRH‐antagonists, indicating that the release of dopamine and dopamine‐dependent effects on light adaptation of retinal neurons are affected by the terminal nerve complex. Recent data have shown that olfactory information has an impact on retinal physiology, but its precise role is not clear. The efferent fiber of the terminal nerve complex is one of the first retinopetal fiber systems for which the sources of the fibers, their cellular targets, and several physiological, morphological, and behavioral effects are known. The terminal nerve complex is therefore a model system for the analysis of local information processing which is influenced by a distinct fiber projection. Microsc. Res. Tech. 65:25–32, 2004. © 2004 Wiley‐Liss, Inc.
Hyperchaos of arbitrary order generated by a single feedback circuit, and the emergence of chaotic walks
2004-09-01

It is shown that hyperchaos of order m (i.e., with m positive Lyapunov exponents) can be generated by a single feedback circuit in n=2m+1 variables. This feedback circuit is constructed such that, dividing phase space into hypercubes, it changes sign wherever the trajectory passes from one hypercube into an adjacent one. Letting the negative diagonal elements in the Jacobian tend to zero, the dynamics becomes conservative. Instead of chaotic attractors, unbounded chaotic walks are then generated. Here we report chaotic walks emerging from a continuous system rather than the well known chaotic walks present in “Lorentz gas” and “couple map lattices.”
Submicroscopic Plasmodium falciparum infections and multiplicity of infection in matched peripheral, placental and umbilical cord blood samples from Gabonese women
2004-09-01

Summary In malaria‐endemic regions, pregnant women are more susceptible to malarial infections than non‐pregnant women. The main objective of this study, which was conducted in the malaria hyperendemic town of Lambaréné (Gabon, Central Africa), was to characterize Plasmodium falciparum infections in peripheral, placental and cord blood from women of different gravidities with submicroscopic infections. Using the P. falciparum merozoite surface protein 2 (MSP 2) * gene as a polymorphic marker in polymerase chain reactions, we analysed genetic diversity and multiplicity of infection in isolates from all three kinds of samples of 184 pregnant women at delivery. We detected infection in 44% of the women who were originally negative by microscopy. Equally important was the finding that the placenta had the highest prevalence of infection ( P &lt; 0.001). There was no correlation with gravidity status or age of the patients. The multiplicities of infection in the peripheral and placental blood samples did not differ and single infection was observed in cord blood, independently of the gravidity. The FC27/MSP 2 was the predominant allelic family. The major FC27 alleles detected in the peripheral, placental and cord blood were sequenced and found to be closely related to the published K1 form sequence. Below microscopy level, the placenta remains the most infected organ and this submicroscopic carriage of parasites may contribute to the development and maintenance of immunity to malaria during pregnancy.
Ordovician and Silurian protolith ages of metamorphosed clastic sedimentary rocks from the southern Schwarzwald, SW Germany: a palynological study and its bearing on the Early Palaeozoic geotectonic evolution
2004-09-01

Sedimentation ages of metamorphosed clastic sedimentary rocks in the southern Schwarzwald were determined by associations of palynomorphs. In the northern subunit of the Badenweiler–Lenzkirch Zone, two lithostratigraphic assemblages could be discerned in low-grade metamorphic units by their facies and age, thus revealing a more complex internal structure of this zone than previously assumed. Lower Ordovician metagreywackes and metapelites were discerned from Silurian metasiltstones. In the cataclastically overprinted metasiltstones and phyllites of the southern subunit of the Badenweiler–Lenzkirch Zone, only poorly preserved microfossil remains could be detected. These show that the sedimentation ages must be Ordovician or younger, but still probably Early Palaeozoic. High-grade metapelitic rocks of the South Schwarzwald Gneiss Complex contain chitinozoans in lenses and layers of schists, that are rich in biotite and graphite. They yielded mid-Silurian ages and show that this crystalline complex does not represent an older basement unit but was the result of marine sedimentation at that time. The new age determinations have a bearing on geodynamic reconstructions of the internal Variscides in Early Palaeozoic time. They show that sedimentation in the oceanic realm of the Badenweiler–Lenzkirch Zone or its margins did not occur before the Ordovician. After transformation of the northern passive into an active continental margin, younger greywackes not older than Middle Devonian received detritus from a volcanic arc, forming above the subduction zone.
Tuberculina-Rusts: A Unique Basidiomycetous Interfungal Cellular Interaction with Horizontal Nuclear Transfer
2004-09-01

Cellular interaction of the basidiomycete Tuberculina persicina with the haploid stages of two rusts Puccinia silvatica and Tranzschelia pruni-spinosae was analyzed by serial-section electron microscopy of chemically fixed samples and samples subjected to high-pressure freezing and freeze substitution. Tuberculina persicina is a contact parasite, forming neither haustoria nor other intracellular structures. However, at contact areas between T. persicina and its hosts, distinct interfungal interactions are present. At the beginning, a hyphal cell of T. persicina invades the host cell wall with a protuberance and the cell walls of both protuberance and host cell dissolve at the point of contact. Thus, the plasma membranes of the two organisms contact and fuse to form a pore that enlarges to a final diameter of approximately 1 μm. The membrane of the fusion pore is continuous with the plasma membranes of both cells, and Tuberculina nuclei and other organelles are transferred to the rust cells. Phylogenetic and functional aspects of this curious basidiomycetous interfungal interaction are discussed, and a hypothesis of the evolutionary derivation of the Tuberculina mycoparasitism from a sexual interaction is presented.
Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylationin vitroandin vivo
2004-09-01

The effect of cytochrome P450 (CYP) 2C9 polymorphisms on the stereoselective biotransformation of the oral anticoagulant phenprocoumon (PPC) to inactive, monohydroxylated metabolites was studied in vitro and in vivo. In human liver microsomes, the (S)-7-hydroxylation--being the major metabolic pathway--was significantly compromised in a gene-dose-dependent manner in samples expressing the CYP2C9*2 or CYP2C9*3 allele. The CYP2C9*3/*3 genotype corresponded to an almost fourfold lower (S)-7-hydroxylation rate than CYP2C9*1/*1 (wild-type). The intrinsic clearance of human recombinant CYP2C9*2 and CYP2C9*3 for the (S)-7-hydroxylation was 28.9 and 50.9% lower than of CYP2C9*1, respectively. The area under the plasma concentration-time curve (AUC) of PPC metabolites after oral intake of 12 mg racemic PPC was significantly lower in volunteers expressing the CYP2C9*2 or CYP2C9*3 allele. Increasing plasma AUC metabolic ratios (parent compound/metabolite) in CYP2C9*2 and CYP2C9*3 variant allele carriers were found for each hydroxylation reaction and the CYP2C9*3/*3 genotype corresponded to an about 10-fold higher metabolic ratio of PPC (S)-7-hydroxylation relative to CYP2C9*1/*1. CYP2C9 polymorphisms cause a markedly compromised PPC (S)-7-hydroxylation. However, PPC metabolism appears overall less influenced by CYP2C9 genotype compared with other oral anticoagulants and it may thus be a valuable alternative for therapeutic anticoagulation of patients expressing CYP2C9 variant alleles.
[Possibilities of whole-body MRI for investigating musculoskeletal diseases].
2004-09-01

This contribution outlines possibilities and limitations of whole-body MRI for investigating musculoskeletal diseases. Benefits and drawbacks of the novel whole-body MRI technology are discussed and a possible whole-body MRI sequence protocol for musculoskeletal examinations is proposed. Muscle, joint and bone diseases are discussed in which the application of whole-body MRI may be of advantage. Particularly, polymyositis, muscledystrophy, rheumatoid arthritis, spondylitis ancylosans, multiple trauma, skeletal metastases, multiple myeloma and malignant lymphoma are mentioned. Whole-body MRI opens new advantages for the examination of multifocal musculoskeletal diseases. The clinical benefit of this method for particular diseases has to be evaluated in further studies, however.
Tuberculina-rusts: a unique basidiomycetous interfungal cellular interaction with horizontal nuclear transfer
2004-09-01

Cellular interaction of the basidiomycete Tuberculina persicina with the haploid stages of two rusts Puccinia silvatica and Tranzschelia pruni-spinosae was analyzed by serial-section electron microscopy of chemically fixed samples and samples subjected to high-pressure freezing and freeze substitution. Tuberculina persicina is a contact parasite, forming neither haustoria nor other intracellular structures. However, at contact areas between T. persicina and its hosts, distinct interfungal interactions are present. At the beginning, a hyphal cell of T. persicina invades the host cell wall with a protuberance and the cell walls of both protuberance and host cell dissolve at the point of contact. Thus, the plasma membranes of the two organisms contact and fuse to form a pore that enlarges to a final diameter of approximately 1 μm. The membrane of the fusion pore is continuous with the plasma membranes of both cells, and Tuberculina nuclei and other organelles are transferred to the rust cells. Phylogenetic and functional aspects of this curious basidiomycetous interfungal interaction are discussed, and a hypothesis of the evolutionary derivation of the Tuberculina mycoparasitism from a sexual interaction is presented.