julilili42/papers huggingface dataset:
Regulation of GluR1 abundance in murine hippocampal neurones by serum‐ and glucocorticoid‐inducible kinase 3
2005-03-18

Phosphatidylinositol 3 kinase (PI3‐kinase) is activated during and is required for hippocampal glutamate receptor‐dependent long‐term potentiation. It mediates the delivery of AMPA receptors to the neuronal surface. Among the downstream targets of PI3‐kinase are three members of the serum‐ and glucocorticoid‐inducible kinase family, SGK1, SGK2 and SGK3. In Xenopus oocytes expressing the AMPA subunit GluR1, we show that SGK3, and to a lesser extent SGK2, but not SGK1, increase glutamate‐induced currents by increasing the abundance of GluR1 protein in the cell membrane. We further show Sgk3 mRNA expression in the hippocampus by RT‐PCR and in situ hybridization. According to Western blotting, the hippocampal abundance of GluR1 is significantly lower in gene‐targeted mice lacking SGK3 ( Sgk3 −/− ) than in their wild‐type littermates ( Sgk3 +/+ ). The present observations disclose a novel mechanism in the regulation of GluR1.
Glucocorticoid adrenal steroids and glucocorticoid‐inducible kinase isoforms in the regulation of GluR6 expression
2005-03-18

Generation of memory is enhanced during stress, an effect attributed to stimulation of neuronal learning by adrenal glucocorticoids. The glucocorticoid‐dependent genes include the serum‐ and glucocorticoid‐inducible kinase SGK1. SGK1 is activated through the phosphatidylinositol 3 kinase (PI3‐kinase) pathway by growth factors such as insulin‐like growth factor‐1 (IGF1) or tumour growth factor β (TGF‐β). Previously, a fourfold higher expression of SGK1 has been observed in fast‐learning rats as compared with slow‐learning rats. The mechanisms linking glucocorticoids or SGK1 with neuronal function have, however, remained elusive. We show here that treatment of mice with the glucocorticoid dexamethasone (238 μg day −1 for 8–20 days) enhances hippocampal expression of GluR6. Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice. Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate‐induced currents following treatment with dexamethasone (1 μ m ) and TGF‐β (1 μ m ). In Xenopus oocytes expressing rat GluR6, coexpression of SGK1 strongly increases glutamate‐induced current at least partially by increasing the abundance of GluR6 protein in the plasma membrane. The related kinases SGK2 and SGK3 similarly stimulate GluR6, but are less effective than SGK1. The observations point to a novel mechanism regulating GluR6 which contributes to the regulation of neuronal function by glucocorticoids.
Prevalence of vertebral alterations and the effects of calcium and vitamin D supplementation on calcium metabolism and bone mineral density after gastrectomy
2005-03-18

Abstract Background Bone disease is common after gastrectomy, resulting in decreased bone mass and an increased risk of fracture. No proven therapy is currently available. Methods Serum markers of calcium metabolism in 98 patients after partial or total gastrectomy were compared with those in 30 age- and sex-matched healthy controls. Patients with disorders of calcium metabolism were investigated by conventional radiography and single-energy computed tomography of the spine. Forty patients participated in a 1-year follow-up study to investigate the effects of vitamin D and calcium supplementation on calcium metabolism and bone mineral density. Results Altered serum markers of calcium and phosphate metabolism were observed in 77 (79 per cent) of 98 patients. Sixty (79 per cent) of these had vertebral alterations. Vertebral fractures were detected in 22 patients, grade I vertebral deformities in 50 patients, grade II deformities in 22 patients and osteopenia (Z-score less than − 1) in 30 patients. Calcium and vitamin D supplementation resulted in an increase in 25-hydroxy-vitamin D (P &amp;lt; 0·001), 1,25-dihydroxy-vitamin D (P = 0·048) and osteocalcin (P = 0·045), whereas levels of parathyroid hormone were decreased (P = 0·007). Bone mineral density did not change over time. Conclusion Disturbances of calcium and bone metabolism are common after gastrectomy. Calcium and vitamin D supplementation normalized levels of markers of calcium metabolism and might have prevented age-related bone mass loss, although it did not increase bone mineral density after 1 year.
The World Anti-Doping Code 2003 - Consequences for Physicians Associated with Elite Athletes
2005-03-18

The purpose of the World Anti-Doping Code 2003 and the 2004 Prohibited List is to create a universal international standard to fight doping in competitive sports. The result of this is a whole series of changes for doctors with regard to their work with competitive athletes. The revised definition of doping now includes physicians in the group of persons who can fulfil the elements of a doping offence. Moreover, the mere possession of substances appearing on the Prohibited List represents a violation of anti-doping regulations. The 2004 Prohibited List includes several changes to the Olympic Movement List from 2003. Caffeine, for example, was removed from the list. Cannabinoids, on the other hand, are now prohibited in competition for all sports. The same is true for all forms of glucocorticosteroids. Therapeutic use exemptions in an abbreviated process are possible for the administration of glucocorticosteroids by non-systemic routes, as well as inhalative therapy with the beta-2-agonists formoterol, salbutamol, salmeterol, and termbutalin. In other cases, a therapeutic use exemption is possible using a standard application process. Further changes will become effective in the 2005 Prohibited List. In 2005, it is essential that beta-2-agonists are prohibited in and out of competition. HCG and LH are prohibited for all athletes. Dermatological preparations of glucocorticosteroids are no longer prohibited, and intravenous infusions will be a prohibited method in 2005, except as a legitimate acute medical treatment. In cases of violations of anti-doping regulations where it is permissible for the affected person to furnish proof of exoneration, the burden of proof is not higher than that required to prove the violation. The sanctions provided for in the World Anti-Doping Code follow a principle of rules and exceptions which at first glance seems difficult to understand. In the case of doping violations by physicians, the anti-doping code provides--as a general rule--for exclusion from sports associations for at least four years. Since several of the changes are questionable under constitutional aspects, it remains to be seen whether the World Anti-Doping Code 2003 will allow the achievement of a universal standard to combat doping.
Crystal Structure of Himalayan Mistletoe Ribosome-inactivating Protein Reveals the Presence of a Natural Inhibitor and a New Functionally Active Sugar-binding Site
2005-03-18

Ribosome-inactivating proteins (RIPs) are toxins involved in plant defense. How the plant prevents autotoxicity is not yet fully understood. The present study is the first structural evidence of a naturally inhibited form of RIP from a plant. Himalayan mistletoe RIP (HmRIP) was purified from Viscum album leaves and crystallized with lactose. The structure was determined by the molecular replacement method and refined at 2.8-A resolution. The crystal structure revealed the presence of high quality non-protein electron density at the active site, into which a pteridine derivative (2-amino 4-isopropyl 6-carboxyl pteridine) was modeled. The carboxyl group of the ligand binds strongly with the key active site residue Arg(162), nullifies the positive charge required for catalysis, and thereby acts as a natural inhibitor. Lectin subunits of RIPs have two active sugar-binding sites present in 1alpha- and 2gamma-subdomains. A third functionally active site has been identified in the 1beta-subdomain of HmRIP. The 1beta-site is active despite the absence of conserved polar sugar-binding residues. Loss of these residues is compensated by the following: (i) the presence of an extended site where the penultimate sugar also interacts with the protein; (ii) the interactions of galactose with the protein main chain carbonyl and amide nitrogen atoms; (iii) the presence of a well defined pocket encircled by four walls; and (iv) a favorable stacking of the galactose ring with Tyr(66) besides the conserved Phe(75). The mode of sugar binding is also distinct at the 1alpha and 2gamma sugar-binding sites.
Objective Measurement of Tactile Mislocalization
2005-03-21

Stimulating the skin with intensities close to the sensory threshold causes erroneous localization of the site of stimulation. Previous studies using manual methods for applying faint tactile stimuli have shown that localization errors obey a somatotopic principle in which tactile stimuli are preferentially mislocalized to sites adjacent to the stimulated skin region. However, manual testing of mislocalization is time consuming and only partially objective because results depend on the skills of the tester. To improve the testing procedure, an automated apparatus was developed. The procedure adjusted stimulus intensity adaptively during testing to remain near the individual subject's sensory threshold, so that mislocalizations occurred often enough to assess somatotopic organization. The new method was applied to 12 healthy subjects. In each subject, the five digits of the right hand were stimulated singly in random order. Localization errors were distributed preferentially to fingers close to the stimulated finger rather than to distant fingers. The profile of mislocalization differed significantly from that expected on the basis of response bias or guessing behavior. The present results replicate previous findings obtained for manual testing with improved sensitivity and indicate that the new technique is a useful tool for the study of somatosensory processing on a perceptual level.
A memetic clustering algorithm for the functional partition of genes based on the gene ontology
2005-03-21

With the invention of high throughput methods, researchers are capable of producing large amounts of biological data. During the analysis of such data the need of a functional grouping of genes arises. We propose a new clustering algorithm for the partition of genes or gene products according to their known biological function based on Gene Ontology terms. Ontologies offer a mechanism to capture knowledge in a shareable form that is also processable by computers. Our functional cluster algorithm promises to automatize, speed up and therefore improve biological data analysis.
Effect of retinoids, histondeacetylase inhibitors and glitazones on the differentiation of cultured transformed thyrocytes
2005-03-21

Purpose of the experiment: For the treatment of thyroid carcinomas differentiating substances usually are applied after application of recombinant TSH in order to increase the efficiency of the treatment. Some authors claim that these substances increase differentiation mainly by decreasing proliferation. The study aims to clarify 1) whether changes in differentiation and proliferation correlate or occur independently and 2) whether TSH-levels affect the action. The effect oh histone deacetylase inhibitors, retinoids and glitazones on differentiation, proliferation and apoptosis of follicular carcinoma cell lines was evaluated.
Staphylococcus aureusDeficient in Lipidation of Prelipoproteins Is Attenuated in Growth and Immune Activation
2005-03-22

ABSTRACT A lipoprotein diacylglyceryl transferase ( lgt ) deletion mutant of Staphylococcus aureus SA113 was constructed. The lipoprotein and prelipoprotein expression, the growth behavior, and the ability of the mutant to elicit an immune response in various host cells were studied. In the wild type, the majority of [ 14 C]palmitate-labeled lipoproteins were located in the membrane fraction, although some lipoproteins were also present on the cell surface and in the culture supernatant. The lgt mutant completely lacked palmitate-labeled lipoproteins and released high amounts of some unmodified prelipoproteins, e.g., the oligopeptide-binding protein OppA, the peptidyl-prolyl cis-trans isomerase PrsA, and the staphylococcal iron transporter SitC, into the culture supernatant. The growth of the lgt mutant was hardly affected in rich medium but was retarded under nutrient limitation. The lgt mutant and its crude lysate induced much fewer proinflammatory cytokines and chemokines in human monocytic (MonoMac6), epithelial (pulmonary A549), and endothelial (human umbilical vein endothelial) cells than the wild type. However, in whole blood samples, the culture supernatant of the lgt mutant was equal or even superior to the wild-type supernatant in tumor necrosis factor alpha induction. Lipoprotein fractionation experiments provided evidence that a small proportion of the mature lipoproteins are released by the S. aureus wild type despite the lipid anchor and are trapped in part by the cell wall, thereby exposing the immune-activating lipid structure on the cell surface. Bacterial lipoproteins appear to be essential for a complete immune stimulation by gram-positive bacteria.
Multiple regions of α‐synuclein are associated with Parkinson's disease
2005-03-22

Abstract α‐Synuclein is considered to play an important role in the pathogenesis of both the rare familial and the common sporadic forms of Parkinson's disease. Previous reports primarily have tested the association of α‐synuclein promoter polymorphisms with idiopathic Parkinson's disease, but results are controversial. We first characterized the linkage disequilibrium structure of the α‐synuclein gene region with a dense set of 56 genetic markers and subsequently performed two independent case–control association analyses using tagging markers. We could distinguish two large linkage disequilibrium blocks spanning the α‐synuclein gene. Several markers within the 3′‐block around exons 5 and 6 showed strong association with Parkinson's disease ( p = 0.00009). Effects of the associated variants might be mediated by regulatory elements in this highly conserved region or by a frequency shift in a previously described splice variant lacking exon 5. A direct association with promoter polymorphisms could not be replicated in our sample set. A second set of markers in the 5′‐block of the gene were also significantly associated with Parkinson's disease, when young patients and female subjects were analyzed separately. These findings indicate locus heterogeneity for the pathogenesis of Parkinson's disease in different genetic or physiological environments, related to sex and age. Ann Neurol 2005;57:535–541
Posterior thalamic hemorrhage induces “pusher syndrome”
2005-03-22

Posterior thalamus seems to be fundamentally involved in our control of upright body posture. Higher pressure, swelling, and other secondary pathologic processes associated with posterior thalamic hemorrhage (vs thalamic infarction) may provoke contraversive pushing in combination with additional neurologic symptoms.
Effect of Sunscreen and Clothing on the Number of Melanocytic Nevi in 1,812 German Children Attending Day Care
2005-03-22

The number of melanocytic nevi is the most important risk factor for cutaneous melanoma. This 1998 cross-sectional study of 1,812 children aged 2-7 years from 78 day-care centers in Germany analyzed the protective effect of sunscreen and clothing on the number of melanocytic nevi. Total body nevi were counted, and pigmentary features were assessed. Parents underwent a standardized interview concerning their children's sun exposure and sun-protective behavior. Almost 95% of the children had used sunscreen previously. Children who used sunscreen and wore more clothing spent significantly longer periods on holidays in sunny climates (p < 0.001 and p = 0.006, respectively) and had a higher outdoor activity score at home (p < 0.001 and p = 0.012, respectively). Multivariate analysis adjusted for confounders showed no significant protective effects of applying sunscreen. Examination of the potential protective effect of clothing revealed an inverse dose-response correlation between the number of clothes worn at the beach or outdoor swimming pool and the number of melanocytic nevi (p < 0.001, adjusted for confounding). Randomized controlled trials are needed to confirm these results. Meanwhile, public education should aim to protect children primarily by sun avoidance and protective clothing, while sunscreen should also be used.
A Chinese Birth Cohort: Theoretical Implications
2005-03-22

Research on delinquency has shown consistent results across Western industrialized countries. Few studies have been done in non-Western cultures. This study reports on the results of a birth cohort study in China, which was started by Marvin Wolfgang but never completed. The cohort, born in 1973, was traced through official and community files. The amount of delinquency is significantly low. However, significant differences were found between delinquents and nondelinquents in terms of peer influences, family influences, and school. Regression results show that the most important school factors associated with offending are those relating to level of education completed and dropout status and interactions between students and teachers. Offenders were found to be approximately five times more likely than nonoffenders to associate with delinquent peers. This study reinforces previous findings—there are critical sociological variables related to social integration, family, and school experiences that significantly differentiate between those who become offenders and those who do not.
Immunoglobulin G Isotype Responses to Erythrocyte Surface-Expressed Variant Antigens of Plasmodium falciparum Predict Protection from Malaria in African Children
2005-03-22

ABSTRACT We assessed immunoglobulin G (IgG) isotype responses to variant surface antigens (VSA) expressed on parasite-infected erythrocytes of a panel of heterologous isolates during and after acute episodes in groups of Gabonese children presenting with either mild or severe Plasmodium falciparum malaria. In the acute and convalescent phases IgG3 and IgG1 anti-VSA antibodies, respectively, predominated. In the absence of infection, the levels of both cytophilic isotypes waned, while those of IgG4 increased, particularly in those admitted with severe malaria. Prospective analyses showed significantly longer delays between malaria attacks associated both (i) with increasing IgG1 responses with specificity for VSA of isolates from children with mild malaria and (ii) with increasing IgG4 responses with specificity for VSA of isolates from children with severe malaria. These findings imply that the predictive value of prospectively measured cross-reactive VSA-specific IgG antibodies with respect to protection against malaria in African children depends both on their isotype and on their fine specificity.
Evaluation of normal and neoplastic human mast cells for expression of CD172a (SIRPα), CD47, and SHP-1
2005-03-22

Abstract Signal regulatory proteins (SIRPs) and tyrosine phosphatases have recently been implicated in the control of receptor tyrosine kinase (RTK)-dependent cell growth. In systemic mastocytosis (SM), neoplastic cells are driven by the RTK KIT, which is mutated at codon 816 in most patients. We examined expression of SIRPα, SIRPα ligand CD47, and Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), a tyrosine phosphatase-type, negative regulator of KIT-dependent signaling, in normal human lung mast cells (HLMC) and neoplastic MC obtained from nine patients with SM. As assessed by multicolor flow cytometry, normal LMC expressed SIRPα, CD47, and SHP-1. In patients with SM, MC also reacted with antibodies against SIRPα and CD47. By contrast, the levels of SHP-1 were low or undetectable in MC in most cases. Corresponding data were obtained from mRNA analysis. In fact, whereas SIRPα mRNA and CD47 mRNA were detected in all samples, the levels of SHP-1 mRNA varied among donors. To demonstrate adhesive functions for SIRPα and CD47 on neoplastic MC, an adhesion assay was applied using the MC leukemia cell line HMC-1, which was found to bind to immobilized extracellular domains of SIRPα1 (SIRPα1ex) and CD47 (CD47ex), and binding of these cells to CD47ex was inhibited by the CD172 antibody SE5A5. In summary, our data show that MC express functional SIRPα and CD47 in SM, whereas expression of SHP-1 varies among donors and is low compared with LMC. It is hypothesized that CD172 and CD47 contribute to MC clustering and that the “lack” of SHP-1 in MC may facilitate KIT-dependent signaling in a subgroup of patients.
Influence of tumor biological factors on tumor cell dissemination in primary breast cancer.
2005-03-22

The presence of disseminated tumor cells in the BM was not influenced by tumor load as reflected by tumor size and lymph node involvement, whereas tumor biological factors were independently correlated to BM involvement. The results substantiate the important role of tumor biological factors of the primary tumor for tumor cell dissemination.
Cross-section measurements of neutron-deuteron breakup at 13.0 MeV
2005-03-23

Cross-section measurements of seven exit-channel configurations in the neutron-deuteron breakup at 13.0 MeV are reported and compared to rigorous calculations. Our data are consistent with those of previous measurements in four of six configurations. The present data for five configurations are in good agreement with theoretical predictions. The cross-section data for the space-star and another out-of-plane configuration are larger than the theoretical predictions by more than three standard deviations. The previously observed 20% discrepancy between theory and data for the space-star configuration is confirmed in the present work. The inclusion of the Tucson-Melbourne -exchange three-nucleon force changes the predicted cross section by only 2% and in the wrong direction needed to bring theory into agreement with data.
Hypothermia-Induced Platelet Aggregation: No Effect of Aprotinin (Trasylol®) but Inhibition by Eptifibatide (Integrilin®)
2005-03-23

Aprotinin has no procoagulatory effect on platelet function during hypothermia but is not protective either. Eptifibatide inhibits hypothermia-induced platelet aggregation in vitro and may prevent aggregate sequestration in the microvasculature and consecutive ischemic organ damage in vivo.
Die Kristallstrukturen von (DDI)2[Sb2F6O] und (DDI)2[Sb3F7O2] (DDI = 1, 3‐Diisopropyl‐4, 5‐dimethylimidazolium) — Ein Beitrag zur Hydrolyse von SbF3 [1]
2005-03-23

Abstract The Crystal Structures of (DDI) 2 [Sb 2 F 6 O] and (DDI) 2 [Sb 3 F 7 O 2 ] (DDI = 1,3‐Diisopropyl‐4,5‐dimethylimidazolium) — a Contribution to the Hydrolysis of SbF 3 [1] The salts (DDI) 2 [Sb 2 F 6 O] ( 2 ) and (DDI) 2 [Sb 3 F 7 O 2 ] ( 3 ), (DDI = 1,3‐diisopropyl‐4,5‐dimethylimidazolium) are obtained by hydrolysis of C 11 H 20 N 2 SbF 3 ( 1 ). The anion [Sb 2 F 6 O] 2− consists of two SbF 2 fragments linked by a symmetrical oxygen bridge and two unsymmetrical fluorine bridges to form a distored ψ ‐octahedral coordination sphere at the antimony atoms. In [Sb 3 F 7 O 2 ] 2− , two SbF 2 units are linked by a symmetrical fluorine bridge, while the third antimony atom is connected with each SbF 2 fragment by a symmetrical oxygen and an unsymmetrical fluorine bridge. The antimony atoms adopt the centres of strongly distored ψ ‐polyhedra.