julilili42/papers huggingface dataset:
Radiation-induced Epidermal Growth Factor Receptor Nuclear Import Is Linked to Activation of DNA-dependent Protein Kinase
2005-07-07

Ionizing radiation, but not stimulation with epidermal growth factor (EGF), triggers EGF receptor (EGFR) import into the nucleus in a probably karyopherin alpha-linked manner. An increase in nuclear EGFR is also observed after treatment with H2O2, heat, or cisplatin. During, this process, the proteins Ku70/80 and the protein phosphatase 1 are transported into the nucleus. As a consequence, an increase in the nuclear kinase activity of DNA-dependent kinase (DNA-PK) and increased formation of the DNA end-binding protein complexes containing DNA-PK, essential for repair of DNA-strand breaks, occurred. Blockade of EGFR import by the anti-EGFR monoclonal antibody C225 abolished EGFR import into the nucleus and radiation-induced activation of DNA-PK, inhibited DNA repair, and increased radiosensitivity of treated cells. Our data implicate a novel function of the EGFR during DNA repair processes.
Effective Nucleon Masses in Symmetric and Asymmetric Nuclear Matter
2005-07-07

The momentum and isospin dependence of the in-medium nucleon mass are studied. Two definitions of the effective mass, i.e., the Dirac mass m*D and the nonrelativistic mass m*NR which parametrizes the energy spectrum, are compared. Both masses are determined from relativistic Dirac-Brueckner-Hartree-Fock calculations. The nonrelativistic mass shows a distinct peak around the Fermi momentum. The proton-neutron mass splitting in isospin asymmetric matter is m*D,n<m*D,p and opposite for the nonrelativistic mass, i.e., m*NR,n>m*NR,p, which is consistent with nonrelativistic approaches.
Supraagonistic, bispecific single‐chain antibody purified from the serum of cloned, transgenic cows induces T‐cell‐mediated killing of glioblastoma cells in vitro and in vivo
2005-07-07

Abstract Here we characterize the antitumor activity of a recombinant bispecific single‐chain antibody isolated from the serum of cloned transgenic cows. The antibody, termed r28M, is directed to a melanoma‐associated proteoglycan, also expressed on glioblastoma cells, and to human CD28. Bound to tumor cells, r28M induced exceedingly efficient supraagonistic T‐cell activation via the CD28 molecule without an additional stimulus via the TCR/CD3 complex. In vitro , T cells and NK cells contributed to tumor cell killing after r28M‐mediated activation of peripheral blood mononuclear cells. However, NK activity depended on T‐cell‐derived cytokines. In vivo , r28M markedly inhibited the growth of human glioblastoma cells in nude mice. The serum half‐life of the protein after i.v. injection was approximately 6 hr. Thus, r28M is unique not only in inducing supraagonistic CD28‐mediated T‐cell activation against tumor cells in vitro and in vivo , it also meets 2 additional requirements that are critical for clinical application: a relatively long serum half‐life and the possibility of obtaining large amounts of active material from cloned transgenic livestock. © 2005 Wiley‐Liss, Inc.
Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers
2005-07-08

Background— Antidiabetic thiazolidinediones (TZDs), like rosiglitazone or pioglitazone, improve endothelial function in patients with type 2 diabetes or metabolic syndrome, but it is currently unknown, whether these beneficial effects of TZDs depend on their metabolic action or may be caused by direct effects on the endothelium. Therefore, the present study examined whether short-term rosiglitazone treatment influences endothelium-dependent vasodilation as well as serum levels of vascular disease biomarkers in healthy, nondiabetic subjects. Methods and Results— Short-term treatment (21 days) of healthy subjects (n=10) did not significantly change blood glucose levels or lipid profile. In contrast, rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation already within the first day from 5.3±2.7% at baseline to 7.8±2.6%, further increasing it to 9.4±3.0% at day 21. In addition, the early improvement of endothelium-dependent vasodilation was paralleled by a rapid reduction of serum levels of the biomarkers C-reactive protein (CRP), serum amyloid A (SAA), and sE-selectin. Moreover, after drug withdrawal all markers remained suppressed for the whole follow-up period of 7 days. In contrast, rosiglitazone treatment did not significantly affect tumor necrosis factor (TNF)-α, interleukin (IL)-6, sICAM-1, sVCAM-1, and sCD40L levels. Conclusions— Our study suggests a direct effect of TZD treatment on endothelial function and inflammatory biomarkers of arteriosclerosis, promoting the concept that TZDs, independent of their metabolic action, may exhibit protective effects in the vessel wall.
Selected E-ISNR 2004 Conference Presentation Abstracts
2005-07-08

NEUROTHERAPYof this paradigm were considered and open discussion was encouraged.Current knowledge about the role of theta in psychological processing was covered.Can other interventions such as autonomic biofeedback, meditation, hypnosis and energy medicine achieve similar goals?Comparative studies are underway.
The Use of Nutritional Supplements Among Master Athletes
2005-07-11

We assessed the use of nutritional supplements among master athletes focusing on their source of information and source of supply of nutritional supplements. 1560 standardized, anonymous questionnaires were distributed among participants of the World Masters Athletics Championships Indoors 2004. These questions were related to biometric parameters, social indicators, training parameters, illicit drugs, and nutritional supplements. Chi2-tests were computed to reveal meaningful associations between basic information (age, gender, family status, children, education, country of origin, disciplines, training years, smoking, and the use of alcohol, illicit drugs, and doping) and the intake of nutritional supplements. Descriptive information on the history of their use of nutritional supplements was also provided. 60.5 % of all participants reported the actual use of nutritional supplements. We found no significant differences between nutritional supplement users and non-users with regard to basic information. The substances predominantly used were vitamins (35.4 %) and minerals (29.9 %). In contrast to elite athletes who use nutritional supplements to increase their athletic performance, master athletes use these substances predominantly for health reasons and, thus, have a closer contact to the health care system. Physicians are their preferred source of information about nutritional supplements. More than half of the interviewed athletes obtain their nutritional supplements from pharmacies or physicians. The results of this study indicate that nutritional supplement users in master athletics show no specific user profile. Since it is not rare for nutritional supplements to contain trace contaminations of anabolic androgenic steroids or pro-hormones, physicians should also inform master competitive athletes of the dangers of testing positive for doping substances due to their intake of nutritional supplements and advise them accordingly.
Ambivalent effect of member portraits in virtual groups
2005-07-11

Abstract Knowledge exchange with shared databases can be seen as a public‐goods dilemma. People are reluctant to contribute information because they save time, effort and perhaps social power if they withhold their knowledge and socially loaf. But if all people choose this individually efficient strategy, then no information exchange can take place, and the group is less effective than it would have been if all members contributed. Thus, in the knowledge‐exchange situation, group norms and individual norms oppose each other. In order to strengthen people's orientation towards the group, virtual collaborative tools sometimes provide member portraits. But based on the Social Identity Model of Deindividuation Effect (SIDE)‐Model, ambivalent effects of these member portraits are expected according to people's social categorization: when people identify more strongly with the group, such portraits enhance participation, whereas when people have a stronger individual identity, they undermine participation. This study links the concepts of social value orientation to identity salience. The assumption is that in the information‐exchange dilemma, the social value orientation of a group member will determine whether group identity or individual identity becomes salient for that group member. We then extend the SIDE‐model to the domain of social loafing and expect that portraits of the group members will have different effects for people with individual orientation and for people with prosocial orientation. An experiment confirmed this expectation and revealed a significant interaction between social value orientation and portraits. Especially striking is the result that for prosocials the provision of member portraits leads to an increase in social loafing. This is analogous to the predictions of the SIDE‐model.
SGK1 as a determinant of kidney function and salt intake in response to mineralocorticoid excess
2005-07-12

Mineralocorticoids modify salt balance by both stimulating salt intake and inhibiting salt loss. Renal salt retention is accomplished by upregulation of reabsorption, an effect partially mediated by serum- and glucocorticoid-inducible kinase 1 (SGK1). The present study explored the contribution of SGK1 to the regulation of renal function, salt intake, and blood pressure during mineralocorticoid excess. DOCA/1% NaCl treatment increased blood pressure and creatinine clearance to a similar extent in SGK1-deficient sgk1 −/− and wild-type sgk1 +/+ mice but led to more pronounced increase of proteinuria in sgk1 +/+ mice (by 474 ± 89%) than in sgk1 −/− mice (by 154 ± 31%). DOCA/1% NaCl treatment led to significant increase of kidney weight (by 24%) and to hypokalemia (from 3.9 ± 0.1 to 2.7 ± 0.1 mmol/l) only in sgk1 +/+ mice. The treatment enhanced renal Na + excretion significantly more in sgk1 +/+ mice (from 3 ± 1 to 134 ± 32 μmol·24 h −1 ·g body wt −1 ) than in sgk1 −/− mice (from 4 ± 1 to 49 ± 8 μmol·24 h −1 ·g body wt −1 ), pointing to SGK1-dependent stimulation of salt intake. With access to two drinking bottles containing 1% NaCl or water, DOCA treatment did not significantly affect water intake in either genotype but increased 1% NaCl intake in sgk1 +/+ mice (within 9 days from 3.5 ± 0.9 to 16.5 ± 2.4 ml/day) consistent with DOCA-induced salt appetite. This response was significantly attenuated in sgk1 −/− mice (from 2.6 ± 0.6 to 5.9 ± 0.9 ml/day). Thus SGK1 contributes to the stimulation of salt intake, kidney growth, proteinuria, and renal K + excretion during mineralocorticoid excess.
Synthesis and Properties of an Unsymmetrical Triazole‐Functionalized (Phthalocyaninato)zinc Complex
2005-07-14

Abstract The synthesis of 5,6‐dicyano‐1 H ‐1,2,3‐benzotriazole ( 2 ) was significantly simplified and its overall yield was increased. This opens up the possibility for an extended use of 2 as a precursor for triazole‐functionalized phthalocyanines. One of them, the unsymmetrical {9,10,16,17,23,24‐hexakis(3,5‐di‐ tert ‐butylphenoxy)[1,2,3]triazolo[4,5‐ b ]phthalocyaninato}‐zinc ( 5 ) was prepared in a statistical condensation of 2 and 4,5‐bis(3,5‐di‐ tert ‐butylphenoxy)phthalonitrile ( 3 ) with subsequent separation by column chromatography. The triazole‐functionalized (phthalocyanine)zinc complex 5 shows interesting spectral properties in solutions depending on the chemical medium because of the reactions which are typical for the triazole fragment. These are acid ionization of NH, coordination to metal ions, N ‐alkylation and N ‐acylation, among others. Compound 5 was characterized in detail using UV/Vis, 1 H and 13 C NMR spectroscopy, mass spectrometry (MALDI‐TOF), and elemental analysis. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)
Structure and Biosynthesis of Staphyloxanthin from Staphylococcus aureus
2005-07-15

Most Staphylococcus aureus strains produce the orange carotenoid staphyloxanthin. The staphyloxanthin biosynthesis genes are organized in an operon, crtOPQMN, with a sigma(B)-dependent promoter upstream of crtO and a termination region downstream of crtN. The functions of the five encoded enzymes were predicted on the basis of their sequence similarity to known enzymes and by product analysis of gene deletion mutants. The first step in staphyloxanthin biosynthesis is the head-to-head condensation of two molecules of farnesyl diphosphate to form dehydrosqualene (4,4'-diapophytoene), catalyzed by the dehydrosqualene synthase CrtM. The dehydrosqualene desaturase CrtN dehydrogenates dehydrosqualene to form the yellow, main intermediate 4,4'-diaponeurosporene. CrtP, very likely a mixed function oxidase, oxidizes the terminal methyl group of 4,4'-diaponeurosporene to form 4,4'-diaponeurosporenic acid. CrtQ, a glycosyltransferase, esterifies glucose at the C(1)'' position with the carboxyl group of 4,4'-diaponeurosporenic acid to yield glycosyl 4,4'-diaponeurosporenoate; this compound was the major product in the clone expressing crtPQMN. In the final step, the acyltransferase CrtO esterifies glucose at the C(6)'' position with the carboxyl group of 12-methyltetradecanoic acid to yield staphyloxanthin. Staphyloxanthin overexpressed in Staphylococcus carnosus (pTX-crtOPQMN) and purified was analyzed by high pressure liquid chromatography-mass spectroscopy and NMR spectroscopy. Staphyloxanthin was identified as beta-D-glucopyranosyl 1-O-(4,4'-diaponeurosporen-4-oate)-6-O-(12-methyltetradecanoate).
Natural Killer Cell–Mediated Lysis of Hepatoma Cells via Specific Induction of NKG2D Ligands by the Histone Deacetylase Inhibitor Sodium Valproate
2005-07-15

Abstract Natural killer (NK) cells as components of the innate immunity substantially contribute to antitumor immune responses. However, the tumor-associated ligands engaging activating NK cell receptors are largely unknown. An exception are the MHC class I chain-related molecules MICA and MICB and the UL16-binding proteins (ULBP) which bind to the activating immunoreceptor NKG2D expressed on cytotoxic lymphocytes. A therapeutic induction of NKG2D ligands that primes cancer cells for NK cell lysis has not yet been achieved. By microarray studies, we found evidence that treatment of human hepatocellular carcinoma cells with the histone deacetylase inhibitor (HDAC-I) sodium valproate (VPA) mediates recognition of cancer cells by cytotoxic lymphocytes via NKG2D. VPA induced transcription of MICA and MICB in hepatocellular carcinoma cells, leading to increased cell surface, soluble and total MIC protein expression. No significant changes in the expression of the NKG2D ligands ULBP1-3 were observed. The induction of MIC molecules increased lysis of hepatocellular carcinoma cells by NK cells which was abolished by addition of a blocking NKG2D antibody. Importantly, in primary human hepatocytes, VPA treatment did not induce MIC protein expression. Taken together, our data show that the HDAC-I VPA mediates specific priming of malignant cells for innate immune effector mechanisms. These results suggest the clinical evaluation of HDAC-I in solid tumors such as hepatocellular carcinoma, especially in combination with immunotherapy approaches employing adoptive NK cell transfer.
Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo
2005-07-15

Abstract The immunoreceptor NKG2D stimulates activation of cytotoxic lymphocytes upon engagement with MHC class I-related NKG2D ligands of which at least some are expressed inducibly upon exposure to carcinogens, cell stress, or viruses. In this study, we investigated consequences of a persistent NKG2D ligand expression in vivo by using transgenic mice expressing MHC class I chain-related protein A (MICA) under control of the H2-Kb promoter. Although MICA functions as a potent activating ligand of mouse NKG2D, H2-Kb-MICA mice appear healthy without aberrations in lymphocyte subsets. However, NKG2D-mediated cytotoxicity of H2-Kb-MICA NK cells is severely impaired in vitro and in vivo. This deficiency concurs with a pronounced down-regulation of surface NKG2D that is also seen on activated CD8 T cells. As a consequence, H2-Kb-MICA mice fail to reject MICA-expressing tumors and to mount normal CD8 T cell responses upon Listeria infection emphasizing the importance of NKG2D in immunity against tumors and intracellular infectious agents.
Dendritic Cell Aggresome-Like-Induced Structure Formation and Delayed Antigen Presentation Coincide in Influenza Virus-Infected Dendritic Cells
2005-07-15

Abstract Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC class I Ag presentation. Our findings provide the first evidence for a connection between DC maturation, MHC class I-restricted Ag presentation, and DALIS formation, which is further supported by the observation that DALIS contain ubiquitinated influenza nucleoprotein.
The Evolutionarily Conserved TOUGH Protein Is Required for Proper Development ofArabidopsis thaliana
2005-07-15

Abstract In this study, we characterize the evolutionarily conserved TOUGH (TGH) protein as a novel regulator required for Arabidopsis thaliana development. We initially identified TGH as a yeast two-hybrid system interactor of the transcription initiation factor TATA-box binding protein 2. TGH has apparent orthologs in all eukaryotic model organisms with the exception of the budding yeast Saccharomyces cerevisiae. TGH contains domains with strong similarity to G-patch and SWAP domains, protein domains that are characteristic of RNA binding and processing proteins. Furthermore, TGH colocalizes with the splicing regulator SRp34 to subnuclear particles. We therefore propose that TGH plays a role in RNA binding or processing. Arabidopsis tgh mutants display developmental defects, including reduced plant height, polycotyly, and reduced vascularization. We found TGH expression to be increased in the amp1-1 mutant, which is similar to tgh mutants with respect to polycotyly and defects in vascular development. Interestingly, we observed a strong genetic interaction between TGH and AMP1 in that tgh-1 amp1-1 double mutants are extremely dwarfed and severely affected in plant development in general and vascular development in particular when compared with the single mutants.
Coccidioidomycosis and blastomycosis: Advances in molecular diagnosis
2005-07-18

Clinical isolates of Coccidioides spp. and Blastomyces dermatitidis can be identified by chemiluminescent DNA probes and PCR assays targeting multicopy genes. In fixed tissue samples, cells of the two fungi are specified by in situ hybridization and PCR assays targeting 18S rDNA but sequencing of the products is mandatory. Nested PCR assays targeting genes encoding species- or genus-specific proteins like proline rich antigen of Coccidioides spp. and B. dermatitidis adhesin facilitate amplification of specific DNA from fixed tissue samples. The value of DNA amplification from native specimens of suspected cases of coccidioidomycosis or blastomycosis still needs to be determined.
Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington's disease mutation
2005-07-18

The authors would like to make the following comment on the above paper. Due to recent re-evaluation of the data we disregard all reported preliminary PET data including related figures. The core findings of the paper as summarized in the abstract and in the conclusion chapter are not affected by this revision.
Gene expression of the repulsive guidance molecules during development of the mouse intestine
2005-07-19

Abstract Repulsive guidance molecules (RGMs) are recently identified proteins implicated in neuronal differentiation, migration, and apoptosis. However, in non‐neural tissues a specific biological function of RGM is still unknown. In this study, we describe the expression patterns of the RGM members (a, b, and c) during embryonic and postnatal development of the small and large murine intestine. We demonstrated by RT‐PCR, in situ hybridization, Western blot, and immunocytochemistry that subtypes RGMa and RGMb but not RGMc were strongly expressed in enteric ganglia cells of the fetal and adult gut. In contrast to the enteric nervous system, RGMa and RGMb expression in the intestinal epithelium started during postnatal gut development. Interestingly, both subtypes were predominantly expressed in the proliferative crypt compartment of the gut epithelium and in paneth cells of small intestine. The development‐dependent expression in enteric ganglia and intestinal epithelial cells suggests that RGM may be involved in cell migration, differentiation, and apoptosis with similar cellular mechanisms as described in the central nervous system. Developmental Dynamics 234:169–175, 2005. © 2005 Wiley‐Liss, Inc.
FasL (CD95L/APO-1L) Resistance of Neurons Mediated by Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B-Dependent Expression of Lifeguard/Neuronal Membrane Protein 35
2005-07-20

The contribution of Fas (CD95/APO-1) to cell death mechanisms of differentiated neurons is controversially discussed. Rat cerebellar granule neurons (CGNs) express high levels of Fas in vitro but are resistant to FasL (CD95L/APO-1L/CD178)-induced apoptosis. We here show that this resistance was mediated by a phosphatidylinositol 3-kinase (PI 3-kinase)-Akt/protein kinase B (PKB)-dependent expression of lifeguard (LFG)/neuronal membrane protein 35. Reduction of endogenous LFG expression by antisense oligonucleotides or small interfering RNA lead to increased sensitivity of CGNs to FasL-induced cell death and caspase-8 cleavage. The inhibition of PI 3-kinase activity sensitized CGNs to FasL-induced caspase-8 and caspase-3 processing and caspase-dependent fodrin cleavage. Pharmacological inhibition of PI 3-kinase, overexpression of the inhibitory protein IκB, or cotransfection of an LFG reporter plasmid with dominant-negative Akt/PKB inhibited LFG reporter activity, whereas overexpression of constitutively active Akt/PKB increased LFG reporter activity. Overexpression of LFG in CGNs interfered with the sensitization to FasL by PI 3-kinase inhibitors. In contrast to CGNs, 12 glioma cell lines, which are sensitive to FasL, did not express LFG. Gene transfer of LFG into these FasL-susceptible glioma cells protected against FasL-induced apoptosis. These results demonstrate that LFG mediated the FasL resistance of CGNs and that, under certain circumstances, e.g., inhibition of the PI 3-kinase-Akt/PKB pathway, CGNs were sensitized to FasL.