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At least 541 records · Page 30Linked to original sources
PubMed2004

Ca(2.5)Sr(0.5)GaMn2O8: diamagnetic Ga in control of the structural and electronic properties of a bilayered manganate.

The temperature dependence of the crystal structure and electronic properties of brownmillerite-like Ca(2.5)Sr(0.5)GaMn(2)O(8) has been studied by neutron powder diffraction and muSR spectroscopy. The results show that short-range 2D magnetic order begins to develop within the perovskite-like bilayers of MnO(6) octahedra approximately 50 K above the 3D Néel temperature of approximately 150 K. The bilayers show a structural response to the onset of magnetism throughout this temperature range whereas the GaO(4) layers that separate the bilayers only respond below the 3D ordering temperature. XANES spectroscopy shows that the sample contains Mn(3+) and Mn(4+) cations in a 1:1 ratio, and the behavior in the region of the Néel transition is interpreted as a local charge ordering. Electron diffraction and high-resolution electron microscopy have been used to show that the local microstructure is more complex than the average structure revealed by neutron diffraction, and that microdomains exist in which the GaO(4) tetrahedra show different orientations. It is argued that the bonding requirements of diamagnetic gallium control the electronic behavior within the perovskite-like bilayers.

Journal Article↗
PubMed2004

Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC.

Telomerase is a ribonucleoprotein complex that is required to synthesize DNA repeats at the ends of each chromosome. The RNA component of this reverse transcriptase is mutated in the bone marrow failure syndrome autosomal dominant dyskeratosis congenita. Here we show that disease anticipation is observed in families with this disease and that this is associated with progressive telomere shortening.

Adolescent↗
PubMed2003

Identification of the p16-Arc subunit of the Arp 2/3 complex as a substrate of MAPK-activated protein kinase 2 by proteomic analysis.

The p38 MAPK pathway regulates multiple neutrophil functional responses via activation of the serine-threonine kinase MAPK-activated protein kinase 2 (MAPKAPK2). To identify substrates of MAPKAPK2 that mediate these responses, a proteomic approach was used in which in vitro phosphorylation of neutrophil lysates by exogenously added active recombinant MAPKAPK2 was followed by protein separation using two-dimensional electrophoresis. Peptide mass fingerprinting of peptides defined by MALDI-MS was then utilized to identify phosphorylated proteins detected by autoradiography. Six candidate substrates were identified, including the p16 subunit of the seven-member Arp2/3 complex (p16-Arc). In vitro studies confirmed that MAPKAPK2 interacts with and phosphorylates the A isoform, but not the B isoform, of p16-Arc with a stoichiometry of 0.6 to 0.7. MAPKAPK2 also phosphorylated p16-Arc in intact Arp2/3 complexes precipitated from neutrophil lysates. Mutation of serine-77 to alanine on the A isoform prevented phosphorylation by MAPKAPK2. The ability of MAPKAPK2 to phosphorylate one isoform of p16-Arc suggests a possible mechanism by which the p38 MAPK cascade regulates remodeling of the actin cytoskeleton.

Actin-Related Protein 2↗
PubMed1997

Relationship between the peptide-sensitive channel and the mitochondrial outer membrane protein translocation machinery.

The peptide-sensitive channel (PSC), a cationic channel of the mitochondrial outer membrane, is blocked by synthetic mitochondrial presequences and by nonmitochondrial basic peptides such as dynorphin B(1-13). Both types of peptides are imported into mitochondria. However, the import of dynorphin B(1-13) had to be further characterized since its properties differed from those of the general import pathway used by mitochondrial peptides. Cross-linking experiments with iodinated dynorphin B(1-13) led to the labeling of TOM 40/ISP 42, a component of the protein import machinery of the outer membrane. Accordingly, dynorphin B(1-13) could also be used as a presequence to direct the import of a cytosolic protein into the mitochondria. Pretreatment of intact mitochondria by trypsin removed components capable of discriminating between true mitochondrial presequences and other basic peptides active on the PSC. After proteolysis, both types of peptides appeared to cross the outer membrane through the same pathway. Involvement of the PSC in the translocation complex was shown by immunoprecipitation of the PSC activity by anti-ISP 42 antibodies. Taken together, the present data reinforce the hypothesis that the PSC is the pore responsible for the translocation of protein through the outer membrane.

Animals↗
PubMed2005

Cornelia de Lange Syndrome and the link between chromosomal function, DNA repair and developmental gene regulation.

Cornelia de Lange Syndrome (CdLS) is a rare multiple malformation disorder with characteristic facial features, growth and cognitive retardation, and many other abnormalities. CdLS individuals were recently shown to have heterozygous mutations in a previously uncharacterised gene, NIPBL, which encodes delangin, a homologue of fungal Scc2-type sister chromatid cohesion proteins and the Drosophila Nipped-B developmental regulator. Nipped-B and vertebrate delangins are also now known to regulate sister chromatid cohesion, probably as part of oligomeric complexes required to load cohesin subunits onto chromatin. CdLS is likely to be one of several developmental disorders resulting from defective expression of a multi-functional protein with roles in chromosome function, gene regulation and double-strand DNA repair - a combination of properties shared by certain bacterial proteins responsible for structural maintenance of chromatin.

Animals↗
PubMedDate not supplied

Triplex staples: DNA double-strand cross-linking at internal and terminal sites using psoralen-containing triplex-forming oligonucleotides.

A method has been developed to attach 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen to the 5 position of thymine bases during solid-phase oligonucleotide synthesis. UV irradiation of triplex-forming oligonucleotides (TFOs) containing internally attached psoralens produces photoadducts at TpA steps within target duplexes, thus relaxing the constraints on selection of psoralen target sequences. Photoreaction of TFOs containing two psoralens, located at the 5'- and 3'-ends, has been used to create double-strand cross-links (triplex staples) at both termini of the TFO. Such complexes have no free single-stranded ends. TFOs containing 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen, 3-methyl-2-aminopyridine, and 5-(3-aminoprop-2-ynyl)deoxyuridine formed photoadducts with target duplexes under near-physiological conditions.

Cross-Linking Reagents↗
PubMed2002

Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1.

The toxic effect of cholera toxin (CT) on target cells is caused by its A1 chain. This polypeptide is released from the holotoxin and unfolded in the lumen of the ER by the action of protein disulfide isomerase (PDI), before being retrotranslocated into the cytosol. The polypeptide is initially unfolded by binding to the reduced form of PDI. We show that upon oxidation of the COOH-terminal disulfide bond in PDI by the enzyme Ero1, the A1 chain is released. Both yeast Ero1 and the mammalian Ero1alpha isoform are active in this reaction. Ero1 has a preference for the PDI-toxin complex. We further show that the complex is transferred to a protein at the lumenal side of the ER membrane, where the unfolded toxin is released from PDI by the action of Ero1. Taken together, our results identify Ero1 as the enzyme mediating the release of unfolded CT from PDI and characterize an additional step in retrotranslocation of the toxin.

Animals↗
PubMed2004

Proposal to accommodate Burkholderia cepacia genomovar VI as Burkholderia dolosa sp. nov.

Phenotypic and genotypic studies revealed new tools for differentiating Burkholderia cepacia genomovar VI from Burkholderia multivorans and other B. cepacia-complex species. Hence, the name Burkholderia dolosa sp. nov. is proposed, with LMG 18943(T) (=CCUG 47727(T)) as the type strain. B. dolosa can be differentiated from other B. cepacia-complex bacteria by its inability to assimilate tryptamine, azelaic acid and salicin and by its failure to grow on the B. cepacia-selective medium PCAT. Both 16S rDNA and recA RFLP analysis revealed unique B. dolosa restriction patterns. In addition, new 16S rDNA- and recA-based PCR assays allowed its specific identification.

Base Sequence↗
PubMed2004

Platelet count, previous infection and FCGR2B genotype predict development of chronic disease in newly diagnosed idiopathic thrombocytopenia in childhood: results of a prospective study.

About 25-30% of children with acute idiopathic thrombocytopenia (ITP) develop chronic disease. It is not well known which patient characteristics influence the course of the ITP. A prospective study in 60 children with newly diagnosed ITP was performed. The aim of the study was to identify patient characteristics at the onset of thrombocytopenia that predicts the progression to chronic ITP. Clinical data and blood samples were collected at several time points during the first 6 months of the disease. Variables predicting chronic disease, as calculated in a multivariate logistic regression analysis, were a platelet count >10 x 10(9)/l at the onset [odds ratio (OR) 1.1, 95% confidence interval (CI) 1.01-1.14], the absence of infection shortly before the onset of the disease (OR 4.8, CI 1.16-19.57) and FGR2B-232I/T genotype (OR 7.9, CI 0.96-65.27). The latter may point at an immune-modulating role of Fc gamma RIIb in ITP. Although only three patients had serious bleeds, 35 patients received immune-modulating treatment for low platelet counts only. Seventeen patients were treated with intravenous immunoglobulin (IVIG) and 18 patients received corticosteroids. Patient variables did not differ between these treatment groups. However, patients receiving IVIG had significantly lower risk for chronic disease.

Adolescent↗
PubMed2005

Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins.

BACKGROUND: Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD). METHODS: Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study [study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m(2) and study B GFR 13 to 24 mL/min/1.73 m(2)]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5'-phosphate (PLP) and 6 mug of vitamin B(12). Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year. RESULTS: The prevalence of hyperhomocysteinemia (tHcy >15 mumol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B(12), and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to < or =15 micromol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10). CONCLUSION: Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population.

Analysis of Variance↗
PubMed2004

Universal predictive models on octanol-air partition coefficients at different temperatures for persistent organic pollutants.

Owing to the importance of octanol-air partition coefficients (KOA) in describing the partition of organic pollutants from air to environmental organic phases, the paucity of KOA data at different environmental temperatures, and the difficulty or high expenditures involved in experimental determination, the development of predictive models for KOA is necessary. Approaches such as this are greatly needed to evaluate the environmental fate of the ever-increasing list of production chemicals. Partial least squares (PLS) regression with 18 molecular structural descriptors was used to develop predictive models based on directly measured KOA values of selected chlorobenzenes, polychlorinated biphenyls (PCBs), polychlorinated naphthalenes, polychlorinated dibenzo-p-dioxins/dibenzofurans, polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons, and organochlorine pesticides (OPs). An optimization procedure resulted in two temperature-dependent universal predictive models that explained at least 91 % of the variance of log KOA. Model 1 was the more general of the two models that could be used for all the persistent organic pollutant (POP) classes investigated. Although model 1 performed poorly for select OPs, this was attributed to wide variability in structural types within this subset of POPs and their diversity compared to the other POP classes that were investigated. The exclusion of the structurally complex OP subset resulted in a more precise model, model 5. Intermolecular dispersive interactions (induced dipole-induced dipole forces) between octanol and solute molecules play a decisive role in governing KOA and its temperature dependence. Further investigations are needed to better characterize the steric structures of the POPs under study, especially of OPs.

Air↗
PubMed2004

Precise temperature control in microfluidic devices using Joule heating of ionic liquids.

Microfluidic devices for spatially localised heating of microchannel environments were designed, fabricated and tested. The devices are simple to implement, do not require complex manufacturing steps and enable intra-channel temperature control to within +/-0.2 degrees C. Ionic liquids held in co-running channels are Joule heated with an a.c. current. The nature of the devices means that the internal temperature can be directly assessed in a facile manner.

Equipment Design↗
PubMed2006

The neuronal basis and ontogeny of empathy and mind reading: review of literature and implications for future research.

Social neuro-science has recently started to investigate the neuronal mechanisms underlying our ability to understand the mental and emotional states of others. In this review, imaging research conducted on theory of mind (ToM or mentalizing) and empathy is selectively reviewed. It is proposed that even though these abilities are often used as synonyms in the literature these capacities represent different abilities that rely on different neuronal circuitry. ToM refers to our ability to understand mental states such as intentions, goals and beliefs, and relies on structures of the temporal lobe and the pre-frontal cortex. In contrast, empathy refers to our ability to share the feelings (emotions and sensations) of others and relies on sensorimotor cortices as well as limbic and para-limbic structures. It is further argued that the concept of empathy as used in lay terms refers to a multi-level construct extending from simple forms of emotion contagion to complex forms of cognitive perspective taking. Future research should investigate the relative contribution of empathizing and mentalizing abilities in the understanding of other people's states. Finally, it is suggested that the abilities to understand other people's thoughts and to share their affects display different ontogenetic trajectories reflecting the different developmental paths of their underlying neural structures. In particular, empathy develops much earlier than mentalizing abilities, because the former relys on limbic structures which develop early in ontogeny, whereas the latter rely on lateral temporal lobe and pre-frontal structures which are among the last to fully mature.

Brain↗
PubMed2002

Essential role of NF-kappa B-inducing kinase in T cell activation through the TCR/CD3 pathway.

NF-kappa B-inducing kinase (NIK) is involved in lymphoid organogenesis in mice through lymphotoxin-beta receptor signaling. To clarify the roles of NIK in T cell activation through TCR/CD3 and costimulation pathways, we have studied the function of T cells from aly mice, a strain with mutant NIK. NIK mutant T cells showed impaired proliferation and IL-2 production in response to anti-CD3 stimulation, and these effects were caused by impaired NF-kappa B activity in both mature and immature T cells; the impaired NF-kappa B activity in mature T cells was also associated with the failure of maintenance of activated NF-kappa B. In contrast, responses to costimulatory signals were largely retained in aly mice, suggesting that NIK is not uniquely coupled to the costimulatory pathways. When NIK mutant T cells were stimulated in the presence of a protein kinase C (PKC) inhibitor, proliferative responses were abrogated more severely than in control mice, suggesting that both NIK and PKC control T cell activation in a cooperative manner. We also demonstrated that NIK and PKC are involved in distinct NF-kappa B activation pathways downstream of TCR/CD3. These results suggest critical roles for NIK in setting the threshold for T cell activation, and partly account for the immunodeficiency in aly mice.

Animals↗
PubMed2006

Usefulness of coronary computed tomographic angiography to assess suitability for revascularization in patients with significant coronary artery disease and angina pectoris.

Coronary computed tomographic angiography (CTA) accurately excludes the presence of coronary stenoses in selected patient populations. However, it remains unclear whether coronary CTA has the potential to replace invasive coronary angiography as a tool to assess a patient's suitability for revascularization as determined by the characterization of lesion morphology in patients with significant coronary artery disease. Coronary CTA (64-slice computed tomography) was performed before invasive coronary angiography in 29 patients. We evaluated the accuracy of CTA for the detection of complex lesion morphology, including the presence of severe calcium, total occlusions, and ostial or bifurcation location, and compared the results with those of invasive angiography. On CTA, 10 of 69 lesions (15%) were not evaluable for any feature of complex lesion morphology. Of the evaluable lesions, CTA detected >or=1 feature of complexity in 58% of lesions, corresponding to a sensitivity of 88% (23 of 26) and a specificity of 83% (24 of 29). For those single features, the sensitivity of CTA was 100% for the presence of severe calcium, 93% for total occlusions, and 60% and 80% for the detection of ostial and bifurcation lesions, respectively. The specificity was high for total occlusions (97%), ostial lesions (97%), and bifurcations (100%). It was moderate (85%) for severe calcium. Severe calcium precluded the evaluation of other features of complex lesion morphology in 6 lesions (11%). In conclusion, invasive selective coronary angiography remains the cornerstone to assess a patient's suitability for revascularization given the high proportion of unevaluable segments and segments with severe calcium that precluded adequate revascularization planning on CTA.

Angina Pectoris↗
PubMed2003

Control of mitochondrial protein import by pH.

Protein import into mitochondria is inhibited by protons (IC(50) pH 6.5). The channels of the import machinery were examined to further investigate this pH dependence. TOM and TIM23 are the protein translocation channels of the mitochondrial outer and inner membranes, respectively, and their single channel behaviors at various pHs were determined using patch-clamp techniques. While not identical, increasing H(+) concentration decreases the open probability of both TIM23 and TOM channels. The pattern of the pH dependences of protein import and channel properties suggests TIM23 open probability can limit import of nuclear-encoded proteins into the matrix of yeast mitochondria.

Blotting, Western↗
PubMed2003

Selective interference with verbal short-term memory for serial order information: a new paradigm and tests of a timing-signal hypothesis.

Many recent computational models of verbal short-term memory postulate a separation between processes supporting memory for the identity of items and processes supporting memory for their serial order. Furthermore, some of these models assume that memory for serial order is supported by a timing signal. We report an attempt to find evidence for such a timing signal by comparing an item probe task, requiring memory for items, with a list probe task, requiring memory for serial order. Four experiments investigated effects of irrelevant speech, articulatory suppression, temporal grouping, and paced finger tapping on these two tasks. In Experiments 1 and 2, irrelevant speech and articulatory suppression had a greater detrimental effect on the list probe task than on the item probe task. Reaction time data indicated that the list probe task, but not the item probe task, induced serial rehearsal of items. Phonological similarity effects confirmed that both probe tasks induced phonological recoding of visual inputs. Experiment 3 showed that temporal grouping of items during list presentation improved performance on the list probe task more than on the item probe task. In Experiment 4, paced tapping had a greater detrimental effect on the list probe task than on the item probe task. However, there was no differential effect of whether tapping was to a simple or a complex rhythm. Overall, the data illustrate the utility of the item probe/list probe paradigm and provide support for models that assume memory for serial order and memory for items involve separate processes. Results are generally consistent with the timing-signal hypothesis but suggest further factors that need to be explored to distinguish it from other accounts.

Adult↗
PubMed2002

Precursor of a beta-lactamase inhibitor: allyl (4S,8S,9R)-10-[(E)-ethylidene]-4-methoxy-11-oxo-1-azatricyclo[7.2.0.0(3,8)]undec-2-ene-2-carboxylate.

The molecular structure of the title tricyclic compound, C(17)H(21)NO(4), which is the immediate precursor of a potent synthetic inhibitor [Lek157: sodium (8S,9R)-10-[(E)-ethylidene]-4-methoxy-11-oxo-1-azatricyclo[7.2.0.0(3,8)]undec-2-ene-2-carboxylate] with remarkable potency, provides experimental evidence for the previously modelled relative position of the fused cyclohexyl ring and the carbonyl group of the beta-lactam ring, which takes part in the formation of the initial tetrahedral acyl-enzyme complex. In this hydrophobic molecule, the overall geometry is influenced by C[bond]H...O intramolecular hydrogen bonds [3.046 (4) and 3.538 (6) A, with corresponding normalized H.O distances of 2.30 and 2.46 A], whereas the molecules are interconnected through intermolecular C[bond]H...O hydrogen bonds [3.335 (4)-3.575 (5) A].

Aza Compounds↗