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At least 1,315 records · Page 73Linked to original sources
PubMed2000

Molecular neurobiology of ingestive behavior.

The concepts and tools of molecular biology may be applied to almost any component of the animal involved in ingestion, but two categories of model system are particularly relevant for molecular analysis: homeostatic regulation of neuropeptide expression in the hypothalamus and neuronal plasticity underlying persistent changes in ingestive behavior. Molecular approaches to these models are reviewed, focusing on our strategy for analyzing conditioned taste aversion learning. Three questions must be answered: Where do the long-term changes occur within the distributed neural network that mediates feeding? This answer reveals the site of neuronal restructuring mediated by gene expression. When does the transition occur from short-term expression to long-term persistence of the change in behavior? This transition reveals the critical time of gene expression. What genes are expressed during the change in behavior? The expression of thousands of genes in discrete subpopulations of cells is likely to be required during critical periods of neuronal restructuring. The identification of these genes is a general challenge for molecular neurobiology. The analysis of ingestive behavior can profit from molecular tools, but ingestion also provides informative models that elucidate the principles of time- and neuron-specific gene expression mediating complex behaviors.

Animals↗
PubMed1993

Abnormal T-cell costimulation by proteins of the extracellular matrix in human renal allografting.

T cells interact with extracellular matrix (ECM) proteins as they pass through the endothelium and move about in various microenvironments. Recent data indicate that such proteins provide strong costimulation to CD3-TCR-complex-mediated T-cell activation. Thus, ECM proteins can regulate T-cell responses via their integrin and non-integrin receptors. We have shown that the costimulating activity of interstitial ECM proteins (collagen type I, fibronectin) is abolished in renal allograft recipients treated with cyclosporin A (CsA) but not azathioprine. In contrast, cyclosporin treatment does not affect potent costimulation provided by the major component of basement membranes, collagen type IV. We suggest that these disturbances in T-cell interactions with ECM proteins caused by CsA therapy may contribute to cyclosporin-induced transplant arteriosclerosis.

Arteritis↗
PubMed1999

The inhibitory receptor superfamily: potential relevance to atopy.

The role of inhibitory receptor superfamily (IRS) members in the pathophysiology of atopy is still largely unexplored but the past year or so has brought at least three important advances in the understanding of IRS member function: first, several targets of an inositol-phosphatase-dependent inhibitory signaling pathway utilized by some IRS members were identified; second, there is accumulating evidence from murine models supporting the importance of inhibitory Fc gamma receptors in modulating immune-complex-mediated inflammation; third, the inhibitory signaling capability of several previously identified candidate IRS members--including several expressed on cell types implicated in atopy and allergic reactions--has been demonstrated.

Animals↗
PubMed2002

Sec61beta--a component of the archaeal protein secretory system.

Sec61p/SecYEG complexes mediate protein translocation across membranes and are present in both eukaryotes and bacteria. Whereas homologues of Sec61alpha/SecY and Sec61gamma/SecE exist in archaea, identification of the third component (Sec61beta or SecG) has remained elusive. Using PSI-BLAST, the archaeal counterpart of Sec61beta has been detected. With the identification of the Sec61beta motif, functions for a universal family of archaeal proteins can be predicted and the archaeal translocon system can be definitively detected.

Amino Acid Motifs↗
PubMed1996

A dominant role for mast cell Fc receptors in the Arthus reaction.

Antibody-antigen complexes are central to the inflammatory response and are implicated in the development of such diverse diseases as systemic lupus erythematosis, rheumatoid arthritis, immune glomerulonephritis, and vasculitis. We recently demonstrated that experimental immune complex-mediated injury in mice, as modeled by the cutaneous Arthus reaction, requires receptors for the Fc portion of the antibody and is unaffected by deficiencies in complement components. However, the responsible cell type(s) and Fc receptor(s) were not known. We now demonstrate by differential reconstitution in vivo that Fc gamma RIII on mast cells is necessary for this inflammatory response. We propose a general model of antibody-mediated diseases as an immunopathologic spectrum whose specific manifestations are determined by the Fc receptor and cell type engaged.

Animals↗
PubMed2003

The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses.

Originally the only known heterodimeric cytokine, IL-12 is now part of a family of five cytokines and shares important functions in the regulation of both innate and adaptive immunity with two of them, IL-23 and IL-27. Although initially these three cytokines were considered to have largely overlapping immunological functions, more recent studies, including two articles in this issue of Immunity (Hamano et al., 2003; Villarino et al., 2003), indicate that they mediate complex and well-differentiated functions.

Animals↗
PubMed2002

Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction.

The bacterial Hfq protein modulates the stability or the translation of mRNAs and has recently been shown to interact with small regulatory RNAs in E. coli. Here we show that Hfq belongs to the large family of Sm and Sm-like proteins: it contains a conserved sequence motif, known as the Sm1 motif, forms a doughnut-shaped structure, and has RNA binding specificity very similar to the Sm proteins. Moreover, we provide evidence that Hfq strongly cooperates in intermolecular base pairing between the antisense regulator Spot 42 RNA and its target RNA. We speculate that Sm proteins in general cooperate in bimolecular RNA-RNA interaction and that protein-mediated complex formation permits small RNAs to interact with a broad range of target RNAs.

Amino Acid Sequence↗
PubMed2001

Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth.

The biofilm mode of growth is the survival strategy of environmental bacteria like Pseudomonas aeruginosa. Such P. aeruginosa biofilms also occur in the lungs of chronically infected cystic fibrosis patients, where they protect the bacteria against antibiotics and the immune response. The lung tissue damage is due to immune complex mediated chronic inflammation dominated by polymorphonuclear leukocytes releasing proteases and oxygen radicals.

Animals↗
PubMed2001

Safety becomes danger: dilemmas of drug-use in public space.

This paper provides a socio-spatial analysis of injecting drug-use in public space. It focuses on one urban district in Melbourne, Australia, which has become strongly identified with heroin sale and use in public space. Selling activities are camouflaged within a diverse street life while injecting sites are dispersed through a broad diversity of laneways, car parks and toilets. These injecting zones occupy liminal places which slide between categories of private and public, and which mediate complex and paradoxical relations between safety and danger. Those who inject in public space are caught in a dilemma--needing both privacy and exposure in the event of an overdose, safety from police becomes danger from an overdose. This empirical work, based on interview and spatial analysis, is presented as a basis for theorizing the socio-spatial construction of heroin use and for assessing the prospects for safe injecting.

Drug Overdose↗
PubMed2004

When Ras signaling reaches the mediator.

Numerous sequence-specific DNA binding proteins that couple extracellular stimuli to transcriptional regulation have been described. Less well understood is how these transcriptional regulators interact with the Mediator complex to initiate transcription and how those interactions are coordinated with the activation of signaling pathways. Recent work has begun to shed light on this important area of research.

Animals↗
PubMed1988

Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice.

Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes (greater than 90%) and platelets (greater than 85%), and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) response to schistosomular antigens (as determined by footpad swelling, 24 h after injection of antigen). However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were essentially similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity (as determined by footpad swelling, 5 h after injection of antigen) nor serum anti-schistosomulum extract antibody levels (as determined by ELISA) were affected. In addition, the pattern of 125I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.

Animals↗
PubMed1990

Interaction of the Escherichia coli Gal repressor protein with its DNA operators in vitro.

The binding of Escherichia coli Gal repressor to linear DNA fragments containing two binding sites (OE and OI) within the gal operon was analyzed in vitro with quantitative footprint and mobility-shift techniques. In vivo analysis of the regulation of the gal operon [Haber, R., & Adhya, S. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 9683-9687] has suggested the role of a regulatory "looped complex" mediated by the association of Gal repressor dimers bound at OE and OI. The binding of Gal repressor to a single site can be described by a model in which monomer and dimer are in equilibrium and only the dimer binds to DNA. At pH 7.0, 25 mM KCl, and 20 degrees C, the binding and dimerization free energies are comparable, suggesting that the equilibrium governing the formation of dimers may be important to regulation. The two intrinsic binding constants, delta GI and delta GE, and a constant describing cooperativity, delta GIE, were determined by footprint titration analysis as a function of pH, [KCl], and temperature. Only at 4 and 0 degrees C was delta GIE negative, signifying cooperative binding. These results are thought to be due to a weak dimer to tetramer association interface. delta GE and delta GI had maximal values between pH 6 and pH 7. The dependence of these constants on [KCl] corresponded to the displacement of approximately 2 ion equiv. The temperature dependence could be described by a change in the heat capacity, delta Cp, of -2.3 kcal mol-1 deg-1. Mobility-shift titration experiments conducted at 20 and 0 degrees C yielded values for delta GIE that were consistent with those resolved from the footprint analysis. Unique values of delta GIE were determined by analysis of mobility-shift titrations of Gal repressor with wild-type operator subject to the constraint that delta GE = delta GI: a procedure that eliminates the need to simultaneously analyze wild-type titrations with titrations of OE- and OI- operators.

Base Sequence↗
PubMed2003

Gas-phase SN2 and bromine abstraction reactions of chloride ion with bromomethane: reaction cross sections and energy disposal into products.

Reaction cross sections and product velocity distributions are presented for the bimolecular gas-phase nucleophilic substitution (S(N)2) reaction Cl(-) + CH(3)Br --> CH(3)Cl + Br(-) as a function of collision energy, 0.06-24 eV. The exothermic S(N)2 reaction is inefficient compared with phase space theory (PST) and ion-dipole capture models. At the lowest energies, the S(N)2 reaction exhibits the largest cross sections and symmetrical forward/backward scattering of the CH(3)Cl + Br(-) products. The velocity distributions of the CH(3)Cl + Br(-) products are in agreement with an isotropic PST distribution, consistent with a complex-mediated reaction and a statistical internal energy distribution of the products. Above 0.2 eV, the velocity distributions become nonisotropic and nonstatistical, exhibiting CH(3)Cl forward scattering between 0.2 and 0.6 eV. A rebound mechanism with backward scattering above 0.6 eV is accompanied by a new rising feature in the CH(3)Cl + Br(-) cross sections. The competitive endothermic reaction Cl(-) + CH(3)Br --> CH(3) + ClBr(-) rises from its thermochemical threshold at 1.9 +/- 0.4 eV, showing nearly symmetrically scattered products just above threshold and strong backward scattering above 3 eV associated with a second feature in the cross section.

Journal Article↗
PubMed2000

Preheating effects on the textural strength of canned green beans. 1. Cell wall chemistry.

Variable preheating conditions allowed the modification of the firmness of two green bean cultivars after processing. The aim of this study was to elucidate the biochemical basis of this phenomenon and to relate pectin differences to different inherent firmness of two cultivars. The preheating temperature, which resulted in the highest retention of firmness after sterilization, corresponded with the optimal temperature for pectin methylesterase activity. After this preheating treatment, there was an overall reduction of the degree of methylation of the cell wall pectin. In addition, the yields of the buffer and chelator soluble fractions, as well as their average molecular mass, were higher after sterilization. Firmness differences between the two cultivars seemed to be related to the degree of methylation, the degree of acetylation, and the total amount of pectins. Preheating of green beans affects texture after sterilization most likely by demethylation of pectin by pectin methylesterase thereby (i) decreasing the beta-eliminative degradation of pectin and (ii) increasing the capacity of pectin to form Ca(2+)-mediated complexes.

Carboxylic Ester Hydrolases↗
PubMed2004

Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases.

Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.

Animals↗
PubMed2000

Synthetic receptors for CG base pairs.

Hydrogen-bond-mediated complexation of a CG base pair by a hexylureido phthalimide and a hexylureido isoindolin-1-one was studied by (1)H NMR spectroscopy in an organic solvent. Chemical shift data indicate that both receptors effectively bind the CG base pair from the major groove side.

Base Pairing↗
PubMed1999

Immunocytochemical accumulation of p53 in corticotroph adenomas: relationship with heat shock proteins and apoptosis.

The pathogenesis of corticotroph adenomas is unknown. In a recent study accumulation of p53 protein was detected by immunohistochemistry in a substantial proportion of pituitary corticotroph adenomas, and it has been suggested that it may be causally related to their development. However, other immunohistochemical studies have not confirmed the high incidence of p53 accumulation in this tumor type. Therefore, in the present study, p53 protein accumulation was re-examined in a series of 31 cases of corticotroph adenomas, using different sets of well validated anti-p53 antibodies. Furthermore, in view of the known association of p53 protein with apoptosis, and the known property of p53 to form complexes with heat shock proteins (HSPs), the relationship of p53 accumulation in corticotroph adenomas with apoptosis and HSP-70 was also investigated. Tumor samples from 31 patients with Cushing's disease or Nelson's syndrome were studied. Accumulation of p53 protein was tested by the standard ABC method using two different sets of clone Pab1801 and DO-7 monoclonal antibodies, applied after incubation of sections in a microwave oven. Using the DO-7 antibody, nuclear accumulation of p53 protein was detected in a total of 15 cases, with cytoplasmic staining observed in only 3 tumors. In contrast, using the Pab1801 antibody nuclear staining was observed in only 5 adenomas, with 11 adenomas demonstrating focal cytoplasmic immunoreactivity. Parallel sections of all corticotroph tumors demonstrating cytoplasmic accumulation of p53 protein were tested for the immunohistochemical presence of heat shock protein HSP-70. A striking similar distribution pattern of these two proteins was observed. Apoptosis, identified by the in situ end labeling technique, was detected in a total of 15 out of 28 corticotroph adenomas tested. Calculation of the apoptotic labeling index (ALI) by image analysis showed a significantly lower ALI in those corticotroph adenomas demonstrating nuclear p53 accumulation compared to those with no nuclear p53 immunostaining (p < 0.05). There was no significant difference in the ALI between cytoplasmic p53 positive and negative tumors. It is concluded that depending on the antibody used there is a significant variation of p53 protein detection in corticotroph adenomas. Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. Although such a complex-mediated cytoplasmic exclusion of p53 has no significant effect on apoptosis, nuclear accumulation of p53 protein is associated with a significantly lower apoptotic index indicating a failure of p53 protein to exert its apoptotic action in at least a subset of this tumor type.

Adenoma↗
PubMed2002

The process through which an advocacy intervention resulted in positive change for battered women over time.

A prior experimental evaluation of a community-based advocacy program for women with abusive partners demonstrated positive change in the lives of women even 2 years postintervention (C M. Sullivan & D. I. Bybee, 1999). The current study explored the complex mediational process through which this change occurred, using longitudinal structural equation modeling and formal tests of mediation. As hypothesized, the advocacy intervention first resulted in women successfully obtaining desired community resources and increasing their social support, which enhanced their overall quality of life. This improvement in well-being appeared to serve as a protective factor from subsequent abuse, as women who received the intervention were significantly less likely to be abused at 2-year follow-up compared with women in the control condition. Increased quality of life completely mediated the impact of the advocacy intervention on later reabuse. Discussion places advocacy for women in the context of other efforts that are needed to build an effective community response to preventing intimate violence against women.

Battered Women↗