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At least 595 records · Page 33Linked to original sources
PubMed1998

Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries.

OBJECTIVE: To study the prevalence of multiple dideoxynucleoside (ddN)-resistant (MddNR) HIV-1 in European patients under treatment with multiple ddN analogues, and to characterize MddNR strains genotypically and phenotypically. DESIGN AND METHODS: Blood samples from patients after > or = 6 months of treatment with multiple ddN were screened for the MddNR mutation Q151M. After confirmation of MddNR in 15 patients from five European countries, genotypic resistance was evaluated by DNA sequencing of the reverse transcriptase (RT) gene. Phenotypic resistance was measured by the recombinant virus assay. Results were compared with the clinical evolution of the patients. RESULTS: The prevalence of MddNR strains in European patients treated with multiple ddN analogues was 3.5%. Viruses typically contained amino acid substitutions V75F, F77L, F116Y and Q151M in the RT gene. A new mutation, S68G, was frequently associated with MddNR. Phenotypically, viruses displayed high-level resistance to zidovudine (ZDV), didanosine (ddl), zalcitabine (ddC), stavudine (d4T) and partial resistance to lamivudine (3TC) once multiple mutations were present. Under in-vivo treatment pressure, some MddNR strains additionally developed resistance to protease inhibitors or non-nucleoside RT inhibitors (NNRTI). Clinically, most patients had advanced HIV disease with low CD4 cell counts, high viral loads and a rapid progression, but two patients harbouring MddNR virus responded well to dual protease inhibitor associations. CONCLUSIONS: MddNR resistant HIV-1 can be found in European patients. MddNR is characterized by a specific set of drug resistance mutations, cross-resistance to most ddN analogues and a fast clinical progression. MddNR can be associated with protease inhibitor or NNRTI resistance.

Amino Acid Sequence↗
PubMed2004

[Absence of antiosteopenic effect of hormone replacement therapy in postmenopausal women].

BACKGROUND: Several studies suggest that hormone replacement therapy (HRT) stops bone loss in postmenopausal women while increasing their bone mineral density up to 20%; however, there are studies where hormone replacement therapy does not increase bone density, only prevents it. OBJECTIVE: To analyze the effect of hormone replacement therapy upon bone mineral density of hip and lumbar spine in postmenopausal women. MATERIAL AND METHODS: Clinical files of several patients with sudden menopause diagnosis seen at the Hospital Juarez of Mexico were reviewed in the year 2000. They received hormone replacement therapy of conjugated estrogens and medroxyprogesterone acetate, with annual controls of estradiol in blood, equal or higher than 50 pg/mL and bone mineral density measurement (BMD) with DEXA (dual energy X-ray absortiometry) central (hip and lumbar spine), and at least one control within a period of four years. 89 patients were included and four groups were determined: all of them had basal densitometry in one (group 1), two (group 2), three (group 3), and four years (group 4) of monitoring. The percentage of bone mineral density was calculated in both anatomic areas and per group. In each study group the number or patients that showed gain, loss or whose mineral bone density stayed the same was assessed. The statistical analysis was made using the Student t test. RESULTS: The 89 patients mean age was of 50.5 (SD +/- 6.42) years. All of them showed spontaneous menopause. The average time of menopause evolution was of 6.9 (SD +/- 4.7) years. The body mass index (BMI) average was of 27.5 (SD +/- 3.97) kg/m2. After admittance, all patients received hormone replacement therapy with conjugated equine estrogens (0.625 mg and medroxyprogesterone acetate 2.5 mg/day). A gain of bone mineral density in the second and third year of treatment in the left hip and in the lumbar spine was observed; however, there were no important differences in any study group when results were treated statistically. CONCLUSION: Hormone replacement therapy was not effective to prevent bone loss, neither to increase bone density. Only one treatment was tested, and might be necessary to investigate the effect of other routes of administration or formulations.

Bone Density↗
PubMed1983

Management of tachyarrhythmias with dual-chamber pacemakers.

Multiprogrammable dual-demand AV sequential (DVI, MN) pacemakers were implanted in twenty-three patients (in one of them a DVI, MN unit was used as a VVI, MN with the aid of an atrial plug) with supraventricular tachycardias after electrophysiological studies revealed a great variety of AV reentry circuits. The latter included tachycardias involving accessory pathways of the Kent type, manifest or concealed Wolff-Parkinson-White syndromes, nodo-ventricular (Mahaim) tracts, "enhanced" AV node (or extra AV nodal) pathways and dual AV pathways. In addition, multiprogrammable "non-committed" AV sequential (DVI, MN and DDD, M) pacemakers were permanently implanted to treat different forms of ventricular tachyarrhythmias that included: torsade de pointes in the Romano-Ward syndrome and Chagas' cardiomyopathy, ventricular tachycardia which is bradycardia-dependent (in Chagas' cardiomyopathy) and reciprocal beats induced by, and producing severe hemodynamic derangements in a patient with a conventional VVI unit. With small-size multiprogrammable units, arrhythmias may be treated by changing parameters non-invasively. By temporary inhibition, one may analyze the underlying rhythm and pacemaker dependency. In patients without chronic atrial flutter/fibrillation who require pacing and possibly tachyarrhythmia control, our experience with multiprogrammable "non-committed" AV sequential pacing has been very satisfactory. The evolution toward newer pacing modes which provide atrial sensing and tracking (DDD), and thus preserve AV synchrony over a wider range of atrial rates, may contribute even further to successful patient management. This may be applicable to pediatric patients as well.

Adolescent↗
PubMed2001

fMRI of auditory stimulation with intermolecular double-quantum coherences (iDQCs) at 1.5T.

An intermolecular double-quantum coherence (iDQC) imaging technique was used to study auditory activation in the human brain at 1.5T with a dual temporal lobe surface phased array coil and a quadrature head coil. Preliminary results demonstrate that it is feasible to obtain auditory activation maps using iDQC imaging at 1.5T, both in individual subjects using the surface coil array and with multisubject averaging of data using the head coil. The most robust activation map was obtained when a spin-echo (SE) acquisition was combined with an iDQC excitation. Since SE with conventional single quantum coherence (SQC) and similar parameters showed much reduced activation in spite of its higher signal-to-noise ratio (SNR), it was determined that activation resulting from the SE-iDQC acquisition almost entirely originates from iDQCs. In addition, the fact that the robust activation was obtained using signals at an evolution time more sensitive to changes in magnetic susceptibilities also suggests the sensitivity of iDQCs to the BOLD effect upon activation. iDQCs provide a novel MRI method which is potentially more sensitive to the BOLD effect traditionally measured with SQC. Magn Reson Med 45:356-364, 2001.

Acoustic Stimulation↗
PubMed2004

Dual growth hormone (GH) response to repeated GH releasing hormone stimulus in children and adults.

Several authors have demonstrated that plasma growth hormone (GH) levels as response to acute GH releasing hormone (GHRH) stimulation in adults are decreased by a previous GHRH injection whereas they are maintained in children. Probably the most accepted hypothesis for this finding is the increase in the somatostatinergic tone. The aim of the present study was to evaluate the dual GH response to repeated GHRH stimuli to clarify the possible influence of somatostatinergic activity in the type of response. Eighteen healthy prepubertal children, mean age 9.2 years (range: 6.0-12.9 years) and 19 healthy adult volunteers, mean age 25.5 years (range: 17-35 years) were studied with the GHRH test. An additional group of 10 normal adults with similar characteristics (mean age 31 years, range 25-35 years) were also recruited as a control group for somatostatinergic assessment. The GH response to the first GHRH bolus was similar in both children and adults. However, while children showed a preserved response to the second stimulus, it was diminished in adults. As expected, thyroid stimulating hormone (TSH) was within the normal range in all subjects. When the evolution of TSH was compared between the group of non-responders and the control group, no significant differences were found either at basal time or at 120 min, showing a similar decreasing trend for serum TSH level. The variation of TSH levels were also expressed as the proportion of TSH response after 2 hours compared to the basal level (TSH-120/TSH-0) but no significant differences were found (GHRH non-responders group mean: 73.6%, range: 51.3-93.7; control group mean: 70.7%, range: 62.9-92.5). In conclusion, the results confirm that in adults but not in children, the somatotrope responsiveness to GHRH is inhibited by a previous bolus of GHRH. The finding that the plasma TSH level diminishes in a similar manner in both non-responders and the control group is in agreement with the rejection of the hypothesis of the influence of somatostatin.

Adolescent↗
PubMed1999

Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort.

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of > 1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro- and macrovascular outcomes. RESEARCH DESIGN AND METHODS: Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram. Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy. At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end. RESULTS: Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men). HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA1c difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA1c remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT. CONCLUSIONS: Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term follow-up in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications.

Adult↗
PubMed2026

Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.

Hedgehog family morphogens present an interesting paradox: Despite being hydrophobic because of dual-lipid modifications, they form spatial concentration gradients that are highly conserved and essential for many aspects of metazoan development. Using live-cell single-molecule tracking and engineered synthetic signaling ligands, we isolated the distinct contribution of each lipid modification to Hedgehog diffusion and signaling potency. We found that although both lipid modifications enhance signaling potency, they do so through different mechanisms. Palmitate directly promotes receptor engagement, whereas cholesterol topologically confines secreted morphogens on the cell surface, effectively using the lipid membrane as a nonsignaling co-receptor that enriches ligands locally at the cost of restricting long-range diffusion. Our results on the function of cholesterol point to an intrinsic trade-off between signaling potency and gradient formation, with implications for the evolution and mechanism of nonsignaling co-receptors.

Signal Transduction↗
PubMed1996

The dual expression of minor and major bcr/abl chimeric mRNA in blast crisis of chronic myelogenous leukemia.

The hypothesis that minor bcr/abl fusion mRNA is produced in blast crisis of chronic myelogenous leukemia (CML) is examined. The RNA transcripts encoding the minor and major bcr/abl fused protein were detected by polymerase chain reaction (PCR) using RNA from peripheral blood or bone marrow cells of eight patients with blast crisis or accelerated phase of CML. The mRNA encoding for major bcr/abl was detected in all eight cases. In four patients, however, transcripts encoding for minor bcr/abl mRNA were detected, as well as major bcr/abl mRNA. The presence of minor bcr/abl mRNA was verified with the hybridization with a junction-specific probe and DNA sequencing analysis of PCR products. The appearance of minor bcr/abl fusion mRNA was associated with the lymphoblastic immunophenotype of the blast cells. In two of these four patients, samples of initial diagnosis of chronic phase of CML were available, which did not show minor bcr/abl transcript. We conclude that the appearance of minor bcr/abl mRNA transcript is associated with the terminal evolution of CML in lymphoblastic crisis.

Adolescent↗
PubMed2005

Mso1 is a novel component of the yeast exocytic SNARE complex.

The yeast exocytic SNARE complex consists of one molecule each of the Sso1/2 target SNAREs, Snc1/2 vesicular SNAREs, and the Sec9 target SNARE, which form a fusion complex that is conserved in evolution. Another protein, Sec1, binds to the SNARE complex to facilitate assembly. We show that Mso1, a Sec1-interacting protein, also binds to the SNARE complex and plays a role in mediating Sec1 functions. Like Sec1, Mso1 bound to SNAREs in cells containing SNARE complexes (i.e. wild-type, sec1-1, and sec18-1 cells), but not in cells in which complex formation is inhibited (i.e. sec4-8 cells). Nevertheless, Mso1 remained associated with Sec1 even in sec4-8 cells, indicating that they act as a pair. Mso1 localized primarily to the plasma membrane of the bud when SNARE complex formation was not impaired but was mostly in the cytoplasm when assembly was prevented. Genetic studies suggest that Mso1 enhances Sec1 function while attenuating Sec4 GTPase function. This dual action may impart temporal regulation between Sec4 turnoff and Sec1-mediated SNARE assembly. Notably, a small region at the C terminus of Mso1 is conserved in the mammalian Munc13/Mint proteins and is necessary for proper membrane localization. Overexpression of Mso1 lacking this domain (Mso1-(1-193)) inhibited the growth of cells bearing an attenuated Sec4 GTPase. These results suggest that Mso1 is a component of the exocytic SNARE complex and a possible ortholog of the Munc13/Mint proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Heat shock protein 70 is a potent activator of the human complement system.

According to new hypotheses, extracellular heat shock proteins (Hsps) may represent an ancestral danger signal of cellular death or lysis-activating innate immunity. Recent studies demonstrating a dual role for Hsp70 as both a chaperone and cytokine, inducing potent proinflammatory response in human monocytes, provided support for the hypothesis that extracellular Hsp is a messenger of stress. Our previous work focused on the complement-activating ability of human Hsp60. We demonstrated that Hsp60 complexed with specific antibodies induces a strong classical pathway (CP) activation. Here, we show that another chaperone molecule also possesses complement-activating ability. Solid-phase enzyme-linked immunosorbent assay was applied for the experiments. Human Hsp70 activated the CP independently of antibodies. No complement activation was found in the case of human Hsp90. Our data further support the hypothesis that chaperones may messenger stress to other cells. Complement-like molecules and primitive immune cells appeared together early in evolution. A joint action of these arms of innate immunity in response to free chaperones, the most abundant cellular proteins displaying a stress signal, may further strengthen the effectiveness of immune reactions.

Complement Pathway, Classical↗
PubMed1995

Evolution of spinal bone loss and biochemical markers of bone remodeling after menopause in normal women.

The main objective of this study was to describe longitudinal patterns of spinal bone loss in normal women who undergo a natural menopause. The second objective was to determine if a proportion of women suffer excessively rapid postmenopausal bone loss from the spine. If this was the case it was the aim to devise a means of predicting the woman at excess risk; but if all women lost bone at similar rates, the aim was to document changing loss rates over the first 5-8 postmenopausal years. Responding women in six suburban general practices recalled for cervical smears who had their last menstrual period 9- 36 months previously were invited to participate in a longitudinal study of bone loss and the biochemical markers plasma osteocalcin and urinary hydroxyproline. Sixty-four subjects agreed to participate, a response rate of 80%. In the ensuing 5 years, six received hormone replacement therapy and are not reported on. The main outcome measures were rates of spinal bone loss over 5 years, measured by dual photon absorptiometry, and radial bone loss over the first 2 years measured to quantitative computed tomography. Spinal bone loss was similar between individuals, with 94% of the variability in the data being accounted for by a statistical model that assumed parallel rates of bone loss. A less restrictive model allowing women to have different rates of spinal bone loss accounted for 12% more of the remaining variance in the data than the previous model. However, rates of radial bone loss were more dissimilar between women than rates of spinal loss. The results of the biochemical data collected serially showed that the plasma osteocalcin rose slowly to a plateau at 5 years postmenopause; in contrast, the hydroxyproline fell progressively with time over the whole period of study. These results were interpreted as being consistent with diminishing rates of bone destruction which gradually reequilibrated with bone formation as time passed after menopause.

Absorptiometry, Photon↗
PubMed1997

Targeting determinants and proposed evolutionary basis for the Sec and the Delta pH protein transport systems in chloroplast thylakoid membranes.

Transport of proteins to the thylakoid lumen is accomplished by two precursor-specific pathways, the Sec and the unique Delta pH transport systems. Pathway selection is specified by transient lumen-targeting domains (LTDs) on precursor proteins. Here, chimeric and mutant LTDs were used to identify elements responsible for targeting specificity. The results showed that: (a) minimal signal peptide motifs consisting of charged N, hydrophobic H, and cleavage C domains were both necessary and sufficient for pathway-specific targeting; (b) exclusive targeting to the Delta pH pathway requires a twin arginine in the N domain and an H domain that is incompatible with the Sec pathway; (c) exclusive targeting to the Sec pathway is achieved by an N domain that lacks the twin arginine, although the twin arginine was completely compatible with the Sec system. A dual-targeting signal peptide, constructed by combining Delta pH and Sec domains, was used to simultaneously compare the transport capability of both pathways when confronted with different passenger proteins. Whereas Sec passengers were efficiently transported by both pathways, Delta pH passengers were arrested in translocation on the Sec pathway. This finding suggests that the Delta pH mechanism evolved to accommodate transport of proteins incompatible with the thylakoid Sec machinery.

Amino Acid Sequence↗
PubMed2006

Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity.

Human short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity (RODH-like enzymes) are thought to contribute to the oxidation of retinol for retinoic acid biosynthesis and to the metabolism of androgenic and neuroactive 3alpha-hydroxysteroids. Here, we investigated the phylogeny and orthology of these proteins to understand better their origins and physiological roles. Phylogenetic and genomic analysis showed that two proteins (11-cis-RDH and RDHL) are highly conserved, and their orthologs can be identified in the lower taxa, such as amphibians and fish. Two other proteins (RODH-4 and 3alpha-HSD) are significantly less conserved. Orthologs for 3alpha-HSD are present in all mammals analyzed, whereas orthologs for RODH-4 can be identified in some mammalian species but not in others due to species-specific gene duplications. Understanding the evolution and divergence of RODH-like enzymes in various vertebrate species should facilitate further investigation of their in vivo functions using animal models.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed1995

A panel of subchromosomal painting libraries representing over 300 regions of the human genome.

DNA samples from about 100 human-hamster somatic cell hybrids, previously characterized by conventional banding techniques, were amplified with dual-Alu PCR. The products were then used as probes in FISH experiments on normal human metaphases for an accurate cytogenetic characterization of the human material retained in each hybrid. In addition to entire chromosomes, most hybrids were found to contain one or a few chromosome fragments, as a result of rearrangements that had occurred in vitro. Forty additional primary hybrids, in which conventional cytogenetic analysis failed to reveal any complete human chromosome, contained many human chromosome fragments. More than 300 chromosome fragments were scored and their precise chromosomal location recorded. We show data indicating that subchromosomal painting libraries generated from these hybrids can be favorably used in the fine characterization of chromosomal rearrangements encountered in clinical cytogenetics or in tumor cytogenetics, and in tracking chromosomal changes that occurred in primate evolution.

Animals↗
PubMed2006

Evidence from nuclear DNA sequences sheds light on the phylogenetic relationships of Pinnipedia: single origin with affinity to Musteloidea.

Considerable long-standing controversy and confusion surround the phylogenetic affinities of pinnipeds, the largely marine group of "fin-footed" members of the placental mammalian order Carnivora. Until most recently, the two major competing hypotheses were that the pinnipeds have a single (monophyletic) origin from a bear-like ancestor, or that they have a dual (diphyletic) origin, with sea lions (Otariidae) derived from a bear-like ancestor, and seals (Phocidae) derived from an otter-, mustelid-, or musteloid-like ancestor. We examined phylogenetic relationships among 29 species of arctoid carnivorans using a concatenated sequence of 3228 bp from three nuclear loci (apolipoprotein B, APOB; interphotoreceptor retinoid-binding protein, IRBP; recombination-activating gene 1, RAG1). The species represented Pinnipedia (Otariidae: Callorhinus, Eumetopias; Phocidae: Phoca), bears (Ursidae: Ursus, Melursus), and Musteloidea (Mustelidae: Mustela, Enhydra, Melogale, Martes, Gulo, Meles; Procyonidae: Procyon; Ailuridae: Ailurus; Mephitidae: Mephitis). Maximum parsimony, maximum likelihood, and Bayesian inference phylogenetic analyses of separate and combined datasets produced trees with largely congruent topologies. The analyses of the combined dataset resulted in well-resolved and well-supported phylogeny reconstructions. Evidence from nuclear DNA evolution presented here contradicts the two major hypotheses of pinniped relationships and strongly suggests a single origin of the pinnipeds from an arctoid ancestor shared with Musteloidea to the exclusion of Ursidae.

Animals↗
PubMed2002

Orientation-dependent influence of an intergenic enhancer on the promoter activity of the divergently transcribed mouse Shsp/alpha B-crystallin and Mkbp/HspB2 genes.

The mouse Shsp/alphaB-crystallin and Mkbp/HspB2 genes are closely linked and divergently transcribed. In this study, we have analyzed the contribution of the intergenic enhancer to Shsp/alphaB-crystallin and Mkbp/HspB2 promoter activity using dual-reporter vectors in transient transfection and transgenic mouse experiments. Deletion of the enhancer reduced Shsp/alphaB-crystallin promoter activity by 30- and 93-fold and Mkbp/HspB2 promoter activity by 6- and 10-fold in transiently transfected mouse lens alpha-TN4 and myoblast C2C12 cells, respectively. Surprisingly, inversion of the enhancer reduced Shsp/alphaB-crystallin promoter activity by 17-fold, but did not affect Mkbp/HspB2 promoter activity in the transfected cells. In contrast, enhancer activity was orientation-independent in combination with a heterologous promoter in transfected cells. Transgenic mouse experiments established the orientation dependence and Shsp/alphaB-crystallin promoter preference of the intergenic enhancer in its native context. The orientation dependence and preferential effect of the Shsp/alphaB-crystallin enhancer on the Shsp/alphaB-crystallin promoter provide an example of adaptive changes in gene regulation accompanying the functional diversification of duplicated genes during evolution.

Animals↗
PubMed2004

Molecular design of the photosystem II light-harvesting antenna: photosynthesis and photoprotection.

The photosystem II (PSII) light-harvesting system carries out two essential functions, the efficient collection of light energy for photosynthesis, and the regulated dissipation of excitation energy in excess of that which can be used. This dual function requires structural and functional flexibility, in which light-harvesting proteins respond to an external signal, the thylakoid DeltapH, to induce feedback control. This process, referred to as non-photochemical quenching (NPQ) depends upon the xanthophyll cycle and the PsbS protein. In nature, NPQ is heterogeneous in terms of kinetics and capacity, and this adapts photosynthetic systems to the specific dynamic features of the light environment. The molecular features of the thylakoid membrane which may enable this flexibility and plasticity are discussed.

Adaptation, Physiological↗
PubMed2006

Evolutionarily-conserved role of the NF-kappaB transcription factor in neural plasticity and memory.

NF-kappaB is an evolutionarily conserved family of transcription factors (TFs) critically involved in basic cellular mechanisms of the immune response, inflammation, development and apoptosis. In spite of the fact that it is expressed in the central nervous system, particularly in areas involved in memory processing, and is activated by signals such as glutamate and Ca2+, its role in neural plasticity and memory has only recently become apparent. A surprising feature of this molecule is its presence within the synapse. An increasing number of reports have called attention to the role of this TF in processes that require long-term regulation of the synaptic function underlying memory and neural plasticity. Here we review the evidence regarding a dual role for NF-kappaB, as both a signalling molecule after its activation at the synapse and a transcriptional regulator upon reaching the nucleus. The specific role of this signal, as well as the general transcriptional mechanism, in the process of memory formation is discussed. Converging lines of evidence summarized here point to a pivotal role for the NF-kappaB transcription factor as a direct signalling mechanism in the regulation of gene expression involved in long-term memory.

Animals↗