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At least 1,063 records · Page 59Linked to original sources
PubMed1987

Inferences about age impairments in inferential reasoning.

Two experiments are reported in which specially constructed series completion tests were administered to samples of young and older adults to determine why increased age is associated with poorer performance on measures of inductive reasoning. The results indicated that young and older adults did not differ significantly in the effectiveness of processes concerned with determining simple relations, but that older adults were impaired when the relations are complex or when different problems involve alternative organizational patterns. We conclude that the poorer performance of older adults relative to young adults on tasks of this type may be due to inadequate (e.g., overly simplistic or temporally instable) relational structures for the integration of problem elements.

Achievement↗
PubMed1999

Financial aspects of haemophilia care in Puerto Rico and other Latin American countries.

The present cost of optimal care in haemophilia is very high. The paradigm of comprehensive care approach, including the essential elements of continuous integrated multidisciplinary health services and the provision of home care with early use of antihaemophilic products requires abundant economic resources that usually are not readily available in nonaffluent countries. A cost-effective comprehensive paediatric haemophilia programme has been operating in Puerto Rico during the last 15 years that provides quality care to over 90% of paediatric haemophiliacs, and is financed mainly by the local government health system. Efforts are also being made to provide and/or coordinate health care to all adult haemophilic patients through the Puerto Rico Pediatric Hemophilia Treatment Center. Information on the haemophilia care available in Latin American countries is scanty. The data available indicate that with a few exceptions, haemophilia care in this vast region is suboptimal. Apparently, early diagnosis is not common, there is lack of accessibility of services in most countries, comprehensive care is not the rule, safe high-purity AHF concentrates are used infrequently, and home care is used rarely. The main antihaemophilic products used are fresh frozen plasma and cryoprecipitate due to the high cost of modern antihaemophilic factor concentrates. The average per capita income of the main Latin American countries is about one-quarter of that of the USA and Canada. The existing economic situation of most Latin American countries would make it very difficult for them to purchase modern antihaemophilic products regularly and provide quality comprehensive care to their haemophilia patients, unless they make special efforts and get some type of external help. As a result of this study recommendations are made to improve the quality and accessibility of services to haemophilia patients in Latin America and other nonaffluent countries.

Adolescent↗
PubMed1996

Late-term fetal thymectomy does not prevent the development of gut-homing T cells after birth.

Tissue-specific circulation of T cells is a critical element in the integration of systemic immune responses. Current models of T-cell migration suggest that homing specificities of T cells for tissues such as gut and skin are generated outside the thymus as a result of activation of virgin T cells by antigen in lymph nodes. We have used the sheep fetus (which is immunologically virgin and contains no memory or effector T-cell subsets) to examine the migration of 51Cr-labelled T cells in vivo. We report that gut-homing T cells are not present in the fetus and that gut-homing T cells from postnatal lambs home normally to fetal gut. Fetal thymectomy performed immediately prior to birth failed to prevent the development of gut-homing T cells in postnatal life. Gut-homing specificities on T cells are thus acquired extrathymically.

Animals↗
PubMed1995

Blockade of neurotensin receptor by SR 48692 potentiates the facilitatory effect of haloperidol on the evoked in vivo dopamine release in the rat nucleus accumbens.

The present experiments assessed the effects of SR 48692, a selective nonpeptide antagonist of neurotensin receptors, on mesolimbic dopaminergic neurotransmission. Dopamine release evoked by the electrical stimulation of the median forebrain bundle (20 Hz, 10 s) was measured in the nucleus accumbens of urethane-anesthetized rats using differential pulse amperometry combined with carbon fiber electrodes. SR 48692 (0.1 mg/kg, i.p.) alone did not affect this release, whereas it dose-dependently (0.03-1 mg/kg, i.p.) enhanced the haloperidol (50 micrograms/kg, i.p.)-induced facilitation of the electrically evoked DA release. The increase induced by haloperidol (92 +/- 26% above control values 30 min after injection) was potentiated by SR 48692 (264 +/- 75% at 0.03 mg/kg, 428 +/- 113% at 0.1 mg/kg, and 480 +/- 135% at 1 mg/kg). Effects identical to those of SR 48692 were obtained with SR 48527, a chemically related compound with a high affinity for neurotensin receptors, but not with SR 49711, its low-affinity antipode. The potentiating effects of SR 48692 were positively related to the stimulation frequency (from 6 to 20 Hz) and to the dose of haloperidol (from 12.5 to 50 micrograms/kg) and were abolished after prior kainic acid lesion (1 microgram/1 microliter) of the nucleus accumbens. Thus, the effects of SR 48692 required the integrity of postsynaptic elements of the nucleus accumbens and occurred under the combination of two, at least partly, interdependent conditions: strong D2 autoreceptor blockade and high-intensity stimulation likely to release neurotensin. It is interesting that these potentiating effects of SR 48692 did not appear in the striatum. In conclusion, these findings suggest that endogenous neurotensin may attenuate the facilitation of D2 receptor blockade on mesolimbic but not nigrostriatal dopamine transmission.

Animals↗
PubMed2005

Magnetic resonance imaging in the oncology patient: evaluation of the extrahepatic abdomen.

In the oncology patient MR imaging provides excellent depiction of all forms of extrahepatic tumor. Rapid breath-hold imaging techniques are combined with intravenous and intraluminal contrast material to demonstrate tumors of the solid visceral organs, the gastrointestinal tract, peritoneum, mesentery, omentum, bile ducts, lymph nodes, and osseous structures. The unmatched soft tissue contrast of MR imaging allows one to depict subtle tumors involving all of these extrahepatic sites. MR imaging has become an integral and essential element in the management of oncology patients.

Abdominal Neoplasms↗
PubMed1999

Asymmetric DDE (D35E)-like sequences in the RAG proteins: implications for V(D)J recombination and retroviral pathogenesis.

Experimental evidence suggests that the mechanism of vertebrate V(D)J recombination catalyzed by the vertebrate RAG proteins is similar to both retroviral integration and the transposition of IS630/Tc1-family transposons. The mechanism of both retroviral integration and IS630/Tc1 element transposition is well characterized and utilizes a functional metal ion binding site termed the DDE (or D35E) motif. We have previously identified a DDE-like region in the RAG-2 protein and a similar region within the RAG-1 protein. In this work, we propose that interference between DDE-like regions in the RAG proteins and the DDE-site of the HIV integrase may be a mechanism of retroviral pathogenesis in cells in which both the RAG proteins and retroviral integrase are co-expressed.

Amino Acid Sequence↗
PubMed2003

Affective language and humor appreciation after right hemisphere brain damage.

Many adults with right hemisphere brain damage exhibit difficulties in the comprehension and expression of emotional language and humor. Affective comprehension deficits range in severity and can be modulated by task and response demands as well as by the strength of emotional content. Expressive emotional language deficits, as characterized by reduced emotional intensity, are more pervasive than comprehension deficits. Deficits in humor appreciation generally affect the ability to integrate an incongruous element (e.g., a punch line) with the preceding context. Several co-occurring disorders (e.g., depression, cognitive and visuoperceptual deficits, and reduced auditory comprehension) may exacerbate problems with affective language and humor. Although some formal measures evaluate humor appreciation, none specifically addresses emotional language. While no hard data exist regarding efficacy of treatment for deficits in affective language or humor processing, several suggestions for such treatment are provided.

Affect↗
PubMed2004

Coupled-cluster singles and doubles for extended systems.

Coupled-cluster theory with connected single and double excitation operators (CCSD) and related approximations, such as linearized CCSD, quadratic configuration interaction with single and double excitation operators, coupled-cluster with connected double excitation operator (CCD), linearized CCD, approximate CCD, and second- and third-order many-body perturbation theories, are formulated and implemented for infinitely extended one-dimensional systems (polymers), on the basis of the periodic boundary conditions and distance-based screening of integrals, density matrix elements, and excitation amplitudes. The variation of correlation energies with the truncation radii of short- and long-range lattice sums and with the number of wave vector sampling points in the first Brillouin zone is examined for polyethylene, polyacetylene, and polyyne, and is shown to be a function of the degree of pi-electron conjugation or the fundamental band gaps. The t2 and t1 amplitudes in the atomic orbital (AO) basis are obtained by first computing the t amplitudes in the Bloch-orbital basis and subsequently back-transforming them into the AO basis. The plot of these AO-based t amplitudes as a function of unit cells also indicates that the t2 amplitudes of polyacetylene and polyyne exhibit appreciably slower decay than those of polyethylene, although the asymptotic decay behavior is invariably 1/r3. The AO-based t1 amplitudes appear to correlate strongly with the electronic structure, and they decay seemingly exponentially for polyethylene whereas they stay at a constant magnitude across the seventh nearest neighbors of polyacetylene and polyyne, which attests to far reaching effects of nondynamical electron correlation mediated by orbital rotation. Nonetheless, the unit cell contributions to the correlation energies taper below 10(-6) hartree after 15 A for all three polymers. The basis set dependence of the decay behavior of t2 amplitudes is also examined for linear hydrogen fluoride polymer (HF)infinity and linear beryllium polymer (Be)infinity employing the STO-3G, 6-31G, and 6-31G* basis sets, and proves to be rather small.

Journal Article↗
PubMed2001

Cell-type specificity of short-range transcriptional repressors.

Transcriptional repressors can be classified as short- or long-range, according to their range of activity. Functional analysis of identified short-range repressors has been carried out largely in transgenic Drosophila, but it is not known whether general properties of short-range repressors are evident in other types of assays. To study short-range transcriptional repressors in cultured cells, we created chimeric tetracycline repressors based on Drosophila transcriptional repressors Giant, Drosophila C-terminal-binding protein (dCtBP), and Knirps. We find that Giant and dCtBP are efficient repressors in Drosophila and mammalian cells, whereas Knirps is active only in insect cells. The restricted activity of Knirps, in contrast to that of Giant, suggests that not all short-range repressors possess identical activities, consistent with recent findings showing that short-range repressors act through multiple pathways. The mammalian repressor Kid is more effective than either Giant or dCtBP in mammalian cells but is inactive in Drosophila cells. These results indicate that species-specific factors are important for the function of the Knirps and Kid repressors. Giant and dCtBP repress reporter genes in a variety of contexts, including genes that were introduced by transient transfection, carried on episomal elements, or stably integrated. This broad activity indicates that the context of the target gene is not critical for the ability of short-range repressors to block transcription, in contrast to other repressors that act only on stably integrated genes.

Animals↗
PubMed1997

Nucleus reticularis neurons mediate diverse inhibitory effects in thalamus.

Detailed information regarding the contribution of individual gamma-aminobutyric acid (GABA)-containing inhibitory neurons to the overall synaptic activity of single postsynaptic cells is essential to our understanding of fundamental elements of synaptic integration and operation of neuronal circuits. For example, GABA-containing cells in the thalamic reticular nucleus (nRt) provide major inhibitory innervation of thalamic relay nuclei that is critical to thalamocortical rhythm generation. To investigate the contribution of individual nRt neurons to the strength of this internuclear inhibition, we obtained whole-cell recordings of unitary inhibitory postsynaptic currents (IPSCs) evoked in ventrobasal thalamocortical (VB) neurons by stimulation of single nRt cells in rat thalamic slices, in conjunction with intracellular biocytin labeling. Two types of monosynaptic IPSCs could be distinguished. "Weak" inhibitory connections were characterized by a significant number of postsynaptic failures in response to presynaptic nRt action potentials and relatively small IPSCs. In contrast, "strong" inhibition was characterized by the absence of postsynaptic failures and significantly larger unitary IPSCs. By using miniature IPSC amplitudes to infer quantal size, we estimated that unitary IPSCs associated with weak inhibition resulted from activation of 1-3 release sites, whereas stronger inhibition would require simultaneous activation of 5-70 release sites. The inhibitory strengths were positively correlated with the density of axonal swellings of the presynaptic nRt neurons, an indicator that characterizes different nRt axonal arborization patterns. These results demonstrate that there is a heterogeneity of inhibitory interactions between nRt and VB neurons, and that variations in gross morphological features of axonal arbors in the central nervous system can be associated with significant differences in postsynaptic response characteristics.

Action Potentials↗
PubMed1997

RNA-dependent phosphorylation of a nuclear RNA binding protein.

The human C1 heterogeneous nuclear ribonucleoprotein particle protein (hnRNP protein) undergoes a cycle of phosphorylation-dephosphorylation in HeLa cell nuclear extracts that modulates the binding of this protein to pre-mRNA. We now report that hyperphosphorylation of the C1 hnRNP protein is mediated by a kinase activity in nuclear extracts that is RNA-dependent. Although the basal phosphorylation of the C1 hnRNP protein in nuclear extracts reflects a casein kinase II-type activity, its RNA-dependent hyperphosphorylation appears to be mediated by a different kinase. This is indicated by the unresponsiveness of the RNA-stimulated hyperphosphorylation to casein kinase II inhibitors, and the distinct glycerol gradient sedimentation profiles of the basal versus RNA-stimulated C1 hnRNP protein phosphorylation activities from nuclear extracts. RNA-dependent phosphorylation was observed both for a histidine-tagged recombinant human C1 hnRNP protein added to nuclear extracts and also for the endogenous C1 hnRNP protein. Additional results rule out protein kinase A, protein kinase C, calmodulin-dependent protein kinase II, and double-stranded RNA-activated protein kinase as the enzymes responsible for the RNA-dependent hyperphosphorylation of the C1 hnRNP protein. These results reveal the existence in nuclear extracts of an RNA-dependent protein kinase activity that hyperphosphorylates a known pre-mRNA binding protein, and define an additional element to be integrated into the current picture of how nuclear proteins are regulated by phosphorylation.

Casein Kinase II↗
PubMed1997

Gypsy retrotransposon as a tool for the in vivo analysis of the regulatory region of the optomotor-blind gene in Drosophila.

We report here a method for the in vivo dissection of the regulatory region of a gene in the Drosophila genome. Our system includes (i) the reporter genes lacZ and white to detect transcriptional enhancer and silencer activities in a target gene, (ii) an efficient way to induce integration of gypsy elements in the genome, and (iii) unidirectional blocking of regulatory activities by the gypsy element, which is dependent on the su(Hw) protein. The optomotor-blind (omb) gene was analyzed. In the omb(P1) line, a P[lacW] construct is inserted about 1.4 kb upstream of the omb transcription start site. The lacZ reporter gene within P[lacW] exhibits the same expression pattern as omb. The white reporter gene is expressed in a "bipolar" pattern. We induced high frequency gypsy mobilization in omb(P1) and identified two lines (D11 and D13-1) with altered eye pigmentation pattern, which is dependent on su(Hw) activity. A gypsy element was found inserted in the first intron of omb in D13-1 and in P[lacW] in D11. These results indicate that it is the blocking of regulatory activities by gypsy that caused the changes in the white reporter gene expression. The effect of these gypsy insertions on the expression patterns allowed us to predict several aspects of the organization of the regulatory elements in the omb locus.

Animals↗
PubMed1999

Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F x DP, in B-amyloid-induced neuronal death.

Previous evidence by others has indicated that a variety of cell cycle-related molecules are up-regulated in brains of Alzheimer's disease patients. The significance of this increase, however, is unclear. Accordingly, we examined the obligate nature of cyclin-dependent kinases and select downstream targets of these kinases in death of neurons evoked by B-amyloid (AB) protein. We present pharmacological and molecular biological evidence that cyclin-dependent kinases, in particular Cdk4/6, are required for such neuronal death. In addition, we demonstrate that the substrate of Cdk4/6, pRb/p107, is phosphorylated during AB treatment and that one target of pRb/p107, the E2F x DP complex, is required for AB-evoked neuronal death. These results provide evidence that cell cycle elements play a required role in death of neurons evoked by AB and suggest that these elements play an integral role in Alzheimer's disease-related neuronal death.

Alzheimer Disease↗
PubMed2001

A central role for the T1 domain in voltage-gated potassium channel formation and function.

To interpret the recent atomic structures of the Kv (voltage-dependent potassium) channel T1 domain in a functional context, we must understand both how the T1 domain is integrated into the full-length functional channel protein and what functional roles the T1 domain governs. The T1 domain clearly plays a role in restricting Kv channel subunit heteromultimerization. However, the importance of T1 tetramerization for the assembly and retention of quarternary structure within full-length channels has remained controversial. Here we describe a set of mutations that disrupt both T1 assembly and the formation of functional channels and show that these mutations produce elevated levels of the subunit monomer that becomes subject to degradation within the cell. In addition, our experiments reveal that the T1 domain lends stability to the full-length channel structure, because channels lacking the T1 containing N terminus are more easily denatured to monomers. The integration of the T1 domain ultrastructure into the full-length channel was probed by proteolytic mapping with immobilized trypsin. Trypsin cleavage yields an N-terminal fragment that is further digested to a tetrameric domain, which remains reactive with antisera to T1, and that is similar in size to the T1 domain used for crystallographic studies. The trypsin-sensitive linkages retaining the T1 domain are cleaved somewhat slowly over hours. Therefore, they seem to be intermediate in trypsin resistance between the rapidly cleaved extracellular linker between the first and second transmembrane domains, and the highly resistant T1 core, and are likely to be partially structured or contain dynamic structure. Our experiments suggest that tetrameric atomic models obtained for the T1 domain do reflect a structure that the T1 domain sequence forms early in channel assembly to drive subunit protein tetramerization and that this structure is retained as an integrated stabilizing structural element within the full-length functional channel.

Animals↗
PubMed2001

Coordination between arm and leg movements during locomotion.

To evaluate the contrasting dynamical and biomechanical interpretations of the 2:1 frequency coordination between arm and leg movements that occurs at low walking velocities and the 1:1 frequency coordination that occurs at higher walking velocities, the authors conducted an experiment in which they quantified the effect of walking velocity on the stability of the frequency and phase coordination between the individual limb movements. Spectral analyses revealed the presence of 2:1 frequency coordination as a constant feature of the data in only 3 out of 8 participants at walking velocities ranging from 1.0 to 2.0 km/h, in spite of the fact that the eigenfrequencies of the arms were rather similar across participants. The degree of interlimb coupling, as indexed by weighted coherence and variability of relative phase, was lower for the arm movements and for ipsilateral and diagonal combinations of arm and leg movements than for the leg movements. Furthermore, the coupling between all pairs of limb movements was found to increase with walking velocity, whereas no clear signs were observed that the switches from 2:1 to 1:1 frequency coordination and vice versa were preceded by loss of stability. Therefore, neither a purely biomechanical nor a purely dynamical model is optimally suited to explain these results. Instead, an integrative model involving elements of both approaches seems to be required.

Adult↗
PubMed2005

Surgical education and Internet-based simulation: The World Virtual University.

The new means and modalities of communication and information technologies have significantly revolutionized access to surgical education. The introduction of the Internet information highway into mainstream clinical practice as an information sharing medium offers a wide range of opportunities to healthcare professionals. High-speed Internet broadcasting allows the display of high-quality full-screen videos. Access to surgical procedures through the Internet already plays a major role in continuing medical education nowadays and will undoubtedly be gaining grounds in the future. WebSurg.com, the World Virtual University, a web-based surgical university, is dedicated to minimally invasive laparoscopic surgery. Using brand-new multimedia data, the electronic university provides thorough descriptions of over 150 procedures in minimal access surgery and 265 videos of surgical interventions. Such a teaching tool recreates all the prerequisites and requirements of a traditional School of Medicine, incorporating the manifold standpoints of world-renowned experts about specific topics and hands-on hints in various surgical specialities. Following the evolution of technologies, recent advances have made it possible to display items of Websurg.com on handheld devices (personal data/digital assistance also known as PDAs, Pocket PCs, and smart phones). Integrating all these elements into a unique World Virtual University, Websurg.com epitomizes the concept of a unified academic center providing teaching and tutorials administered by international experts. The Internet assuredly contributes to the worldwide diffusion of scientific information in an easy and user-friendly way.

Journal Article↗
PubMed2003

Group II introns: structure and catalytic versatility of large natural ribozymes.

Group II introns are large, natural catalytic RNAs or ribozymes that were discovered in organelles of certain protists, fungi, algae, and plants and more recently also in prokaryotic organisms. In vitro, some members were found to self-splice from their pre-RNAs by two consecutive transesterification reactions joining the flanking exons and releasing the intron in a typical lariat form. Apart from self-splicing, a variety of other in vitro activities have been detected for group II introns demonstrating their amazing catalytic versatility. Group II introns fold into a conserved secondary structure consisting of six domains radiating from a central wheel that brings the 5' and 3' splice junction into close proximity. Domain 1 is the largest domain that is assumed to deliver the molecular scaffold assembling the intron in its active structure, while domain 5 is the phylogenetically most conserved part that represents the active site of the ribozyme. In vivo, the splicing reaction of many, if not all group II introns is assisted by proteins either encoded by the introns themselves (maturases), or encoded by other genes of the host organisms. The host proteins known to date have additional cellular functions and seem to have been adapted for splicing during evolution. Some of the protein-encoding group II introns were also shown to act as mobile genetic elements. They can integrate efficiently into intronless alleles of the same gene (homing) and at much lower frequencies into ectopic sites (transposition). The mobility process depends on intron encoded protein functions (endonuclease and reverse transcriptase) and on the intron RNA. This review provides a comprehensive survey of the structure/function relationships and the reaction potential of group II introns, the structurally most complicated, but also most fascinating ribozymes when looking at their catalytic repertoire in vitro and in vivo.

Base Sequence↗
PubMed2002

Updating of form factor tabulations for coherent scattering of photons in tissues.

An updating of photon transport modelling in tissues is carried out by including the effect of molecular interference in the coherent (Rayleigh) scattering. To this end, the present tabulations--which permit us to obtain the linear differential scattering coefficient of compounds from a simple weighted sum of the elemental components--are integrated by adding files for a limited set of molecular interference functions. This set originates from a four-component model which is found to be capable of reproducing human tissues in situations involving bony and soft tissues. The proposed procedure overcomes, in the computation, the hindrance that the dependence on molecular interference effects leads every tissue to have its own diffraction pattern, which is not easily obtained by means of measurements or calculations.

Algorithms↗