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PubMedDate not supplied

[Transmission in the sensorimotor synapses of the lumbar spinal cord in Rana ridibunda tadpoles].

In experiments on preparations of isolated spinal cord of the tadpoles, intracellular studies have been made on the synaptic potentials evoked in the lumbar motoneurones during total activation of the fibers within the 9th dorsal root. It was shown that primary afferents form monosynaptic contacts with motoneurones at stages XIV-XXV. During larval development, the number of motor cells in which monosynaptic EPSPs are recorded increases, whereas the number of motoneurones with only polysynaptic reactions decreases. From the moment of formation of monosynaptic contacts, transmission in direct sensory-motor synapses is realised by a dual (electrical-chemical) mode. The data obtained are discussed in relation to the problem of evolution of synaptic transmission between heterotypic neurones in vertebrates.

Animals↗

PubMed2005

The mouse RNase 4 and RNase 5/ang 1 locus utilizes dual promoters for tissue-specific expression.

The ribonuclease A (RNase A) superfamily has been the subject of extensive studies in the areas of protein evolution, structure and biochemistry and are exciting molecules in that they appear to be responding to unique selection pressures, generating proteins capable of multiple and diverse activities. The RNase 4 and RNase 5/ang 1 shared locus breaks a pattern that is otherwise canonical among the members of the RNase A gene superfamily. Conserved among humans, mice and rats, the locus includes two non-coding exons followed by two distinct exons encoding RNase 4 and RNase 5/ang 1. Transcription from this locus is controlled by differential splicing and tissue-specific expression from promoters located 5' to each of the non-coding exons. Promoter 1, 5' to exon I, is universally active, while Promoter 2, 5' to exon II, is active only in hepatic cells in promoter assays in vitro. Transcription from Promoter 2 is dependent on an intact HNF-1 consensus binding site which binds the transcription factor HNF-1alpha. In summary, RNase 4 and RNase 5/ang 1 are unique among the RNase A ribonuclease genes in that they maintain a complex gene locus that is conserved across species with transcription initiated from tissue-specific dual promoters followed by differential exon splicing.

Amino Acid Sequence↗

PubMedDate not supplied

Alzheimer's disease and idiopathic Parkinson's disease coexistence.

Idiopathic Parkinson's disease (IPD) and Alzheimer's disease (AD) are common neurologic diseases of old age. Parkinson syndrome is easy to recognize even at an early stage, but identifying early AD is often difficult. Accurate clinical diagnosis is important for assigning the prognosis and for studies aimed at assessing the efforts to slow down progression of these diseases. During 22 years, we identified six patients who had clinical features of parkinsonism and dementia and who at autopsy had both IDP and AD and 20 parkinsonian patients without dementia who at autopsy had only IPD. The clinical profile in these two groups was compared. The onset of Parkinson syndrome in the patients with dual pathology had a bimodal distribution--before or after age 65 years. In the three cases with onset before age 65 years, there was sequential evolution of IPD and AD. In contrast, those older than 65 years at onset manifested the clinical features of both IPD and AD simultaneously. The mode of onset and the dominant parkinsonian features in the three patients with sequential clinical evolution were similar to those seen in the nondemented IPD cases; however, lack of self-confidence and inability to make decisions resulted in considerably greater functional disability than could be accounted for by parkinsonism alone. These characteristics may be helpful in early recognition of dual IPD and AD pathology. Psychiatric side effects of levodopa therapy were more common in those with dual pathology than in those with IPD alone.

Age Factors↗

PubMed1999

Involvement of ribosomal proteins in regulating cell growth and apoptosis: translational modulation or recruitment for extraribosomal activity?

Gene recruitment is a mechanism of molecular evolution whereby a gene product can function in more than one distinct capacity. The 'one gene-dual function' phenomenon is well illustrated by crystallins, structural proteins that play both specialized roles in the eye lens and also 'housekeeping' enzyme roles. Ribosomal proteins are integral components of the basal cellular machinery involved in protein synthesis, whose roles have been regarded collectively as important, but individually somewhat mundane. However, various individual ribosomal proteins and also translation initiation and elongation factors have been found to play roles in regulating cell growth, transformation and death, giving rise to increasing speculation that components of the translational apparatus can act as multifunctional proteins. Recently, we have shown that ribosomal protein S3a (RPS3a) plays important roles in cell transformation and death, whereby constitutively or transiently enhanced RPS3a expression can be regarded as 'priming' a cell for apoptosis and suppression of such enhanced expression as 'execution'. While it is unclear whether RPS3a acts in a capacity mechanistically distinct from that in translation, such a possibility is discussed in this article in the light of recent, although not exhaustively reviewed, findings implicating the involvement of other individual ribosomal proteins in modulating and/or effecting changes in cellular responses and growth patterns in an extraribosomal capacity independent of their conventional role in translation.

Animals↗

PubMed2004

Time-reversal-based SU(2) x Sn scalar invariants as (Lie Algebraic) group measures: a structured overview of generalised democratic-recoupled, uniform non-Abelian [AX]n NMR spin systems, as abstract [Formula: see text] chain networks.

The physics of dual group scalar invariants (SIs) as (Lie algebraic) group measures (L-GMs) and its significance to non-Abelian NMR spin systems motivates this overview of uniform general-2n [AX](2n) spin evolution, which represents an extensive addendum to Corio's earlier (essentially restricted) view of Abelian spin system SU(2)-based SI-cardinalities. The [Formula: see text] values in [J. Magn. Reson., 134 (1998) 131] arise from strictly linear recoupled time-reversal invariance (TRI) models. In contrast, here we discuss the physical significance of an alternative polyhedral combinatorics approach to democratic recoupling (DR), a property inherent in both the TRI and statistical sampling. Recognition of spin ensemble SIs as being L-GMs over isomorphic algebras is invaluable in many DR-based NMR problems. Various [AX]n model spin systems, including the [AX]3 bis odd-odd parity spin system, are examined as direct applications of these L-GM- and combinatorial-based SI ideas. Hence in place of /SI/=15 (implied by Corio's [Formula: see text] approach), the bis 3-fold spin system cardinality is seen now as constrained to a single invariant on an isomorphic product algebra under L-GMs, in accord with the subspectral analysis of Jones et al. [Canad. J. Chem., 43 (1965) 683]. The group projective ideas cited here for DR (as cf. to graph theoretic views) apply to highly degenerate non-Abelian problems. Over dual tensorial bases, they define models of spin dynamical evolution whose (SR) quasiparticle superboson carrier (sub)spaces are characterised by SIs acting as explicit auxiliary labels [Physica, A198 (1993) 245; J. Math. Chem., 31 (2002) 281]. A deeper [Formula: see text] network-based view of spin-alone space developed in Balasubramanian's work [J. Chem. Phys., 78 (1983) 6358] is especially important, (e.g.) in the study of spin waves [J. Math. Chem., 31 (2002) 363]. Beyond the specific NMR SIs derived here, there are DR applications where a sporadic, still higher, 2n-fold regular uniform spin ensemble exhibits a topological FG duality to some known modest /SI/(2i<2n) cardinality--in principle providing for the (sparce) existence of other /SI/(2n) DR-based values.

Algorithms↗

PubMed1990

Evolution of blood coagulation and fibrinolysis.

The key steps in the evolution of blood coagulation and fibrinolysis have been reconstructed from an analysis of the molecular evolution of their constituents. The data suggest that the blood coagulation and complement cascades are descendants of an ancestral defence system that served the dual role of immobilization and destruction of invading bacteria and the prevention of loss of body fluids. The enzymes of the fibrinolytic, tissue-remodelling cascades form a distinct group, more closely related to the proteases of the digestive tract than to the components of the blood coagulation and complement cascades. Molecular evolution of these enzymes therefore suggests that they are descendants of an ancestral protease responsible for degradation of extracellular proteins. It is shown that the regulatory extensions of the proteases of the blood coagulation, fibrinolytic and complement cascades were assembled from domains borrowed from other proteins. Most non-protease components of these systems were also constructed by this evolutionary mechanism.

Animals↗

PubMed2001

The structure and function of the helical heart and its buttress wrapping. II. Interface between unfolded myocardial band and evolution of primitive heart.

The unfolded myocardial band containing a central fold, extending between the pulmonary artery and aorta, has been used to explain the intact or wrapped cardiac structure, composed of a basal and apical loop forming a buttress and helix, connected to the outflow vessels of both ventricles. The interface between this simple structure, and embryologic development of the primitive heart evolving from a singular tube, into a dual pumping chamber with separate left and right sides, must be explained. The objective is to suggest that a simple and integrated triple figure-eight spiral band, with three S-shaped helixes and their apices may correlate the conventional embryologic development of the primitive heart (bulbus cordis, ventricle, and arterial outflow vessels), with the three stages of spatial orientation of the myocardial band (basal and apical loops), which extends between dual ventricular outflow vessels, in the sequence defined by the unwrapped myocardial band.

Biological Evolution↗

PubMed1979

[Perspective on the history of psychiatry in Québec : the case of the asylum in Québec City.].

The history of insanity in whatever setting often introduces a dual interest : from a non-medical perspective, it reveals the repressive nature of society and the evolution of groups in power within this society : in that sense, one discovers that the objectives of the organization taking charge of insanity translates differently according its social definition of insanity at a moment in time and according to the interests that dominate at this same time. On the other hand, from a medical perspective, such history tends to illustrate original social deviancy and social norms and professional concepts of insanity and its treatment tend nonetheless to be inspired by the existing social order indirectly justified. It's in this perspective that we have elaborated the history of the Centre Hospitalier Robert-Giffard, the first psychiatric hospital in Lower Canada. The history covers 5 specific periods : the political and religious period, the period of professional colonialism during the union with Lower Canada, the asylum period, the hospital period or franco-religious when a neurological concept of insanity prevailed, the psychiatric period where insanity becomes a mental illness that is treatable both biologically and psychologically and finally the period where insanity tends to fall back to social deviancy that must be taken in charge by social science experts. The authors end their article with an overview of a more community-oriented period.

English Abstract↗

PubMed1986

Induction of malignant transformation of cocultivated hematopoietic stem cells by X-irradiation of murine bone marrow stromal cells in vitro.

X-irradiation of purified primary cultures of mouse bone marrow stroma or permanent cloned marrow stromal cell lines in plateau phase decreases production of macrophage progenitor cell-specific colony-stimulating factor to a plateau minimum of 40% of control levels after doses of 50 to 500 Gy delivered at 2 Gy/min. After 50 Gy there is increased bioavailability of another growth factor(s) that is distinct from macrophage progenitor cell-specific colony-stimulating factor, granulocyte-macrophage progenitor cell colony-stimulating factor, or colony-stimulating factor for multipotential hematopoietic stem cells (interleukin 3). Liquid-phase cocultivation of irradiated stromal cells with either nonadherent cells from continuous marrow cultures or cloned dual granulocyte-macrophage progenitor cell colony-stimulating factor/interleukin 3-dependent hematopoietic progenitor cell lines induces evolution over 5 weeks of factor-independent colony-forming cells. Subcultured factor-independent colonies generated clonal malignant cell lines with multiple distinct karyotypic alterations. Inoculation of 10(6) cells s.c. from factor-independent clones into syngeneic mice produces local granulocytic monomyeloid tumors with spread to spleen, lymph nodes, and bone marrow. These data provide the first demonstration in vitro of indirect X-irradiation leukemogenesis through cells of the marrow stroma.

Animals↗

PubMed1996

Evolution of a persistent aphthovirus in cytolytic infections: partial reversion of phenotypic traits accompanied by genetic diversification.

Foot-and-mouth disease virus (FMDV) shows a dual potential to be cytolytic or to establish persistent infections in cell culture. FMDV R100, a virus rescued after 100 passages of carrier BHK-21 cells persistently infected with FMDV clone C-S8c1, showed multiple genetic and phenotypic alterations relative to the parental clone C-S8c1. Several FMDV R100 populations have been subjected to 100 serial cytolytic infections in BHK-21 cells, and the reversion of phenotypic and genetic alterations has been analyzed. An extreme temperature sensitivity of R100 reverted totally or partially in some passage series but not in others. The small-plaque morphology reverted to normal size in all cases. The hypervirulence for BHK-21 cells did not revert, and even showed an increase, upon cytolytic passage. Most of the mutations that had been fixed in the R100 genome during persistence did not revert in the course of cytolytic passages, but the extended polyribocytidylate tract of R100 (about 460 residues, versus 290 in C-S8c1) decreased dramatically in length, to the range of 220 to 260 residues in all passage series examined. In passages involving very large viral populations, a variant with two amino acid substitutions (L-144-->V and A-145-->P) next to the highly conserved Arg-Gly-Asp (RGD motif; positions 141 to 143) within the G-H loop of capsid protein VP1 became dominant. A clonal analysis allowed isolation of a mutant with the single replacement A-145-->P. Viral production and growth competition experiments showed the two variants to have a fitness very close to that of the parental virus. The results provide evidence that the repertoire of variants that could potentially become dominant in viral quasispecies may be influenced by the population size of the evolving virus. The net results of a series of persistent-infection passages followed by a series of cytolytic passages was progressive genomic diversification despite reversion or stasis of phenotypic traits. Implications for the evolution of RNA viruses are discussed.

Animals↗

PubMed2004

The prokaryotic selenoproteome.

In the genetic code, the UGA codon has a dual function as it encodes selenocysteine (Sec) and serves as a stop signal. However, only the translation terminator function is used in gene annotation programs, resulting in misannotation of selenoprotein genes. Here, we applied two independent bioinformatics approaches to characterize a selenoprotein set in prokaryotic genomes. One method searched for selenoprotein genes by identifying RNA stem-loop structures, selenocysteine insertion sequence elements; the second approach identified Sec/Cys pairs in homologous sequences. These analyses identified all or almost all selenoproteins in completely sequenced bacterial and archaeal genomes and provided a view on the distribution and composition of prokaryotic selenoproteomes. In addition, lineage-specific and core selenoproteins were detected, which provided insights into the mechanisms of selenoprotein evolution. Characterization of selenoproteomes allows interpretation of other UGA codons in completed genomes of prokaryotes as terminators, addressing the UGA dual-function problem.

Amino Acid Sequence↗

PubMed1993

Identification and characterization of a gene cluster involved in nitrate transport in the cyanobacterium Synechococcus sp. PCC7942.

The nrtA gene, which has been proposed to be involved in nitrate transport of Synechococcus sp. PCC7942 (Anacystis nidulans R2), was mapped at 3.9 kb upstream of the nitrate reductase gene, narB. Three closely linked genes (designated nrtB, nrtC, and nrtD), which encode proteins of 279, 659, and 274 amino acids, respectively, were found between the nrtA and narB genes. NrtB is a hydrophobic protein having structural similarity to the integral membrane components of bacterial transport systems that are dependent on periplasmic substrate-binding proteins. The N-terminal portion of NrtC (amino acid residues 1-254) and NrtD are 58% identical to each other in their amino acid sequences, and resemble the ATP-binding components of binding protein-dependent transport systems. The C-terminal portion of NrtC is 30% identical to NrtA. Mutants constructed by interrupting each of nrtB and nrtC were unable to grow on nitrate, and the nrtD mutant required high concentration of nitrate for growth. The rate of nitrate-dependent O2 evolution (photosynthetic O2 evolution coupled to nitrate reduction) in wild-type cells measured in the presence of L-methionine D,L-sulfoximine and glycolaldehyde showed a dual-phase relationship with nitrate concentration. It followed saturation kinetics up to 10 mM nitrate (the concentration required for half-saturation = 1 microM), and the reaction rate then increased above the saturation level of the first phase as the nitrate concentration increased. The high-affinity phase of nitrate-dependent O2 evolution was absent in the nrtD mutant. The results suggest that there are two independent mechanisms of nitrate uptake and that the nrtB-nrtC-nrtD cluster encodes a high-affinity nitrate transport system.

Amino Acid Sequence↗

PubMed2006

Nef alleles from human immunodeficiency virus type 1-infected long-term-nonprogressor hemophiliacs with or without late disease progression are defective in enhancing virus replication and CD4 down-regulation.

Infection with human immunodeficiency virus (HIV)-encoding defective nef variants may contribute to a relatively benign course of disease in a minority of long-term nonprogressors (LTNP). We have examined the functions of nef alleles from six individuals belonging to the same cohort of hemophiliacs infected with HIV-1 prior to 1985 and classified as LTNP in 1995. Three out of six individuals have progressed to HIV disease (late progressors [LP]), whereas the three remainders have maintained their LTNP status at least up to 2003. The nef alleles were obtained from both plasma virus and peripheral blood mononuclear cells of all six individuals in 1995 and 1998. The proportion of sequences containing mutations not yielding Nef expression significantly diminished in 1998 versus that in 1995. Several previously defined functional regions of intact nef alleles were highly conserved. However, the major variant obtained in 1998 from plasma RNA of five out of six individuals significantly reduced HIV infectivity/replication and impaired Nef-mediated CD4 but not major histocompatibility complex class I antigen down-modulation from the cell surface. Thus, functional alterations of the nef gene are present in both LP and LTNP, suggesting that Nef defectiveness in vitro is not necessarily associated with the long-term maintenance of LTNP status. Of interest is the fact that isolates from three out of three LP showed a dual CCR5/CXCR4 coreceptor use (R5X4), in contrast to those from LTNP, which were exclusively R5. Thus, in vivo evolution of gp120 Env to CXCR4 use appears to be associated with HIV disease progression in individuals infected with nef-defective viruses.

Alleles↗

PubMed2002

[Systematic circumferential (360 degree) decompression treatment of major arthrotic cervical stenosis].

PURPOSE OF THE STUDY: Worsening and irreducible evolution of neural involvement in cervical stenosis requires cord decompression. Different techniques have been proposed. We associated a dual posterior then anterior approach to achieve 360 degrees decompression. We evaluated results on the basis of neurological and mechanical outcome. MATERIAL AND METHODS: Twenty-eight patients, 16 men and 12 women, mean age 60.2 years (range 40-82) underwent surgery between 1989 and 1999 for severe cervical canal stenosis. Patients were referred for neurological symptoms: 20 for radicular symptoms (8 pain, 11 motor deficit, 12 sensitive deficit). Fifteen patients presented myelopathic symptoms. Pyramidal syndrome in 11 and tetraparesia in 3. Neurological involvement was scored according to Nurick (average 1.74) and JOA (average 12.6). Pain was scored on the Robinson scale. Levels to decompress were identified on static and dynamic plain x-rays, CT scans and MRI. Myelography was rarely used (first case only). MRI demonstrated preoperative myelomalacia in 5 patients and syringomyelia in 2. The surgical technique for 360 degrees fusion involved two steps, performed with a 1-week interval for 12 patients and during the same procedure for the others. The first approach was posterior enabling spine fixation with bilateral Roy-Camille plates and decompression by laminectomy using the lobster shell technique. The anterior approach consisted in corpectomy with the Simmons technique (22 cases or multilevel interbody fusion according to Robinson. Iliac bone grafting was used in all but one patient who had a fibular bone graft. Mean follow-up was 18.5 months (6-78). RESULTS: Neurological improvement was 1.74 to 0.92 on the Nurick sclae and from 12.6 to 15.2 on the JOA scale at last follow-up. Fusion was obtained in all cases. There were 2 cases of neurological worsening and one transient dysphagia. Operative bleeding for the two steps was 700 ml (150 ml for the posterior procedure and 400 ml for the anterior procedure). CONCLUSION: 360 degrees arthrodesis for severe cervical canal stenosis provides a satisfactory solution to mechanical problems and substantial neurological improvement. Fusion is regularly obtained without complementary anterior instrumentation. Neurological improvement is correlated with disease duration and the degree of deficit at onset. Anteroposterior decompression and 360 degrees fusion provide cure for all the components of stenotic disease. The dual approach is indicated in severe cases with cord involvement as recognized by myleopathic clinical manifestations and on the MRI.

Adult↗

PubMed2004

The "dual degree". Does it change the scope of practice for oral and maxillofacial surgery?

The scope of practice for OMS is not, nor should it ever be, an issue of single or dual degree but must be related to the surgeon being trained to competence in the procedures performed. Future evolution will be based on continual advancements in the specialty and related areas as well as the development of new techniques. While the medical education may improve a core fund of general knowledge, the surgical residency and/or fellowship is the determinant of surgical competence and scope of practice.

Clinical Competence↗

PubMed2004

Evolution of the multifunctional protein tyrosine phosphatase family.

The protein tyrosine phosphatase (PTP) family plays a central role in signal transduction pathways by controlling the phosphorylation state of serine, threonine, and tyrosine residues. PTPs can be divided into dual specificity phosphatases and the classical PTPs, which can comprise of one or two phosphatase domains. We studied amino acid substitutions at functional sites in the phosphatase domain and identified putative noncatalytic phosphatase domains in all subclasses of the PTP family. The presence of inactive phosphatase domains in all subclasses indicates that they were invented multiple times in evolution. Depending on the domain composition, loss of catalytic activity can result in different consequences for the function of the protein. Inactive single-domain phosphatases can still specifically bind substrate and protect it from dephosphorylation by other phosphatases. The inactive domains of tandem phosphatases can be further subdivided. The first class is more conserved, still able to bind phosphorylated tyrosine residues and might recruit multiphosphorylated substrates for the adjacent active domain. The second has accumulated several variable amino acid substitutions in the catalytic center, indicating a complete loss of tyrosine-binding capabilities. To study the impact of substitutions in the catalytic center to the evolution of the whole domain, we examined the evolutionary rates for each individual site and compared them between the classes. This analysis revealed a release of evolutionary constraint for multiple sites surrounding the catalytic center only in the second class, emphasizing its difference in function compared with the first class. Furthermore, we found a region of higher conservation common to both domain classes, suggesting a new regulatory center. We discuss the influence of evolutionary forces on the development of the phosphatase domain, which has led to additional functions, such as the specific protection of phosphorylated tyrosine residues, substrate recruitment, and regulation of the catalytic activity of adjacent domains.

Amino Acid Substitution↗

PubMed1997

Dual-color fluorescence cross-correlation spectroscopy for multicomponent diffusional analysis in solution.

The present paper describes a new experimental scheme for following diffusion and chemical reaction systems of fluorescently labeled molecules in the nanomolar concentration range by fluorescence correlation analysis. In the dual-color fluorescence cross-correlation spectroscopy provided here, the concentration and diffusion characteristics of two fluorescent species in solution as well as their reaction product can be followed in parallel. By using two differently labeled reaction partners, the selectivity to investigate the temporal evolution of reaction product is significantly increased compared to ordinary one-color fluorescence autocorrelation systems. Here we develop the theoretical and experimental basis for carrying out measurements in a confocal dual-beam fluorescence correlation spectroscopy setup and discuss conditions that are favorable for cross-correlation analysis. The measurement principle is explained for carrying out DNA-DNA renaturation kinetics with two differently labeled complementary strands. The concentration of the reaction product can be directly determined from the cross-correlation amplitude.

DNA↗

PubMed2004

Junctional adhesion molecules (JAMs): more molecules with dual functions?

Junctional adhesion molecules (JAMs) are members of an immunoglobulin subfamily expressed by leukocytes and platelets as well as by epithelial and endothelial cells, in which they localize to cell-cell contacts and are specifically enriched at tight junctions. The recent identification of extracellular ligands and intracellular binding proteins for JAMs suggests two functions for JAMs. JAMs associate through their extracellular domains with the leukocyte beta2 integrins LFA-1 and Mac-1 as well as with the beta1 integrin alpha4beta1. All three integrins are involved in the regulation of leukocyte-endothelial cell interactions. Through their cytoplasmic domains, JAMs directly associate with various tight junction-associated proteins including ZO-1, AF-6, MUPP1 and the cell polarity protein PAR-3. PAR-3 is part of a ternary protein complex that contains PAR-3, atypical protein kinase C and PAR-6. This complex is highly conserved through evolution and is involved in the regulation of cell polarity in organisms from Caenorhabditis elegans and Drosophila to vertebrates. These findings point to dual functions for JAMs: they appear to regulate both leukocyte/platelet/endothelial cell interactions in the immune system and tight junction formation in epithelial and endothelial cells during the acquisition of cell polarity.

Animals↗