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PubMed2006

Cage motions induced by electronic and vibrational excitations: Cl2 in Ar.

Femtosecond dynamics of molecular vibrations as well as cage motions in the B<--X transition of Cl2 in solid Ar have been investigated. We observed molecular vibrational wave-packet motion in experimental pump-probe spectra and an additional oscillation with a 500 fs period which is assigned to the zone-boundary phonon of the Ar crystal. The cage motion is impulsively driven by the B<--X transition due to the expansion of the electronic cloud of the chromophore. To clarify the underlying mechanism, we performed simulations based on the diatomics-in-molecules method which takes into account the different shapes of the Cl2 electronic wave function in the B and X states as well as the anisotropic interaction with the matrix. The simulation results show that Ar atom motion in the (100) plane is initiated by the electronic transition and that only those Ar atoms oscillate coherently with an approximately 500 fs period which are essentially decoupled from the molecular vibration. Their phase and time evolution are in good agreement with the experimentally observed oscillation, supporting the assignment as a displacive excitation of coherent phonons.

Journal Article↗
PubMed2001

Evolving hardware as model of enzyme evolution.

Organism growth and survival is based on thousands of enzymes organized in networks. The motivation to understand how a large number of enzymes evolved so fast inside cells may be relevant to explaining the origin and maintenance of life on Earth. This paper presents electronic circuits called 'electronic enzymes' that model the catalytic function performed by biological enzymes. Electronic enzymes are the hardware realization of enzymes defined as molecular automata with a finite number of internal conformational states and a set of Boolean operators modelling the active groups of the active site. One of the main features of electronic enzymes is the possibility of evolution finding the proper active site by means of a genetic algorithm yielding a metabolic ring or k-cycle that bears a resemblance to Krebs (k=7) or Calvin (k=4) cycles present in organisms. The simulations are consistent with those results obtained in vitro evolving enzymes based on polymerase chain reaction (PCR) as well as with the general view that suggests the main role of recombination during enzyme evolution. The proposed methodology shows how molecular automata with evolvable features that model enzymes or other processing molecules provide an experimental framework for simulation of the principles governing metabolic pathways evolution and self-organization.

Algorithms↗
PubMedDate not supplied

Changes in serum catecholamine levels in patients who are brain dead.

Prospective blood samplings from 15 patients admitted with a Glasgow Coma Score of less than 7 were obtained to observe and compare epinephrine, norepinephrine, and dopamine serum levels in patients with brain injury before, after, and in the absence of brain death. Nine of the patients developed or were admitted after brain death. Wide variations in catecholamine blood levels over time were documented, and subgroup analysis precluded useful statistical comparison or inference of the data. The data are presented therefore as descriptive observations only. No apparent differences were noted between similarly injured patients in whom brain death did not develop and patients before brain death or between patients with penetrating versus nonpenetrating brain injury. Brain death was preceded by hypertension and corresponding elevations in serum catecholamine levels in one patient with complete data. Catecholamine levels appeared to fall after brain death in most patients. Only minimal changes in myocardial histology were present in three donor hearts, and the two transplanted hearts functioned satisfactorily. Serum catecholamine measurement or monitoring does not provide a precise method of determining potential injury to the donor heart before or after brain death. Other experimental data and clinical observation indicate that some hearts may be injured in the donor during the evolution of brain death. Pharmacologic intervention may prevent such injury in experimental animals but must be used before brain death is induced. Such interventions should be studied in selected human donors before brain death to determine whether cardiac function is improved in the donor or recipient.

Adult↗
PubMed1985

Oncogenes and linkage groups: conservation during mammalian chromosome evolution.

Proto-oncogenes, which represent the cellular progenitors of the transforming genes harbored by acute transforming oncogenic retroviruses, have been highly conserved during vertebrate evolution. In this report, we have assigned experimentally a subset of proto-oncogenes (SRC, ABL, FES, and FMS-all related to the SRC family) to Chinese hamster chromosomes by Southern filter hybridization analyses of DNAs isolated from both somatic cell hybrids and flow-sorted hamster chromosomes. These results demonstrate that several autosomal linkage groups containing proto-oncogenes originated prior to the radiation and speciation of mammals and have remained remarkably stable for nearly 80 million years.

Animals↗
PubMed2005

Small bowel transplantation in experimental and clinical medicine.

Small bowel transplantation (SBT) has recently the attention of clinicians as an alternative to management of patients with irreversible bowel failure. In this paper, the authors provide an overview of basic facts regarding SBT in experimental and clinical medicine. The paper describes the evolution of bowel transplantation in experiment before it was introduced into clinical practice. In the part discussing clinical SBT, the author's report the currently available international data on SBT. In its conclusion, the paper presents the authors own experience with experimental SBT in animals and humans (Ref. 15).

Animals↗
PubMed2000

One-round determination of seven leukocyte subsets in rhesus macaque blood by flow cytometry.

BACKGROUND: Rhesus macaques are frequently used in biomedical research as experimental models for studying infectious diseases and for preclinical vaccination trials. The infection of these monkeys with simian immunodeficiency viruses (SIV) or simian-human immunodeficiency viruses (SHIV) reproduces the clinical and immunological characteristics of human infection by human immunodeficiency virus (HIV). Evolution of the immune response in the infected animals is generally analyzed by determining the lymphocyte subsets on blood samples using flow cytometry but requiring multiple, blood consuming, determinations. METHODS: Cell subsets present in whole-blood samples were labeled with a combination of anti-human monoclonal antibodies to CD2, CD20, CD4, CD8, and CD14 coupled to FITC or PE and analyzed by flow cytometry. RESULTS: In one round, we obtained the precise determination of macaque blood cell composition by flow cytometry. Monocytes, granulocytes, eosinophils, B lymphocytes, helper, and cytotoxic T lymphocytes were distinguished. Results obtained correlated strongly with those obtained with conventional blood cell differential systems and with separate staining of lymphocytes. The analysis of blood from healthy rhesus macaques and SHIV-infected animals demonstrated the accuracy of the determination even in very pathological situations such as macaques with simian AIDS. CONCLUSIONS: Our method allows fast determination of the blood cell composition and will be particularly useful to evaluate the cell subset evolution of macaques involved in large-scale experimental trials.

Animals↗
PubMed1991

Evolution of rhythms during periodic stimulation of embryonic chick heart cell aggregates.

During periodic stimulation of spontaneously beating chick heart cell aggregates, there is often an evolution of coupling patterns between the stimulator and the aggregate action potential. For example, at rapid stimulation frequencies, a rhythm that is initially 1:1 (stimulus frequency:aggregate frequency) can evolve to other rhythms such as 5:4 and 4:3. Time-dependent effects generated during periodic stimulation are characterized by three types of experiments to determine 1) the effect of periodic stimulation on the intrinsic cardiac beat rate (overdrive suppression), 2) the effect of periodic stimulation on the phase resetting properties of the aggregate, and 3) the time-dependent changes in the coupling patterns between the stimulator and the aggregate during periodic stimulation. The protocols involved variations in the duration and rate of periodic stimulation. A mathematical model is developed in the form of a two-dimensional finite difference equation based on the data from experiments 1 and 2. The model is used to predict the data generated by experiment 3. There is good correspondence with the experiments in that the theory reproduces complex transitions between various rhythms and displays irregular rhythms similar to those observed experimentally. These results have implications for the evolution of cardiac arrhythmias such as atrioventricular heart block and modulated parasystole.

Animals↗
PubMed2006

Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools.

The vast amount of protein sequence data now available, together with accumulating experimental knowledge of protein function, enables modeling of protein sequence and function evolution. The PANTHER database was designed to model evolutionary sequence-function relationships on a large scale. There are a number of applications for these data, and we have implemented web services that address three of them. The first is a protein classification service. Proteins can be classified, using only their amino acid sequences, to evolutionary groups at both the family and subfamily levels. Specific subfamilies, and often families, are further classified when possible according to their functions, including molecular function and the biological processes and pathways they participate in. The second application, then, is an expression data analysis service, where functional classification information can help find biological patterns in the data obtained from genome-wide experiments. The third application is a coding single-nucleotide polymorphism scoring service. In this case, information about evolutionarily related proteins is used to assess the likelihood of a deleterious effect on protein function arising from a single substitution at a specific amino acid position in the protein. All three web services are available at http://www.pantherdb.org/tools.

Amino Acid Substitution↗
PubMed2000

Astrocyte-targeted expression of IL-12 induces active cellular immune responses in the central nervous system and modulates experimental allergic encephalomyelitis.

The role of IL-12 in the evolution of immunoinflammatory responses at a localized tissue level was investigated. Transgenic mice were developed with expression of either both the IL-12 subunits (p35 and p40) or only the IL-12 p40 subunit genes targeted to astrocytes in the mouse CNS. Glial fibrillary acidic protein (GF)-IL-12 mice, bigenic for the p35 and p40 genes, developed neurologic disease which correlated with the levels and sites of transgene-encoded IL-12 expression. In these mice, the brain contained numerous perivascular and parenchymal inflammatory lesions consisting of predominantly CD4+ and CD8+ T cells as well as NK cells. The majority of the infiltrating T cells had an activated phenotype (CD44high, CD45Rblow, CD62Llow, CD69high, VLA-4 high, and CD25+). Functional activation of the cellular immune response was also evident with marked cerebral expression of the IFN-gamma, TNF, and IL-1alphabeta genes. Concomitant with leukocyte infiltration, the CNS expression of immune accessory molecules was induced or up-regulated, including ICAM-1, VCAM-1, and MHC class II and B7-2. Glial fibrillary acidic protein-p40 mice with expression of IL-12 p40 alone remained asymptomatic, with no inflammation evident at any age studied. The effect of local CNS production of IL-12 in the development of experimental autoimmune encephalomyelitis was studied. After immunization with myelin oligodendrocyte glycoprotein-peptides, GF-IL-12 mice had an earlier onset and higher incidence but not more severe disease. We conclude that localized expression of IL-12 by astrocytes can 1) promote the spontaneous development of activated type 1 T cell and NK cellular immunity and cytokine responses in the CNS, and 2) promote more effective Ag-specific T cell dynamics but not activity in experimental autoimmune encephalomyelitis.

Animals↗
PubMed1991

Toward an analysis of conscious activity: 1. Evolution of vigilance.

Previous articles (3-6) have presented two experimental methods--the Dynamic Behavioral Stage Analysis Method (DBSAM) and the Micro-sleep and Micro-wakefulness Processing Method (MMP)--as investigational approaches oriented in the direction of developing a theoretical concept. MMP employs a simplified method that uses duration of sleep and wakefulness (ti) as the parameter to alter the time units and reverse diagnose sleep and wakefulness as wakefulness and sleep, respectively. Results of vigilance (O) standard diagnosis and those of vigilance (+/- n) standard diagnosis (evaluating apparent sleep and wakefulness based on vigilance (+/- n)) werer compared using model data. This paper discusses the conceptual background necessary to understand the correlation between sleep, wakefulness, and consciousness, using model data. It also hypothesizes that conscious activity level, generated by sleep and wakefulness vectors, acts as an address specifier of information that is input and output within the brain.

Animals↗
PubMed1994

On the origin of protein synthesis: a speculative model based on hairpin RNA structures.

A speculative model for the origin of protein synthesis based on aminoacylated hairpin RNAs is presented. The model shows how dimerization of these hairpin structures might have triggered the initial synthesis of oligopeptides. The evolution of these dimers seems to lead naturally both to the origin of the tRNA molecule and to the origin of protein synthesis. This co-evolution seems to be confirmed in the determinants of the tRNA identity that might represent the vestiges of the hypothesized model. Finally, the model lends itself to direct experimentation.

Animals↗
PubMed1987

Molecular epizootiology and evolution of vesicular stomatitis virus New Jersey.

Vesicular stomatitis virus (VSV) has been shown previously to be capable of undergoing rapid mutational change during sequential experimental infections in various tissue culture cell systems (J. Holland, K. Spindler, F. Horodyski, E. Grabau, S. Nichol, and S. Vandepol, Science 215:1577-1585, 1982). The present study was undertaken to determine the degree of genetic diversity and evolution of the virus under natural infection conditions and to gain insight into the epizootiology of the disease. Between 1982 and 1985, numerous outbreaks of VSV of the New Jersey serotype were reported throughout regions of the United States and Mexico. A T1 RNase fingerprint analysis was performed on the RNA genomes of 43 virus isolates from areas of epizootic and enzootic virus activity. This indicates that virus populations were genetically relatively homogeneous within successive U.S. virus epizootics. The data included virus isolates from different epizootic stages, geographical locations, host animals, and host lesion sites. In contrast, only distant genome RNA T1 fingerprint similarities were observed among viruses of the different U.S. epizootics. However, Mexican viruses isolated before or concurrent with U.S. epizootics had very similar RNA genome fingerprints, suggesting that Mexico may have been the possible origin of virus initiating recent U.S. VSV New Jersey outbreaks. Comparison of T1 fingerprints of viruses with enzootic disease areas revealed a greater extent of virus genetic diversity in these areas relative to that observed in epizootic areas. The evolutionary significance of these findings and their relationship to experimental data on VSV evolution are discussed.

Animals↗
PubMed1986

Hospital swing-bed care in the United States.

As a result of federal legislation implemented in 1982, hospital beds that are used to provide both long-term care and acute care are now proliferating rapidly throughout the country. Termed swing beds, such beds are currently restricted to rural areas. However, due largely to the impacts of Medicare DRG reimbursement, pressure is mounting to expand the swing-bed approach to urban settings. Swing beds appear to fill a significant gap between the relatively intense medical needs of post-acute care patients (now discharged earlier) and the capacity of our current nursing home delivery system to meet such needs. The evolution of swing beds is marked by an unusual blend of experimentation, scientific investigation, and public policy response to community and personal health care needs. This article summarizes that evolution, highlighting research findings and key policy developments. It concludes with the current status of the national swing-bed program and issues pertinent to future directions.

Bed Conversion↗
PubMed2003

Life-history evolution and the microevolution of intermediary metabolism: activities of lipid-metabolizing enzymes in life-history morphs of a wing-dimorphic cricket.

Although a considerable amount of information is available on the ecology, genetics, and physiology of life-history traits, much more limited data are available on the biochemical and genetic correlates of life-history variation within species. Specific activities of five enzymes of lipid biosynthesis and two enzymes of amino acid catabolism were compared among lines selected for flight-capable (LW[f]) versus flightless (SW) morphs of the cricket Gryllus firmus. These morphs, which exist in natural populations, differ genetically in ovarian growth (100-400% higher in SW) and aspects of flight capability including the size of wings and flight muscles, and the concentration of triglyceride flight fuel (40% greater in LW[f]). Consistently higher activity of each enzyme in LW(f) versus SW-selected lines, and strong co-segregation between morph and enzyme activity, demonstrated genetically based co-variance between wing morph and enzyme activity. Developmental profiles of enzyme activities strongly paralleled profiles of triglyceride accumulation during adulthood and previous measures of in vivo lipid biosynthesis. These data strongly imply that genetically based elevation in activities of lipogenic enzymes, and enzymes controlling the conversion of amino acids into lipids, is an important cause underlying the elevated accumulation of triglyceride in the LW(f) morph, a key biochemical component of the trade-off between elevated early fecundity and flight capability. Global changes in lipid and amino-acid metabolism appear to have resulted from microevolutionary alteration of regulators of metabolism. Finally, strong genotype x environment (diet) interactions were observed for most enzyme activities. Future progress in understanding the functional causes of life-history evolution requires a more detailed synthesis of the fields of life-history evolution and metabolic biochemistry. Wing polymorphism is a powerful experimental model in such integrative studies.

Adipose Tissue↗
PubMedDate not supplied

[Consideration of a priori information and type of an experimental error using the method of system identification based on the minimal quadratic discrepancy criterion].

The variants of the identification method were considered that take the a priori information about the evolution of a system under study and the type of experimental errors of the dynamic parameters of the system into account. An example of using this method for the identification of a biochemical reaction is given where the error in measuring the dynamic parameters (concentration of substances) has both an absolute and a relative components.

Algorithms↗