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Short-term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment.

Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts.

Adult

Isotype, distribution and target analysis of lymphocyte reactive antibodies in patients with human immunodeficiency virus infection.

Anti-lymphocyte (ALA) antibodies were investigated by using both microcytotoxicity and immunofluorescence analyses in 87 subjects with different clinical features of human immunodeficiency virus (HIV) infection. A similar mean percentage of killing in microcytotoxicity assays using heterologous lymphocytes as cellular target was recorded in four groups of patients, including 36 HIV-seropositive asymptomatic subjects, 34 patients with HIV-induced lymphadenopathy syndrome (LAS), 13 with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and 4 patients with the full-blown AIDS. Conversely, an increasing percentage of ALA-positive subjects paralleled the evolution of the HIV infection. The majority of ALA were IgM isotype with a significant reactivity against T cells. This specificity was indifferently directed to CD3+, CD4+, and CD8+ lymphocytes. In additional experiments employing enzymatic digestion of lymphocyte membrane antigens, we demonstrated that CD4 and CD8 receptors were digested by the pronase, whereas CD3 molecules were highly resistant. Subsequent flow cytometry analyses using these pronase-digested T cells showed that reactivity of ALA for their target was unchanged. Our data suggest that antigenic specificities of ALA in HIV infection are resistant to pronase treatment and are not related to CD4 and CD8 molecules.

Antigens, Differentiation, T-Lymphocyte

Effects of disulfiram on the amphetamine-induced behavioral syndrome in the cat as a model of psychosis.

We have previously reported that, from a phenomenological standpoint, the behavioral manifestations of cats chronically intoxicated with amphetamine parallel the evolution of the paranoid psychosis induced by the drug in humans. However, certain manifestations in the cat, such as frozen postures, disjunctive behaviors and postures, cataleptic-like phenomena, obstinate progression, loss of righting reflex and pupillary changes, did not appear to be consistent with the phenomenology of the paranoid psychosis. Since treatment of schizophrenic patients with disulfiram, an inhibitor of norepinephrine synthesis that acts at the level of the enzyme dopamine beta-hydroxylase, thereby leading to increased dopamine concentrations, had been found to profoundly exaggerate psychotic symptomatology, amphetamine behavioral syndrome in the cat as it is modified by pretreatment with disulfiram. Following such pretreatment, a faster development of certain end-stage components of the amphetamine syndrome was obtained. Thus, on the first day, development of a Reactive attitude and of more prominent behavioral disjunction occurred with the combined drug administration as compared with amphetamine alone. In contrast with the facilitation of these behaviors was the absence of dyskinesias and hyperreflexia on that day. Stereotyped behavior, loss of motor initiative and hyperkinetic activity were markedly enhanced and appeared with a shorter latency period on subsequent days of the intoxication cycle. Loss of righting reflex was an early manifestation in these animals. During the later days, the particularly high level of compulsive activity was evident from the occurrence of an obstinate progression syndrome and the performance of stereotyped movements of the head in the presence of a crucifixion posture. In general, modification of the amphetamine effects on behavior was in a direction consistent with comparable features in experimental catatonia and the catatonic form of schizophrenia. The need to integrate such phenomena in any amphetamine model of psychosis is stressed and analogies are drawn with similar features reported in animals treated with bulbocapnine or other psychotogenic compounds and with symptoms of human amphetamine psychosis and schizophrenia.

Animals

Complete congruence between morphological and rbcL-based molecular phylogenies in birches and related species (Betulaceae).

Estimations of phylogenies from morphological and molecular data often show contrasting results. We compared morphological and molecular phylogenies in an ancient family of woody dicots, the Betulaceae (birch family). The phylogeny of the family was estimated from parsimony analysis of morphological characters in the genera Alnus, Betula, Carpinus, Corylus, Ostrya, and Ostryopsis and from parsimony and distance-matrix analyses of DNA sequences of the chloroplast gene encoding the large subunit of ribulose-1,5-biphosphate carboxylase (rbcL) in the genera Alnus, Betula, Carpinus, Corylus, and Ostrya and in two outgroups, Quercus and Liquidambar. The topologies obtained by the different methods were completely congruent, and bootstrapping strongly supported the division of the family Betulaceae into two major clades, Betuleae (Alnus and Betula) and Coryleae (other members). Only slightly more homoplasy was present in the rbcL sequence data set than in the morphological set. Relative-rate tests indicated that the Coryleae clade had a faster rate of rbcL evolution than did the Betuleae clade. Heterogeneity of rates of morphological evolution also paralleled those for rbcL.

Base Sequence

Professionalizing domesticity: a synthesis of selected nursing historiography.

The 19th century consolidation of the ideology of domesticity and the ideology of professionalism paralleled the evolution of nursing as a formal occupation for women. Efforts to combine these ideologies, which are based on markedly different foundational assumptions, have been central to the history of American nursing. A meaningful understanding of nursing's history necessitates a synthesis of the interpretations generated by individual historians who have studied similar events in nursing's past. Three feminist historians have studied the professionalizing process in nursing. Generated from diverse perspectives and source materials, the work of these historians illuminates the tensions resulting from nursing's efforts to blend the ideologies of domesticity and professionalism and provides insight into the lessons that can be learned from history.

Female

Parallel genetic adaptation amid a background of changing effective population sizes in divergent yellow perch (Perca flavescens) populations.

Aquatic ecosystems are highly dynamic environments vulnerable to natural and anthropogenic disturbances. High-economic-value fisheries are one of many ecosystem services affected by these disturbances, and it is critical to accurately characterize the genetic diversity and effective population sizes of valuable fish stocks through time. We used genome-wide data to reconstruct the demographic histories of economically important yellow perch (Perca flavescens) populations. In two isolated and genetically divergent populations, we provide independent evidence for simultaneous increases in effective population sizes over both historic and contemporary time scales including negative genome-wide estimates of Tajima's D, 3.1 times more single nucleotide polymorphisms than adjacent populations, and contemporary effective population sizes that have increased 10- and 47-fold from their minimum, respectively. The excess of segregating sites and negative Tajima's D values probably arose from mutations accompanying historic population expansions with insufficient time for purifying selection, whereas linkage disequilibrium-based estimates of Ne also suggest contemporary increases that may have been driven by reduced fishing pressure or environmental remediation. We also identified parallel, genetic adaptation to reduced visual clarity in the same two habitats. These results suggest that the synchrony of key ecological and evolutionary processes can drive parallel demographic and evolutionary trajectories across independent populations.

Animals

Neurobiorheology. A new branch of biorheology. Historical background and current ideas.

The application of principles of biorheology, hemorheology and perihemorheology on problems of the nervous system in health and disease was suggested by Alfred L. Copley (1982, 1987). Late in 1988 Copley and Sourander considered neurobiorheology to be an appropriate term for a new branch of biorheology bridging the gap between biorheology and neurobiology. Neurobiorheology can be defined as a research field concerned with deformation behaviour of matter including flow and transportation in context with the structure and function of the nervous system at macroscopic, cellular, subcellular and molecular levels. It may be considered a basic life science with important clinical applications. Its "raison d'être" should be to apply various ways of thinking, calculations and techniques used in biorheology to treat and if possible to solve neurobiological problems. Many regionally different chemical, structural and functional properties characterize the developing and adult nervous system and those parts of the circulatory system ("vessel-blood organ") which penetrate the nervous system at all levels. Considering the close metabolic and functional relations between neurons and surrounding non-neuronal ectodermal cells, neuroglial and Schwann cells deriving from common precursor cells in the wall of the neural tube and neural crest respectively, the term neuroectodermal organ appears suitable. The almost parallel ontogenetic evolution of vessel-blood organ and neuroectodermal organ and their interaction during the entire individual life cycle constitutes a challenging stimulus for integrated research. The main purpose of this review is to give some examples of importance concerning still insufficiently elucidated neurobiological problems suitable for biorheological approaches. Particular attention will be paid to the microenvironment at central and peripheral levels of the neuroectodermal organ.

Animals

Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.

Administration, Intranasal

Failla Memorial Lecture. From beans to genes--back to the future.

Developments in radiation biology have inevitably paralleled the evolution of systems and end points in the wider field of biology. I review the development of three areas that have interested me during the 35 years that I have been involved with radiation research. (1) The dose-rate effect. My first graduate student, Joel Bedford, and I demonstrated the dependence of mammalian cell killing on the dose rate at which gamma rays are delivered. These studies led to the recent development of pulsed low-dose-rate brachytherapy and the design of a new machine for clinical use. (2) Hypoxic radiosensitizers and bioreductive drugs. The hypothesis that the presence of foci of hypoxic cells in human tumors could limit their curability by gamma rays led to the development of nitromidazales that preferentially sensitize hypoxic cells. Our contributions included the observation that misonidazole was also cytotoxic to hypoxic cells, that sensitization was increased by prolonged preincubation, and that the mechanism involved depletion of thiols. More recently we have collaborated with Ged Adams and Bob Sutherland in the development of a new generation of hypoxic cell cytotoxins. In particular, we have been concerned with the assessment of oncogenicity in relation to drug structure. (3) Oncogenic transformation in vitro. The use of in vitro assays for oncogenic transformation has represented a major interest for this laboratory largely due to collaborations first with Carmia Borek, and more recently with Richard Miller and Tom Hei. We published the first dose-response curves for gamma rays, and more recently for a range of neutron energies and for charged particles of defined LET. Radiation-induced oncogenic transformation in C3H 10T1/2 cells has been shown to be due to a dominant acting transforming gene, which has been isolated and is in the process of being characterized and sequenced by Greg Freyer.

Animals

Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema.

The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema.

Animals

[Metabolic effects of exposure to air and the post-aeration response in the intertidal anthozoan Actinia equina L].

Metabolic adjustments occurring during air exposure have been studied in a population of Actinia equina submitted to long-lasting emersion periods. Oxygen consumption upon reimmersion seems to account for the discharge of an oxygen debt related to the accumulation of end-products derived from anaerobic pathways. Incorporation of radioactive labelled glucose into both submerged and air exposed animals has allowed identification of these final products. A correspondence between the length of exposure-time and the amount of oxygen debt is encountered, which parallels the evolution of the rate of radioactivity incorporation into amino acids. Increasing levels of amino acid synthesis from glucose in the exposed conditions appear as the main metabolic feature.

Adaptation, Physiological

[Microdissection study of the kidneys of reptiles living under different ecologic conditions].

Microdissectional studies on the kidneys of 24 reptilian species living in different habitats show that the relative length of the distal tubuli is higher in animals adapted to a limited water supply and to fresh-water basins, as compared to animals which have unlimited access to water. No regular changes in the length of proximal, intermediate and connective parts were observed. The increase in the length of the distal tubuli occurs simultaneously among different taxonomic groups of reptiles, indicating the existence of parallelism in evolution of their kidneys.

Adaptation, Physiological

Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.

Tumor evolution is driven by various mutational processes, ranging from single-nucleotide variants (SNVs) to large structural variants (SVs) to dynamic shifts in DNA methylation. Current short-read sequencing methods struggle to accurately capture the full spectrum of these genomic and epigenomic alterations due to inherent technical limitations. To overcome that, here we introduce an approach for long-read sequencing of single-cell derived subclones, and use it to profile 23 subclones of a mouse melanoma cell line, characterized with distinct growth phenotypes and treatment responses. We develop a computational framework for harmonization and joint analysis of different variant types in the evolutionary context. Uniquely, our framework enables detection of recurrent amplifications of putative driver genes, generated by independent SVs across different lineages, suggesting parallel evolution. In addition, our approach revealed gradual and lineage-specific methylation changes associated with aggressive clonal phenotypes. We also show our set of phylogeny-constrained variant calls along with openly released sequencing data can be a valuable resource for the development of new computational methods.

Journal Article

Reproductive Isolation due to Divergent Ecological Selection Is Accompanied by Vast Genomic Instability in Experimentally Evolved Yeast Populations.

Populations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1 and F2 intraspecific hybrids. We found evidence for large-scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability-a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations, on the other hand, remained more reproductively compatible (with exceptions). We found that F2 hybrid genomes contained vast genomic instability, that is, new structural variants (especially insertions, deletions and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.

Reproductive Isolation

[Aging and atherosclerosis of human aorta. Comparative evolution of seven glycosyl-transferases and of lactate-dehydrogenase (author's transl)].

Seven glycosyl-transferases and the lactico-dehydrogenase from human aortas were assayed. These aortas were divided in five classes according to the age and in five steps according to the atherogenesis. These enzymic activities do not show any parallelism in their evolution; their variation with age and with atherogenesis is quite different. For example, the N-acetylgalactosaminyl-transferase activity increases with atherogenesis whereas it diminishes with age; on the other hand the lactate-dehydrogenase activity increases with age and decreases with atherogenesis; the sialyl-transferase activity is nearly constant during adulthood while it hardly declines with atherogenesis. These assays suggest: 1) an effect of energy metabolism on the glycosyl-transferase activities; 2) a qualitative and quantitative variation of the glycosaminoglycans biosynthesis; 3) a structural modification of the glucidic part of the glycoproteins which can induce the formation of antigenic sites.

Adolescent

Global lessons from antibiotic resistance: Metformin-hydrolysing genes in transposable elements, a new threat for type II diabetic patients?

OBJECTIVES: To investigate the evolutionary origin, genomic mobility, and potential dissemination of metformin-hydrolysing genes (mfmAB), and to assess whether environmental selection by metformin pollution may drive the emergence of transferable pharmaceutical-degrading traits analogous to antibiotic resistance. METHODS: Large-scale comparative genomics was performed using publicly available bacterial genomes carrying mfmAB homologs. Phylogenomic reconstruction, average nucleotide identity analysis, genomic context comparison, plasmid characterization, and insertion sequence mapping were used to infer evolutionary history and identify mechanisms of horizontal gene transfer. RESULTS: mfmAB homologs were identified in twelve Aminobacter and three Pseudomonas genomes within a conserved ∼8.2 kb gene cluster. Phylogenomic analyses showed that metformin-degrading capacity emerged independently in multiple Aminobacter lineages across distinct continents, consistent with convergent evolution under anthropogenic selective pressure. Genomic comparisons indicated a chromosomal origin of mfmAB, followed by mobilization onto conjugative plasmids through IS1182-mediated transposition. In Pseudomonas, additional IS3/IS6-mediated transposition events integrated mfmAB into diverse plasmid backbones, frequently within composite transposons also encoding guanylurea and biguanide degradation pathways (guuH, bguH). These findings reveal a dynamic modular assembly of metabolic functions facilitating adaptation to pharmaceutical pollutants. CONCLUSIONS: Metformin pollution appears to promote the emergence and mobilization of pharmaceutical-degrading genes through mechanisms paralleling antibiotic resistance evolution. Although no clinical impact has yet been demonstrated, the potential spread of such genes into human-associated microbiomes and their possible co-selection with antibiotic resistance determinants represent an emerging One Health concern. Environmental surveillance of pharmaceutical-degrading genes is warranted to anticipate future threats to drug efficacy.

Convergent evolution

The evolution of complex sensory systems in mammals.

Much of the forebrain of many extant species of mammals appears to be sensory-perceptual in nature. Thus, much of the forebrain, especially the dorsal thalamus and neocortex, consists of nuclei and areas that are parts of complex systems that analyze sensory information and allow behavior to be guided by accurate inferences about the external world. Since mammals vary tremendously in brain size, they vary in the amount of tissue devoted to sensory processing. In addition, mammals vary in the sizes and numbers of processing nuclei and areas, and in how neurons and neuron groups (modules) are differentiated within such structures. Sensory-perceptual systems with more, larger and more differentiated parts may allow more stimulus parameters to be considered, experience to play a greater role, and speed calculations through increased parallel processing. The evolution of species differences in brain size, the sizes of individual parts, and internal structure of these parts are potentially understandable within a theoretical framework of gradual modifications of developmental processes. In addition to changes in the generation and specialization of neurons, alterations in the developmental timing that modify internal and external influences on neuron activity patterns seem to have a major role in the construction and maintenance of organization in the nervous system. Because similar selection pressures may arise over and over again and the mechanisms for producing changes may be few, similar changes in the nervous system are likely to occur in independent lines of evolution. It is uncertain how new cortical areas and nuclei evolve. Comparative studies suggest that: (1) all mammals have a few basic sensory areas and nuclei in common, (2) the number of areas and nuclei has increased independently in several lines of mammalian evolution, and (3) new areas have been added to the middle levels of cortical processing sequences. New areas and nuclei may have evolved as a result of sudden duplications and/or by the process of single areas or nuclei gradually differentiating into two or more areas or nuclei. The process of gradual differentiation may have involved the initial step of differentiating functionally distinct classes of cells that are mixed in a representation, followed by the local groupings of such cells into functionally distinct sets, and finally the fusion of cell groups of the same types to form separate representations.

Afferent Pathways

[Left ventricular mechanics in Chagas' disease and primary dilated myocardiopathies. A hemodynamic study].

The evolution of several mechanical parameters of left ventricular function was studied in 32 control subjects, 171 chronic chagasic and 60 primary dilated cardiomyopathy patients, which were submitted to an extensive invasive and non-invasive protocol. Preload and afterload (end-diastolic and end-systolic stress), contractile status (ejection fraction), the magnitude (mass/index) and adequacy of hypertrophy (mass/volume ratio) and afterload (systolic stress/volume ratio) were derived from the invasive explorations. There was an increased afterload in 25% of chronic chagasic patients without other evidence of early myocardial damage, which was accompanied by signs of inadequate hypertrophy. Both findings increased further with the progression of the disease. Systolic performance was initially preserved, but showed a progressive depression paralleling the clinical evolution. Patients with dilated cardiomyopathy showed a mechanical profile similar to chagasic patients with advanced degree of myocardial damage. The hemodynamic determination of mass index, mass/volume ratio, end-systolic and end-diastolic stress seem to be the best parameters for detection of early abnormalities in loading conditions of the heart in chronic Chagas, disease, and for indication and evaluation of the results of vasodilator therapy in both groups of patients.

Adult