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PubMed1979

[Size and distribution of a Blattella germanica population].

The abundance and dispersion of a selected genetic homogeneous and isolated population of Blattella germanica was observed by the method of dry incorporation of radioactive porcellain tracer. Under optimal conditions, a medium density of 130 individuals per cubicmetre volume was found. The fluctuations came to 50% from the middle value. The dispersion is unequal and depends as well on the requisites of the room as on the size and the quality of the existing aggregations. An interchange exists between the aggregations. In this respect males are more active than female cockroaches.

Animals↗
PubMed1989

Quinidine blockade of calcium-activated potassium channels in dissociated gastric smooth muscle cells.

The effects of quinidine, an antiarrhythmic alkaloid, on potassium-selective channels in enzymatically dissociated gastric smooth muscle cells from Rana pipiens and Bufo marinus were investigated using excised patches and the patch-clamp technique. The predominant potassium channel in these cells is the calcium- and voltage-activated maxi-K channel with a single-channel conductance greater than 100 pS. Applications of quinidine (100-600 microM) resulted in resolvable rapid flickerings between the open and blocked states with a corresponding reduction in open channel amplitude and an increase in open channel noise. The current-voltage curves in the presence of internal quinidine and symmetrical potassium gradients displayed inward rectification. The time-constant of open-time distributions was found to decrease with increasing quinidine concentrations and membrane depolarization. The power-density spectrum of the channel current noise induced by internal quinidine showed a second Lorentzian component with a corner frequency larger than 300 Hz, suggesting that the noise is caused by rapid fluctuations between the open and blocked states. Apparent dissociation constants of 253 microM and 209 microM for membrane potentials of +20 mV and -60 mV, respectively, were obtained for the quinidine-induced blockade of Ca2+ -activated K+ channels in these smooth muscle cells. Another potassium-selective channel with a single-channel conductance of 40 pS was completely blocked in the presence of 100 microM quinidine. However, a 15 pS potassium channel was not affected by quinidine but was reversibly blocked by tetraethylammonium. Quinidine (500 microM) was also observed to decrease the opening probability of a 40 pS potassium channel from Bufo marinus without affecting its channel amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The population biology and evolutionary significance of Ty elements in Saccharomyces cerevisiae.

The basic structure and properties of Ty elements are considered with special reference to their role as agents of evolutionary change. Ty elements may generate genetic variation for fitness by their action as mutagens, as well as by providing regions of portable homology for recombination. The mutational spectra generated by Ty1 transposition events may, due to their target specificity and gene regulatory capabilities, possess a higher frequency of adaptively favorable mutations than spectra resulting from other types of mutational processes. Laboratory strains contain between 25-35 elements, and in both these and industrial strains the insertions appear quite stable. In contrast, a wide variation in Ty number is seen in wild isolates, with a lower average number/genome. Factors which may determine Ty copy number in populations include transposition rates (dependent on Ty copy number and mating type), and stabilization of Ty elements in the genome as well as selection for and against Ty insertions in the genome. Although the average effect of Ty transpositions are deleterious, populations initiated with a single clone containing a single Ty element steadily accumulated Ty elements over 1,000 generations. Direct evidence that Ty transposition events can be selectively favored is provided by experiments in which populations containing large amounts of variability for Ty1 copy number were maintained for approximately 100 generations in a homogeneous environment. At their termination, the frequency of clones containing 0 Ty elements had decreased to approximately 0.0, and the populations had became dominated by a small number of clones containing > 0 Ty elements. No such reduction in variability was observed in populations maintained in a structured environment, though changes in Ty number were observed. The implications of genetic (mating type and ploidy) changes and environmental fluctuations for the long-term persistence of Ty elements within the S. cerevisiae species group are discussed.

Biological Evolution↗
PubMed1996

The inheritance of phenotypes: an adaptation to fluctuating environments.

We discuss simple models for the evolution of rates of spontaneous and induced heritable phenotypic variations in a periodically fluctuating environment with a cycle length between two and 100 generations. For the simplest case, the optimal spontaneous transition rate between two states is approximately 1/n (where n is the cycle length). It is also shown that selection for the optimal transition rate under these conditions is surprisingly strong. When n is small, this means that the heritable variations are produced by non-classical inheritance systems, including non-DNA inheritance systems. Thus, it is predicted that in genes controlling adaptation to such environments, non-classical genetic effects are likely to be observed. We argue that the evolution of spontaneous and induced heritable transitions played an important role in the evolution of ontogenies of both unicellular and multicellular organisms. The existence of a machinery for producing induced heritable phenotypic variations introduces a "Lamarckian" factor into evolution.

Adaptation, Physiological↗
PubMed1994

Ionic channel activity induced by fusion of Rhodospirillum rubrum chromatophores with a planar bilayer lipid membrane.

The present work concerns mechanisms of ionic conductivity of photosynthetic membranes. It is shown that reconstitution of vesicles of photosynthetic membranes (chromatophores) of purple bacteria Rhodospirillum rubrum into a planar bilayer lipid membrane leads to fluctuations of current showing the existence of a channel with a predominant conductance of approximately 230 pS in the presence of 100 mM KCl. Measurements under the conditions of KCl gradient prove that this channel is cation selective (PK/PCl = 7.2). Voltage inactivation of the channel is demonstrated which is prevented by treatment with trypsin.

Bacterial Chromatophores↗
PubMed1986

The origin of adaptation and dyssymmetry in the evolution of autocatalytic systems.

The evolution of open systems that include several autocatalytic processes in parallel or in series is mathematically analyzed. For the case of two reactions in parallel, such systems progressively and finally select the reaction pathway which involves the better autocatalyst. The effect of parameters influencing the rate of this evolution is discussed. Where catalysts are strictly equivalent, e.g. enantiomers in a symmetrical surrounding, the evolution is amplified by fluctuations and retains finally only one reaction pathway, if the autocatalytic rates of reactions are more than proportional to the catalyst concentrations. When including two reactions in series, these open systems are also able to give oscillations.

Catalysis↗
PubMed2006

Molecular dynamics simulations of a cyclic-beta-(1-->2) glucan containing an alpha-(1-->6) linkage as a 'molecular alleviator' for the macrocyclic conformational strain.

The conformational preferences of a cyclic osmoregulated periplasmic glucan of Ralstonia solanacearum (OPGR), which is composed of 13 glucose units and linked entirely via beta-(1-->2) linkages excluding one alpha-(1-->6) linkage, were characterized by molecular dynamics simulations. Of the three force fields modified for carbohydrates that were applied to select a suitable one for the cyclic glucan, the carbohydrate solution force field (CSFF) was found to most accurately simulate the cyclic molecule. To determine the conformational characteristics of OPGR, we investigated the glycosidic dihedral angle distribution, fluctuation, and the potential energy of the glucan and constructed hypothetical cyclic (CYS13) and linear (LINEAR) glucans. All beta-(1-->2)-glycosidic linkages of OPGR adopted stable conformations, and the dihedral angles fluctuated in this energy region with some flexibility. However, despite the inherent flexibility of the alpha-(1-->6) linkage, the dihedral angles have no transition and are more rigid than that in a linear glucan. CYS13, which consists of only beta-(1-->2) linkages, is somewhat less flexible than other glycans, and one of its linkages adopts a higher energy conformation. In addition, the root-mean-square fluctuation of this linkage is lower than that of other linkages. Furthermore, the potential energy of glucans increases in the order of LINEAR, OPGR, and CYS13. These results provide evidence of the existence of conformational constraints in the cyclic glucan. The alpha-(1-->6)-glycosidic linkage can relieve this constraint more efficiently than the beta-(1-->2) linkage. The conformation of OPGR can reconcile the tendency for individual glycosidic bonds to adopt energetically favorable conformations with the requirement for closure of the macrocyclic ring by losing the inherent flexibility of the alpha-(1-->6)-glycosidic linkage.

Carbohydrate Conformation↗
PubMed2006

Metabolic compensation and behavioral thermoregulation of subtropical rhacophorid (Polypedates megacephalus) tadpoles in container habitats.

We examined the relative importance of behavioral thermoregulation and metabolic compensation used by a subtropical rhacophorid (Polypedates megacephalus) tadpoles living in man-made container habitats to cope with thermal stress. We collected foam nests of P. megacephalus from man-made container habitats, and hatchlings were raised in 150 or 15 L of water (LWB and SWB containers, respectively). Water and air temperatures of containers were monitored using a datalogger. Tadpoles from both types of containers were acclimated at 22 and 32 degrees C for 10 d before measuring oxygen consumption (V(O2)) in a closed-system at 22, 27, and 32 degrees C. Thermal selection of tadpoles from two containers was determined using an aquatic thermal gradient. We observed daily stratification of temperature in the water column of LWB containers but not SWB containers. Tadpoles from LWB and SWB containers exhibited metabolic compensation so that tadpoles acclimated to 22 degrees C had significantly higher V(O2) than those acclimated to 32 degrees C. This was probably related to the variation of environmental temperature experienced by the tadpoles. Tadpoles of LWB and SWB containers selected similar water temperatures with low coefficient of variation, suggesting they are good thermal selectors. Results of this study suggest that P. megacephalus tadpoles use both behavioral thermoregulation and metabolic compensation to cope with the environmental temperature fluctuation, and this is, in part, due to the heterogeneity in the thermal regimes of breeding habitats. Even though metabolic compensation of tadpoles incurs a cost, P. megacephalus tadpoles that experience no daily thermal gradient in the man-made water bodies and/or seasonal variations in temperature over tadpole period evolve metabolic compensation to maintain physiological homeostasis under different thermal regimes.

Acclimatization↗
PubMed2005

Nitrogen isotope ratios in estuarine biota collected along a nutrient gradient in Narragansett Bay, Rhode Island, USA.

Stable nitrogen isotope ratios were used to study the incorporation of anthropogenically-derived nitrogen into the food webs of salt marsh systems along a contamination gradient in Narragansett Bay. Nitrogen isotope ratios (delta(15)N) were measured in six estuarine species collected from three marshes along this gradient, monthly from June to October between 1997 and 1999. A significant decrease in delta(15)N was found with distance along the estuary for four of the six species. Significant differences were found among monthly isotope ratios for some species. Nitrogen isotope ratios in sea lettuce (Ulva lactuca) increased during the summer season with highest delta(15)N values measured during September and October. This trend was most pronounced at the station receiving the highest nutrient inputs. Elevated delta(15)N values at this station appeared to correlate with seawater ammonia/nitrate concentration ratios. The temporal variations in delta(15)N suggest that care should be taken in species selection and the design of sampling schemes of studies using delta(15)N for monitoring anthropogenic nutrients in aquatic systems. Sampling programs designed to determine long-term trends should consider species that do not show rapid fluctuations in isotope ratios. The mud snail, Nassarius obsoletus, responded this way in the present study. Studies designed to measure short-term changes should include species such as U. lactuca, which rapidly respond to isotope changes. The results from this study also help to establish a baseline for nitrogen isotope values in Narragansett Bay. This information can be used to monitor future trends in nitrogen inputs to this estuary.

Animals↗
PubMed2006

Deciphering the ancient and complex evolutionary history of human arylamine N-acetyltransferase genes.

The human N-acetyltransferase genes NAT1 and NAT2 encode two phase-II enzymes that metabolize various drugs and carcinogens. Functional variability at these genes has been associated with adverse drug reactions and cancer susceptibility. Mutations in NAT2 leading to the so-called slow-acetylation phenotype reach high frequencies worldwide, which questions the significance of altered acetylation in human adaptation. To investigate the role of population history and natural selection in shaping NATs variation, we characterized genetic diversity through the resequencing and genotyping of NAT1, NAT2, and the pseudogene NATP in a collection of 13 different populations with distinct ethnic backgrounds and demographic pasts. This combined study design allowed us to define a detailed map of linkage disequilibrium of the NATs region as well as to perform a number of sequence-based neutrality tests and the long-range haplotype (LRH) test. Our data revealed distinctive patterns of variability for the two genes: the reduced diversity observed at NAT1 is consistent with the action of purifying selection, whereas NAT2 functional variation contributes to high levels of diversity. In addition, the LRH test identified a particular NAT2 haplotype (NAT2*5B) under recent positive selection in western/central Eurasians. This haplotype harbors the mutation 341T-->C and encodes the "slowest-acetylator" NAT2 enzyme, suggesting a general selective advantage for the slow-acetylator phenotype. Interestingly, the NAT2*5B haplotype, which seems to have conferred a selective advantage during the past approximately 6,500 years, exhibits today the strongest association with susceptibility to bladder cancer and adverse drug reactions. On the whole, the patterns observed for NAT2 well illustrate how geographically and temporally fluctuating xenobiotic environments may have influenced not only our genome variability but also our present-day susceptibility to disease.

Acetylation↗
PubMed2002

Molecular diagnosis of viral infections in renal transplant recipients.

PURPOSE OF REVIEW: To discuss biological and methodological aspects of virus infection monitoring in the renal transplant setting. RECENT FINDINGS: New insights on the molecular pathogenesis of acute and persistent virus infections and rapid developments in real-time monitoring techniques are changing the current diagnostic routine. Accurate risk-assessment prior to transplantation and quantitative monitoring of parameters that reflect virus activity in the post-transplant period, including genome load fluctuations and aberrant viral mRNA or protein expression, provide early signs of undesired viral behaviour and allow pre-emptive therapeutic intervention. As opposed to prophylactic administration of antiviral drugs, a pre-emptive approach is more selective and will allow for antiviral immune responses to build, which may have a long-term beneficial effect. In addition, these virus-monitoring techniques allow for on-line assessment of therapeutic efficacy and rapid identification of emerging resistant strains. The combination of virus-monitoring techniques with rapid assessment of host immune responses using FACS and ELISPOT techniques, will improve overall patient management and long-term survival. SUMMARY: Viral infections continue to be a significant complication in the transplant setting. Diagnostic monitoring allows timely and accurate therapeutic intervention. Knowledge of pathogenic mechanisms leading to disease is important for clinical decision making as well as for the selection of appropriate molecular parameters discriminating normal and disease-related activity of human pathogenic viruses. The increasing availability of effective antiviral drugs permits pre-emptive intervention that strongly depends on accurate viral monitoring procedures.

DNA, Viral↗
PubMed1983

A new channel-forming antibiotic from Streptomyces coelicolor A3(2) which requires calcium for its activity.

A recently discovered antibiotic (CDA; calcium-dependent antibiotic) of Streptomyces coelicolor A3(2) was found to be effective against a wide range of Gram-positive bacteria only in the presence of calcium ions. Producer and non-producer strains were identified and several media tested for their ability to support antibiotic production. The action of calcium was not simulated by any of the other cations tested. The antibiotic was found to induce discrete conductance fluctuations in planar lipid bilayer consistent with a channel-forming action. The electrical potential difference caused by a concentration difference of various salts across the CDA-containing bilayer, showed the channel to be cation-selective but of a size that discriminated against tetramethyl ammonium and choline ions. The data indicate that the antibiotic activity of CDA is due to its action as a calcium-dependent ionophore.

Anti-Bacterial Agents↗
PubMed1990

Scoring criteria for response latency and habituation in electrodermal research: a study in the context of the orienting response.

Levinson and Edelberg's (1985) recent critique of scoring criteria for electrodermal studies pointed to the need to reduce the latency range used to define the electrodermal response. The present study examined the impact of such a narrowing of the latency window upon habituation and instructional effects in studies of the orienting response to low intensity innocuous stimuli. The first experiment found only a small effect of halving the latency window upon habituation to neutral stimuli, apparent as a strengthening of trends over trials. A second experiment showed somewhat larger effects with significant stimuli, apparent as slightly modified trial and group effects. These data support the view that nothing is to be lost by moving to a narrower latency range to define the electrodermal orienting response to stimulus presentation, and suggest that the advantages of such a change will become increasingly important as nonspecific electrodermal fluctuations increase with increasing electrodermal arousal. An analysis of habituation criteria within this context suggested that the choice of two rather than three no-response trials to define habituation adds to the benefits obtained by the selection of a narrow latency window to define the response.

Adult↗
PubMed2004

ECLAMC: the Latin-American collaborative study of congenital malformations.

DEFINITION: ECLAMC ('Estudio Colaborativo Latino Americano de Malformaciones Congenitas') is a program for the clinical and epidemiological investigation of risk factors in the etiology of congenital anomalies in Latin-American hospitals, using a case-control methodological approach. It is a voluntary agreement among professionals lacking institutional base as well as designated budgets. ECLAMC has been usually funded by research-funding agencies rather than public health ministries. The National Research Councils of Argentina and Brazil have been the main sources of support during its 36 years of existence. Since vital and health statistics are unreliable in South America, ECLAMC collects all the information required for the denominators in a hospital-based sample of births. ECLAMC can be defined as a continental network of persons interested in research and prevention of birth defects. HISTORY AND EVOLUTION: From the institutional point of view, ECLAMC has had headquarters in diverse centers of Argentina and Brazil, but always as an independent research project, without a defined administrative link. ECLAMC began operating in 1967, as an investigation limited to the city of Buenos Aires, Argentina, and it gradually expanded until covering all the 10 countries of South America as well as Costa Rica and the Dominican Republic. Even though ECLAMC has maintained essentially the same original experimental design since 1967, due to the data accumulated by the program, the increasing experience as well as the development in science, technical modifications occurred including a DNA bank and a fully informatized data handling system. Since 1974 ECLAMC has been a founder member of the International Clearinghouse for Birth Defects Monitoring Systems; since 1994 a WHO Collaborating Center for the Prevention of Congenital Malformations, and since 2000 a collaborating member of the NIH Global Netwok for Women's and Children's Health Research. METHODOLOGY: The maternity hospital network of ECLAMC examines around 200,000 births per year. All major and minor anomalies diagnosed at birth in infants weighing 500 g or more are registered according to a manual of procedures. The next non-malformed baby of the same sex born in the same hospital is selected as a control subject for each case. Thus, a one-to-one healthy control group matched by sex, time and place of birth is obtained. As a system of epidemic surveillance, ECLAMC systematically observes the fluctuations in the frequencies of different malformations and, in the case of an alarm for a probable epidemic of a given malformation, at a given moment, and given area, it acts to identify its cause. As termination of pregnancy has severe legal restrictions in South America, prevention of birth defects should concentrate on primary, preconceptional and tertiary measures. Tertiary measures aim to avoid complications of the affected patients from the medical, psychological, and social standpoints.

Biomedical Research↗
PubMed2001

[Qualitative and quantitative detection of hepatitis C virus RNA by PCR technique. Monitoring of viral copies after liver transplantation].

The authors demonstrate the HCV nucleic acid amplification method is not wide-spread in Hungary yet. The HCV-RNA is usually detectable 2-4 weeks after infection independently the immunostate of the patients. The authors help to select the adequate measurement(s) in logical order when HCV infection is suspected. The benefit of the PCR method is emphasized. Monitoring of the HCV-RNA titer of the liver transplanted patients promotes to establish the fluctuation of HCV-RNA copies and the effectivity of therapy following transplantation. The detection of HCV-RNA by PCR method is a proof of an acute or chronic infection and rules out past infection. The quantitative PCR measurement is useful for determination of indication and control of efficacy of antiviral therapy.

Adult↗
PubMed2001

Perceptually bistable three-dimensional figures evoke high choice probabilities in cortical area MT.

The role of the primate middle temporal area (MT) in depth perception was examined by considering the trial-to-trial correlations between neuronal activity and reported depth sensations. A set of moving random dots portrayed a cylinder rotating about its principal axis. In this structure-from-motion stimulus, the direction of rotation is ambiguous and the resulting percept undergoes spontaneous fluctuations. The stimulus can be rendered unambiguous by the addition of binocular disparities. We trained monkeys to report the direction of rotation in a set of these stimuli, one of which had zero disparity. Many disparity-selective neurons in area MT are selective for the direction of rotation defined by disparity. Across repeated presentations of the ambiguous (zero-disparity) stimulus, there was a correlation between neuronal firing and the reported direction of rotation, as found by Bradley et al. (1998). Quantification of this effect using choice probabilities (Britten et al., 1996) allowed us to demonstrate that the correlation cannot be explained by eye movements, behavioral biases, or attention to spatial location. MT neurons therefore appear to be involved in the perceptual decision process. The mean choice probability (0.67) was substantially larger than that reported for MT neurons in a direction discrimination task (Britten et al., 1996). This implies that MT neurons make a different contribution to the two tasks. For the depth task, either the pool of neurons used is smaller or the correlation between neurons in the pool is larger.

Action Potentials↗
PubMed2003

Deep brain stimulation for Parkinson's disease.

Dopaminergic replacement therapy with levodopa/carbidopa is still the cornerstone for the treatment of Parkinson's disease (PD). However, the medical management of PD is complicated by the appearance of disabling motor response fluctuations, levodopa-induced dyskinesias and psychosis. Since the early 1990s, surgical therapies have made a rapid reentry into the therapeutic armamentarium for PD and deep brain stimulation (DBS) of the globus pallidus interna or subthalamic nuclei is currently the most promising of such interventions. Recognition of the physiological changes in basal ganglia circuits in animal models of PD has provided the much-needed theoretic basis for targeting these areas. DBS of these areas has proven to be a safe procedure and effective against all the major motor symptoms of PD. Though not curative it can substantially reduce motor response fluctuations, levodopa-induced dyskinesias, and improve the quality of life of these patients. DBS is an expensive treatment and hardware-related complications are not rare. The results of the procedure are dependent on careful patient selection and the experience of the performing team. An update on the principles, methods and results of such procedures is essential to raise the awareness of this new therapeutic modality and to provide guidelines to the referring physicians.

Electric Stimulation Therapy↗
PubMed1987

R-(-)-deprenyl in the treatment of end-of-dose akinesia.

In two trials, we have studied the effectiveness and tolerability of L-deprenyl, a selective MAO B inhibitor, in the treatment of end of dose akinesia in patients with Parkinson's disease. The first trial was designed as an open controlled trial. In the L-deprenyl phase, an improvement in fluctuations in motor function as well as an overall reduction in the sum score of Webster's rating scale from 12.5 to 8.9 was observed, which almost returned to baseline during the placebo phase. The second trial was designed as a randomized trial comparing L-deprenyl therapy with a low-dose bromocriptine regimen. Both therapeutic approaches yielded the same results with respect to fluctuations; the CURS sum score dropped from 37 to 26. As regards tolerability, however, L-deprenyl was superior to bromocriptine.

Aged↗