Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Fluctuating selection”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,099 records · Page 61Linked to original sources
PubMed1995

Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line.

Somatic mutation of the variable (V) regions of immunoglobulin genes occurs in vivo at rates that have been estimated to be between 10(-3) and 10(-4) per bp per generation. To study this process in vitro, the 18.81 pre-B-cell line and hybrids derived by fusing 18.81 to the NSO myeloma fusion partner were transfected with a mu heavy-chain construct containing a nonsense mutation in the V region (Vn) or the constant region (Cn). Mutation was quantitated by reversion analysis using the ELISA spot assay to detect single cells secreting IgM. Fluctuation analysis revealed that V-region mutations spontaneously occurred in 18.81 cells at an average rate of 5.8 x 10(-6) per bp per cell generation and in selected 18.81-NSO hybrids at greatly increased rates of 1.6 x 10(-3) to 5.8 x 10(-4) per bp per generation. The Vn construct also reverted frequently in transgenic mice, indicating that it contained sufficient information to mutate at high rates both in vivo and in vitro. Sequence analysis of reverted genes revealed that reversion was due to point mutations. Since the rates and nature of the mutations that are occurring in these transfected genes are similar to those reported in vivo, it should be possible to use this system to identify the cis-acting sequences and trans-acting factors that are responsible for V-region somatic hypermutation.

Amino Acid Sequence↗
PubMed1995

The expression of additive and nonadditive genetic variation under stress.

Experimental lines of Drosophila melanogaster derived from a natural population, which had been isolated in the laboratory for approximately 70 generations, were crossed to determine if the expression of additive, dominance and epistatic genetic variation in development time and viability was associated with the environment. No association was found between the level of additive genetic effects and environmental value for either trait, but nonadditive genetic effects increased at both extremes of the environmental range for development time. The expression of high levels of dominance and epistatic genetic variation at environmental extremes may be a general expectation for some traits. The disruption of the epistatic gene complexes in the parental lines resulted in hybrid breakdown toward faster development and there was some indication of hybrid breakdown toward higher viability. A combination of genetic drift and natural selection had therefore resulted in different epistatic gene complexes being selected after approximately 70 generations from a common genetic base. After crossing, the hybrid populations were observed for 10 generations. Epistasis contributed on average 12 hr in development time. Fluctuating asymmetry in sternopleural bristle number also evolved in the hybrid populations, decreasing by > 18% in the first seven generations after hybridization.

Animals↗
PubMed1979

The amino acid sequence of mouse pancreatic ribonuclease. Extremely rapid evolutionary rates of the myomorph rodent ribonucleases.

The complete amino acid sequence of mouse pancreatic ribonuclease has been determined by analysis of tryptic, chymotryptic, thermolytic and CNBr peptides and by automatic sequence analysis of the intact protein. The sequence of mouse RNase differs in 20--30% of the positions from other RNase sequences. Three unique or neraly unique substitutions were found, viz. Gly-68 leads to Arg-68, Arg-85 leads to His-85 and Ser-123 leads to Thr-123. All these three residues might be involved in interactions with substrate molecules. A most parsimonious tree of the myomorph rodent RNase shows that after the divergence of rat and mouse, the ribonuclease of rat accumulated substitutions at a rate 2.5--4.3 times as high as the rates in other branches of the tree and 23 times as high as the average rate in the Bovidae ribonuclease evolution. These extreme fluctuations in substitution rate are difficult to reconcile with the hypothesis of the evolutionary clock. The high evolution rate of rat ribonuclease is thought to be caused by positive selection, leading to new functional properties of the enzyme.

Amino Acid Sequence↗
PubMed1986

Periodic fluctuation of blood pressure in a case of norepinephrine secreting extra-adrenal pheochromocytoma.

A rare case of pheochromocytoma with wide fluctuation of blood pressure at regular 7-min intervals is described. Direct blood pressure monitoring revealed periodic changes between 120/80 mmHg and 220/130 mmHg. The plasma norepinephrine concentration increased selectively in parallel with the elevation of the blood pressure. The tumor was found adjacent to the left kidney, and all abnormal data improved after its resection.

Adrenal Gland Neoplasms↗
PubMed1991

[Establishment of ACNU-resistant rat gliosarcoma cell lines and their characteristics].

One of the most serious problems in cancer chemotherapy is the acquired drug resistance of tumor cells. In order to investigate the mechanism of acquired resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), nine resistant cells were isolated from rat gliosarcoma 9L cells and characterized. ACNU-resistant cells were easily isolated after a single treatment even with low-dose ACNU (5 micrograms/ml). However, in spite of repeatedly high-pressure dose of ACNU, more than 30 fold increase to parental 9L cell resistance was not achieved. At this time, further increase in selection pressure resulted in cell death. The resistant ratios of these resistant cells were stable in the absence of ACNU for more than 1 year. Luria and Delbrück's fluctuation test indicated that the appearance of ACNU-resistant cells occurred spontaneously at a rate of (4.40-8.02) x 10(-7)/cell/generation. In karyotypic analysis, the mode was higher in the resistant cells than in 9L cells, but a homogeneously staining region or double minute chromosome, which was considered to be a result of gene amplification, was not observed. In growth kinetics, all the resistant cells except R1 and R12 cells had higher saturation density and plating efficacy than parental 9L cells. These findings seemed to be due to cellular modification associated with ACNU resistance.

Animals↗
PubMed2006

In vitro three-stage continuous fermentation of gluco-oligosaccharides produced by Gluconobacter oxydans NCIMB 4943 by the human colonic microflora.

Gluco-oligosaccharides produced by Gluconobacter oxydans NCIMB 4943 from maltodextrin as the source, were evaluated for their fermentability by the human colonic microflora. The selectivity of growth of desirable bacteria in the human colon was studied in a three-stage continuous model of the human large intestine. Populations of bacteria, and their fluctuations as a response to the fermentation, were enumerated using fluorescent in situ hybridization (FISH). The gluco-oligosaccharides resulted in increases in numbers of bifidobacteria and the Lactobacillus/Enterococcus group in all 3 vessels of the system, representing the proximal, transverse and distal colonic areas. The prebiotic indices of the gluco-oligosaccharides were 2.29, 4.23 and 2.74 in V1, V2 and V3 respectively.

Bacteria↗
PubMed1977

Three years' experience with computer-based intensive care of patients following open heart and major vascular surgery.

The authors present their experiences with the Roche-5000 Computer-Based Intensive Care System in the management of 100 consecutive patients who have undergone open heart or major vascular surgery. The system performs the following junctions: (1) numerical and graphic display, out-of-limits alarms, storage and printout of 12 biological and surgical parameters, including chest drainage and urine output, by on-line direct monitoring; (2) display, storage, and printout of all additional laboratory and clinical data by manual input; (3) automatic demand-regulated transfusion and infusion program; (4) a program of medical logic, which includes situation analysis based on the above, two way dialogue with the computer, treatment recommendations to the physician, selective nursing and laboratory orders, acid-base analysis, and instructions for respirator setting. It was found that the computer-monitored patients recovered faster and smoother, with fewer fluctuations in the measured parameters and fewer postoperative complications than did those treated by conventional methods. One additional important effect of the system was that the nurse, relieved of the mechanical tasks of measuring, charting, and recording, was left with a greater amount of time for the care of the patient's personal needs. It seems ironic that such a technical advancement in electronics not only made the recovery faster and safer but also created a more humanistic approach in patient care, through better application of basic nursing techniques.

Cardiac Surgical Procedures↗
PubMed2000

Effects of selection for increased body weight, egg production, and shank width on developmental stability in turkeys.

Bilateral asymmetry was measured at 20 wk of age for shank length, shank width (width laterally at the dew claw), shank depth (width perpendicular to the dew claw), and face length (between auditory canal opening and the posterior junction of the upper and lower mandible) in three randombred control lines and three selected lines of turkeys. The data were based on 50 or 51 individuals per line and sex subgroup from a single hatch. The lines were grown intermingled with the sexes being grown in different houses. The selected lines had been selected for increased egg production (38 generations), increased 16-wk BW (32 generations), or increased shank width (19 generations) and had a higher level of inbreeding (average = 36.9%) than the randombred controls (RBC; average = 11.6%). The bilateral differences (right minus left) were analyzed for the presence of fluctuating asymmetry (FA; zero signed mean with normal variation), directional asymmetry (DA; signed mean not zero with normal variation), and antisymmetry (AS; zero mean with non-normal distribution). In order to adjust for possible scaling effects, relative asymmetry (RA), in which the mean of the absolute differences between sides was divided by the mean of the two sides and the resulting value was multiplied by 100, was used as a measure of bilateral asymmetry. The randombred control and selected lines were contrasted to study the effect of homozygosity on RA. Likewise, the large-bodied lines (F, FL, and RBC3) were contrasted to the small-bodied lines (RBC1, E, and RBC2) to study the effect of BW on RA. Only two types (FA and DA) of asymmetry were observed in the present study. The level of asymmetry for the traits was ranked as follows: face length > shank width = shank depth > shank length. The individual lines differed in RA for shank length and shank width for both sexes and for shank depth and face length in females. In general, the influence of BW, as measured in the contrast of large-bodied and small-bodied lines, on RA was larger than that of homozygosity, as measured by the contrast of the selected and randombred control lines.

Animals↗
PubMed1991

Skin conductance activity after intraventricular administration of 6-hydroxydopa in rats.

Absence of skin conductance response (SCR) and failure of its habituation are psychophysiological signs observed in most schizophrenics. In the present experiments, skin conductance activity was studied in rats before and after intraventricular administration of 6-hydroxydopa (6-OHdopa), a neurotoxin that selectively destroys noradrenaline nerve terminals and induces denervation supersensitivity at the synapse. All intact rats studied (n = 32) showed SCR and its habituation to repeated auditory stimuli (500 Hz, 90 dB, 1 sec, 20 times). They also showed some spontaneous fluctuation (SF) of the skin conductance. In the early stage following the 6-OHdopa (100 micrograms) administration (n = 16), it was noted that the SCR disappeared and the SF were markedly reduced in frequency (p less than 0.001). From the third day to the fourth week after this treatment, there was some recovery of the SF rate, and the SCR tended to reappear with a marked slowing down of its habituation. Eight weeks after the treatment, the majority (11/16) of the 6-OHdopa rats showed habituation failure of the SCR (p less than 0.005); vehicle-treated rats (n = 16) did not show these alterations. Estimation of catecholamine concentration after the experiment confirmed the selective depletion of brain noradrenaline. These results suggest that destruction of the noradrenergic fibers after the 6-OHdopa treatment and denervation supersensitivity which developed later are the cause of the nonresponding and nonhabituating changes of SCR, respectively.

Animals↗
PubMed2002

Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease.

Seladin-1 is a gene recently shown to be down-regulated in brain regions selectively degenerated in Alzheimer's disease. The sequence of seladin-1 shares similarities with flavin-adenine-dinucleotide-dependent oxidoreductases and it has been found to protect cells from apoptotic cell death. In this work, we show that the transcription of seladin-1 is selectively down-regulated in the brain areas affected in Alzheimer's disease. The down-regulation in seladin-1 transcription was associated with hyperphosphorylated tau seen as linkage to immunohistochemically detected paired helical filament tau, neuritic plaques and neurofibrillary tangles. In contrast, no association was found between seladin-1 transcription and beta-amyloid deposition when analyzing human samples or tissue from transgenic animals. Furthermore, the relative transcription of seladin-1 was found to fluctuate during aging in the transgenic mouse model of Alzheimer's disease. The fluctuation was enhanced by Alzheimer's disease causing mutations in presenilin-1 and amyloid precursor protein genes. Finally, seladin-1 transcription was found to be up-regulated in mouse N2a cells induced to undergo apoptosis with okadaic acid. The results presented here indicate that seladin-1 transcription is selectively down-regulated in brain regions vulnerable to Alzheimer's disease and this down-regulation is associated with the hyperphosphorylation of tau protein.

Aged↗
PubMed1985

Angioimmunoblastic lymphadenopathy with dysproteinemia. Circulating immune complexes and the review of 18 cases.

Eighteen patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) have been analyzed by reviewing all available biopsy, laboratory, and clinical data. Because of features suggesting the presence of circulating immune complexes (CIC), CIC serial sample determinations were performed throughout their disease in available patients. Age, sex, and clinical and laboratory characteristics were consistent with previously reported series. Six of 18 (33%) patients having a drug exposure associated with onset or exacerbation of symptoms demonstrated a significantly decreased survival (P less than 0.02). Achievement of complete remission was a significant indicator of longevity (P less than 0.001). Only one patient (6%) developed diffuse histiocytic lymphoma. Elevated CIC were detected in the four patients tested. In two patients fluctuating CIC levels could clearly be correlated to clinical remission or exacerbation. Despite the small number of patients tested, it was concluded tha CIC may provide useful information for therapy selection, prediction of relapse, and further insight into pathogenetic mechanisms in AILD.

Adult↗
PubMed1992

Quantitation of T-cell receptor V beta chain expression on lymphocytes from blood, brain, and spinal fluid in patients with multiple sclerosis and other neurological diseases.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system in which large numbers of T cells enter the brain and cerebrospinal fluid (CSF). To determine whether these cells represent restricted populations, we studied expression of T-cell receptor V beta chains on paired samples from the central nervous system and blood of patients with MS or other neurological diseases (OND) using a quantitative polymerase chain reaction. The distribution of V beta chain expression in blood was skewed, with a significant preponderance of message from V beta genes 1 through 8 (p = 0.0001). Such skewing was not present in samples from the CSF and brain. Patterns of V beta gene expression were different among paired samples from spinal fluid and blood and were relatively heterogeneous. Blood and CSF samples from a patient with acute meningitis were studied on two separate occasions. The patterns of V beta expression changed over 72 hours in both the blood and the CSF. With one exception, no oligoclonal populations of T cells were observed nor were there disease-specific patterns of V beta gene expression in the blood or CSF. Samples from 2 MS brains and 1 OND brain expressed patterns of V beta genes that were different and less heterogeneous than those in paired blood. In addition, expression of V beta 12 was remarkably increased in the 2 MS brains, suggesting a selective recruitment or expansion of T cells expressing this gene. These data demonstrate that populations of T cells from blood, spinal fluid, and brain differ from one another and can fluctuate during periods of acute inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗
PubMed1996

Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys.

Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor have been reported to potentiate the antiparkinsonian action of levodopa and reverse levodopa-induced motor fluctuations in animal models of Parkinson's disease. To evaluate the effect of NMDA receptor blockade on dyskinesias complicating the response to long-term levodopa therapy, we studied the selective antagonist LY235959 in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. Drugs were administered subcutaneously, LY235959 at doses of 0.5, 1.0, 3.0, and 5.0 mg/kg and levodopa/benserazide at doses that produced moderate dyskinesias while almost totally reversing parkinsonian signs. Compared with vehicle control injections, LY235959 (3.0 mg/kg) abolished oral dyskinesias and diminished choreic dyskinesias by 68% (p < 0.01). Lower doses had smaller effects, although still significant, on oral dyskinesias (55% reduction at 1.0 mg/kg, p < 0.05). The highest LY235959 dose (5.0 mg/kg) prolonged oral dyskinesia suppression, but tended to increase dystonia severity. LY235959 had no effect on motor function when given alone and did not reduce the antiparkinsonian response to levodopa. These findings suggest that NMDA receptor blockade may ameliorate the dyskinetic complications of long-term levodopa therapy, without diminishing the beneficial effects on parkinsonian signs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1983

Properties of an inward rectifying K channel in the membrane of guinea-pig atrial cardioballs.

Single channel outward current fluctuations are recorded in excised (outside-out) membrane patches of isolated atrial cells in culture (cardioballs) from hearts of adult guinea-pigs. The ionic channel displays a high selectivity to K ions. Accordingly the reversal potential of the single channel current is close to the K equilibrium potential. The open channel conductance is unaffected by the membrane potential but depends on the K concentration of the outside solution (19.7pS at 2 mM Ko to 30.7pS at 20 mM Ko). The open state probability (Po) of the channel shows a marked voltage dependence. Po amounts to c.0.9 at -40 mV and decreases to c.0.1 at +40 mV. Under the assumption of no channel interaction a macroscopic steady state current voltage relationship is reconstructed from the single channel data. The relationship displays inward-going rectification. The rectification is due to the voltage dependence of Po. The I-V curve displays a negative slope at membrane potentials positive to -15 mV. In bathing solutions containing Ba ions (0.2 mM) Po is reduced by rapid closures which interrupt the open state events. The unit channel conductance is unaffected by Ba ions. The channel block exerted by Ba ions is augmented with increasing membrane hyperpolarization. The results suggest that the channel studied may represent a background K conductance.

Animals↗
PubMed2006

Simulation of electroporated cell by chronopotentiometry.

Chronopotentiometry on planar lipid bilayer (BLM) is proposed as a method for modeling the electrical phenomena in electroporated cell. Two techniques are discussed: constant-current and linear-current chronopotentiometry. It is proposed that the constant-current chronopotentiometry may provide basis for modeling the electroporated cell shortly after the removal of the electric field, when activity of cellular pumps counteracts ionic fluxes through the electropore and ionic channels. The linear-current method can be considered for modeling the cell in the later stage after electroporation, when energetical resources of the cell are gradually getting exhausted and the activity of pumps decreases. Based on this idea, it may be postulated that the electropore in the cell has fluctuating dynamics whose stochastic characteristics, similarly as biological channels, shows 1/f noise. The model implies that the fluctuations would disappear leaving the electropore with a constant resistance when efficiency of the pumps becomes very small. The results of chronopotentiometry also may suggest that opening time, conductivity and selectivity of the electropore can be controlled by the cell environment or membrane composition.

Cell Membrane↗
PubMed1999

The nonlinear, complex sequential organization of behavior in schizophrenic patients: neurocognitive strategies and clinical correlations.

BACKGROUND: Thought disorder is a hallmark of schizophrenia and can be inferred from disorganized behavior. Measures of the sequential organization of behavior are important because they reflect the cognitive processes of the selection and sequencing of behavioral elements, which generate observable and analyzable behavioral patterns. In this context, sequences of choices generated by schizophrenic patients in a two-choice guessing task fluctuate significantly, which reflects an "oscillating dysregulation" between highly predictable and highly unpredictable subsequences within a single test session. In this study, we aimed to clarify the significance of dysregulation by seeing whether demographic, clinical, neuropsychological, and psychological measures predict the degree of dysregulation observed on this two-choice task. METHODS: Thirty schizophrenic patients repeatedly performed a LEFT or RIGHT key press that was followed by a stimulus, which occurred randomly on the left or right side of the computer screen. Thus, the stimulus location had nothing to do with the key press behavior. The range of key press sequence predictabilities as measured by the dynamical entropy was used to quantify the dysregulation of response sequences and reflects the range of fixity and randomness of the responses. A factor analysis was performed and step-wise multiple regression analyses were used to relate the factor scores to demographic, clinical, symptomatic, Wisconsin Card Sorting Test (WCST), and Rorschach variables. RESULTS: The LEFT/RIGHT key press sequences were determined by three factors: 1) the degree of win-stay/lose-shift strategy; 2) the degree of contextual influence on the current choice; and 3) the degree of dysregulation on the choice task. Demographic and clinical variables did not predict any of the three response patterns on the choice task. In contrast, the WCST and Rorschach test predicted performance on various factors of choice task response patterns. CONCLUSIONS: Schizophrenic patients employ several rules, i.e., "win-stay/lose-shift" and "decide according to the previous choice," that fluctuate significantly when generating sequences on this task, confirming that a basic behavioral dysregulation occurs in a single schizophrenic subject across a single test session. The organization or the "temporal architecture" of the behavioral sequences is not related to symptoms per se, but is related to deficits in executive functioning, problem solving, and perceptual organizational abilities.

Adult↗
PubMed2002

The synaptic vesicle protein synaptophysin: purification and characterization of its channel activity.

The synaptic vesicle protein synaptophysin was solubilized from rat brain synaptosomes with a relatively low concentration of Triton X-100 (0.2%) and was highly purified (above 95%) using a rapid single chromatography step on hydroxyapatite/celite resin. Purified synaptophysin was reconstituted into a planar lipid bilayer and the channel activity of synaptophysin was characterized. In asymmetric KCl solutions (cis 300 mM/trans 100 mM), synaptophysin formed a fast-fluctuating channel with a conductance of 414 +/- 13 pS at +60 mV. The open probability of synaptophysin channels was decreased upon depolarization, and channels were found to be cation-selective. Synaptophysin channels showed higher selectivity for K(+) over Cl(-) (P(K(+))/P(Cl(-)) > 8) and preferred K(+) over Li(+), Na(+), Rb(+), Cs(+), or choline(+). The synaptophysin channel is impermeable to Ca(2+), which has no effect on its channel activity. This study is the second demonstration of purified synaptophysin channel activity, but the first biophysical characterization of its channel properties. The availability of large amounts of purified synaptophysin and of its characteristic channel properties might help to establish the role of synaptophysin in synaptic transmission.

Animals↗
PubMed1999

Population structure of pathogens: the role of immune selection.

Sunetra Gupta and Roy Anderson discuss how the balance between host immune responses against conserved and variable antigens shapes the population structure of pathogens. At one extreme, immune selection against polymorphic determinants can cause pathogen populations to self-organize spontaneously into discrete antigenic types that may either be maintained over long periods or undergo cyclical or chaotic fluctuations. At the other extreme, diversity may be drastically reduced by competition induced by a strong immune response against a conserved determinant. Where does each pathogen lie along this continuum? How would this knowledge influence our attempts to control an infectious disease?

Alleles↗