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At least 19 recordsLinked to original sources
PubMed2025

Sweeps in Space: Leveraging Geographic Data to Identify Beneficial Alleles in Anopheles gambiae.

As organisms adapt to environmental changes, natural selection modifies the frequency of nonneutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae, a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Animals↗
PubMed2025

Sweeps in space: leveraging geographic data to identify beneficial alleles in Anopheles gambiae.

As organisms adapt to environmental changes, natural selection modifies the frequency of non-neutral alleles. For beneficial mutations, the outcome of this process may be a selective sweep, in which an allele rapidly increases in frequency and perhaps reaches fixation within a population. Selective sweeps have well-studied effects on patterns of local genetic variation in panmictic populations, but much less is known about the dynamics of sweeps in continuous space. In particular, because limited movement across a landscape leads to unique patterns of population structure, spatial dynamics may influence the trajectory of selected mutations. Here, we use forward-in-time, individual-based simulations in continuous space to study the impact of space on beneficial mutations as they sweep through a population. In particular, we show that selection changes the joint distribution of allele frequency and geographic range occupied by a focal allele and demonstrate that this signal can be used to identify selective sweeps. We then leverage this signal to identify in-progress selective sweeps within the malaria vector Anopheles gambiae , a species under strong selection pressure from vector control measures. By considering space, we identify multiple previously undescribed variants with potential phenotypic consequences, including mutations impacting known IR-associated genes and altering protein structure and properties. Our results demonstrate a novel signal for detecting selection in spatial population genetic data that may have implications for genomic surveillance and understanding geographic patterns of genetic variation.

Journal Article↗
PubMed2025

Large future genetic diversity losses are predicted even with habitat protection.

Genetic diversity within species is the basis for evolutionary adaptive capacity and has recently been included as a target for protection in the United Nations' Global Biodiversity Framework (GBF). However, we lack large-scale mathematical frameworks to quantify how much genetic diversity has already been lost, let alone to predict future losses under 21st century conservation scenarios. To fill this gap, we developed an area-based spatio-temporal predictive framework of genetic diversity calibrated with population-scale genomic data of 29 plant and animal species. To estimate present genetic diversity loss with our framework, we used species' habitat area and population sizes losses reported in the Living Planet Index, the Red List, and new GBF indicators across 13,808 species for the last 5 decades. Applying our evolutionary framework across these species, we estimate genetic diversity loss lags behind population and habitat area declines, with an estimated current 13-22% π genetic diversity loss. However, we forecast future genetic diversity losses will reach 41-76% even if populations are not further contracted. These results highlight that safeguarding existing habitats is insufficient to maintain the genetic health of species and relying solely on continuous genetic monitoring underestimates lagging long term impacts.

Genetic diversity↗
PubMedDate not supplied

[Effect of actoprotectors on the work capacity of operators during modeling of various factors of space flight].

This paper presents experimental findings indicating that bemithyl, an actoprotective agent, has a beneficial effect on the health status and work capacity of operators during simulated space flight and 56-hour continuous work. The drug enhanced psychophysiological tolerance of the operators and improved the quality of their work: the quality of their compensatory tracking was on the average 10% higher, the number of errors of their porsuit tracking was 1.8 times lower, and the time of visual signal detection was 2.4 times shorter as compared to the placebo controls.

Adaptation, Physiological↗
PubMed1987

Brachytherapy implants with differently spaced Ir-192 seeds: a dosimetric study.

Brachytherapy implantations traditionally have been carried out with continuous line sources of radium. With the popularity of afterloading implantations, iridium-192 seeds in plastic ribbons have replaced radium in the United States, although continuous sources, such as iridium wires, are widely used in Europe. The authors analyzed the impact of the use of noncontinuous sources in brachytherapy implants. Computer simulations and film dosimetry of a two-planar implant were carried out. Seeds at standard spacing (1 seed/cm), nonstandard spacing (1 seed/6mm), and continuously arranged seeds were studied.

Brachytherapy↗
PubMed1988

Modelling the 1985 influenza epidemic in France.

The Rvachev-Baroyan-Longini model is a space-time predictive model of the spread of influenza epidemics. It has been applied to 128 cities of the USSR, and more recently, to forecasting the spread of the pandemic of 1968-1969 throughout 52 large cities. It is a deterministic, mass-action, space and time continuous model. The model has been applied to the simulation of the influenza epidemic of 1984-1985 in the 22 French Metropolitan districts and results are presented. Estimates of the parameters of the model were made using the French Communicable Diseases Network data. These parameters are the contact rate, a, (estimate = 0.55) which is the number of people with whom an infectious individual will make contact daily sufficient to pass infection and the infectious period, 1/b, estimated as 2.49 days. The mean annual railroad passenger traffic from district i to district j varies from 0 to 1,991,000 persons depending on the districts. The computer spread of the epidemic is presented on weekly maps. Results are also presented on district charts, giving the size of district epidemics and the time of peak of the epidemic. The precision of the computer fittings was judged satisfactory by the calculated size of peak differing from the real one by less than 100 per cent, in 17 out of 18 districts, and by the calculated time of peak differing from the observed by less than two weeks in 14 out of 18 districts. Although precision could be improved with more detailed information about passenger traffic, the French use of the model has been satisfactory.

Computer Simulation↗
PubMed1991

Vector-averaged gravity alters myocyte and neuron properties in cell culture.

To investigate whether changes in the gravitational field of developing neurons and myocytes affect cellular development, we rotated cultures of embryonic spinal neurons and myocytes in a horizontal clinostat. Rotation in the clinostat produces, from the cells' perspective, a "vector-free" gravity environment by continuous averaging of the vector. In this way, rotation in the clinostat simulates the microgravity of space where the gravity vector is substantially reduced. At rotation rates of 1-50 rpm, cellular and nuclear areas of myocytes were significantly enlarged and the number of presumptive nucleoli increased. In neurons, frequent and large swellings appeared along neuritic shafts. Some of these changes were reversible after cessation of rotation. Since our data are generally consistent with findings from other cell types subjected to spaceflight, we suggest that the vector-free gravity environment of the clinostat appears to simulate, at least in part, the microgravity of space. Our data further show that cellular processes are sensitive to altered gravity and suggest that cell development in the microgravity of space may be significantly altered.

Animals↗
PubMed1987

Brownian dynamics simulation of restricted rotational diffusion.

The restricted rotational diffusion of an axially symmetric particle is simulated by the Brownian dynamics technique. In addition to the wobbling-in-a-cone model, several continuous potentials are considered. The particle studied is particularly simple: a sphere anchored to a point fixed in space. However, presenting the results in a convenient, reduced form, they are valid for any axially symmetric particle. From simulated rotational trajectories, we calculate (P2(cos alpha] as a function of t, where alpha is the angle between two orientations separated by time t and P2 is the second Legendre polynomial. This correlation function is closely related to time-resolved electro-optic and spectroscopic properties. Simulated results for the cone model are in excellent agreement with the quasiexact results of Lipari and Szabo (1981, J. Chem. Phys., 75:2971-2976). Thus we confirm the good performance of the simulation technique and the validity of our working conditions. Novel results are presented for continuous restricting potentials, V(theta). The (P2) results for V = 1/2K theta 2 and V = Q(1 - cos theta) are practically the same if K and Q are chosen so tht the long-time (P2) values coincide. Thus, the quadratic potential seems to be a good representation of any monotonically increasing potential. However, for an uniaxial potential such as V = Csin2 theta, the decay is appreciably faster. The (P2) decays simulated for the continuous potentials are analyzed by the monoexponential version of the cone model. We found that such an analysis produces an overestimation of the true rotational diffusion coefficient of approximately 15% only, although for uniaxial potentials the error may be larger.

Biopolymers↗
PubMed1975

Renal effects of continuous negative pressure breathing.

Continuous negative pressure breathing (CNPB) was utilized to simulate the thoracic vascular distension of zero G or Space, in 11 anesthetized rats. The animals underwent renal clearance and micropuncture renal nephron studies before, during, and after CNPB. Four rats were pretreated with a high salt diet and I-M desoxycorticosterone (DOCA) in excess. None of these rats diuresed with CNPB. In contrast, five of the seven remaining rats increased the fraction of the filtered sodium excreted (CNa/GFR, p less than 0.05) and their urinary flow rate (V, p less than 0.05). Potassium excretion increased (UK V, p less than 0.05). End proximal tubular fluid specimen's TF/P inulin ratios were unchanged. Whole kidney and single nephron glomerular filtration rates fell 10%. CNPB, a mechanism for atrial distension, appears to cause in the rat a decrease in distal tubular sodium and water reabsorption. Exogenous mineral-corticoid prevents the diuresis, saluresis, and kaluresis. In a separate group of five rats, the CNPB was prolonged or excessive (CNPB greater than 3.5 cm H2O negative pressure); in these, the diuresis ceased and/or antidiuresis occurred. This confirmed the adequacy of other nonatrial volume control mechanisms in regulating renal salt and water conservation in opposition to the studied atrial-renal (Henry-Gauer) reflex of thoracic vascular distension. It encourages us to suggest that the atrial distension reflex diuresis that occurs with shifts of blood to the thorax in assuming a weightless condition, if comparable to the thoracic vascular distension of this model, will not progressively impair the circulation or the mammal but will be minor and short-lived.

Animals↗
PubMed1979

Whole body transvascular filtration coefficient and interstitial space capacitance.

Infusion experiments with Ringer's solution were performed on 5 splenectomized dogs with continuous monitoring of blood volume and hematocrit. The plasma volume was calculated from these data and followed during the infusion and also during the recovery period. Applying electrical equivalent simulation analysis to the result of the plasma volume, the capacitance of the interstitial fluid space and the transvascular filtration coefficient of water in the whole body were determined simultaneously. The mean values of the capacitance and the coefficient were 5.91 ml/kg-mmHg and 0.314 ml/min-kg-mmHg, respectively. From this simulation study, a transfer function which predicts the fluid shift between the vascular system and the interstitial fluid space was also derived. Using the transfer function, predictions of the changes in plasma volume are possible from any given rate of infusion.

Animals↗
PubMedDate not supplied

High speed electrophoresis simulation for optimization of continuous flow electrophoresis and high performance capillary techniques: Part I. Computer model.

A computer program for high-speed simulation and optimization of electrophoretic processes has been developed for carrier-free systems of all kinds. The calculations are based on the one-dimensional dynamic (transient-state) model. The three-dimensional geometry of the simulation space can be chosen deliberately. With a highly efficient transport algorithm instead of complicated integration schemes for the transport equations, the calculation time can be effectively spent on various important parameters such as ionic strength, temperature, Joule heat, activity coefficients and concentration changes due to membranes. The parameter set of any carrier free electrophoretic method (i.e., continuous-flow electrophoresis, capillary isotachophoresis and high performance capillary zone electrophoresis) can be imported directly into the computer program by means of a graphic user interface. The program performs overnight-simulation of any electrophoretic system containing up to 15 components.

Computer Simulation↗
PubMed1986

Cellular sodium transport in arterial wall--summary of studies by digital computer simulation.

The distribution of electrolytes between extracellular and intracellular compartments is of greater functional significance in biological tissues than the total amount. A method commonly employed for the study of a substance distribution among different spaces is the continuous outflow and radioisotope counting of a fragment of tissue previously incubated with a radioactive tracer (here 22Na+). The experimental data can be analyzed within the frame of a compartmental analysis system which is defined by transport rate constants (kij) and solved when all kij are numerically determined. In practical applications the direct solution requires measurements in different compartments or knowledge of the initial condition for each compartment, but this is not possible in most biological tissues where the experimentally observable data represent the summation of tracer in all compartments at each point in time. The availability of the SAAM (Simulation, Analysis And Modelling) computer program allows for a powerful simulation procedure to arrive at values for kij. Experimental data and specifications for a chosen model are entered in the SAAM format. A simulated 'inflow' experiment is made by the computer by assigning to kij some estimate values. All initial conditions are now zero, since at the beginning there is no radioactive tracer in any compartment. After a time equivalent in the experimental realm to achieving constant specific activity, a 'time change' programmed into the computer takes place so that the outflow part of the experiment is developed with the same kij as for the inflow part, the final conditions for the inflow before the time change being the initial conditions for the outflow. An iterative procedure modifies the initial estimates of kij to seek the best fit. By coupling a powerful simulation procedure to an advanced radionuclide tracer biological methodology, we have been able to find effects of the hormone aldosterone and of experimental hypertension on Na+ distribution in arterial wall years before such effects were demonstrated by purely conventional experimental techniques. This computer simulation procedure may be suited to other experimental situations in which outflow data are the only available.

Aldosterone↗
PubMed1991

Effect of hindlimb suspension simulation of microgravity on in vitro immunological responses.

The effects of microgravity on the immune system are largely unknown, but understanding such effects becomes increasingly important as space exploration continues and mission duration increases. Reductions in postflight human T cell reactivity to mitogens is well documented. Similar results have been obtained using a clinostat as an in vitro model of microgravity. In this study, a rat tail suspension model of weightlessness was used to examine in vitro lymphocyte proliferation in response to mitogens. Experiments were designed to uncover potential deficits in events related to proliferation including cell surface protein and IL-2 receptor (IL-2R) expression, interleukin-2 (IL-2) production, and accessory cells. Suspension of rats for 1 week led to a significant depression in [3H]thymidine incorporation by mitogen-stimulated peripheral blood lymphocytes (PBL) but only a small decrease in the proliferation of lymph node lymphocytes and splenocytes. There were no changes in the percentages of cells expressing CD4, CD5, CD8 or immunoglobulin. Moreover, no changes in IL-2 production or IL-2R expression were observed. More esterase-positive macrophages were detected in all lymphatic tissues of suspended rats, but there was no corresponding increase in the percentage of cells bearing the macrophage markers OX41 or OX42. This increase in the number of macrophages may be related to the observed suppression of lymphocyte proliferation. The tissue specificity of the decrease in mitogen activation indicates that there may be a compartmentalized response in the rats tested in the hindlimb suspension model.

Animals↗
PubMed1976

Mathematical modeling and the redesign of a teaching ambulatory clinic.

Mathematical modeling was utilized in the planning and decision-making process involved in reorganizing a teaching clinic to effect continuity of care. The model interrelated physicians, time and space, facilitating value judgments and decisions. After examining multiple model runs, the authors finally selected a per-clinic-session doctor mix of 5 interns, 2.3 residents, and 1.6 fellows. Group productivity by model simulation was 14.6 pts/hour, utilizing 10.1 rooms. Subsequently, 90 house officers were each assigned to the clinic one-half day a week on a continuing basis. Time-motion data, from 10 sessions five months after the change, showed that during one week 353 patients were seen at a rate of 13.9 patients per hour in the rooms and time available. The fact that the reorganization was successful and the outcomes remarkably similar to model predictions has engendered confidence in the role of modeling in the planning process.

Ambulatory Care↗
PubMed1990

Simulation of motion on the skin. III. Mechanisms used by rapidly adapting cutaneous mechanoreceptors in the primate hand for spatiotemporal resolution and two-point discrimination.

1. The contribution of rapidly adapting (RA) mechanoreceptors to two-point discrimination has been evaluated by examining their ability to resolve the spacing of grating patterns shifted across the skin. The experiments test two different neural coding mechanisms that have been proposed to underlie resolution of spatial detail on the hand: 1) a rate-intensity code in which the spacing of surface features is encoded by the average frequency of firing of individual sensory afferents, and 2) an isomorphic representation of shape in which variations in the firing patterns of individual afferents reflect the spatiotemporal profile of skin indentation. 2. To measure the spatial acuity of RA mechanoreceptors innervating the hands of macaque monkeys, we displayed pairs of horizontal bars spaced 1-13 mm apart on a computer-controlled OPTACON stimulator placed over glabrous skin. Two-point resolution was measured by simultaneously pulsing pairs of rows at rates of 100, 50 and 25 Hz; each pair was shifted in tandem across the hand to simulate lateral motion. Single-fiber recordings were made from physiologically identified RA afferents in anesthetized monkeys. 3. Receptive field diameter appears to be the critical determinant of spatial resolution of gaps between two bars. RAs fire continuously if bar spacing is less than the field diameter but do not summate inputs when both active rows are contained within the field. Response profiles evoked by two bars spaced less than 4.8 mm apart can be predicted from the single-bar profiles, assuming occlusion between overlapping inputs with the strongest member dominating axonal output. Two-thirds of the RAs tested discharge 1 spike/pulse as bar patterns cross the field, yielding a uniform spike train whose frequency reflects stimulus pulse rates but fails to indicate gaps between bars. An additional 17% fire 2 spikes/pulse when the bars contact or straddle the field center, but also fail to differentiate individual stripes spaced less than 3.6 mm apart. 4. Only 17% of RAs represent gaps narrower than the field diameter. These fibers show double-peaked response profiles to bar patterns spaced at least 2.4 mm apart, firing 2 spikes/pulse as first one, and then the second stripe crosses the field center. Timing between peaks corresponds to bar spacing. Responses are reduced in amplitude when adjacent bars straddle the field center, as occlusion between simultaneous inputs prevents summation of inputs from the two stimuli. Fifteen of 16 RAs failed to resolve bars spaced 1.2 mm apart, as double-spike responses were evoked only by the leading stripe.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

The temporal response of bone to unloading.

A model of weightlessness in which the hindlimbs of rats are elevated by their tails at a 40 degrees angle to unload the hindlimbs while maintaining normal weight bearing on the forelimbs has been used to simulate certain conditions of space flight. When we used this model in growing rats, we found that growth in bone weight ceased by 1 week in the hindlimbs and lumbar vertebrae, whereas growth in bone weight in the forelimbs and cervical vertebrae remained unaffected. Within 2 weeks, however, the accretion of bone weight in the hindlimbs and lumbar vertebrae returned to normal despite continued skeletal unloading. Since bone weight in the growing rat is primarily determined by bone formation (bone resorption is modest), we investigated the effects of selective skeletal unloading on bone formation during 2 weeks of hindlimb elevation using radioisotope incorporation (with 45Ca and [3H]proline) and histomorphometry (with tetracycline labeling). The studies using radioisotope incorporation showed that bone formation was inhibited by the fifth day of skeletal unloading. By the 10th to 12th day, bone formation had returned toward normal. In comparison with cortical bone, cancellous bone (lumbar vertebrae and proximal tibiae) incorporated more 45Ca and [3H]proline (indicating greater metabolic activity) and had a greater absolute response to skeletal unloading. The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. We conclude that this model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed by a cessation in the accretion of bone weight, which then resumes at a normal rate by 14 days despite continued skeletal unloading. We believe that this cycle of inhibition and resumption of bone formation has profound implications for understanding bone dynamics during space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Animals↗
PubMed1987

The impact of sequential ultra-low volume ground aerosol applications of malathion on the population dynamics of Aedes aegypti (L.).

The efficacy of sequential, ultra-low volume ground aerosol applications of malathion at current U.S. label rates was evaluated as an emergency control measure for adult populations of Aedes aegypti (L.) in New Orleans, Louisiana. Replicates of 11 sequential aerosol treatments applied 12 hr apart during a 5.5-day period reduced mean adult captures and oviposition rates during the treatment period 73% and 75%, respectively. We hypothesize that oviposition was not completely suppressed because females with a developing egg burden remained sequestered during treatment periods or were more tolerant to the pesticide. We further concluded that adults could not be totally suppressed because of continued emergence. After treatment, adult densities recovered to pretreatment and control levels within approximately 1 week. A simulation study of the results suggested that, under the conditions of closely spaced housing and abundant vegetation that is typical of much of New Orleans, a single aerosol killed an average of 88% of the males and only 30% of the females present.

Aedes↗
PubMed1987

An account of responses of spectrally opponent neurons in macaque lateral geniculate nucleus to successive contrast.

Coloured surfaces in the normal environment may be brighter or dimmer than the mean adaptation level. Changes in the firing rate of cells of the parvocellular layers of macaque lateral geniculate nucleus were studied with such stimuli; chromatic mixtures briefly replaced a white adaptation field. This paradigm is therefore one of successive contrast. Families of intensity-response curves for different wavelengths were measured. When taking sections at different luminance ratios through these families of curves, strongly opponent cells displayed spectrally selective responses at low luminance ratios, while weakly opponent cells had higher chromatic thresholds and responded well to stimuli at higher luminance ratios, brighter than the adaptation field. Strength of cone opponency, defined as the weight of the inhibitory cone mechanism relative to the excitatory one, was thus related to the range of intensity in which cells appeared to operate most effectively. S-cone inputs, as tested with lights lying along tritanopic confusion lines, could either be excitatory or inhibitory. Families of curves for different wavelengths can be simulated mathematically for a given cell by a simple model by using known cone absorption spectra. Hyperbolic response functions relate cone absorption to the output signals of the three cone mechanisms, which are assumed to interact linearly. Parameters from the simulation provided estimates of strength of cone opponency and cone sensitivity which were shown to be continuously distributed. Cell activity can be related to cone excitation in a trichromatic colour space with the help of the model, to give an indication of suprathreshold coding of colour and lightness.

Action Potentials↗