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PubMed2026

Genomic epidemiology of dengue virus 2 and 3 reveals repeated introductions and exportations of several lineages in Colombia.

Dengue fever, a major mosquito-borne viral disease, is transmitted by Aedes mosquitoes and poses a significant global health burden. Despite extensive research, the spatiotemporal dynamics of dengue virus (DENV) lineages in Colombia remain understudied. Here, we analyze 11,443 complete genome sequences from Colombia and the Americas to map the genomic epidemiology of DENV-2 and DENV-3. Phylogeographic reconstruction revealed multiple independent introductions and exportations of the DENV-2 II and III lineages, as well as the DENV-3 lineage III_C.2, underscoring Colombia's critical role as both a source and a sink of viral traffic within the Americas. Antigenic profiling demonstrated distinct clustering of emergent lineages in antigenic space, consistent with immune-escape-driven turnover. These results highlight the necessity of sustained, high-resolution genomic surveillance to guide targeted public health interventions and mitigate dengue transmission across the region.

Dengue Virus↗

PubMedDate not supplied

Two regimes of the Arctic's circulation from ocean models with ice and contaminants.

A two-dimensional barotropic, coupled, ocean-ice model with a space resolution of 55.5 km and driven by atmospheric forces, river run-off, and sea-level slope between the Pacific and the Arctic Oceans, has been used to simulate the vertically averaged currents and ice drift in the Arctic Ocean. Results from 43 years of numerical simulations of water and ice motions demonstrate that two wind-driven circulation regimes are possible in the Arctic, a cyclonic and an anti-cyclonic circulation. These two regimes appear to alternate at 5-7 year intervals with the 10-15 year period. It is important to pollution studies to understand which circulation regime prevails at any time. It is anticipated that 1995 is a year with a cyclonic regime, and during this cyclonic phase and possibly during past cyclonic regimes as well, pollutants may reach the Alaskan shelf. The regime shifts demonstrated in this paper are fundamentally important to understanding the Arctic's general circulation and particularly important for estimating pollution transport.

Arctic Regions↗

PubMed1996

In growth cones of rat cerebral neurons and human neuroblastoma cells, activation of protein kinase C causes a shift from filopodial to lamellipodial actin dynamics.

In cultures of rat cerebral neurons addition of the protein kinase C (PKC) activator 1,2-dioctanoyl-s,n-glycerol (diC8; 5 microM) induces a transient elongation of filopodia which is followed by a striking enhancement of lamellar protrusions. After 30-40 min, lamellipodia are slowly retracted, filopodia reappear and become predominant again. The reappearance of filopodia is accelerated by addition of the potent PKC-inhibitor RO-31-8220 (2 microM). A similar transient promotion of lamellar protrusive activity is obtained in SH-SY5Y neuroblastoma cells upon stimulation by acetylcholine or diC8. Immunostainings showed that the new space created by extending actin-driven lamellipodia is rapidly entered by microtubules. Preincubation with or permanent presence of RO-31-8220 totally inhibits both filopodial and lamellipodial protrusive activity. The data suggest that both filopodial and lamellipodial protrusion require active PKC, however of different levels of activation.

Actins↗

PubMed2005

Topological constraints in nucleic acid hybridization kinetics.

A theoretical examination of kinetic mechanisms for forming knots and links in nucleic acid structures suggests that molecules involving base pairs between loops are likely to become topologically trapped in persistent frustrated states through the mechanism of 'helix-driven wrapping'. Augmentation of the state space to include both secondary structure and topology in describing the free energy landscape illustrates the potential for topological effects to influence the kinetics and function of nucleic acid strands. An experimental study of metastable complementary 'kissing hairpins' demonstrates that the topological constraint of zero linking number between the loops effectively prevents conversion to the minimum free energy helical state. Introduction of short catalyst strands that break the topological constraint causes rapid conversion to full duplex.

Base Pairing↗

PubMed2005

Problems with mitochondrial DNA as a marker in population, phylogeographic and phylogenetic studies: the effects of inherited symbionts.

Mitochondrial DNA (mtDNA) has been a marker of choice for reconstructing historical patterns of population demography, admixture, biogeography and speciation. However, it has recently been suggested that the pervasive nature of direct and indirect selection on this molecule renders any conclusion derived from it ambiguous. We review here the evidence for indirect selection on mtDNA in arthropods arising from linkage disequilibrium with maternally inherited symbionts. We note first that these symbionts are very common in arthropods and then review studies that reveal the extent to which they shape mtDNA evolution. mtDNA diversity patterns are compatible with neutral expectations for an uninfected population in only 2 of 19 cases. The remaining 17 studies revealed cases of symbiont-driven reduction in mtDNA diversity, symbiont-driven increases in diversity, symbiont-driven changes in mtDNA variation over space and symbiont-associated paraphyly of mtDNA. We therefore conclude that these elements often confound the inference of an organism's evolutionary history from mtDNA data and that mtDNA on its own is an unsuitable marker for the study of recent historical events in arthropods. We also discuss the impact of these studies on the current programme of taxonomy based on DNA bar-coding.

Animals↗

PubMed1993

Ontogeny of phosphate transport by rat liver plasma membrane vesicles.

The present studies were designed to characterize the developmental aspects of Na(+)-dependent phosphate transport, across the hepatocyte basolateral membranes of the suckling and weanling rats. A well validated technique of plasma membrane vesicles (BLMV) was utilized. Phosphate uptake was driven into an osmotically active intravesicular space as evident by a linear relationship between uptake and 1/osm with no binding component y = 0.04 x-0.03, r2 = 0.99 and y = 0.035x + 0.01, r2 = 0.95 in suckling and weanling BLMV's respectively. The presence of inwardly directed Na+ and pH gradient stimulated phosphate uptake in suckling and weanling BLMV's, however, uptake values under Na+ and pH gradients were greater in weanling rats compared to suckling rats. Kinetics of Na(+)-dependent phosphate uptake were 0.14 +/- 0.01 and 0.28 +/- 0.035 at pH 6.1 (P < 0.05) and 0.1 +/- 0.007 and 0.15 +/- 0.03 nmoles/mg protein/10s (P < 0.05) at pH 7.4 in suckling and weanling rats respectively. Km values were not significantly different. Na+ arsenate and phosphonoformonic acid inhibited Na(+)-dependent phosphate uptake, whereas ATP and P-MB (para-chlomercuribenzoic acid) did not effect Na(+)-dependent phosphate uptake. These studies demonstrate for the first time the presence of a specialized transport system for phosphate across the basolateral membranes of the rat liver during development. This transport system exhibit ontogenic characteristics in regard to its transport capacity.

Animals↗

PubMed1996

Recent progress in understanding the temporal behavior of unicellular organisms.

This survey summarizes the findings concerning endogenous oscillations of three unicellular organisms: the dinophyte Gonyaulax polyedra, the ciliate Tetrahymena thermophila and the euglenophyte Euglena gracilis. All of them behave rhythmically and show the common features of zeitgeber action, differential sensitivity and temperature compensation; however, they exhibit some species-specific peculiarities that make each of them suitable for addressing particular chronobiological questions. Although ultradian rhythms have been described for Tetrahymena thermophila and Euglena gracilis, they appear under different conditions: in the first case, a modulation of the period in relation to the concentration of nutrients is observed, whereas Euglena oscillates in an ultradian and circadian fashion simultaneously. Transitions between periodic and aperiodic states can be induced in Euglena gracilis and Gonyaulax polyedra: Euglena gracilis can enter an aperiodic state after repeated exposure to short light pulses (up to 10 sec) given at intervals of 40 min or less, whereas in Gonyaulax polyedra the circadian oscillator is arrested at temperatures below 12 degrees C. In the arrhythmic state, the oscillator might be driven into singularity within the phase space of a limit cycle attractor; re-initiation from the holding point occurs by transition to a relatively precisely defined new phase. Photoperiodism as another important chronobiological phenomenon can be studied in Gonyaulax polyedra: cells enter the dormant stage of an asexual cyst under short days and a temperature below 16 degrees C. This response can be mimicked by 5-methoxylated indoleamines such as melatonin and 5-methoxytryptamine, which are synthesized by this organism. Melatonin concentration exhibit an endogenous circadian rhythm characterized by a rapid increase shortly after the onset of darkness. Encystment, as induced by indoleamines, is associated with stimulations of bioluminescence. The coupling of the two processes involves, as a common element, the release of protons from an acidic vacuole.

Animals↗

PubMed1996

Spectral analysis of hemodynamics during left ventricular assistance.

In order to analyze the autonomic nervous system during left ventricular (LV) assistance, fluctuations in hemodynamic derivatives were evaluated by a spectral analyzing method using a fast fourier transform (FFT) methodology. After the left pleural cavity was opened through the fourth intercostal space under general anesthesia, a pneumatically driven ventricular assist system was implanted as in left heart bypasses in chronic animal experiments, using three healthy adult goats. Hemodynamic parameters with and without LV assistance were recorded on a magnetic tape in the awake condition then analyzed in a computer system through an A-D convertor. Power spectral analysis was performed on a beat-to-beat basis for the evaluation of the fluctuations. During copulsation mode LV assistance, Mayer wave fluctuations (0.1 Hz) were significantly increased compared with counterpulsation mode LV assist, suggesting an increase in sympathetic tone. Co-pulsation mode LV assist is reported to increase the afterload of the natural left ventricle, thus, the sympathetic tone may be increased to maintain a natural heart output.

Analysis of Variance↗

PubMed1996

Control of Ca2+ homeostasis in neuronal cells.

The intracellular free Ca2+ concentrations show complex fluctuations in time and space in response to a variety of stimuli, and act as a pluripotent signal for many neuronal functions. Activation of cells is associated with Ca2+ influx from the extracellular space through voltage-dependent and/or receptor-operated Ca2+ channels localized on the plasma membrane, and/or by release of Ca2+ from intracellular stores to reach Ca2+ concentrations of up to micromolar levels. During cell relaxation, calcium concentration decreases to resting levels via ATP-driven Ca2+ transport both to the extracellular space and into the intracellular stores. Thus, Ca2+ homeostasis in neuronal cells is maintained by several systems differing by their mechanisms, biochemical characteristics and intracellular localization. Their biochemical properties and physiological importance as well as cellular localization are discussed in this short review.

Animals↗

PubMed2004

The pathogenesis of syringomyelia associated with lesions at the foramen magnum: a critical review of existing theories and proposal of a new hypothesis.

Syringomyelia is frequently accompanied by an extramedullary lesion at the foramen magnum, particularly a Chiari I malformation. Although syringomyelia associated with foramen magnum obstruction has characteristic clinical, radiological, and neuropathological features, its pathogenesis remains unclear. Currently prevalent hydrodynamical theories assert that obstruction of the subarachnoid space at the foramen magnum interferes with flow of cerebrospinal fluid (CSF) between the spinal and the intracranial subarachnoid compartments. As a result, spinal CSF is driven into the spinal cord through the perivascular spaces to form a syrinx. These theories are implausible biophysically because none postulates a pump adequate to drive fluid through these spaces. None of the theories can explain why syrinx pressure is higher than CSF pressure; why extensive gliosis, edema, and vascular wall thickening regularly occur; and why the composition of syrinx fluid is not identical with that of CSF. A new theory of pathogenesis is proposed to address these difficulties. In the presence of subarachnoid obstruction at the foramen magnum, a variety of activities, such as assuming the erect posture, coughing or straining, and pulsatile fluctuations of CSF pressure during the cardiac cycle, produce transiently higher CSF pressure above the block than below it. There are corresponding changes in transmural venous and capillary pressure favoring dilation of vessels below the block and collapse of vessels above the block. The spatially uneven change of vessel caliber produces mechanical stress on the spinal cord, particularly caudal to the block. The mechanical stress, coupled with venous and capillary dilation, partially disrupt the blood-spinal cord barrier, allowing ultrafiltration of crystalloids and accumulation of a protein-poor fluid. The proposed theory is consistent with the neuropathological findings in syringomyelia and with the pressure and composition of syrinx fluid. It also accounts for the prolonged course of syringomyelia and its aggravation by cough, strain, and assumption of an erect posture. It contributes to understanding the low incidence and the morphology of syringobulbia. It explains the poorly understood presentation of foramen magnum meningiomas with symptoms of a mid- to low-cervical myelopathy. The theory also affords an understanding of the late recurrence of symptoms in children with hydromyelia who are treated with a ventricular shunt.

Arnold-Chiari Malformation↗

PubMed2002

Detecting compensatory covariation signals in protein evolution using reconstructed ancestral sequences.

When protein sequences divergently evolve under functional constraints, some individual amino acid replacements that reverse the charge (e.g. Lys to Asp) may be compensated by a replacement at a second position that reverses the charge in the opposite direction (e.g. Glu to Arg). When these side-chains are near in space (proximal), such double replacements might be driven by natural selection, if either is selectively disadvantageous, but both together restore fully the ability of the protein to contribute to fitness (are together "neutral"). Accordingly, many have sought to identify pairs of positions in a protein sequence that suffer compensatory replacements, often as a way to identify positions near in space in the folded structure. A "charge compensatory signal" might manifest itself in two ways. First, proximal charge compensatory replacements may occur more frequently than predicted from the product of the probabilities of individual positions suffering charge reversing replacements independently. Conversely, charge compensatory pairs of changes may be observed to occur more frequently in proximal pairs of sites than in the average pair. Normally, charge compensatory covariation is detected by comparing the sequences of extant proteins at the "leaves" of phylogenetic trees. We show here that the charge compensatory signal is more evident when it is sought by examining individual branches in the tree between reconstructed ancestral sequences at nodes in the tree. Here, we find that the signal is especially strong when the positions pairs are in a single secondary structural unit (e.g. alpha helix or beta strand) that brings the side-chains suffering charge compensatory covariation near in space, and may be useful in secondary structure prediction. Also, "node-node" and "node-leaf" compensatory covariation may be useful to identify the better of two equally parsimonious trees, in a way that is independent of the mathematical formalism used to construct the tree itself. Further, compensatory covariation may provide a signal that indicates whether an episode of sequence evolution contains more or less divergence in functional behavior. Compensatory covariation analysis on reconstructed evolutionary trees may become a valuable tool to analyze genome sequences, and use these analyses to extract biomedically useful information from proteome databases.

Amino Acid Sequence↗

PubMed1995

Production and evolution of carbonaceous material by ion irradiation in space.

We review recent experimental studies concerning the evolution, driven by ion irradiation, of carbonaceous material from frozen gas to a refractory molecular solid. Under further irradiation the latter changes to a polymer-like material and ultimately to amorphous carbon. Most of the results have been obtained by "in situ" and remote IR and Raman spectroscopy. The results have been applied to demonstrate that molecular solids may be easily formed by irradiation of frozen mantles in dense interstellar clouds. Polymer-like material and amorphous carbons may result by further irradiation of organic mantles on grains in the diffuse interstellar medium. Those grains, during the aggregation to form extended bodies like comets (T-Tau phase of the Sun), are further modified. These latter are also irradiated, after the comet formation, during their long stay in the Oort cloud. In particular it has been suggested that comet may develop an ion-produced cometary organic crust that laboratory evidences show to be stable against temperature increases experienced during passages near the Sun. The comparison between the Raman spectra of some IDP (Interplanetary Dust Particles) and the Raman spectra of some ion-produced amorphous carbons, is also discussed.

Benzene↗

PubMed1990

On the multiple-minima problem in the conformational analysis of polypeptides. IV. Application of the electrostatically driven Monte Carlo method to the 20-residue membrane-bound portion of melittin.

The conformational space of the membrane-bound portion of melittin has been searched using the electrostatically driven Monte Carlo (EDMC) method with the ECEPP/2 (empirical conformational energy program for peptides) algorithm. The former methodology assumes that a polypeptide or protein molecule is driven toward the native structure by the combined action of electrostatic interactions and stochastic conformational changes associated with thermal movements. The algorithm produces a Monte Carlo search in the conformational hyperspace of the polypeptide using electrostatic predictions and a random sampling technique, combined with local minimization of the energy function, to locate low-energy conformations. As a result of 8 test calculations on the 20-residue membrane-bound portion of melittin, starting from six arbitrary and two completely random conformations, the method was able to locate a very low-energy region of the potential with a well-defined structure for the backbone. In all of the cases under study, the method found a cluster of similar low-energy conformations that agree well with the structure deduced from x-ray diffraction experiments and with one computed earlier by the build-up procedure.

Amino Acid Sequence↗

PubMed1995

Control of the head in response to tilt of the body in normal and labyrinthine-defective human subjects.

1. Head movement responses to discrete, unpredictable tilts of the trunk from earth upright were studied in normal and labyrinthine-defective (LD) subjects. Tilts of the seated, restrained trunk, were delivered in pitch and roll about head-centred axes and approximated raised cosine displacements with peak amplitudes of 20-30 deg and durations of 1.5-2 s. Subjects performed mental arithmetic with eyes closed or read earth-fixed text. 2. At the onset of tilt the head momentarily lagged behind the trunk because of inertia. Subsequently, head control varied widely with three broad types: (i) head relatively fixed to the trunk (in normal subjects and some patients); (ii) head unstable, falling in the direction of gimbal tilt (typical of acute patients for pitch motion); (iii) compensatory head movement in the opposite direction to gimbal tilt (observed consistently in normal subjects and in well-adapted patients). 3. EMG was well developed in subjects with compensatory head movement and consisted of an initial burst of activity at minimum latencies of 25-50 ms (means 72-108 ms), followed by a prolonged peak; both occurring in the 'side up' neck muscles, appropriate for righting the head. These muscles are shortened during the initial head lag so the responses cannot be stretch reflexes. In normal subjects their origin is predominantly labyrinthine but in patients they may be an 'unloading response' of the neck. 4. Head stability in space was superior with the visual task for all subjects but vision only partially compensated for labyrinthine signals in unstable patients. 5. Modelling the responses to tilt suggests that, in LD subjects, the short-latency burst could be driven by signals from the neck of the relative acceleration between head and trunk tilt. The longer latency EMG could be driven by a signal of head tilt in space. Normally, this signal is probably otolithic. In patients it could be synthesized from summing proprioceptive signals of position of head on trunk with trunk tilt.

Adaptation, Physiological↗

PubMed2006

Gradient-driven fluctuations experiment: fluid fluctuations in microgravity.

We describe an experimental breadboard developed for the investigation of nonequilibrium fluctuations induced by macroscopic temperature and concentration gradients under microgravity conditions. Under these conditions the amplitude of the fluctuations diverges strongly for long wavelengths. The setup was developed at the University of Milan and at the University of California at Santa Barbara within the gradient-driven fluctuations experiment (GRADFLEX) project of the European Space Agency, in collaboration with the National Aeronautics and Space Administration. The apparatus uses a quantitative shadowgraph technique for characterization of the static power spectrum of the fluctuations S(q) and the measurement of their dynamics. We present preliminary experimental results for S(q) obtained in the presence of gravity for gradient-driven fluctuations for two cases, those induced in a liquid mixture with a concentration gradient produced by the Soret effect and those induced in a single-component fluid by a temperature gradient.

Journal Article↗

PubMed2006

Controlling drift-wave turbulence using time-delay and space-shift autosynchronization feedback.

Drift-wave turbulence control in a one-dimensional nonlinear drift-wave equation driven by a sinusoidal wave is considered. We apply time-delay and space-shift feedback signals, to suppress turbulence. By using global and local pinning strategies, we show numerically that the turbulent state can be controlled to periodic states effectively if appropriate time-delay length and space-shift distance are chosen. The physical mechanism of the control scheme is understood based on the energy-minimum principle.

Journal Article↗

PubMed1997

Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord.

The impetus for the enlargement of syringes is unknown. The authors hypothesize that there is a flow of cerebrospinal fluid (CSF) from perivascular spaces into the central canal and that the flow is driven by arterial pulsations. Using horseradish peroxidase as a tracer, the CSF flow was studied in normal sheep, in sheep with damped arterial pulsations, and in sheep with lowered spinal subarachnoid pressure. The CSF flow from perivascular spaces into the central canal was demonstrated in the normal sheep, and two patterns of flow were identified: 1) from perivascular spaces in the central gray matter; and 2) from perivascular spaces in the ventral white commissure. Flow into the central canal was also observed in the sheep with lowered spinal subarachnoid pressure, but not in those with reduced arterial pulse pressure. This study provides evidence that CSF flow from perivascular spaces into the central canal is dependent on arterial pulsations. Arterial pulsation-driven CSF flow may be the impetus for the expansion of syringes.

Animals↗

PubMed2005

Green's-function reaction dynamics: a particle-based approach for simulating biochemical networks in time and space.

We have developed a new numerical technique, called Green's-function reaction dynamics (GFRD), that makes it possible to simulate biochemical networks at the particle level and in both time and space. In this scheme, a maximum time step is chosen such that only single particles or pairs of particles have to be considered. For these particles, the Smoluchowski equation can be solved analytically using Green's functions. The main idea of GFRD is to exploit the exact solution of the Smoluchoswki equation to set up an event-driven algorithm, which combines in one step the propagation of the particles in space with the reactions between them. The event-driven nature allows GFRD to make large jumps in time and space when the particles are far apart from each other. Here, we apply the technique to a simple model of gene expression. The simulations reveal that spatial fluctuations can be a major source of noise in biochemical networks. The calculations also show that GFRD is highly efficient. Under biologically relevant conditions, GFRD is up to five orders of magnitude faster than conventional particle-based techniques for simulating biochemical networks in time and space. GFRD is not limited to biochemical networks. It can also be applied to a large number of other reaction-diffusion problems.

Algorithms↗