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Free-grazing ducks and highly pathogenic avian influenza, Thailand.

Thailand has recently had 3 epidemic waves of highly pathogenic avian influenza (HPAI); virus was again detected in July 2005. Risk factors need to be identified to better understand disease ecology and assist HPAI surveillance and detection. This study analyzed the spatial distribution of HPAI outbreaks in relation to poultry, land use, and other anthropogenic variables from the start of the second epidemic wave (July 2004-May 2005). Results demonstrate a strong association between H5N1 virus in Thailand and abundance of free-grazing ducks and, to a lesser extent, native chickens, cocks, wetlands, and humans. Wetlands used for double-crop rice production, where free-grazing duck feed year round in rice paddies, appear to be a critical factor in HPAI persistence and spread. This finding could be important for other duck-producing regions in eastern and southeastern Asian countries affected by HPAI.

Animals↗

[Equilibrium intramolecular mobility in proteins].

The critical analysis of available information on equilibrium intramolecular mobility in proteins is performed and an attempt is made to systematize it in relation to characteristic times tau, probability and spatial scale. We propose to discriminate fast (tau less than 10(-6) s) and slow (tau greater than 10(-6) s) mobility. The methods are considered for investigating fast mobility (X-ray analysis temperature-dependent factor, broadening of absorption spectra, thermal perturbation difference spectra and thermal ring-current shifts of 1H-NMR, fluorescence dipolar relaxation and quenching, 13C-NMR spin-lattice relaxation times and nuclear Overhauser enhancement and others) and the principal results obtained. Fast mobility is widely spread within the molecules. Its existence results in a population of dynamic microstates, the distribution of which depends on local packing density and secondary bonding. The fast movements are local and of very small activation energies. tau depends on the group size and are much longer than those of diffusion in simple liquids. Therefore, this kind of mobility may be characterized as a limited diffusion process in a medium with high and nonuniform viscosity. The significance of the fast mobility for the protein function is discussed. No function significant transglobular change of protein conformation could be obtained by subnanosecond, fast movements, but they depend on the level of "viscosity' of protein interior, produced by fast mobility. The fast dynamic microstates results in distribution of activation parameters for protein reactions.

Kinetics↗

The spatial pattern of the vacuolation in patients with sporadic Creutzfeldt-Jakob disease.

1600 microm in diameter and, in the majority of tissue sections, the vacuole clusters were distributed with regular periodicity parallel to the tissue boundary. The size of the vacuole clusters was positively correlated with patient age in the lower laminae of the occipital cortex and the inferior temporal gyrus (ITG) and negatively correlated with age in the hippocampus. In addition, the size of the vacuole clusters was positively correlated with disease duration in the upper laminae of the ITG. The size and distribution of the vacuole clusters suggests that the vacuolation in CJD reflects the degeneration of specific brain pathways and supports the hypothesis that prion pathology may spread through the brain along well defined anatomical pathways.

Aged↗

The extent of crowding in peripheral vision does not scale with target size.

Identifying a target is more difficult when distracters are present within a zone of interaction around the target. We investigated whether the spatial extent of the zone of interaction scales with the size of the target. Our target was a letter T in one-of-four orientations. Our distracters were four squared-thetas in one-of-two orientations, presented one in each of the four cardinal directions, equidistant from the target. Target-distracter separation was varied and the proportion of correct responses at each separation was determined. From these the extent of interaction was estimated. This procedure was repeated for different target sizes spread over a 5-fold range. In each case, the contrast of the target was adjusted so that its visibility was constant across target sizes. The experiment was performed in the luminance domain (grey targets on grey background) and in the chromatic domain (green target on equiluminant grey background). In the luminance domain, target size had only a small effect on the extent of interaction; these interactions did not scale with target size. The extents of interaction for chromatic stimuli were similar to those for luminance stimuli. For a fixed target visibility, decreasing the duration of the stimulus resulted in an increase in the extent of interaction. The relevance of our findings is discussed with regard to a variety of proposed explanations for crowding. Our results are consistent with an attention-based explanation for crowding.

Attention↗

Groundwater contamination by nitrates associated with intensive potato culture in Québec.

In rural areas, groundwater contamination by nitrates is a problem related to the spreading of organic and chemical fertilizers by farmers and, to some extent, to effluents from domestic sewage systems. Health effects of groundwater contamination by nitrates have been assessed several times and may lead to important consequences for infants. Following pressures from citizens in 1990, a survey of well water quality around potato fields of the Portneuf county (Québec) found that nitrate contamination was frequently above the 10 mg-N/1 standard. Because this first survey was limited to areas of intensive potato culture, it was not possible to evaluate the real impact on the groundwater quality for the whole county and the subsequent public health intervention was spread over the entire region. A second survey was carried out in 1995 to reevaluate the situation using random sampling methods. This latter study took into account drinking water habits of the population, the relative importance of potato culture as a source of nitrogen loading, the effects of soil types, and waste-water disposal systems as well as land use on nitrate concentration in private well water. The data analysis was carried out by combining GIS and statistical methods to test hypotheses about the spatial relationship linking measured nitrate concentrations with their immediate environment. This paper presents the major findings from this second study which confirm the impact of intensive potato culture on groundwater nitrate concentrations, mainly localized in sandy soil areas within 2 km of fields. Finally, it illustrates the usefulness of GIS to focus public health interventions.

Agriculture↗

A moment closure model for sexually transmitted disease transmission through a concurrent partnership network.

A moment closure model of sexually transmitted disease spread through a concurrent partnership network is developed. The model employs pair approximations of higher-order correlations to derive equations of motion in terms of numbers of pairs and singletons. The model is derived from an underlying stochastic process of partnership network formation and disease transmission. The model is analysed numerically; and the final size and time evolution are considered for various levels of concurrency, as measured by the concurrency index kappa3 of Kretzschmar and Morris. Additionally, a new way of calculating R0 for spatial network models is developed. It is found that concurrency significantly increases R0 and the final size of a sexually transmitted disease, with some interesting exceptions.

Humans↗

Keratin 17 gene expression during the murine hair cycle.

Keratin 17 (K17) expression is currently considered to be associated with hyperplastic or malignant growth of epithelial cells. The functions of this keratin in normal skin physiology and the regulation of its gene expression, however, are still unclear. As one possible approach to further explore K17 functions, we have studied the differential patterns of mouse K17 (MK17) transcription during the murine hair cycle by means of in situ hybridization, using a digoxigenin-labeled riboprobe. Cycling hair follicles in the skin of C57BL/6 mice were found to be the only skin structures expressing MK17 under physiologic conditions. MK17 transcripts were constantly observed throughout all hair cycle stages in the suprainfundibular outer root sheath (ORS). The MK17 expression was also evident in the isthmus part of the ORS, where it was expressed weakly and was spatially restricted during telogen, with an increase in early anagen and stable expression during mid- and late anagen, localizing to the zone of so-called trichilemmal keratinization. In addition, in early anagen, a group of epithelial cells in or next to the bulge region stained weakly for MK17. With progressing anagen development, MK17 expression in this region increased and was consistently localized to keratinocytes at the advancing front of the emerging epithelial hair bulb. In mid- and late anagen, this zone of MK17 expression spread along the proximal ORS, with a maximal level of expression in the innermost cell layer of the ORS. Overall, these findings provide data on the MK17 expression profile of normal murine skin and demonstrate hair-cycle-dependent regulation of MK17 expression.

Animals↗

Neural field model of receptive field restructuring in primary visual cortex.

Receptive fields (RF) in the visual cortex can change their size depending on the state of the individual. This reflects a changing visual resolution according to different demands on information processing during drowsiness. So far, however, the possible mechanisms that underlie these size changes have not been tested rigorously. Only qualitatively has it been suggested that state-dependent lateral geniculate nucleus (LGN) firing patterns (burst versus tonic firing) are mainly responsible for the observed cortical receptive field restructuring. Here, we employ a neural field approach to describe the changes of cortical RF properties analytically. Expressions to describe the spatiotemporal receptive fields are given for pure feedforward networks. The model predicts that visual latencies increase nonlinearly with the distance of the stimulus location from the RF center. RF restructuring effects are faithfully reproduced. Despite the changing RF sizes, the model demonstrates that the width of the spatial membrane potential profile (as measured by the variance sigma of a gaussian) remains constant in cortex. In contrast, it is shown for recurrent networks that both the RF width and the width of the membrane potential profile generically depend on time and can even increase if lateral cortical excitatory connections extend further than fibers from LGN to cortex. In order to differentiate between a feedforward and a recurrent mechanism causing the experimental RF changes, we fitted the data to the analytically derived point-spread functions. Results of the fits provide estimates for model parameters consistent with the literature data and support the hypothesis that the observed RF sharpening is indeed mainly driven by input from LGN, not by recurrent intracortical connections.

Electroencephalography↗

Bidirectional compartmental approximation of realistic nerve cell structures.

Passive electrotonic activity of anatomically complex nerve cells has been computed through a simplified anisotropic "smoothing" of the original structures. The algorithm for this "smoothing" involves a recursive matching of the amplitude, zero and pole of the input impedances for each segment. This algorithm can be used for both spatially and/or electrically inhomogeneous cables. The directional sensitivity of the voltage transfer in non-smooth dendrites has been characterized by a decomposition which reveals the bidirectional segmentation of the core geometry according to the opposite wave fronts of electronic potentials in dendrites. The impedance diagrams can be used to estimate the goodness of the whole procedure in the frequency domain. The bidirectional segmentation of the core geometry may serve as a basis of the compartment simulations of those excitable nerve cells where the voltage spread is modulated by irregular dendritic structures, such as spines.

Algorithms↗

Inhibition of return spreads across 3-D space.

Focusing attention to a location in 3-D space operates much the same as in 2-D space. Attending a location in 2-D space is followed by a selective inhibitory aftereffect known as inhibition of return (IOR). Here, we report the results of two 3-D reflexive cuing studies in which depth was defined by binocular disparity. As has been shown before, attentional cuing was specific for x-y-z locations. However, the present results show that IOR is not depth specific. After a specific location in x-y-z is cued, IOR occurs for the depth plane in front of and behind the cued location. The finding that IOR spreads across depth planes may be related to how inhibited locations are encoded in the superior colliculus. We argue that the functional role of a depth-blind IOR is to bias attention against going back to any part of a previously attended object.

Attention↗

Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system.

Gap junctions play essential roles in the normal function of the heart and arteries, mediating the spread of the electrical impulse that stimulates synchronized contraction of the cardiac chambers, and contributing to co-ordination of activities between cells of the arterial wall. In common with other multicellular systems, cardiovascular tissues express multiple connexin isotypes that confer distinctive channel properties. This review highlights how state-of-the-art immunocytochemical and cellular imaging techniques, as part of a multidisciplinary approach in gap junction research, have advanced our understanding of connexin diversity in cardiovascular cell function in health and disease. In the heart, spatially defined patterns of expression of three connexin isotypes-connexin43, connexin40, and connexin45-underlie the precisely orchestrated patterns of current flow governing the normal cardiac rhythm. Derangement of gap junction organization and/or reduced expression of connexin43 are associated with arrhythmic tendency in the diseased human ventricle, and high levels of connexin40 in the atrium are associated with increased risk of developing atrial fibrillation after coronary by-pass surgery. In the major arteries, endothelial gap junctions may simultaneously express three connexin isotypes, connexin40, connexin37, and connexin43; underlying medial smooth muscle, by contrast, predominantly expresses connexin43, with connexin45 additionally expressed at restricted sites. In normal arterial smooth muscle, the abundance of connexin43 gap junctions varies according to vascular site, and shows an inverse relationship with desmin expression and positive correlation with the quantity of extracellular matrix. Increased connexin43 expression between smooth muscle cells is closely linked to phenotypic transformation in early human coronary atherosclerosis and in the response of the arterial wall to injury. Current evidence thus suggests that gap junctions in both their guises, as pathways for cell-to-cell signaling in the vessel wall and as pathways for impulse conduction in the heart, contribute to the initial pathogenesis and eventual clinical manifestation of human cardiovascular disease.

Cardiovascular Diseases↗

Velocity estimation of spots in three-dimensional confocal image sequences of living cells.

BACKGROUND: The analysis of three-dimensional (3D) motion is becoming increasingly important in life cell imaging. A simple description of sometimes complex patterns of movement in living cells gives insight in the underlying mechanisms governing these movements. METHODS: We evaluate a velocity estimation method based on intensity derivatives in spatial and temporal domain from 3D confocal images of living cells. Cells of the sample contain intense spots throughout the cell nucleus. In simulations, we model these spots as Gaussian intensity profiles which are constant in intensity and shape. To quantify the quality of the estimated velocity, we introduce a reliability measure. RESULTS: For constant linear velocity, the velocity estimation is unbiased. For accelerated motion paths or when a neighboring spot disturbs the intensity profile, the method results are biased. The influence of the point-spread function on the velocity estimation can be compensated for by introducing anisotropic derivative kernels. The insight gained in the simulations is confirmed by the results of the method applied on an image sequence of a living cell with fluorescently labeled chromatin. CONCLUSIONS: With the velocity estimation method, a tool for estimating 3D velocity fields is described which is successfully applied to a living cell sequence. With the estimated velocity fields, motion patterns can be observed, which are a useful starting point for the analysis of dynamic processes in living cells.

Animals↗

Spatiotemporal characterization of intracellular Ca2+ rise during the acrosome reaction of mammalian spermatozoa induced by zona pellucida.

The mammalian sperm acrosome reaction (AR) is an essential event prior to sperm-egg fusion at fertilization, and it is primarily dependent on an increase in intracellular Ca2+ concentration ([Ca2+]i). Spatiotemporal aspects of the [Ca2+]i increase during the AR induced by solubilized zona pellucida (ZP) in hamster spermatozoa were precisely investigated with a Ca2+ imaging technique using confocal laser scanning microscopy with two fluorescent Ca2+ indicators. A rapid rise in [Ca2+]i occurred immediately after the application of ZP solution through a micropipette. The rise was always initiated in the sperm head, even when the application was directed toward the tail. The elevated [Ca2+]i was little attenuated during measurement for 30-40 s. Acrosomal exocytosis was detected as a sudden decrease of fluorescence in the acrosomal vesicle approximately 20 s after the onset of the [Ca2+]i rise. High-resolution imaging revealed that the [Ca2+]i rise in the sperm head began at the region around the equatorial segment and spread over the posterior region of the head within 0.6 s, whereas Ca2+ concentration in the acrosomal vesicle appeared to be unaltered. The [Ca2+]i rise was completely abolished under Ca2+-free extracellular conditions, indicating that it is totally attributable to Ca2+ influx. Nifedipine, an inhibitor of L-type Ca2+ channels, did not affect the rising phase of the ZP-induced Ca2+ response, but accelerated the decline of the [Ca2+]i rise and inhibited acrosomal exocytosis. The present study provides implicative information about the spatial organization of functional molecules involved in the signal transduction in mammalian AR.

Acrosome↗

Intracellular oxygen measurements of mouse liver cells using quantitative fluorescence video microscopy.

Our currently developed fluorescence video microscope can measure fluorescence intensities with an error of +/- 1.5% of full scale in 65536 different positions of a microscope field. With a video frame freeze acquisition time of 33 ms, time-dependent changes of this order of time or slower can be followed. Using cells which have absorbed pyrene-1-butyrate to an intracellular concentration of 0.05 to 1 mM, the changes in fluorescence intensity with oxygen concentration are easily measured. The spatial resolution for data collection is 0.5 micron when a 54X objective is used. The individual Stern-Volmer quenching constants of each individual pixel were measured for agar slices and mouse liver cells treated with pyrenebutyric acid. The distribution of quenching constants for agar follows a normal curve about a mean value of 16 . 10(-4) torr-1. The data for mouse liver cells gave a non-normal distribution of quenching constants with a mean value of 18 . 10(-4) torr-1. The greater spread of the data from cells is interpreted as evidence for a real biological variation in the solubility coefficient of oxygen in different locations within the cell. In all the cells examined, this distribution has been observed to be non-random and appears to be associated with specific cell structures.

Animals↗

Warned, but not well armed: preventing viral upper respiratory infections in households.

The purpose of this state-of-the-science review was to identify strategies and household-level interventions for public health nurses to help prevent the acquisition and spread of viral upper respiratory infections (URI) in the community. Even though viral URI are a major global economic and social problem, surprisingly little research has been conducted to attempt to prevent them or reduce their transmission, probably because URI (with the exception of epidemic influenza) are generally considered to be mild and self-limited. Based on the research to date, public health nurses can use several promising strategies for prevention: (a) provide more tailored educational messages regarding preventive strategies such as vaccination, hand hygiene, spatial separation of infected household members, avoidance of antibiotics to treat viral URI, and environmental cleaning (e.g., for toys or other shared items), which are delivered personally rather than passively (e.g., pamphlets placed in a waiting room); (b) use each patient encounter in any setting to encourage influenza vaccination for relevant risk groups; (c) encourage use of alcohol hand sanitizers by household members during the cold and flu season; and (d) provide opportunities for skill development for adult and child household members (e.g., cover your cough, when to seek care or an antibiotic).

Adult↗

Potassium buffering by Müller cells isolated from the center and periphery of the frog retina.

Müller (radial glial) cells span the retina from the outer to the inner limiting membranes. They are the only glial cells found in the amphibian retina. The thickness of the frog (Rana pipiens) retina decreases by a factor of about four from the center to the periphery. Thus, Müller cells were isolated, by enzymatic dissociation, with stalk lengths from 20 to 140 microm. Their ability to transfer K(+) via the stalk between soma and endfoot was studied. Membrane currents were recorded using the whole-cell voltage-clamp technique with the pipette sealed to either the endfoot or the soma. Inward (I(KIN)) or outward (I(KO)) currents were elicited by rapid increases (3 to 10 mM) or decreases (3 to 1 mM) of the extracellular K(+) concentration ([K(+)](o)) either by local application (close or distant to the recording pipette) or around the entire cell (whole cell perfusion). For the long central cells, the ratio I(KIN)/I(KO) was 4.6 +/- 0.6 SE (n = 9) at the endfoot and 1.7 +/- 0.1 SE (n = 8) at the soma. In cells from the retinal periphery, the ratio I(KIN)/I(KO) was higher, 7.0 +/- 0.27 (n = 8) at the endfoot and 3.2 +/- 0.1 (n = 10) at the soma. The results suggest that there is less inward rectification in the somatic than in the endfoot membrane. As expected from previous studies, the sensitivity of the cells to K(+) was higher at the endfoot than at the soma. The amplitude of I(KIN) at the endfoot compared to the soma was about 8-fold for the long central cells but only about 1.5-fold for the short peripheral cells. Currents spread readily from endfoot to soma in the peripheral cells. In the long central Müller cells the soma and endfoot appeared electrotonically isolated. The "functional length constant", lambda, of cell stalk processes was about 70 microm. The relative decrement of large inward currents was stronger than that of smaller outward currents; this difference ("artificial rectification") is explained by a simple model, where larger currents (inward) are attenuated more than smaller (outward) currents. The data support the hypothesis that in the retinal periphery, Müller cells provide extensive spatial K(+) buffering from both plexiform layers into the vitreous body. In the central retina, however, such currents are limited within a short (interlaminar) range.

Animals↗

Ontogenic expression of TGFbeta 1, 2, and 3 and its receptors in the rat gastric mucosa.

The stomach of the rat undergoes extensive changes during the formation and maturation of gastric glands. The presence of transforming growth factor beta (TGFbeta) in rat milk and in the gastrointestinal tract of pups may suggest its role in this process. The current study evaluated the in vivo dynamic expression and distribution of TGFbeta1, beta2, beta3 and their receptors TbetaRI and TbetaRII in the gastric epithelium of 20-day fetal rats and 1-, 14-, 21-, and 30-day-old pups. Immunohistochemistry was used to detect the proteins, and staining was classified according to intensity and cell type. The results showed that the gastric epithelium expresses TGFbeta isoforms and receptors throughout development. We found that immunoreactivity paralleled the appearance of differentiated cells, such that surface mucous cells were the first to be immunostained and chief cells were the last. The intensity of reactions followed this same pattern, showing that the expression of TGFbeta isoforms spread along the gland with growth. Of interest, the highest apparent activity of TGFbeta was observed from 21 days onward, a period that is concomitant with weaning and maturation of most gastric cell types. In addition, surface mucous cells were strongly labeled at the basal cytoplasm at 14 days, suggesting an interaction with the connective tissue. In conclusion, the dynamic expression of TGFbeta1, beta2, beta3, and TbetaRI and TbetaRII through stomach development suggests significant paracrine and autocrine roles for this growth factor. We propose that temporal and spatial differences may be regulated by dietary changes, which in turn control cell proliferation and differentiation in the gastric epithelium.

Animal Feed↗