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HLA-DRB1*, -DQB1* in Piramalai Kallars and Yadhavas, two Dravidian-speaking castes of Tamil Nadu, South India.

Two Dravidian-speaking castes of Tamil Nadu, Piramalai Kallars (PKs, n = 205) and Yadhavas (YDs, n = 239) and a random panel (84) were studied for HLA-DRB1* and -DQB1* polymorphisms by DNA-SSOP typing methods. XI and XII International Histocompatibility primers and non-radioactive-labelled oligo probes were employed to identify the alleles. Results revealed that PKs possessed >0.1 allele frequencies of HLA-DRB1*15011, 0301, -DQB1*0201, 0501 and 0601; YDs, HLA-DRB1*0301, 0401, 07 and -DQB1*0601; and the random panel, DRB1*15021, 0401, 07, -DQB1 0201, 0301, 0302 and 0501. The highest frequency of DRB1*1501 in the world (GF = 0.225) was found in PKs. The most frequent two-locus haplotype (>500/10,000) in all the study samples was DRB1*10-DQB1*0501, while 1501-0601 was frequent in PKs and YDs. Comparison of the HLA-DRB1* data with Eastern European and South-East Asian populations suggested migration as the prime cause of the observed diversity in DRB1* allele frequencies. Nonetheless, the heterozygocity test and Watterson's homozygosity test indicated that balancing selection still operates on HLA-DRB1* locus, in this endemic region of various infectious diseases. This and spatial autocorrelation analysis support the view that selection may be a cause of "generating" new variants and allelic diversity in different ancient settlements. The study suggested that South Indian, inbred, endogamous, sympatrically isolated castes or similar well-defined breeding isolates around the world, living under the same milieu-epidemiology, may be ideal models to test the immunogenetic basis of disease susceptibility.

Adult↗

Effect of surface medium on visual search for orientation and size features.

By using a visual search task, this study examined the encoding of orientation and size for stimuli defined in five different surface media: luminance, color, texture, relative motion, and binocular disparity. Results indicated a spatially parallel analysis of size and orientation features for all surface media, with the possible exception of binocular disparity. The data also revealed a search rate asymmetry in the orientation task for all media: Parallel or shallow search functions were obtained for oblique targets in vertical distractors, whereas steeper serial search functions were obtained for vertical targets in oblique distractors. No consistent asymmetry was found for the large and small targets in the size task. There seemed to be common principles of coding in all these different media, suggesting either a single analysis of shape features applied to a common representation or multiple analyses, one for each surface medium, with each extracting a similar set of features. The shared coding principles may facilitate the use of redundancy across media to reduce ambiguities in the locations and shapes of contours in the visual scene.

Adult↗

Perceptual processes that may create stick figures and balance.

A series of experiments looked at the pattern of dot placements created when people individually placed a single dot inside empty outline figures. The superimposed results were found to compare better with the predictions of Blum's grassfire model than with a size-constancy process. The pattern of superimposed dots conformed to the stick figure of the outlined contours. A perceptual model based on spatial harmonic analysis of complex visual scenes is offered as an explanation for the pattern of results.

Cognition↗

Internal representation of visual texture as the basis for the judgment of similarity.

The relationship between Fourier spectra of visual textures (represented both by the actual frequency components and by the response of four hypothetical channels selectively sensitive to spatial frequency) and the perceptual appearance of the textures was investigated. Thirty textures were synthesized by combining seven spatial frequencies whose amplitudes were randomly chosen and then scaled to give an overall contrast of .9. Similarity judgments were collected using both the method of triadic comparison (two subjects, 4,060 trials each) and the method of paired comparison (six subjects, 435 trials each). The similarity judgments were subjected to MDSCAL and INDSCAL dimensions were found to be optimally oriented in terms of spatial frequency information without rotation. The seven spatial frequency components accounted for 90.6% of the variance in the 3-D INDSCAL space, while the four channels accounted for 91.8% of the variance in the first two dimensions. The data further suggest that the four channels may interact in an opponent process manner. The results support the idea that the visual internal representation of stimuli is based on spatial frequency analysis rather than feature extraction.

Discrimination Learning↗

Mapping the visual field in mental imagery.

We describe a simple psychophysical technique for measuring the size and shape of visual fields in mental imagery, and use this technique to compare fields in imagery and perception within which bar gratings of various spatial frequencies can be resolved. The first experiment demonstrates that the size of fields of resolution obtained when bar gratings are imagined decreases with increasing spatial frequency of the gratings, in the same way that the size of fields obtained when the gratings are actually observed decreases. This experiment also shows that imagery and perceptual fields are very similar in shape, both being elongated horizontally and extending farther below the point to which one's gaze is directed than above. The second experiment shows that experimental subjects are not able to anticipate the more subtle characteristics of these fields, such as the precise rate at which field size decreases with increasing spatial frequency--characteristics that most clearly reveal the very close correspondence between the imagery and perceptual fields. The third experiment shows that the size of the imagery fields can serve to discriminate between vivid and nonvivid imagers when the task of imagining the gratings is made sufficiently difficult. We interpret these findings as evidence that visual imagery involves the activation of mechanisms in the visual system that are specifically designed to process information about spatial frequency. In particular, we claim that constraints that these mechanisms impose on the resolution of high spatial frequencies in perception are also imposed in mental imagery, restricting how well fine details of an object can be imagined. We then discuss implications of these findings for theories about spatial-frequency analysis in vision and for the general issue of the functional value of mental imagery.

Form Perception↗

High-performance digital image analyzer for quantitative autoradiography.

A digital image-processing system was developed for high-spatial resolution analysis of autoradiograms. The system uses a linear array of charge-coupled devices operating under computer control to scan and digitize autoradiograms into 512 X 512 matrices with 256 gray levels. Software was developed to facilitate quantitative analysis of autoradiograms produced in single- and multiple-tracer studies. Because of the high output, linearity, and accuracy of the solid-state detectors, the system was found to digitize autoradiograms significantly more precisely and accurately than previously described video camera- or photomultiplier tube-based scanning densitometers.

Autoradiography↗

Evolutionary fingerprints of epithelial-to-mesenchymal transition.

Mesenchymal plasticity has been extensively described in advanced epithelial cancers; however, its functional role in malignant progression is controversial1-5. The function of epithelial-to-mesenchymal transition (EMT) and cell plasticity in tumour heterogeneity and clonal evolution is poorly understood. Here we clarify the contribution of EMT to malignant progression in pancreatic cancer. We used somatic mosaic genome engineering technologies to trace and ablate malignant mesenchymal lineages along the EMT continuum. The experimental evidence clarifies the essential contribution of mesenchymal lineages to pancreatic cancer evolution. Spatial genomic analysis, single-cell transcriptomic and epigenomic profiling of EMT clarifies its contribution to the emergence of genomic instability, including events of chromothripsis. Genetic ablation of mesenchymal lineages robustly abolished these mutational processes and evolutionary patterns, as confirmed by cross-species analysis of pancreatic and other human solid tumours. Mechanistically, we identified that malignant cells with mesenchymal features display increased chromatin accessibility, particularly in the pericentromeric and centromeric regions, in turn resulting in delayed mitosis and catastrophic cell division. Thus, EMT favours the emergence of genomic-unstable, highly fit tumour cells, which strongly supports the concept of cell-state-restricted patterns of evolution, whereby cancer cell speciation is propagated to progeny within restricted functional compartments. Restraining the evolutionary routes through ablation of clones capable of mesenchymal plasticity, and extinction of the derived lineages, halts the malignant potential of one of the most aggressive forms of human cancer.

Animals↗

Investigations of the proximity effect for pollutants in the indoor environment.

More than a dozen indoor air quality studies have reported a large discrepancy between concentrations measured by stationary indoor monitors (SIMs) and personal exposure monitors (PEMs). One possible cause of this discrepancy is a source proximity effect, in which pollutant sources close to the respondent cause elevated and highly variable exposures. This paper describes three sets of experiments in a home using real-time measurements to characterize and quantify the proximity effect relative to a fixed distant location analogous to a SIM. In the first set of experiments, using sulfur hexafluoride (SF6) as a continuously emitting tracer pollutant from a point source, measurements of pollutant concentrations were made at different distances from the source under different air exchange rates and source strengths. A second set of experiments used a continuous point source of carbon monoxide (CO) tracer pollutant and an array of high time resolution monitors to collect simultaneous concentration readings at different locations in the room. A third set of experiments measured particle count density and particle-bound polycyclic aromatic hydrocarbon (PAH) concentrations emitted from a continuous particle point source (an incense stick) using two particle counters and two PAH monitors, and included human activity periods both before and during the source emission period. Results from the SF6 and CO experiments show that while the source is emitting, a source proximity effect can be seen in the increases in the mean and median and in the variability of concentrations closest to the source, even at a distance of 2.0 m from the source under certain settings of air exchange rate and source strength. CO concentrations at locations near the source were found to be higher and more variable than the predictions of the mass balance model. For particles emitted from the incense source, a source proximity effect was evident for the fine particle sizes (0.3 to 2.5 microm) and particle-bound PAH up to at least 1.0 m from the source. Analysis of spatial and temporal patterns in the data for the three tracer pollutants reveal marked transient elevations of concentrations as seen by the monitor, referred to as "microplumes," particularly at locations close to the source. Mixing patterns in the room show complex patterns and directional effects, as evidenced by the variable intensity of the microplume activity at different locations. By characterizing the spatial and temporal variability of pollutant concentrations in the home, the proximity effect can be quantified, leading to improved indoor monitoring designs and models of human exposure to air pollutants.

Air Pollutants↗

Novel approaches for understanding the mechanisms of wound repair.

Mechanisms that drive wound repair are complex and have challenged wound-healing investigators for many years. In this review, we present four examples of new tools that are being utilized to discover events that drive wound repair and regeneration. Laser capture microdissection facilitates the focused collection of tissue for purposes of genomic or proteomic analysis from specific cell populations within the wound bed. Tissue profiling and protein imaging by matrix-assisted laser desorption ionization mass spectrometry are two proteomic-based tools that permit rapid analysis with spatial orientation and relative abundance of hundreds to thousands of molecules from intact tissues. Another approach uses an in vivo porcine model to harness a strategy of adenoviral-driven receptor overexpression. This biological model closely mimics the human setting and permits transient stimulation along a specific cytokine pathway to tip the balance in favor of accelerated repair. The advent of new approaches that collect cell samples from within their in vivo circumstance while preserving discrete cellular localizations is likely to move the field of wound repair forward.

Adenoviridae↗

Viral clostridial light chain gene-based control of penicillin-induced neocortical seizures.

Restraining excitatory neurotransmission within a seizure focus provides a nondestructive treatment strategy for intractable neocortical epilepsy. Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a critical vesicle-docking protein, synaptobrevin, without directly altering neuronal health. This study tests the treatment efficacy of adenoviral vector delivered LC (AdLC) on a model of seizures in rats induced by motor cortex penicillin (PCN) injection. LC expression significantly reduced electroencephalogram (EEG) frequency, amplitude, duration, and latency compared to control groups injected with either an adenoviral vector bearing green fluorescent protein (AdGFP) or phosphate buffered solution (PBS). Correspondingly, LC gene expression improved behavioral manifestations including seizure severity and latency. There was no statistical difference in motor function before and after vector administration between treatment and control groups. Histological analysis revealed spatially discrete LC expression with corresponding synaptobrevin depletion in the cortex surrounding the injection site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG and behavioral manifestations of PCN-induced focal neocortical seizures through synaptobrevin depletion.

Animals↗

Leucine aminopeptidase during meiotic development.

We found a leucine aminopeptidase (LAP; EC 3.4.11.1) to be abundant in meiotic prophase tissue of a basidiomycete, Coprinus cinereus. After direct purification of the aminopeptidase component from meiocytes, we cloned the gene by degenerate PCR using partial amino-acid sequences of the purified enzyme and 5' and 3' RACE. It was homologous to the eukaryotic leucine aminopeptidase gene. The recombinant protein possesses the characteristic activities of a Coprinus leucine aminopeptidase (CoLAP) with a molecular mass of 52.4 kDa, and forms a homohexamer. Northern blot and spatial distribution analysis by immunohistochemical staining indicated CoLAP to be abundant in meiotic prophase cells and the supporting cells around meiocytes, but scarce in mycelium cells. Interestingly, from zygotene to pachytene, CoLAP was mostly present in supporting cells around meiocytes, but from diplotene onwards, it was plentiful in meiocytes themselves, suggesting that its expression is required to control some of the biochemical events at meiotic prophase. Moreover, the strong expression of CoLAP mRNA immediately after treatment with methyl methanesulfonate in mycelium implies that CoLAP has a role in somatic DNA repair.

Amino Acid Sequence↗

Object attention revisited: identifying mechanisms and boundary conditions.

Multiple attributes of a visual array are often more efficiently processed when they are attributes of a single object than when they are attributes of different objects-a pattern reflecting the limitations of object attention. This study used psychophysical methods to evaluate the object attention limitations in the report of attributes (orientation and phase) computed early in visual analysis for spatially separated objects. These limitations had large effects on dual-object report thresholds when different judgments were required for the two objects (orientation for one object and phase for the other), but the effects were small or nonexistent when the same judgment was made about both objects. Judgment consistency reduced or eliminated the expression of object attention deficits. Thus, the deficits in dual-object report reflect both division of attention over objects and the calculation of independent reference or judgment operations. Dual-object deficits, when they occurred, were substantial in displays with external noise masks. Smaller effects were observed in clear displays, even when difficulty was equated by stimulus contrast. Thus, the primary consequence of object attention is the exclusion of external noise, or mask suppression, and enhancement of the stimulus in clear displays is a secondary consequence.

Attention↗

The contribution of haploids, diploids and clones to fine-scale population structure in the seaweed Cladophoropsis membranacea (Chlorophyta).

Local populations of Cladophoropsis membranacea exist as mats of coalesced thalli composed of free-living haploid and diploid plants including clonally reproduced plants of either phase. None of the phases are morphologically distinguishable. We used eight microsatellite loci to explore clonality and fine-scale patch structure in C. membranacea at six sites on the Canary Islands. Mats were always composites of many individuals; not single, large clones. Haploids outnumbered diploids at all sites (from 2:1 to 10:1). In both haploid and diploid plants, genetic diversity was high and there was no significant difference in allele frequencies. Significant heterozygote deficiencies were found in the diploid plants at five out of six sites and linkage disequilibrium was associated with the haploid phase at all sites. Short dispersal distances of gametes/spores and small effective population sizes associated with clonality probably contribute to inbreeding. Spatial autocorrelation analysis revealed that most clones were found within a radius of approximately 60 cm and rarely further than 5 m. Dominance of the haploid phase may reflect seasonal shifts in the relative frequencies of haploids and diploids, but may alternatively reflect superiority of locally adapted and competitively dominant, haploid clones; a strategy that is theoretically favoured in disturbed environments. Although sexual reproduction may be infrequent in C. membranacea, it is sufficient to maintain both life history phases and supports theoretical modelling studies that show that haploid-diploid life histories are an evolutionarily stable strategy.

Chlorophyta↗

Microsatellite markers to assess the influence of population size, isolation and demographic change on the genetic structure of the UK butterfly Polyommatus bellargus.

Five microsatellite DNA markers were isolated and used to quantify population genetic structure among a subset of UK populations of the Adonis blue (Polyommatus bellargus Rottemburg). Specifically, whether population size, degree of isolation or history of bottlenecking in 1976-1978 can explain current patterns of genetic variation. The butterfly is at its northern range limit in the UK, where it exists as a highly fragmented metapopulation on isolated pockets of calcareous grassland. Most populations were affected by a severe bottleneck in the late 1970s, when a drought caused the host plant (Hippocrepis comosa) to wilt. Mantel tests and spatial autocorrelation analysis indicated a significant effect of isolation by distance among the UK populations, a relationship that broke down at greater geographical scales (> 23.85 km), probably because of large areas of unsuitable habitat presenting barriers to gene flow. Similarly, amova revealed that variation among geographical regions was almost double that observed within regions. Larger populations were found to support significantly higher levels of genetic diversity, suggesting that small populations may lose genetic diversity through drift. If, as in other butterfly species, low genetic diversity increases the probability of population extinction, then these populations are likely to be under threat. Neither isolation nor a history of bottlenecks appeared to influence genetic diversity. The results indicate that adequate population size a crucial factor in the conservation of genetic diversity in P. bellargus in the UK.

Alleles↗

Differential activation of the primary auxin response genes, PS-IAA4/5 and PS-IAA6, during early plant development.

The plant growth hormone auxin typified by indoleacetic acid (IAA) transcriptionally activates early genes in pea, PS-IAA4/5 and PS-IAA6, that are members of a multigene family encoding short-lived nuclear proteins. To gain first insight into the biological role of PS-IAA4/5 and PS-IAA6, promoter-beta-glucuronidase (GUS) gene fusions were constructed and their expression during early development of transgenic tobacco seedlings was examined. The comparative analysis reveals spatial and temporal expression patterns of both genes that correlate with cells, tissues, and developmental processes known to be affected by auxin. GUS activity in seedlings of both transgenic lines is located in the root meristem, sites of lateral root initiation and in hypocotyls undergoing rapid elongation. In addition, mutually exclusive cell-specific expression is evident. For instance, PS-IAA4/5-GUS but not PS-IAA6-GUS is expressed in root vascular tissue and in guard cells, whereas only PS-IAA6-GUS activity is detectable in glandular trichomes and redistributes to the elongating side of the hypocotyl upon gravitropic stimulation. Expression of PS-IAA4/5 and PS-IAA6 in elongating, dividing, and differentiating cell types indicates multiple functions during development. The common and yet distinct activity patterns of both genes suggest a combinatorial code of spatio-temporal co-expression of the various PS-IAA4/5-like gene family members in plant development that may mediate cell-specific responses to auxin.

Cell Differentiation↗

An empirical malaria distribution map for West Africa.

The objective of this study was to produce a malaria distribution map that would constitute a useful tool for development and health planners in West Africa. The recently created continental database of malaria survey results (MARA/ARMA 1998) provides the opportunity for producing empirical models and maps of malaria distribution at a regional and eventually at a continental level. This paper reports on the mapping of malaria distribution for sub-Saharan West Africa based on these data. The strategy was to undertake a spatial statistical analysis of malaria parasite prevalence in relation to those potential bio-physical environmental factors involved in the distribution of malaria transmission intensity which are readily available at any map location. The resulting model was then used to predict parasite prevalence for the whole of West Africa. We also produced estimates of the proportion of population of each country in the region exposed to various categories of risk to show the impact that malaria is having on individual countries. The data represent a very large sample of children in West Africa. It constitutes a first attempt to produce a malaria risk map of the West African region, based entirely on malariometric data. We anticipate that it will provide useful additional guidance to control programme managers, and that it can be refined once sufficient additional data become available.

Adolescent↗

What does the study of the spatial patterns of pathological lesions tell us about the pathogenesis of neurodegenerative disorders?

Discrete pathological lesions, which include extracellular protein deposits, intracellular inclusions and changes in cell morphology, occur in the brain in the majority of neurodegenerative disorders. These lesions are not randomly distributed in the brain but exhibit a spatial pattern, that is, a departure from randomness towards regularity or clustering. The spatial pattern of a lesion may reflect pathological processes affecting particular neuroanatomical structures and, therefore, studies of spatial pattern may help to elucidate the pathogenesis of a lesion and of the disorders themselves. The present article reviews first, the statistical methods used to detect spatial patterns and second, the types of spatial patterns exhibited by pathological lesions in a variety of disorders which include Alzheimer's disease, Down syndrome, dementia with Lewy bodies, Creutzfeldt-Jakob disease, Pick's disease and corticobasal degeneration. These studies suggest that despite the morphological and molecular diversity of brain lesions, they often exhibit a common type of spatial pattern (i.e. aggregation into clusters that are regularly distributed in the tissue). The pathogenic implications of spatial pattern analysis are discussed with reference to the individual disorders and to studies of neurodegeneration as a whole.

Brain↗

The life cycle and seasonal changes in the occurrence of Pomphorhynchus laevis (Palaeacanthocephala, Pomphorhynchidae) in a small isolated lake.

In a small isolated lake in Slovakia, the fish acanthocephalan Pomphorhynchus laevis using Gammarus balcanicus and the minnow Phoxinus phoxinus, respectively, as its intermediate and final hosts, represented a dominant helminth species. Its prevalence and intensity of infection in fish showed no significant variation during a year fluctuating above the mean values of 89% and 6.6 worms per fish. The mean prevalence of P. laevis larvae in Gammarus was 41.4% with a maximum in the late summer and autumn; individual crustaceans were infected by 1-9 larvae. There was one generation of P. laevis per year. Following up an annual cycle, an occurrence of new infections of Gammarus culminated in October and in the next May for Phoxinus. The sex ratios of both the adults and larvae of acanthocephalans were near unity but favoured slightly males in spring and autumn. The distribution of P. laevis in minnows and crustaceans was highly aggregated and fitted with the negative binomial model. The spatial distribution analysis of parasites along the fish alimentary tract showed a clear preference of P. laevis for its proximal half, with the maximum numbers in the site of the first intestinal loop. Immature worms of both sexes predominated in the proximal region and moved slightly down the alimentary tract during their growth and maturation.

Acanthocephala↗