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PubMed2026

Single-cell and spatial transcriptomic technologies for lung cancer tumor microenvironment analysis.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide; beyond its rising incidence, its marked molecular heterogeneity and complex tumor microenvironment (TME) hinder treatment response and drive resistance, contributing directly to its high mortality rate. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) provide complementary approaches for dissecting these features. scRNA-seq enables high-resolution analysis of cellular diversity and transcriptional states but requires tissue dissociation and therefore loses spatial context. In contrast, ST preserves tissue architecture and provides insights into how gene-expression programs within the TME are organized, although no currently available spatial platform combines whole-transcriptome coverage with true single-cell resolution over large tissue areas. Together, these technologies have enabled detailed mapping of tumor, immune and stromal populations and of their spatial interactions, revealing functionally distinct cellular niches that contribute to immune evasion, metastasis and response to therapy. In this narrative review we organize the primary literature around a single question, how spatially structured cellular ecosystems, rather than individual cell types, determine therapeutic response and resistance in lung cancer - and we explicitly separate observations that are reproducible across independent cohorts and platforms from those that remain confined to single studies. We further summarize the technical, analytical and logistic barriers that currently prevent spatially resolved signatures from entering routine diagnostic pathology. Understanding dysregulated pathways and spatially constrained intercellular communication within the TME helps identify candidate biomarkers and may support the identification of therapeutic approaches directed at tumor-intrinsic programs as well as at microenvironment-driven resistance mechanisms.

Cell-cell communication↗

PubMed2000

Genetic hitchhiking.

Selection on one or more genes inevitably perturbs other genes, even when those genes have no direct effect on fitness. This article reviews the theory of such genetic hitchhiking, concentrating on effects on neutral loci. Maynard Smith and Haigh introduced the classical case where the perturbation is due to a single favourable mutation. This is contrasted with the apparently distinct effects of inherited variation in fitness due to loosely linked loci. A model of fluctuating selection is analysed which bridges these alternative treatments. When alleles sweep between extreme frequencies at a rate lambda, the rate of drift is increased by a factor (1 + E[1/pq]lambda/(2(2lambda + r))), where the recombination rate r is much smaller than the strength of selection. In spatially structured populations, the effects of any one substitution are weaker, and only cause a local increase in the frequency of a neutral allele. This increase depends primarily on the rate of recombination relative to selection (r/s), and more weakly, on the neighbourhood size, Nb = 4(pi rho sigma)2. Spatial subdivision may allow local selective sweeps to occur more frequently than is indicated by the overall rate of molecular evolution. However, it seems unlikely that such sweeps can be sufficiently frequent to increase significantly the drift of neutral alleles.

Animals↗

PubMed1975

Change of cytochrome c structure during development of the mouse.

The structure of cytochrome c during mouse development is investigated. For this purpose the amino acid sequence of cytochrome c of the adult mouse had to be determined. The structure of cytochrome c of adult differentiated mouse cells differs in two amino acid residues from the known amino acid sequence of rabbit cytochrome c. No indication of different forms of cytochrome c in the adult differentiated cells was obtained. The structure of cytochrome c from 11.5-day-old mouse embryos is identical with that of adult mouse tissues. Since germ cells after meiotic division are the immediate precursors of a new individual, the structure of cytochrome c from sperm-containing mice testes was investigated. By means of chromatography of the cytochrome c and of peptide maps and amino acid analyses of its tryptic peptides, it is shown that mouse testis contains two isocytochromes c in about equal amount. The structure of one of these two isocytochromes c is identical with the structure of the adult-type cytochrome c of mouse. The testis-specific cytochrome c, which is assumed to be located in the sperm cells, differs in 13 of its 104 amino acid residues from the adult-type cytochrome c. From comparison of the primary and the spatial structures of the adult-type and the sperm-type isocytochromes c with the known structures of cytochrome c of more than 65 different species it is concluded that the duplication of the cytochrome c structural gene, causing the existence of the two ontogenetic-specific isocytochromes c in mouse, has occurred early in the evolution of eucaryotes.

Aging↗

PubMed2003

Artifacts in spatiochromatic stimuli due to variations in preretinal absorption and axial chromatic aberration: implications for color physiology.

The spatiochromatic receptive-field structure of neurons in the macaque visual system has been studied almost exclusively with stimuli based on the human foveal cone fundamentals of Smith and Pokorny [Vision Res. 15, 161 (1975)] and generated on cathode ray tube displays. In the current study the artifacts evoked by cone-isolating, spatially structured stimuli due to variations in the eye's preretinal absorption characteristics and axial chromatic aberration are quantified. In addition, the luminance artifacts evoked by nominally isoluminant sinusoidal grating stimuli due to the same factors are quantified. The results indicate that the spatiochromatic stimuli commonly employed to map receptive fields of neurons at eccentricities > 10 deg are especially prone to artifacts and that these artifacts are maximal for the high-contrast S-cone-isolating stimuli that are often used. On the basis of these simulations, a method is introduced that improves spatiochromatic receptive-field estimates by compensating for response contributions from the incompletely silenced cone mosaics during cone-isolating stimulation.

Absorption↗

PubMed2003

Multilayer thin-film structures with high spatial dispersion.

We demonstrate how to design thin-film multilayer structures that separate multiple wavelength channels with a single stack by spatial dispersion, thus allowing compact manufacturable wavelength multiplexers and demultiplexers and possibly beam-steering or dispersion-control devices. We discuss four types of structure--periodic one-dimensional photonic crystal superprism structures, double-chirped structures exploiting wavelength-dependent penetration depth, coupled-cavity structures with dispersion that is due to stored energy, and numerically optimized nonperiodic structures utilizing a mixture of the other dispersion effects. We experimentally test the spatial dispersion of a 200-layer periodic structure and a 66-layer nonperiodic structure. Probably because of its greater design freedom, the nonperiodic structure can give both a linear shift with wavelength and a larger usable shift than the thicker periodic structure gives.

Journal Article↗

PubMed2003

Fine-scale genetic structure and gene flow within Costa Rican populations of mahogany (Swietenia macrophylla).

Fine-scale structure of genetic diversity and gene flow were analysed in three Costa Rican populations of mahogany, Swietenia macrophylla. Population differentiation estimated using AFLPs and SSRs was low (38.3 and 24%) and only slightly higher than previous estimates for Central American populations based on RAPD variation (20%). Significant fine-scale spatial structure was found in all of the surveyed mahogany populations and is probably strongly influenced by the limited seed dispersal range of the species. Furthermore, a survey of progeny arrays from selected mother trees in two of the plots indicated that most pollinations involved proximate trees. These data indicate that very little gene flow, via either pollen or seed, is occurring between blocks of mahogany within a continuous or disturbed forest landscape. Thus, once diversity is removed from a forest population of mahogany, these data suggest that recovery would be difficult via seed or pollen dispersal, and provides an explanation for mahogany's apparent susceptibility to the pressures of logging. Evidence is reviewed from other studies of gene flow and seedling regeneration to discuss alternative extraction strategies that may maintain diversity or allow recovery of genetic resources.

Biological Evolution↗

PubMed1994

Five-stranded beta-sheet sandwiched with two alpha-helices: a structural link between restriction endonucleases EcoRI and EcoRV.

Examination of crystal structures of restriction endonucleases EcoRI and EcoRV complexes with their cognate DNA revealed a common structural element, which forms the core of both proteins. This element consists of a five-stranded beta-sheet and two alpha-helices packed against it and could be described as alpha-beta sandwich in which helices and beta-strands lie in two stacked layers. While the spatial structure of this alpha-beta sandwich is conserved in both enzymes, there are not detectable similarities between amino acid sequences except of a few residues involved in active site formation. Probably, other restriction endonucleases which have similar organization of the active site might possess similar structural element regardless of DNA sequence recognized and recognition elements in the enzyme used.

Amino Acid Sequence↗

PubMed2005

Metabolism and receptor binding of serotonin in brain structures during performance of a conditioned passive avoidance response.

The levels of serotonin and its metabolite 5-hydroxyindoleacetic acid, monoamine oxidase activity, and the specific binding of the radioligand [3H]serotonin were measured in the prefrontal cortex, striatum, amygdaloid complex, hippocampus, and periacqueductal gray matter of the midbrain in rats at different time points after training to a conditioned passive avoidance reaction. Changes in serotoninergic activity were found to be characteristic only for the process of reproducing the conditioned reaction. The metabolism and serotonin receptor binding in these brain structures did not change immediately after the training period or one day after this, or in conditions of failure to reproduce the reaction because of amnesia, or in untrained animals. The involvement of the brain serotoninergic system in the process of performing the conditioned reaction was found to demonstrate a spatial-structural selectivity: the metabolism and receptor binding of serotonin changed in the amygdaloid complex, periacqueductal gray matter, and the striatum, while no changes were seen in the hippocampus or prefrontal cortex. All three brain structures showed decreases in [3H]serotonin receptor binding of. Serotonin levels did not change, though the amygdaloid complex and periacqueductal gray matter showed increases in oxidative deamination of serotonin and increases in the active transport of the metabolite, while the striatum showed decreases in serotonin catabolism. The differences in the catabolism of this neurotransmitter suggest that the decrease in serotonin receptor binding in these brain structures depends on different synaptic processes--presynaptic in the striatum and postsynaptic in the amygdaloid complex and periacqueductal gray matter. It is concluded that the decrease in the functional activity of serotoninergic transmission in the amygdaloid complex and periacqueductal gray matter is one of the mechanisms involved in activation of the emotiogenic system triggering the process of reproduction of the memory trace.

Animals↗

PubMed1989

The amino-terminal domain of LexA repressor is alpha-helical but differs from canonical helix-turn-helix proteins: a two-dimensional 1H NMR study.

The amino-terminal DNA binding domain of LexA repressor consisting of 84 amino acid residues has been studied by two-dimensional 1H NMR. Sequence-specific 1H resonance assignments were made for the first 60 amino acid residues. The secondary structure of this part of the protein contains three alpha-helices in the peptide segments 8-20, 28-35, and 41-54. The last helix has a distortion around residues 47-48. The peptide segment 28-47 shows weak homology with other helix-turn-helix proteins. To investigate the spatial structure of this region of the molecule distance-geometry calculations were performed based on proton-proton distance constraints from nuclear Overhauser effects. The resulting structure shows that the segment 28-47 contains two helices with a loop region between them. The relative orientation of the two helices is similar to that found in helix-turn-helix proteins, but the helices are further apart, with the phenyl ring of Phe-37 located between them. The Brookhaven Protein Data Bank was searched for structurally homologous peptide segments in other proteins. The result of this search was that the two-helical structure of LexA is not more closely related to the canonical helix-turn-helix motif than it is to similar substructures found in other classes of proteins.

Amino Acid Sequence↗

PubMed2003

Nonveridical visual perception in human amblyopia.

PURPOSE: Amblyopia is a developmental disorder of spatial vision. There is evidence to suggest that some amblyopes misperceive spatial structure when viewing with the affected eye. However, there are few examples of these perceptual errors in the literature. This study was an investigation of the prevalence and nature of misperceptions in human amblyopia. METHODS: Thirty amblyopes with strabismus and/or anisometropia participated in the study. Subjects viewed sinusoidal gratings of various spatial frequencies, orientations, and contrasts. After interocular comparison, subjects sketched the subjective appearance of those stimuli that had nonveridical appearances. RESULTS: Nonveridical visual perception was revealed in 20 amblyopes ( approximately 67%). In some subjects, misperceptions were present despite the absence of a deficit in contrast sensitivity. The presence of distortions was not simply linked to the depth of amblyopia, and anisometropes were affected as well as those with strabismus. In most cases, these spatial distortions arose at spatial frequencies far below the contrast detection acuity cutoff. Errors in perception became more severe at higher spatial frequencies, with low spatial frequencies being mostly perceived veridically. The prevalence and severity of misperceptions were frequently found to depend on the orientation of the grating used in the test, with horizontal orientations typically less affected than other orientations. Contrast had a much smaller effect on misperceptions, although there were cases in which severity was greater at higher contrasts. CONCLUSIONS: Many types of misperceptions documented in the present study have appeared in previous investigations. This suggests that the wide range of distortions previously reported reflect genuine intersubject differences. It is proposed that nonveridical perception in human amblyopia has its origins in errors in the neural coding of orientation in primary visual cortex.

Adolescent↗

PubMedDate not supplied

[Analysis of structural characteristics of alpha-tubulins in plants with enhanced cold tolerance].

The uniqueness of the point substitutions in the sequences of two alpha-tubulin isotypes from psychrophilic alga Chloromonas that can determine the increased cold tolerance of this alga was analyzed. The comparison of all known amino acid sequences of plant alpha-tubulins enabled to ascertain that only M268-->V replacement is unique and may have a significant influence on spatial structure of plant alpha-tubulins. Modeling of molecular surfaces of alpha-tubulins from Chloromonas, Chalmydomonas reinhardtii and goose grass Eleusine indica showed that insertion of the amino acid replacement M268-->V into the sequence of goose grace tubulin led to the likening of this protein surface to the surface of native alpha-tubulin from Chloromonas. Alteration of local hydrophobic properties of alpha-tubulin molecular surface in interdimeric contact zone as a result of the mentioned replacement was shown that may play important role in increasing the level of cold resistance of microtubules. The crucial role of amino acid residue in 268 position for forming the interdimeric contact surface of alpha-tubulin molecule was revealed. The assumption is made about the importance of replacements at this position for plant tolerance to abiotic factors of different nature (cold, herbicides).

Amino Acid Sequence↗

PubMed2004

The effects of extracellular polymeric substances on the formation and stability of biogranules.

Biogranulation is a promising biotechnology developed for wastewater treatment. Biogranules exhibit a matrix microbial structure, and intensive research has shown that extracellular polymeric substances (EPS) are a major component of the biogranule matrix material in both anaerobic and aerobic granules. This paper aims to review the role of EPS in biogranulation, factors influencing EPS production, the effect of EPS on cell surface properties of biogranules, and the relationship of EPS to the structural stability of biogranules. EPS production is substantially enhanced when the microbial community is subject to stressful culture conditions, and the stimulated EPS production in the microbial matrix in turn favours the formation of anaerobic and aerobic granules. EPS can also play an essential role in maintaining the integrity and stability of spatial structure in mature biogranules. It is expected that this paper can provide deep insights into the functions of EPS in the biogranulation process.

Bacteria↗

PubMed1998

A Knowledge-Based Systems Approach to Design of Spatial Decision Support Systems for Environmental Management

/ This paper describes a framework for designing spatial decision support systems for environmental management using a knowledge-based systems approach. An architecture for knowledge-based spatial decision supportsystems (KBSDSS) is presented that integrates knowledge-based systems with geographical information systems (GIS) and other problem-solving techniques. A method based on spatial influence diagrams is developed for representation of environmental problems. The spatial influence diagram provides an interface through which knowledge-based systems techniques can be applied to build capabilities for problem formulation, automated design, and execution of a solution process. In addition to the flexibility and developmental advantages of knowledge-based systems, the KBSDSS incorporates expert knowledge to provide assistance for structuring spatial influence diagrams and executing a solution process that automatically integrates the GIS, data base, knowledge base, and different types of models. The framework is illustrated with a system, known as the Islay Land Use Decision Support System (ILUDSS), designed to assist planners in strategic planning of land use for the development of the island of Islay, off the west coast of Scotland.KEY WORDS: Geographical information systems; Spatial decision support systems; Knowledge-based systems; Spatial influence diagrams; Environmental management

Journal Article↗

PubMed2003

Spatial variation in springtime food resources influences the winter body mass of roe deer fawns.

It is well established that the dynamics of mammalian populations vary in time, in relation to density and weather, and often in interaction with phenotypic differences (sex, age and social status). Habitat quality has recently been identified as another significant source of individual variability in vital rates of deer, including roe deer where spatial variations in fawn body mass were found to be only about a tenth of temporal variations. The approach used was to classify the habitat into blocks a priori, and to analyse variation in animal performance among the predefined areas. In a fine-grained approach, here we use data collected over 24 years on 1,235 roe deer fawns captured at known locations and the plant species composition sampled in 2001 at 578 sites in the Chizé forest to determine the spatial structure at a fine scale of both vegetation and winter body mass of fawns, and then to determine links between the two. Space and time played a nearly equal role in determining fawn body masses of both sexes, each accounting for about 20% of variance and without any interaction between them. The spatial distribution of fawn body mass was perennial over the 24 years considered and predicted values showed a 2 kg range according to location in the reserve, which is much greater than suggested in previous work and is enough to have strong effects on fawn survival. The spatial distribution and the range of predicted body masses were closely similar in males and females. The result of this study is therefore consistent with the view that the life history traits of roe deer are only weakly influenced by sexual selection. The occurrence of three plant species that are known to be important food items in spring/summer roe deer diets, hornbeam ( Carpinus betulus), bluebell ( Hyacinthoides sp.) and Star of Bethlehem ( Ornithogalum sp.) was positively related to winter fawn body mass. The occurrence of species known to be avoided in spring/summer roe deer diets [e.g. butcher's broom ( Ruscus aculeatus) and beech ( Fagus sylvatica)], was negatively related to fawn body mass. We conclude that the spatial variation in the body mass of fawns in winter in this forest is as important as the temporal variation, and that the distribution of plant species that are actively selected during spring and summer is an important determinant of spatial variation in winter fawn body mass. The availability of these plants is therefore likely to be a key factor in the dynamics of roe deer populations.

Adaptation, Physiological↗

PubMedDate not supplied

Visualization of barrier tree sequences.

Dynamical models that explain the formation of spatial structures of RNA molecules have reached a complexity that requires novel visualization methods that help to analyze the validity of these models. Here, we focus on the visualization of so-called folding landscapes of a growing RNA molecule. Folding landscapes describe the energy of a molecule as a function of its spatial configuration; thus they are huge and high dimensional. Their most salient features, however, are encapsulated by their so-called barrier tree that reflects the local minima and their connecting saddle points. For each length of the growing RNA chain there exists a folding landscape. We visualize the sequence of folding landscapes by an animation of the corresponding barrier trees. To generate the animation, we adapt the foresight layout with tolerance algorithm for general dynamic graph layout problems. Since it is very general, we give a detailed description of each phase: constructing a supergraph for the trees, layout of that supergraph using a modified DoT algorithm, and presentation techniques for the final animation.

Base Sequence↗

PubMed2006

Mixing of propagules from discrete sources at long distance: comparing a dispersal tail to an exponential.

BACKGROUND: Rare long distance dispersal events impact the demography and the genetic structure of populations. When dispersal is modelled via a dispersal kernel, one possible characterisation of long-distance dispersal is given by the shape of the tail of the kernel, i.e. its type of decay. This characteristic is known to directly act on the speed and pattern of colonization, and on the spatial structure of genetic diversity during colonization. In particular, colonization waves behave differently depending on whether the kernel decreases faster or slower than an exponential (i.e. is thin-tailed vs. fat-tailed). To interpret and extend published results on the impact of long-distance dispersal on the genetic structure of populations, we examine a classification of dispersal kernels based on the shape of their tails and formally demonstrate qualitative differences among them that can influence the predicted diversity of a propagule pool sampled far from two distinct sources. RESULTS: We show that a fat-tailed kernel leads asymptotically to a diverse propagule pool containing a balanced mixing of the propagules from the two sources, whereas a thin-tailed kernel results in all propagules originating from the closest source. We further show that these results hold for biologically relevant distances under certain circumstances, and in particular if the number of propagules is large enough, as would be the case for pollen or seeds. CONCLUSION: To understand the impact of long-distance dispersal on the structure and dynamics of a metapopulation, it might be less important to precisely estimate an average dispersal distance than to determine if the tail of the dispersal kernel is fatter or thinner than that of an exponential function. Depending solely on this characteristic, a metapopulation will behave similarly to an island model with a diverse immigrant pool or to a stepping-stone model with migrants from closest populations. Our results further help to understand why thin-tailed dispersal kernels lead to a colonization wave of constant speed, whereas fat-tailed dispersal kernels lead to a wave of increasing speed. Our results also suggest that the diversity of the pollen cloud of a mother plant should increase with increasing isolation for fat-tailed kernels, whereas it should decrease for thin-tailed kernels.

Demography↗

PubMed1976

[Study of aseptic inflammation using the scanning electron microscope].

A focus of inflammation in the subcutaneous connective tissue in white rats was investigated in a scanning electron microscope. Lymphocytes, polyblasts, macrophages, fibroblasts, collagenous fibres, gigantic multinuclear cells, vessels are described. Similiarity in the form and structure of the surface in agranulocytes of the blood, polyblasts and macrophages was established. A considerable change in morphology of fibroblasts, particularly in the period of synthesis os of the cell, was observed. Collagenous fibres and fibroblasts played a leading role in the creation of the supporting-mechanical carcass and in spatial structure of the regenerating connective tissue.

Animals↗

PubMed2026

Genome-wide SNP data reveal geographic structure and landscape-associated genomic differentiation in a widespread lizard in arid Eastern Central Asia.

Arid landscapes provide important systems for examining how geographic structure and environmental heterogeneity shape genomic differentiation. In topographically complex desert regions, however, it remains challenging to determine whether population structure primarily reflects landscape resistance, geographic distance, or contemporary environmental variation. Here, we use genome-wide SNP data to investigate population structure, phylogenetic relationships, historical gene flow, demographic history, and landscape correlates of genomic differentiation in the variegated racerunner (Eremias vermiculata), a widespread lacertid lizard across arid Eastern Central Asia. Analyses of 164 individuals recovered six geographically structured nuclear clusters associated with major desert basins and mountain-bounded regions. Nuclear phylogenies resolved two broad regional clades corresponding to northeastern and southwestern parts of the species' range, while PCA and ADMIXTURE analyses recovered six finer-scale genetic clusters. Mitochondrial phylogenies, based on combined NCBI-derived Cyt b and COI sequences from the same individuals, recovered four deeper maternal lineages. These patterns indicate overall phylogeographic agreement between nuclear and mitochondrial datasets, with genome-wide SNPs providing finer-scale resolution of population structure. Demographic reconstructions further uncovered regionally heterogeneous Late Pleistocene histories among clusters, including signals of expansion, stability, and decline. Landscape genomic analyses revealed that genomic differentiation is primarily associated with landscape resistance, particularly elevation and land cover, as well as geographic distance, whereas contemporary environmental variables explained comparatively little variation after controlling for spatial structure. Together, our results suggest that genomic differentiation in E. vermiculata reflects the interplay of persistent landscape configuration, historical connectivity, and region-specific demographic histories across arid Eastern Central Asia. More broadly, this study highlights the value of integrating phylogeographic and landscape genomic approaches for understanding population differentiation and evolutionary history in topographically heterogeneous desert ecosystems.

Arid Eastern Central Asia↗