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Biomedical subjects

A Tikhonov

Publications and source records attributed to A Tikhonov.

10 recordsLinked to original sources

Cortical substrates of perceptual stability during eye movements.

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements, the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. This example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual structures, which do not move, will also be perceived as nonmoving. If, however, the reference signal is too small or too large, a false eye-movement-induced motion of the external world will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to reveal the structures in visual cortex, encoding the perception of self-induced visual motion rather than the retinal motion signal. Using EEG and lately also MEG recordings in human subjects and single-unit recordings in monkeys, we have been able to show that our ability to perceive the world as stationary despite eye-movement-induced retinal image slip is based on "late" parts of the cortical hierarchy of motion processing, sparing the early stages up to cortical area MT and, among others, involving cortex at the junction between the parietal and temporal lobes close to the parieto-insular-vestibular cortex. Lesions of this network in humans render the visual system unable to compensate for the visual consequences of eye movements, giving rise to severe dizziness, whenever the eyes move smoothly.

Animals↗

Evolution of endogenous retrovirus-like elements of the woolly mammoth (Mammuthus primigenius) and its relatives.

Endogenous retrovirus-like elements characterizable by a leucine tRNA primer (ERV-Ls) are reiterated genomic sequences known to be widespread in mammals, including humans. They may have arisen from an ancestral foamy virus-like element by successful germ line infection followed by copy number expansion. However, among mammals, only primates and rodents have thus far exhibited high copy number amplification and sequence diversification. Conventionally, empirical studies of proviral amplification and diversification have been limited to extant species, but taxa having good Quaternary fossil records could potentially be investigated using the techniques of "ancient" DNA research. To examine evolutionary parameters of ERV-Ls across both time and taxa, we characterized this proviral class in the extinct woolly mammoth (Mammuthus primigenius) and living elephants, as well as extant members of the larger clade to which they belong (Uranotheria, a group containing proboscideans, sirenians, hyraxes, and their extinct relatives). Ungulates and carnivores previously analyzed demonstrated low copy numbers of ERV-L sequences, and thus it was expected that uranotheres should as well. Here, we show that all uranothere taxa exhibit unexpectedly numerous and diverse ERV-L sequence complements, indicating active expansion within this group of lineages. Selection is the most parsimonious explanation for observed differences in ERV-L distribution and frequency, with relative success being reflected in the persistence of certain elements over a variety of sampled time depths (as can be observed by comparing sequences from fossil and extant elephantid samples).

Animals↗

Grass genomes.

For the most part, studies of grass genome structure have been limited to the generation of whole-genome genetic maps or the fine structure and sequence analysis of single genes or gene clusters. We have investigated large contiguous segments of the genomes of maize, sorghum, and rice, primarily focusing on intergenic spaces. Our data indicate that much (>50%) of the maize genome is composed of interspersed repetitive DNAs, primarily nested retrotransposons that insert between genes. These retroelements are less abundant in smaller genome plants, including rice and sorghum. Although 5- to 200-kb blocks of methylated, presumably heterochromatic, retrotransposons flank most maize genes, rice and sorghum genes are often adjacent. Similar genes are commonly found in the same relative chromosomal locations and orientations in each of these three species, although there are numerous exceptions to this collinearity (i.e., rearrangements) that can be detected at the levels of both the recombinational map and cloned DNA. Evolutionarily conserved sequences are largely confined to genes and their regulatory elements. Our results indicate that a knowledge of grass genome structure will be a useful tool for gene discovery and isolation, but the general rules and biological significance of grass genome organization remain to be determined. Moreover, the nature and frequency of exceptions to the general patterns of grass genome structure and collinearity are still largely unknown and will require extensive further investigation.

Journal Article↗

Matrix attachment regions and structural colinearity in the genomes of two grass species.

In order to gain insights into the relationship between spatial organization of the genome and genome function we have initiated studies of the co-linear Sh2/A1- homologous regions of rice (30 kb) and sorghum (50 kb). We have identified the locations of matrix attachment regions (MARs) in these homologous chromosome segments, which could serve as anchors for individual structural units or loops. Despite the fact that the nucleotide sequences serving as MARs were not detectably conserved, the general organizational patterns of MARs relative to the neighboring genes were preserved. All identified genes were placed in individual loops that were of comparable size for homologous genes. Hence, gene composition, gene orientation, gene order and the placement of genes into structural units has been evolutionarily conserved in this region. Our analysis demonstrated that the occurrence of various 'MAR motifs' is not indicative of MAR location. However, most of the MARs discovered in the two genomic regions were found to co-localize with miniature inverted repeat transposable elements (MITEs), suggesting that MITEs preferentially insert near MARs and/or that they can serve as MARs.

Base Composition↗

The paleontology of intergene retrotransposons of maize.

Retrotransposons, transposable elements related to animal retroviruses, are found in all eukaryotes investigated and make up the majority of many plant genomes. Their ubiquity points to their importance, especially in their contribution to the large-scale structure of complex genomes. The nature and frequency of retro-element appearance, activation and amplification are poorly understood in all higher eukaryotes. Here we employ a novel approach to determine the insertion dates for 17 of 23 retrotransposons found near the maize adh1 gene, and two others from unlinked sites in the maize genome, by comparison of long terminal repeat (LTR) divergences with the sequence divergence between adh1 in maize and sorghum. All retrotransposons examined have inserted within the last six million years, most in the last three million years. The structure of the adh1 region appears to be standard relative to the other gene-containing regions of the maize genome, thus suggesting that retrotransposon insertions have increased the size of the maize genome from approximately 1200 Mb to 2400 Mb in the last three million years. Furthermore, the results indicate an increased mutation rate in retrotransposons compared with genes.

Alcohol Dehydrogenase↗

Nested retrotransposons in the intergenic regions of the maize genome.

The relative organization of genes and repetitive DNAs in complex eukaryotic genomes is not well understood. Diagnostic sequencing indicated that a 280-kilobase region containing the maize Adh1-F and u22 genes is composed primarily of retrotransposons inserted within each other. Ten retroelement families were discovered, with reiteration frequencies ranging from 10 to 30,000 copies per haploid genome. These retrotransposons accounted for more than 60 percent of the Adh1-F region and at least 50 percent of the nuclear DNA of maize. These elements were largely intact and are dispersed throughout the gene-containing regions of the maize genome.

Chromosomes, Artificial, Yeast↗

Gene identification in a complex chromosomal continuum by local genomic cross-referencing.

Most higher plants have complex genomes containing large quantities of repetitive DNA interspersed with low-copy-number sequences. Many of these repetitive DNAs are mobile and have homology to RNAs in various cell types. This can make it difficult to identify the genes in a long chromosomal continuum. It was decided to use genic sequence conservation and grass genome co-linearity as tools for gene identification. A bacterial artificial chromosome (BAC) clone containing sorghum genomic DNA was selected using a maize Adh1 probe. The 165 kb sorghum BAC was tested for hybridization to a set of clones representing the contiguous 280 kb of DNA flanking maize Adh1. None of the repetitive maize DNAs hybridized, but most of the low-copy-number sequences did. A low-copy-number sequence that did cross-hybridize was found to be a gene, while one that did not was found to be a low-copy-number retrotransposon that was named Reina. Regions of cross-hybridization were co-linear between the two genomes, but closer together in the smaller sorghum genome. These results indicate that local genomic cross-referencing by hybridization of orthologous clones can be an efficient and rapid technique for gene identification and studies of genome organization.

Alcohol Dehydrogenase↗

The Hybaid Lecture. Microcollinearity and segmental duplication in the evolution of grass nuclear genomes.

Recent studies have shown that grass genomes have very similar gene compositions and regions of conserved gene order, as exemplified by collinear genetic maps of DNA markers. We have begun the detailed study of sequence organization in large (100-500 kb) segments of the nuclear genomes of maize, sorghum and rice. Our results indicate collinearity of genes in the regions homoeologous to the maize adh1 and sh2-a1 genes. Comparable genes were found to be physically closer to each other in grasses with small genomes (rice and sorghum) than they are in maize. In several instances, we have found evidence of tandem and 'distantly tandem' duplications of segments containing maize and sorghum genes. These duplications complicate characterizations of microcollinearity and could also interfere with some map-based approaches to gene isolation.

Biological Evolution↗

[X-ray study in the examination of patients with perineal fistulas].

The paper discusses whether X-ray study of patients with perineal fistulas is required and justified. The main reason is that there is a diversity of diseases which display the same signs as paraproctitis. Of 426 examinees, perineal fistulas were mainly caused by chronic paraproctitis in 85% and by other various diseases showing the similar symptoms in 15%. The basic studies of these patients included fistulography made in 300 patients with external fistulas and proctofistulography performed in 126 patients with incomplete internal fistulas. Comparing the data of X-ray study with those of clinical and morphological ones showed the sensitivity of the former to be 94.5%. Based on the results of their own observations, the authors defined indications for fistulography or proctofistulography. In addition to the analysis of the findings, they present the main points of differential X-ray diagnosis of different diseases manifested by perineal fistulas.

Adolescent↗