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PubMed2004

Genetic relationships and admixture among sheep breeds from Northern Spain assessed using microsatellites.

Although many research papers have studied diversity and differentiation within livestock species, genetic relationships among neighboring populations remain poorly understood. Here we apply recent methodologies to analyze the polymorphism of 14 microsatellites in 238 unrelated individuals belonging to six sheep breeds from Northern Spain to ascertain their historical relationships and the relative genetic contributions existing between populations. Individual genotypes were analyzed to assess the existence of an underlying genetic structure. Long-term and recent migration rates were estimated to identify patterns of relative genetic contribution among breeds. The complete data set showed a strong population structure derived from both different ancestral origins and some geographical patterns of recent gene flow. Two of the analyzed breeds (Black-faced Latxa and Churra) had a marked genetic background, supporting the hypothesis that, regardless of their phenotypical similarities, they have different ancestral origins. Some of the more presumably related breeds had negative long-term admixture coefficients, showing that they diverged only recently. In addition, we show how methodologies for estimation of long-term gene flow and recent patterns of migration are complementary, providing information about migration rates on different timescales.

Animals↗
PubMed1992

Laminin expression in the mouse lung increases with development and stimulates spontaneous organotypic rearrangement of mixed lung cells.

The recent establishment of a role for laminin in mouse lung organogenesis (Schuger et al. 1990a,b, 1991) prompted us to study its expression in the developing lung. Laminin A and B chains were detected in the murine lung from the first hours of development onward. In situ hybridization of mRNA as well as SDS-PAGE studies of lung cells in monoculture indicated that both epithelium and mesenchyme produce complete laminin molecules. Quantitative analysis of the in situ hybridization studies showed a gradual increase in laminin expression during development which was further supported by immunohistochemistry and ELISA. The overall pattern of expression suggested that the effects of laminin in morphogenesis were not restricted to a particular stage of development. Furthermore, the increase in expression during late development supported a role for the molecule in the fetal lung, which was not previously established. We next determined whether the increase in laminin production modulated the behavior of fetal lung cells as compared with their embryonic counterparts. We previously showed that organotypic pattern formation does not occur in cultures of mixed embryonic lung cells unless exogenous laminin is added (Schuger et al., 1990b). Organotypic pattern formation is the result of cell sorting into epithelial and mesenchymal compartments and further rearrangement in a pattern resembling the tissue of origin. In the present study, we demonstrated that organotypic pattern formation occurs spontaneously in cultures of mixed fetal lung cells, which express high laminin levels. Pattern formation was abolished by antibodies to laminin. These studies suggest a correlation between laminin expression and the ability of lung cells in culture to reproduce normal tissue patterns. We conclude that laminin is critical for epithelial-mesenchymal recognition and further morphogenic interaction during both the embryonic and fetal stages of lung development.

Animals↗
PubMed2003

Sensory deprivation changes the pattern of synaptic connectivity in rat barrel cortex.

We examined whether sensory deprivation during formation of the cortical circuitry influences the pattern of intracortical single-cell connections in rat barrel cortex. Excitatory postsynaptic potentials from layer 5 pyramidal neurons were recorded in vitro using patch-clamp techniques. In order to evoke such postsynaptic potentials presumptive presynaptic neurons were stimulated by photolytically applied glutamate thus generating action potentials. Synaptic connections between the stimulated and the recorded neuron were identified by the occurrence of postsynaptic potentials following photostimulation. Sensory deprivation altered the projections from layer 2/3 neurons to layer 5 pyramidal cells (L2/3-->L5 projections). In slices of non-deprived rats the input probability of L2/3-->L5 projections showed a periodic pattern with more synaptic connections originating from the borders of the barrel columns, and less synaptic connections originating from the centres. After whisker clipping this periodic pattern disappeared completely and the input probability declined monotonically with increasing distance between stimulated and recorded neuron. These results indicate that sensory input is a prerequisite to establish a synaptic projection pattern which is correlated to the columnar organisation of the anatomical barrel structure.

Animals↗
PubMedDate not supplied

Acoustic and electrical pattern analysis of consonant perceptual cues used by cochlear implant users.

It is hypothesized that for postlingually deafened adult cochlear implant (CI) users, a significant source of their perceptual performance variability is attributable to differences in their ability to discriminate the basic perceptual cues that are important in speech recognition. Previous research on 'electric hearing' has identified consistent perceptual cues for vowel recognition. However, the results on consonant perception by CI users are less clear. The primary purpose of this study is to present a quantitative method of evaluating potential 'electric cues' used by CI users in consonant identification. Since the actual input signals to the auditory periphery of CI users are electric in nature, we elected to measure the CI electric discharge patterns in addition to the original acoustic waveforms. The characteristics of the electric discharge patterns in response to intervocalic consonants were quantified and correlated with the dimensions of CI patients' perceptual spaces, which were computed from multidimensional scaling analyses of their consonant confusion matrices. The results agree with most, but not all, commonly accepted acoustic cues used by normal-hearing listeners. The correlation findings also suggest that CI users employ different sets of 'electric cues' in perceiving consonants that differ in their manner of articulation. Specifically, spectral and temporal cues associated with slowly changing formant structures and transitions, and features associated with frication and high-frequency noise, are all highly correlated with the perceptual dimensions of all CI users. However, rapidly changing formant transitions, such as those present in stop consonants, did not appear to play a significant role in consonant recognition by more poorly performing CI subjects. The perceptual results were consistent with our physical findings that the SPEAK coding strategy partially degraded the rapidly changing formant transitions.

Acoustic Stimulation↗
PubMed2002

Simulated graft recession in endoscopic ACL reconstruction: influence on graft strain.

Eight fresh cadaveric knee specimens underwent arthroscopic-assisted ACL reconstruction to examine the influence of femoral graft recession on graft strain pattern. Length changes between tibial origin and femoral insertion (simulating graft strain or isometry pattern) were measured throughout knee motion (0 degrees-90 degrees) with a simulated ACL construct. Measurements were taken at the "endo" position (replicating the normal endoscopic position) and in progressive 1.5-mm increments proximally within the femoral tunnel (mimicking femoral graft recession). After recession up to a maximum of 15 mm, a block was placed anterior to the "recessed" graft construct (simulating placement of bone graft anterior to the recessed graft) and strain patterns were remeasured. Graft strain patterns were altered with as little as 1.5 mm recession in two of eight specimens. Compared to the "endo" position, all specimens showed a statistically significant decrease in strain by 3 mm of graft recession (P<.001 for 7 of 8, and P=.0138 for 1 of 8). A direct relationship exists between graft placement and ACL strain patterns, with more proximal graft "recession" adversely influencing normal graft strain. Bone graft placement anterior to the recessed graft restores strain patterns to those seen at the normal "endoscopic" position.

Analysis of Variance↗
PubMed1990

Human neuroblastoma cell growth in xenogeneic hosts: comparison of T cell-deficient and NK-deficient hosts, and subcutaneous or intravenous injection routes.

We have examined two features of neuroblastoma cells that had not been well-characterized in a xenogeneic model: The cells display unusual immunologic properties in other experimental systems, and the original tumors display widespread and characteristic patterns of metastasis. To determine the most appropriate immunodeficient host for primary tumor growth, T cell-deficient nude mice, NK-deficient beige mice, beige-nudes, and controls were injected with the well-characterized line CHP-100. To define the pattern of tumor spread, complete autopsies were performed following subcutaneous, intraperitoneal and intravenous injections. CHP-100 consistently formed subcutaneous tumors in T cell-deficient mice (nude and beige-nude), but not in T cell-competent mice (beige, heterozygous nu/+ and bg/+, or wild-type). The growth rate and final size of the subcutaneous tumors were not greater in beige-nudes than in nudes. All mice showed early CHP-100 cell death after subcutaneous injection; the nature of the immunodeficiency was more relevant for the surviving subpopulation. Widespread dissemination was seen following intravenous injection, particularly in beige-nudes. Aspects of the growth patterns were appropriate to the tumor of origin. The behavior in immunodeficient mice suggests that T cells can play a role in controlling the growth of these cells; the next steps will be to define the effector mechanisms, and to determine if they can be exploited for human patients. The hematogenous spread following intravenous injection suggests that insights into the control of blood-borne tumor may also come from further study of this model.

Animals↗
PubMed2000

Automated identification of symmetry in CBED patterns: a genetic approach

The genetic algorithm has been applied for automated identification of symmetry in CBED patterns. A normalized inner product between an original and its symmetry operated CBED patterns was found to be a good measure of similarity between them, and this inner product was used as the objective function in the genetic algorithm. A real floating number implementation of this genetic approach has been applied successfully in identifying rotation axes and mirror planes in experimental CBED patterns obtained from a single crystal of silicon. In particular a three-fold rotation axis reflecting the true three-dimensional symmetry of silicon is clearly distinguished from a six-fold rotation axis as expected from a two-dimensional crystal in the experimental <1 1 1> zone axis CBED pattern.

Journal Article↗
PubMedDate not supplied

Homology, limbs, and genitalia.

Similarities in genetic control between the main body axis and its appendages have been generally explained in terms of genetic co-option. In particular, arthropod and vertebrate appendages have been explained to invoke a common ancestor already provided with patterned body outgrowths or independent recruitment in limb patterning of genes or genetic cassettes originally used for purposes other than axis patterning. An alternative explanation is that body appendages, including genitalia, are evolutionarily divergent duplicates (paramorphs) of the main body axis. However, are all metazoan limbs and genitalia homologous? The concept of body appendages as paramorphs of the main body axis eliminates the requirement for the last common ancestor of limb-bearing animals to have been provided with limbs. Moreover, the possibility for an animal to express complex organs ectopically demonstrates that positional and special homology may be ontogenetically and evolutionarily uncoupled. To assess the homology of animal genitalia, we need to take into account three different sets of mechanisms, all contributing to their positional and/or special homology and respectively involved (1) in the patterning of themain body axis, (2) in axis duplication, followed by limb patterning mechanisms diverging away from those still patterning the main body axis (axis paramorphism), and (3) in controlling the specification of sexual/genital features, which often, but not necessarily, come into play by modifying already developed and patterned body appendages. This analysis demonstrates that a combinatorial approach to homology helps disentangling phylogenetic and ontogenetic layers of homology.

Animals↗
PubMed1995

Molecular genetic evidence for unifocal origin of advanced epithelial ovarian cancer and for minor clonal divergence.

Detection of loss of heterozygosity (LOH) and DNA flow cytometry (FCM) were used to trace the origin of bilateral ovarian cancer from 16 patients. From each tumour the DNA index (DI) and LOH patterns for chromosomes 1, 3, 6, 11, 17, 18, 22 and X were determined with 36 microsatellite markers. Formalin-fixed, paraffin-embedded as well as frozen specimens were used. Flow cytometric cell sorting was used to enrich tumour cells for polymerase chain reaction (PCR)-driven LOH analysis. Analysis of the LOH data showed that in 12 of the 16 cases concordance was observed for all informative markers, namely retention of heterozygosity (ROH) or loss of identical alleles in both tumour samples. In four cases discordant LOH patterns were observed. In two cases the discordant LOH was found for one of the chromosomes tested while other LOH patterns clearly indicated a unifocal origin. This suggests limited clonal divergence. In the other two cases all LOH patterns were discordant, most likely indicating an independent origin. The number of chromosomes showing LOH ranged from 0 to 6. Comparison of DNA FCM and the LOH data showed that the latter technique has a higher sensitivity for the detection of a unifocal origin. In 14/16 cases evidence was found for a unifocal origin, while in two cases clonal divergence was found at LOH level and in two other cases clonal divergence at DNA ploidy level. In 12 cases the complete observed allelotype had developed before the formation of metastases, including the two cases showing a large DNA ploidy difference.

Carcinoma↗
PubMed1980

A silver impregnation technique to demonstrate muscle-bone-cartilage relationships in fishes.

A modification of the Winkelmann and Schmitt (1957) technique originally designed to investigate patterns of peripheral nervous innervation is given for demonstration of developing bone growth centers and associated muscle origins and insertions in larval and small fishes. This technique offers a simpler and faster way of obtaining such ontogenetic information than the standard method of double staining with alizarin red S and Alcian blue followed by clearing with potassium hydroxide. Muscles also stain, facilitating the location of their origins and insertions.

Animals↗
PubMed1976

Amylase polymorphism: studies of sera and duodenal aspirates in normal individuals and in cystic fibrosis.

Prior genetic studies of the human pancreatic amylase (Amy2) locus have been directed principally to the electrophoretic analysis of serum and urine, on the assumption that these fluids receive negligible contributions from the salivary (Amy 1) locus. In support of that assumption was the observation that the isozyme bands were lacking in patients with cystic fibrosis and in a postpancreatectomy patient. We have examined the sera of 97 patients having cystic fibrosis and find normal levels of serum amylase. On electrophoresis, three-quarters of the cystic fibrosis patients have a pattern (F-pattern) not observed in normal sera. The pattern is characterized by the absence of Pa 1. Comparative electrophoresis and mixing experiments indicate that the F-pattern is of salivary origin and is unmasked in cystic fibrosis by the absence of a pancreatic contribution. The normal serum pattern is considered to be an admixture of salivary and pancreatic amylase. On the assumption that duodenal fluids might more closely reflect the pancreatic (Amy 2) locus, electrophoretic studies were performed on 148 normal individuals and 37 individuals with cystic fibrosis. Electrophoretic phenotypes in duodenal aspirates are more complex than previously reported in studies of urine and serum; presumably because of the higher concentrations of amylase in the aspirates. Comparative electrophoresis and mixing experiments indicate that the phenotypes observed in duodenal aspirates also reflect admixture of pancreatic and salivary amylase. This recognition of pancreatic and salivary admixture in sera fortunately does not alter our prior understanding of the genetics of the Amy 2 polymorphism. The extensive studies which led to the delineation of the Amy 2 polymorphism were essentially based on the presence or absence of a variant band which proves now to be outside the zone of admixture.

Amylases↗
PubMed1976

Histogenesis of tumors from the nasal cavities induced by diethylnitrosamine.

Chronic subcutaneous (s.c.) or single intravenous (i.v.) injections of diethylnitrosamine (DEN) to gerbils (Meriones unguiculatus) led to the induction of carcinomas of the nasal cavities in a high incidence. These neoplasms were multifocal in origin, frequently showing mixed cellular patterns of the following cell types: large cuboidal cells, nonciliated columnar cells, ciliated columnar cells, small cells, and squamous epithelial cells. No sensory cells of the olfactory mucosa or neurofibrillar differentiations were found in these neoplasms, although several showed rosette- and pseudorosette-like formations. Dose and route of administration seemed to influence the site of origin and the patterns of cellularity of these tumors. Whereas chronic s.c. injections resulted in carcinomas of the olfactory region, being mostly composed of large cuboidal cells, single i.v. injections led to the development of carcinomas mainly originating from the respiratory-olfactory mucosal junction and composed preferentially of nonciliated and ciliated columnar cells.

Adenocarcinoma↗
PubMed1998

Spatial temporal patterns in childhood leukaemia: further evidence for an infectious origin. EUROCLUS project.

The EUROCLUS project included information on residence at diagnosis for 13351 cases of childhood leukaemia diagnosed in the period 1980-89 in defined geographical regions in 17 countries. A formal algorithm permits identification of small census areas as containing case excesses. The present analysis examines spatial-temporal patterns of the cases (n = 970) within these clustered areas. The objectives were, first, to compare these results with those from an analysis conducted for UK data for the period 1966-83, and, second, to extend them to consider infant leukaemias. A modification of the Knox test investigates, within the small areas, temporal overlap between cases in a subgroup of interest at a putative critical time and all other cases at any time between birth and diagnosis. Critical times were specified in advance as follows: for cases of acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months after birth. Each of the analyses found evidence of excess space-time overlap compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26% (P= 0.03) respectively. The results are interpreted in terms of an infectious origin of childhood leukaemia.

Adolescent↗
PubMed1995

RAPD analysis of isolates of Burkholderia pseudomallei from patients with recurrent melioidosis.

Twenty-seven isolates of Burholderia pseudomallei (formerly Pseudomonas pseudomallei) from ten patients with recurrent melioidosis were analysed by RAPD. In two cases RAPD patterns in recurrent isolates differed from the original isolates; one was considered a likely reinfection while the other may represent relapse from one of two strains initially infecting the patient. In two cases where a change in antibiotic resistance had occurred between original and relapse isolates, slight changes in RAPD patterns were found with one of the four primers used. In the other six cases the relapse was clearly due to the original strain re-emerging unchanged, with identical RAPD patterns with all four primers.

Adult↗
PubMed2000

Mechanisms and streams for processing of "what" and "where" in auditory cortex.

The functional specialization and hierarchical organization of multiple areas in rhesus monkey auditory cortex were examined with various types of complex sounds. Neurons in the lateral belt areas of the superior temporal gyrus were tuned to the best center frequency and bandwidth of band-passed noise bursts. They were also selective for the rate and direction of linear frequency modulated sweeps. Many neurons showed a preference for a limited number of species-specific vocalizations ("monkey calls"). These response selectivities can be explained by nonlinear spectral and temporal integration mechanisms. In a separate series of experiments, monkey calls were presented at different spatial locations, and the tuning of lateral belt neurons to monkey calls and spatial location was determined. Of the three belt areas the anterolateral area shows the highest degree of specificity for monkey calls, whereas neurons in the caudolateral area display the greatest spatial selectivity. We conclude that the cortical auditory system of primates is divided into at least two processing streams, a spatial stream that originates in the caudal part of the superior temporal gyrus and projects to the parietal cortex, and a pattern or object stream originating in the more anterior portions of the lateral belt. A similar division of labor can be seen in human auditory cortex by using functional neuroimaging.

Acoustic Stimulation↗
PubMed2005

Expression of CDX2, cytokeratins 7 and 20 in sinonasal intestinal-type adenocarcinoma.

CDX2 is a transcription factor expressed by intestinal epithelium. It is considered as a sensitive marker for a colorectal or-less frequently-gastric origin of adenocarcinomas. The pattern of coordinated expression of cytokeratin (CK) 7 and CK20 is also useful for the diagnosis of the origin of metastatic adenocarcinomas. Expression of CDX2, CK7 and CK20 was investigated in 14 cases of sinonasal intestinal-type adenocarcinoma (SIA), a particular tumor with an enteric-cell-type appearance. Formalin-fixed, paraffin embedded tissue sections were immunostained with monoclonal antibodies using the biotin-labeled streptavidin technique. All of the cases expressed CDX2, being stained 50 to 100% of the tumor cells (mean: 87.2%). CK7 positivity was detected in 8 cases (57.1%), with the staining of 10 to 100% of cells (mean: 65.6%), and CK20 was found in all the tumors (10 to 100% of cells; mean: 78.8%). The histologic resemblance between SIA and colorectal adenocarcinoma is reinforced by the expression of CDX2 and CK20, which are virtually constant in both neoplasms. CDX2 seems to be a marker for cellular phenotype better than an indicator of the origin of adenocarcinomas. CK7 is expressed in SIA less frequently than in colonic adenocarcinoma, but with a rate similar to the subset of rectal tumors, making the differential diagnosis between the two neoplasms difficult.

Adenocarcinoma↗
PubMed1990

Large-cell lymphomas: clinical and prognostic features.

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.

Actuarial Analysis↗
PubMed2005

Emergent patterning phenomena in 2D cellular automata.

This article discusses mechanisms of pattern formation in 2D, self-replicating cellular automata (CAs). In particular, we present mechanisms for structure replication that provide insight into analogous processes in the biological world. After examining self-replicating structures and the way they reproduce, we consider their fractal properties and scale invariance. We explore the space of all possible mutations, showing that despite their apparent differences, many patterns produced by CAs are based on universal models of development and that mutations may lead either to stable or to unstable development dynamics. An example of this process for all possible one-step mutations of one specific CA is given. We have demonstrated that a self-replicating system can carry out many slightly different but related entities, realizing new different growth models. We infer that self-replicating systems exist in an intermediate regime between order and chaos, showing that these models degrade into chaotic configurations, passing through a series of transition stages. This process is quantified by measuring the Hamming distances between the pattern produced by the original self-replicator and those produced by mutated systems. The analysis shows that many different mechanisms may be involved in patterning phenomena. These include changes in the external or internal layers of the structure, substitution of elements, differential rates of growth in different parts of the structure, structural modifications, changes in the original model, the emergence of different structures governed by different CA rules, and changes in the self-replication process.

Algorithms↗