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Observations on epidermal exsorption in mice following injections of procion dyes and ethidium bromide and topically applied dimethyl sulfoxide.

Back skin of hairless mice and external ears of CD-1 white mice were used to study the details of epidermal exsorption . Ethidium bromide, a DNA ligand, and two dichlorotriazinyl (procion) dyes were injected, i.v. or i.p. Migration patterns from the skin vasculature into the epidermis were observed by fluorescence microscopy and microspectrofluorometry . Topically applied DMSO greatly enhanced the exsorption process and produced intensely labeled epidermis. Ethidium bromide reacted primarily with nuclear DNA of living cells while the procion dyes tended to migrate intercellularly to label the stratum corneum. External ears of white mice treated topically with DMSO showed a pattern of labeling which included intense fluorescence of the cartilage and perichondrium as well as the ear epidermis.

Administration, Topical↗

Decay of genetic variability in geographically structured populations.

The ultimate rate and pattern of approach to equilibrium of a diploid, monoecious population subdivided into a finite number of equal, large, panmictic colonies are calculated. The analysis is restricted to a single locus in the absence of selection, and every mutant is assumed to be new to the population. It is supposed that either the time-independent backward migration pattern is symmetric in the sense that the probability that an individual at position x migrated from y equals the probability that one at y migrated from x, or it depends only on displacements and not on initial and final positions. Generations are discrete and nonoverlapping. Asymptotically, the rate of convergence is approximately (I-u)2t[I-(2NT)-1]t, where u, NT, and t denote the mutation rate, total population size, and time in generations, respectively; the transient part of the probability that two homologous genes are the same allele is approximately independent of their spatial separation. Thus, in this respect the population behaves as if it were panmictic.

Genetic Variation↗

Spatial distribution of immature Culicoides variipennis (Coq.).

Circadian fluctuation in the spatial distribution of immature Culicoides variipennis (Coq.) was studied in Saltville, Virginia, USA during the summer of 1983. Pupae and early instar larvae (1st and 2nd) were localized above the shoreline in the top cm of mud and displayed little migration from this region during the 24 hr sampling period, however, later instar larvae (3rd and 4th) showed marked migration patterns. Most larval movement was horizontal rather than vertical and was confined to the top cm of mud. Late instar larvae moved towards the water during the day but migrated up above shoreline during the night. Seasonal fluctuation in larval spatial distribution was also studied. Larvae appeared to move progressively downward into the mud during the autumn. However, when the site became frozen the majority of larvae occupied a narrow liquid interface between the ice cover and the frozen mud beneath.

Animals↗

Analysis of Epstein-Barr virus (EBV) type and variant in spontaneous lymphoblastoid cells and Hu-SCID mouse tumours.

Epstein-Barr virus (EBV) type and strain variations were examined using both lymphoblastoid cell lines (LCLs), spontaneously derived in vitro from peripheral blood mononuclear cells (PBMC) of 15 HIV-1-seropositive individuals; and SCID mouse tumours induced by inoculation of PBMC from 11 healthy human donors (Hu-SCID tumours). Polymerase chain reaction (PCR) analysis disclosed that all but one of the 26 EBV + samples harboured EBV nuclear antigen (EBNA) 2 and 3C type A virus. On the other hand, single strand conformation polymorphism (SSCP) analysis using Epstein-Barr encoded RNA (EBER) specific primers detected an AG876-like (type B) band pattern in 21 of the 26 EBV + samples. Three Hu-SCID tumours scored as B95.8-like (type A), and two showed neither a type A nor a type B SSCP migration pattern. Sequence analysis of the amplified EBER fragments confirmed the PCR-SSCP findings; moreover, additional mutations were present not only in the two EBV + samples with anomalous SSCP pattern, but also in two other samples with a standard SSCP profile. Thus, EBER analysis did not correlate with EBNA typing, and appeared to be unsuitable for EBV type assessment. Latent membrane protein (LMP) analysis disclosed, on the whole, sever size variants: as expected, the differences were due to the variable numbers of a 33-bp repeat in the amplified fragment, as assessed by direct sequencing. The broader variability detected by LMP analysis should prove more useful than typing for assessing the presence of single and/or mixed variants resulting from EBV reactivation and/or reinfection.

Animals↗

branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching.

The molecular basis for patterning of complex organ structures like the lung and insect tracheal system is unknown. Here, we describe the Drosophila gene branchless (bnl) and demonstrate that it is a key determinant of the tracheal branching pattern. bnl is required for tracheal branching and is expressed dynamically in clusters of cells surrounding the developing tracheal system at each position where a new branch will form and grow out. Localized misexpression of bnl can direct branch formation and outgrowth to new positions. Generalized misexpression activates later programs of tracheal gene expression and branching, resulting in massive networks of branches. bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase, an FGF receptor homolog expressed on developing tracheal cells. The results suggest that this FGF pathway specifies the tracheal branching pattern by guiding tracheal cell migration during primary branch formation and then activating later programs of finer branching at the ends of growing primary branches.

Animals↗

Does migration exaggerate the relationship between deprivation and limiting long-term illness? A Scottish analysis.

Few epidemiological studies of the links between health and environmental variables account for the potentially confounding effects of population migration. Here we explore the relationship between self-reported limiting long-term illness and material deprivation, using individual-level 1991 census data extracted for Scotland. The aim is to investigate whether the migration patterns of ill individuals influences the relationship between limiting long-term illness and material deprivation. Specifically, we seek to determine whether individuals who are well are more likely to migrate away from deprived areas and whether ill individuals are more likely to migrate towards deprived areas. If true, this would suggest that the apparent relationship between deprivation and limiting long-term illness is exaggerated by the effects of migration. We then examine the issue controlling for individual-level characteristics expected to influence limiting long-term illness and pay special attention to the role of public housing in these relationships.

Adolescent↗

Migration pathways of CD4 T cell subsets in vivo: the CD45RC- subset enters the thymus via alpha 4 integrin-VCAM-1 interaction.

The present investigation examines the localization and migration of purified T cell subsets in comparison with B cells, CD8 T cells and CD4+ CD8- single-positive thymocytes. CD4 T cell subsets in the rat are defined by mAb MRC OX22 (anti-CD45RC), which distinguishes resting CD4 T cells (CD45RC+) from those (CD45RC-) which have encountered antigen in the recent past--subpopulations often referred to as 'naive' and 'memory'. Purified, 51Cr-labelled CD45RC+ CD4 T cells broadly reflected the migration pattern of CD8 T cells and B cells. Early localization to the spleen was followed by a redistribution to mesenteric lymph nodes (MLN) and cervical lymph nodes (CLN), B cells migrating at a slightly slower tempo. There was almost no localization of these subpopulations to the small or large intestine [Peyer's patches (PP) excluded]. In contrast, CD45RC- CD4 T cells (indistinguishable in size from the CD45RC+ subset) localized in large numbers to the intestine; they were present here at the earliest time point (0.5 h), persisted for at least 48 h but did not accumulate, indicating a rapid exit. Numerically, localization of CD45RC- CD4 T cells in the MLN could be accounted for entirely by afferent drainage from the intestine. Unexpectedly, CD45RC- CD4 T cells (but not other subsets) localized and accumulated in the thymus. In vivo treatment with mAb HP2/1 against the integrin alpha 4 subunit inhibited almost entirely CD45RC- CD4 T cell migration into the PP (98.1%), intestine (87.1%), MLN (89.1%) and thymus (93.5%); migration into the CLN was only reduced by half. To distinguish between recognition of MAdCAM-1 and VCAM-1 by alpha 4-containing integrins, recipients were treated with mAb 5F10 against rat VCAM-1. Except for the thymus and a small reduction in CLN, localization of CD45RC- CD4 T cells was unaffected; entry to the thymus was almost completely blocked (92.3%) by anti-VCAM-1. The results indicated (i) that CD45RC- CD4 T cells alone showed enhanced localization to the gut and PP, probably via alpha 4 beta 7-MAdCAM-1 interaction; (ii) that many CD45RC- cells entered non-mucosal LN independently of alpha 4 integrin or VCAM-1; and (iii) that entry of mature recirculating CD45RC- CD4 T cells into the thymus across thymic endothelium was apparently regulated by alpha 4 integrin-VCAM-1 interaction.

Animals↗

Avian collision risk at an offshore wind farm.

We have been the first to investigate whether long-lived geese and ducks can detect and avoid a large offshore wind farm by tracking their diurnal migration patterns with radar. We found that the percentage of flocks entering the wind farm area decreased significantly (by a factor 4.5) from pre-construction to initial operation. At night, migrating flocks were more prone to enter the wind farm but counteracted the higher risk of collision in the dark by increasing their distance from individual turbines and flying in the corridors between turbines. Overall, less than 1% of the ducks and geese migrated close enough to the turbines to be at any risk of collision.

Accident Prevention↗

Anthropometric variation and population structure of the island of Pag, Croatia.

Anthropometric variation in the population of the island of Pag (eastern Adriatic, Croatia) was investigated by using data on 14 head and 24 body dimensions. The data were related to past and present migration patterns, geography, and linguistics. The analyses revealed heterogeneity among three population groups inhabiting geographically defined regions of the island and heterogeneity among the village populations. The congruence between anthropometric variation, migration history, geographic distances, and current linguistic features says much for the strength of the isolating factors on this ecologically uniform island, which have effected the genetic structure of the population.

Adult↗

Clonal patterns of cell proliferation, migration, and dispersal in the brainstem of the chicken embryo.

Retroviral-mediated gene transfer was used to study clonal patterns of proliferation, migration, and dispersal in the brainstem of the chicken embryo. Clones were generated at stages 13-17 (Hamburger and Hamilton, 1951), a period of neurogenesis in the brainstem neural tube subsequent to the formation of rhombomeres. Clones were examined in separate experiments at stages 24-27, when many neurons migrate and differentiate; at stages 28-29, when brainstem nuclei begin to form; and at stages 34-35, when brainstem nuclei are fully formed. Stages 24-29 are characterized by a general variability in proliferative kinetics and migratory behavior. Clone sizes range from 1 to 29 cells, and migration patterns range from strictly radial (i.e., normal to the ventricular surface) to combined radial and tangential (i.e., perpendicular to the radial component). There is, however, an underlying systematic variation: (1) clones exhibiting tangential migration contain on average more cells than clones exhibiting only radial migration, and (2) the proportion of tangentially migrating clones increases from medial to lateral. By stages 34-35 some individual clones have apparently dispersed to disparate neuronal groups. The regional diversity observed among clones suggests that position along the mediolateral axis may determine the proliferative potential of progenitors and the migratory behavior and subsequent dispersal of their descendants.

Animals↗

Migration and household change in the population aged 65 and over, 1971-1991.

"This analysis uses the ONS [Office for National Statistics] Longitudinal Study, a record linkage study including individual-level data from three national Censuses (1971, 1981 and 1991) and linked vital registration data, to examine migration patterns among older people [in Great Britain]. The aims of this study are to examine regional differences in household composition, to look at changes in the relationship between household change and migration over time, and finally, to analyse the interrelationships between changes in household composition, health and migration in the 1981-91 period.... Despite...dramatic changes in the living arrangements of older people, results show that mobility among the elderly remained relatively stable between the 1971-81 and 1981-91 decades."

Adult↗

A spatial analysis of 100 surnames in England and Wales.

Spatial patterns are described and analysed for the 84 most common surnames in England and Wales, as well as 16 others selected for various reasons. At least three-quarters of the surname frequencies show spatial structure and are heterogeneous over the area of study. While they do not exhibit clines extending over the entire area of study, they do divide into four characteristics patterns. Spatial autocorrelation, while significant, is relatively low; similarity in surname frequency does not extend much beyond 100 km. Correlograms could be clustered to yield groups of surfaces denoting partial clines, isolation by distance, and differentiation at far distances. A method for detecting zones of rapid change found 21 such zones, mostly near the periphery of the study area. These boundaries do not indicate barriers to gene flow, but appear to be patterns brought about by historical factors. There are diffusion patterns between areas that differ greatly in surname composition, such as Wales and central England. There is little evidence of long-distance movements involving several surnames. At least three characteristic migration patterns, east-west and north-south diffusion and local dispersal, were found.

England↗

Geographical variation in a quantitative character.

A model for the evolution of the local averages of a quantitative character under migration, selection, and random genetic drift in a subdivided population is formulated and investigated. Generations are discrete and nonoverlapping; the monoecious, diploid population mates at random in each deme. All three evolutionary forces are weak, but the migration pattern and the local population numbers are otherwise arbitrary. The character is determined by purely additive gene action and a stochastically independent environment; its distribution is Gaussian with a constant variance; and it is under Gaussian stabilizing selection with the same parameters in every deme. Linkage disequilibrium is neglected. Most of the results concern the covariances of the local averages. For a finite number of demes, explicit formulas are derived for (i) the asymptotic rate and pattern of convergence to equilibrium, (ii) the variance of a suitably weighted average of the local averages, and (iii) the equilibrium covariances when selection and random drift are much weaker than migration. Essentially complete analyses of equilibrium and convergence are presented for random outbreeding and site homing, the Levene and island models, the circular habitat and the unbounded linear stepping-stone model in the diffusion approximation, and the exact unbounded stepping-stone model in one and two dimensions.

Biological Evolution↗

Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma.

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.

Animals↗

The role of Hoxa-3 in mouse thymus and thyroid development.

Targeted disruption of Hoxa-3 results in a number of regionally restricted defects in tissues and structures derived from or patterned by mesenchymal neural crest. However, analysis of mutant embryos with injections of a carbocyanine dye or with molecular markers that label these cells indicates that neither the amount nor the migration patterns of this neural crest population are grossly affected. Therefore, it appears that the loss of Hoxa-3 affects the intrinsic capacity of this neural crest cell population to differentiate and/or to induce proper differentiation of the surrounding pharyngeal arch and pouch tissues. Hoxa-3 mutant mice are athymic and show thyroid hypoplasia. Thymus development is first evident as an expansion of mesenchymal neural crest in the posterior part of the 3rd pharyngeal pouch. Prior to this expansion, a marked reduction in pax-1 expression is observed in these cells in the mutant embryos. As pax-1 mutant mice also show thymic hypoplasia, these results suggest that Hoxa-3 may be required to maintain pax-1 expression in these cells and that the reduction of pax-1 expression is part of the athymic teleology in Hoxa-3 mutant mice. The thyroid gland is formed from the fusion of two structures of separate embryonic origin, the thyroid diverticulum, which is formed from endodermal epithelium in the floor of the pharynx, and the ultimobranchial body, formed from mesenchymal neural crest in the 4th pharyngeal pouch. Both of these sites express Hoxa-3 and are defective in mutant mice. Often a vesicle is observed in mutant mice that is exclusively composed of calcitonin-producing cells, suggesting the persistence of an ultimobranchial body. Both aspects of the thyroid phenotype show variable expressivity among mutant animals, even on the two sides of the same mutant animal. This variability suggests the presence of a compensating gene or genes, whose utilization is stochastic. A reasonable candidate for providing this compensatory function is the paralogous gene Hoxb-3.

Animals↗

Migration of the acetabular socket after total hip replacement determined by roentgen stereophotogrammetry.

UNLABELLED: In order to evaluate the feasibility of a roentgen stereophotogrammetric method for the analysis of the migration pattern of joint prostheses, tantalum balls were implanted into the acetabular socket and the pelvic bone during total hip replacement in four patients with rheumatoid arthritis. During the postoperative period, the migration of the acetabular socket was determined. The observation period varied from 5-24 months. No clinical or radiographic signs of mechanical loosening or infection were noted. All the investigated patients showed a gradual migration of the acetabular socket. The cranial migration measured up to 1.8 mm in 2 years. The migration along the transverse and sagittal axes was less but not constantly directed. The rotatory movements about the three axes varied and measured up to 5.5 degrees in 2 years. The translation and rotation were greatest during the first few months. The results indicate a gradual migration of the acetabular socket in hip arthroplasty in the osteopenic skeleton in rheumatoid arthritis. IN CONCLUSION: roentgen stereophotogrammetry may prove to be a valuable means of analysing the migration of implanted prostheses and detecting prosthetic loosening, thereby increasing the possibility of early and correct diagnosis and therapy.

Acetabulum↗

Fasting canine biliary secretion and the sphincter of Oddi.

This study correlates duodenal bile acid delivery with motility of the sphincter of Oddi during the fasting state. Dogs were prepared with a functional cholecystectomy, a duodenal cannula for direct vision cannulation of the common bile duct, and 12 bipolar electrodes serosally implanted from stomach to terminal ileum. In one set of experiments, the bile acid pool was depleted, and during a continuous i.v. infusion of sodium taurocholate (20 mumol/min), duodenal bile acid delivery was assessed over 6 h by a marker perfusion technique. In other experiments, a double-lumen continuously perfused manometry catheter was placed to record motility in the bile duct and sphincter of Oddi for a period of 6 h. Station pull-throughs of the sphincter of Oddi were performed in each phase of the migrating motor complex. Bile acid secretion rates fluctuated about the i.v. infusion rate during duodenal phase I and II, peaked in late phase II, and then fell to barely detectable levels during duodenal phase III. There was no peristaltic contractile activity in the common bile duct in any phase of the migrating motor complex. The sphincter of Oddi maintained a baseline pressure above common bile duct pressure. It was highest during phase III. Phasic contractions of the sphincter of Oddi were intermittent during phase I, increasingly frequent during phase II, and continuous during duodenal phase III of the migrating motor complex. Contractions were frequently peristaltic. We concluded that the occurrence and amplitude of phasic peristaltic contractions of the sphincter of Oddi are cyclically coordinated with the fasting intestinal motor pattern (migrating motor complex), and with cyclical variations in the delivery of bile acids into the duodenum. Both resting pressure and phasic contractions of the sphincter appear to play a role in coordinating the cyclic delivery of bile acids into the duodenum with the migrating motor complex. Intense phasic motor activity appears to impede bile flow, and less intense activity allows or facilitates flow.

Action Potentials↗

Murine p53 is phosphorylated within the PAb421 epitope by protein kinase C in vitro, but not in vivo, even after stimulation with the phorbol ester o-tetradecanoylphorbol 13-acetate.

The p53 tumour suppressor protein is thought to play a major role in the defence of the cell against agents which damage DNA. p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro. In this report, we have examined the phosphorylation of murine p53 by protein kinase C (PKC). Phosphopeptide mapping, phosphoamino acid analysis and radiosequence analysis of p53 phosphorylated by PKC in vitro indicated that serine 370 and threonine 377 were the major targets for phosphorylation and suggested that serine 372 and threonines 365 and 371 were minor phosphorylation sites. Site-directed mutagenesis confirmed that residues 370-372, all of which lie within the epitope for monoclonal antibody PAb421, were phosphorylated in vitro. The p53 from 32P-labelled SV3T3 cells showed a phosphopeptide pattern which includes peptides with mobilities similar to those arising from phosphorylation of residues 370-372 by PKC in vitro. Only two of these in vivo-labelled phosphopeptides co-migrated in two dimensions with peptides labelled in vitro within the PAb421 epitope and their phosphorylation was not stimulated by the addition of the PKC activator o-tetradecanoylphorbol 13-acetate (TPA) to the cells, even though this treatment led to a fourfold stimulation of p53 phosphorylation by MAP kinase. Moreover, when the p53 proteins containing mutations at residues 370-372 were expressed in COS cells, there was no loss of any of the in vivo phosphopeptides, indicating that phosphorylation within the PAb42I epitope was undetectable in the cell. These data suggest that p53 and PKC may not interact in vivo. The two-dimensional migration pattern of the novel group of peptides is consistent with phosphorylation of previously uncharacterised sites within the central DNA binding region of p53.

3T3 Cells↗