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Analysis of cranial neural crest cell migration and early fates in postimplantation rat chimaeras.
Rat embryos were grown in vitro during the period of cranial neural crest cell migration. In order to study the pathways and positional fates of cells from different regions of the neural crest, labelled premigratory crest cells from donor embryos were microinjected orthotopically into host embryos of the same developmental stage except for area 1 (forebrain) grafts which were, for technical reasons, injected into area 2. After various periods of time in whole embryo culture, the embryos were examined by immunohistochemical staining in order to determine the new positions of the labelled cells, and a map of their migration pathways was constructed. The observed patterns of migration were consistent with predictions from morphological studies in mammals and with extrapolations from transplantation studies in birds. However, crest cell migratory behaviour in rat and chick embryos was not identical; possible reasons for this are discussed.
[Rapid demonstration of mutations previously identified in parents at risk of patients with autosomic dominant retinitis pigmentosa].
PURPOSE: We have previously identified rhodopsin gene mutations in France in autosomal dominant (ADRP) retinitis pigmentosa in France, using a combination of SSCP (single-strand conformation polymorphism) and direct sequence analysis. The aim of this study was to perform a more rapid tool to identify a mutation in a ADRP family, when this mutation has been identified for one affected member of this family. METHODS: We looked for a restriction site, created or abolished by a mutation in the rhodopsin gene. We performed in vitro DNA amplification using PCR (polymerase chain reaction), enzymatic digestion, and migration on agarose gel. RESULTS: Abnormal patterns of migration were observed for affected ADRP members. DISCUSSION: This technique is useful and rapid (less than 5 hours) to recognize a previously identified mutation. However, previous precise identification of the mutation in one member of the family is needed.
New approaches to the estimation of migration flows from census and administrative data sources.
Census data represent an important source of information about migration flows. However, existing estimation procedures based on intercensal projection are often inconvenient to apply and are sensitive to even quite small changes in enumeration completeness. 2 new estimation procedures applicable to data from 2 censuses are developed and illustrated using US data. The 1st method is essentially a modification of traditional intercensal projection techniques, but as a result of working with age groups rather than cohorts, it is simpler to apply and allows mortality of the migrants to be incorporated over the intercensal period. The 2nd method also uses information from 2 censuses, but also uses independent information on the age pattern of migration from administrative sources or from other census questions. The method uses the fact that the age pattern of recent migration is likely to be different from the age distribution of the overall population to distinguish between intercensal change due to migration and apparent intercensal change due to changes in enumeration completeness. If the method's assumptions are met, it is possible to estimate the relative coverage of the 2 censuses as well as the scale of the independent age pattern of migration relative to the coverage of 1 or other of the censuses. The illustrative applications of the methods to US data suggest that both can work reasonably well.
Effective size in management and conservation of subdivided populations.
A numerical method for computing the eigenvalue variance effective size of a subdivided population connected by any fixed pattern of migration is described. Using specific examples it is shown that total effective size of a subdivided population can become less than the sum of the subpopulation sizes as a result of directionalities in the pattern of migration. For an extension of the model with threshold harvesting and local deterministic logistic population dynamic we consider the problem of maximizing the total harvesting yield with constraints on the total effective size. For some simple source-sink systems and more complicated population structures where subpopulations differ in their degree of isolation, it is shown to be optimal, for a given total effective size, to raise the harvesting thresholds relatively more in small and in isolated populations. Finally, we show how the method applies to populations which are supplemented, either intentionally or unintentionally. It is shown that the total effective size can be reduced by several orders of magnitude if the captive component of a population is much smaller than the wild component, even with symmetric backward migration.
Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis: further support for a triple-stranded folding unit model of the spectrin heterodimer contact site.
Six individuals with hereditary elliptocytosis (HE) or hereditary pyropoikilocytosis (HPP) from three unrelated families were evaluated. Defects in the ability of spectrin (Sp) to undergo self-association were present, and associated with increased recovery of the Sp alpha I 74-kD fragment after limited tryptic digestion (Sp alpha I/74 variant). Because mutations associated with the Sp alpha I/74 variant described to date have been localized to the 5' coding region of the alpha-Sp gene (exon 2) or at the 3' coding end of the beta-Sp gene (exon 30), the polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) method was used to detect mutations in these two regions. In one family with HE, an abnormal pattern of migration of PCR-amplified fragments containing exon 2 was observed, and led to the detection of a new mutation (Ile24Ser) in helix 3 of repeating segment alpha 1. In the two other families, an abnormal pattern of migration of PCR-amplified fragments containing exon 30 was observed in affected individuals, and sequencing led to the identification of two new mutations (Ala2023Val and Trp2024Arg) in helix 1 of repeating segment beta 17. The elliptogenic potential of these mutations emphasizes the importance of the conformational integrity of each of the three helices involved in the formation of the Sp heterodimer contact site, and will help identify critical amino acids involved in this interaction.
Mortality and migration in Britain, first results from the British Household Panel Survey.
This study investigates the extent to which current geographical variations in mortality are influenced by patterns of migration since birth. It is based on a longitudinal study of migrants which consists of a representative sample of 10264 British residents born after 1890 and enumerated as part of the British Household Panel Study in 1991. Between 1991 and 1996, 527 of the study members died and these deaths were analysed by area of residence at birth and in 1991 at both the regional and local district geographical scales. These were compared with findings from the Office for National Statistics Longitudinal Study. The British Household Panel Survey sample replicates the results of work conducted on the Longitudinal Study which finds that geographical variations in age-sex standardised mortality ratios at the regional scale cannot be attributed to selective migration. However, for the British Household Panel Survey sample, the major geographical variations at district level could be attributed to selective migration. Geographical variations in mortality are not well understood. Restrictions on what it is possible to analyse in the Office for National Statistics Longitudinal Study may have resulted in the underestimation of the importance of local lifetime selective migration in producing the contemporary map of mortality variation across Britain. The British Household Panel Survey is a small, recent, but very flexible study, which can be used to investigate the effects of lifetime migration on mortality patterns for all of Britain. This first report of its results on mortality shows that it produces findings which accord with the much larger Longitudinal Study, but which can be taken further to show that selective migration over the whole life-course at the local level does appear to have significantly altered the geographical pattern of mortality seen in Britain today.
Duodenal nutrients inhibit canine jejunal fasting motor patterns through a hormonal mechanism.
Ingestion of a meal converts the fasting motor pattern, the migrating motor complex (MMC), to a fed pattern of motility. The role of specific anatomic gut regions involved in these changing patterns of motility and the neurohormonal factors which mediate these changes, however, are unknown. Our aim was to determine the neurohormonal mechanisms by which nutrients within the duodenal lumen alter proximal jejunal motility. Fifteen dogs were prepared with a gastric cannula, duodenal infusion catheter, duodenal and proximal jejunal manometry catheters, and a totally diverting cannula in the most proximal portion of the jejunum. Ten of the dogs also underwent complete in situ neural isolation of the entire jejunoileum. Experiments were performed in the fasting state with no infusion (0 ml/min) and during a 5-hr duodenal infusion (3 ml/min) of either a nonnutrient electrolyte solution or a mixed nutrient solution while diverting distal duodenal chyme from the jejunum. During sham infusion (0 ml/min), the MMC was present in neurally intact dogs (group 1) and dogs with neurally isolated jejunoileum (group 2). Nonnutrient infusion did not inhibit or consistently alter the MMC in either group. Nutrient infusion limited to the duodenum inhibited the MMC in both duodenum and jejunum in dogs with neurally intact and neurally isolated jejunoileum. Latency of onset of the fed pattern in the duodenum and jejunum did not differ between groups. We conclude that postprandial inhibition of the MMC in the jejunum is mediated, in part, by a hormonal mechanism induced by duodenal lumenal nutrients.
Jejunoileal transplantation. Effects on characteristics of canine jejunal motor activity in vivo.
This study was designed to determine if extrinsic innervation and intrinsic neural continuity with the duodenum (neuroenteric physiologic pathways disrupted during intestinal transplantation) modulate the characteristics of interdigestive motor activity in the canine small bowel. Five dogs served as neurally intact controls (group 1) and 10 dogs (group 2) underwent a model of jejunal autotransplantation involving in situ neural isolation of the jejunoileum. Fasting duodenal and jejunal motor activity was recorded on-line to a microcomputer using closely spaced duodenal and jejunal manometry catheters. Characteristics of global motor patterns, the migrating motor complex (MMC), and local motor patterns, including individual contractions and grouped clustered contractions, were determined. Neural isolation of the jejunoileum disrupted coordination of duodenal and jejunal phase III activity, increased the variability of cycling of the MMC, decreased the period of the jejunal MMC, and increased motility indices in the neurally isolated jejunum. In contrast, single pressure waves and clustered contractions in the neurally isolated jejunum were not altered significantly in incidence or direction, distance, or velocity of spread. In situ neural isolation of the jejunoileum leads to temporal dissociation of the MMC between the transplanted segment (jejunum) and the duodenum but does not appear to alter markedly the characteristics of local contractile activity as measured by individual or grouped contractions. The occurrence of interdigestive jejunal motor patterns and the local organization of individual and grouped small intestinal contractions are not controlled by extrinsic innervation or intrinsic neural continuity with the duodenum.
The non-Markovian nature of migration: a case study in the Aland Islands, Finland.
Markov theory is applied frequently to the study of human migration processes. A Markovian migration process is one in which the pattern of migration in one generation depends only on that of the previous generation. Several Markovian migration models are discussed here. It may be, however, that the presence of ancestors in a particular place had a significant bearing on the decision to migrate, in which case the process is not independent of the past. One example of such a process may be the parish of Kökar in the Aland Islands, Finland. Parent-offspring migration data which span the last two centuries of migration in Kökar are used here to test the assumption that the migration process in this parish is Markovian. Matrices of observed parent-, grandparent- and great grandparent-offspring migration are constructed and compared to the respective matrices expected on the basis of Markovian migration, using a X2 test for independence in a contingency table. Results indicate that a Markovian model does not describe adequately the migration process in this parish. Possible genetic implications of a non-Markovian migration process are discussed, with particular reference to populations of the type presented here which are experiencing the transition to urbanization.
Profile of HIV disease in an American border city.
A previous study on patterns of migration of HIV-infected persons suggested that most patients in a rural setting in eastern Tennessee acquired their disease in an urban area, typically during a period of prolonged residence. Disease and disability were the most common reasons for returning to their hometown. We studied our urban, border-city HIV clinic population to see whether similar patterns of migration were discernible. Fifty-one of the 103 patients studied lived outside the El Paso/Juarez area when they contracted HIV infection. The major reason cited for returning home was a desire to return to family (25%). Those who returned and those who had never left showed no statistically significant difference in age, race, or risk factors. This study suggests that migration of HIV-infected patients back to their hometown does not appear to be an exclusively rural phenomenon.
The developing mouse thyroid: embryonic vessel contacts and parenchymal growth pattern during specification, budding, migration, and lobulation.
Normal mouse thyroid development has been revised to identify critical morphogenetic events. The early thyroid primordium associates with the aortic sac endothelium at the time of specification and budding. The vascular contact is lost after the thyroid buds from the pharyngeal endoderm, but is resumed before the gland divides to form two lobes. Lateral expansion of parenchyma takes place along the course of the third pharyngeal arch arteries. Thyroid precursor cells expressing Titf1/Nkx2.1 do not proliferate until the migration stage, implicating that progenitors likely are recruited from outside the thyroid placode. Early lobulation involves engulfment of the entire ultimobranchial bodies by the growing midline thyroid. At the same time, proliferation of the ultimobranchial body epithelium is silenced preceding the differentiation of C cells. Before folliculogenesis, thyroid lobe enlargement is reminiscent of a budding-branching-like growth pattern. It is suggested that thyroid inductive signals arise from embryonic vessels, and that this provides ideas to conceptually new pathogenetic mechanisms of thyroid dysgenesis.
A role for the polysialic acid-neural cell adhesion molecule in PDGF-induced chemotaxis of oligodendrocyte precursor cells.
Directed migration of oligodendrocyte precursor cells (OPCs) is important for myelin formation and repair but the mechanisms of directional control are poorly understood. Here we have tested the role of polysialic acid-neural cell adhesion molecule (PSA-NCAM) in the directional migration of OPCs towards platelet-derived growth factor (PDGF). Using a Boyden microchemotaxis chamber and the Dunn direct viewing chamber, we show that in concentration gradients of PDGF, PSA-positive OPCs polarize and efficiently migrate towards the source of PDGF (chemotaxis). The loss or inactivation of the polysialic tail of NCAM leads to an altered pattern of OPC migration in response to PDGF gradients. Cells under these conditions, while being polarized and migrating, show no bias of displacement towards the source of PDGF and make random turns. By contrast, directed migration of OPCs towards basic fibroblast growth factor was not affected by the removal of PSA. Moreover, inactivation of PSA does not interfere with the random migration pattern of cells in uniform concentrations of PDGF (chemokinesis). These results suggest that PSA-NCAM is specifically involved in establishing the directionality of OPC migration in response to the concentration gradient of PDGF, but it is not essential for cell motility per se.
Muscle development in the four-winged Drosophila and the role of the Ultrabithorax gene.
BACKGROUND: In the fruitfly Drosophila melanogaster, segment identity is specified by the homoeotic selector genes of the bithorax and Antennapedia complexes. The functions of these genes in the segmental specification of the Drosophila ectoderm have been well studied, but their roles in muscle development have been relatively poorly investigated. Recent experiments have strongly suggested that homeotic selector genes are directly involved in one aspect of mesodermal patterning during Drosophila embryogenesis. But muscle development is a complex process, requiring for its completion the correct positioning of the epidermis, the nervous system and the developing muscles in a segment-specific manner. Many aspects of homeotic selector gene function in this process remain to be understood. RESULTS: In flies that are homozygous for three mutant alleles (anterobithorax, bithorax3, postbithorax) of the Ultrabithorax gene, the third thoracic segment (T3) is transformed towards the second (T2). The adults have two pairs of wings, but the homeotically transformed T3 (HT3) has only rudimentary indirect flight muscles. We used the 'four-winged' fly to study the role of homeotic selector genes in the development of the indirect flight muscles, which we classify into four 'events'. First, the determination of the segment-specific pattern of myoblasts in the larval thorax; second, the specific pattern of migration of myoblasts during metamorphosis; third, the fusion of myoblasts to form adult indirect flight muscles and fourth, the development of the branching pattern of adult motor innervation. Our study shows that the segmental identity of the epidermis determines the segment-specific pattern and number of myoblasts on the larval discs, and the pattern of their migration during metamorphosis. The segmental identity of the mesoderm, however, is crucial for the fusion of myoblasts to form indirect flight muscles, and also influences the branching pattern of innervation of indirect flight muscles. CONCLUSIONS: Segmental information expressed in the ectoderm, and the autonomous function of homeotic selector genes in the mesoderm, are both required for the complete development of indirect flight muscles.
A paraxial exclusion zone creates patterned cranial neural crest cell outgrowth adjacent to rhombomeres 3 and 5.
Cranial neural crest cell migration is patterned, with neural crest cell-free zones adjacent to rhombomere (R) 3 and R5. These zones have been suggested to result from death of premigratory neural crest cells via upregulation of BMP-4 and Msx-2 in R3 and R5, consequent to R2-, R4-, and R6-derived signals. We reinvestigated this model and found that cell death detected by acridine orange staining in avian embryos varied widely numerically and in pattern, but with a tendency for an elevated zone centered at the R2/3 boundary. In situ hybridization of BMP-4 mRNA resolved to centers at R3 and R5 but Msx-2 resolved to the R2/3 border with only a faint smear from R5 to R6. Outgrowth of neural crest cells was less in isolated R3 cultures than in R1+2, R2, and R4 cultures, but R3 showed neither a decrease in outgrowth of neural crest cells nor an increase in cell death when cocultured with R1+2, R2, or R4. In addition, in serum-free culture, exogenous BMP-4 strikingly reduced neural crest cell outgrowth from R1+2 and R4 as well as R3. Thus we cannot confirm the role of intraneural cell death in patterning rhombomeric neural crest outgrowth. However, grafting quail R2 or R4 adjacent to the chick hindbrain demonstrated a neural crest cell exclusion zone next to R3 and R5. We suggest that one important pattern determinant for rhombomeric neural crest cell migration involves the microenvironment next to the neural tube.
Mechanisms of neural crest cell migration.
Neural crest cells are remarkable in their extensive and stereotypic patterns of migration. The pathways of neural crest migration have been documented by cell marking techniques, including interspecific neural tube grafts, immunocytochemistry and DiI-labelling. In the trunk, neural crest cells migrate dorsally under the skin or ventrally through the somites, where they move in a segmental fashion through the rostral half of each sclerotome. The segmental migration of neural crest cells appears to be prescribed by the somites, perhaps by an inhibitory cue from the caudal half. Within the rostral sclerotome, neural crest cells fill the available space except for a region around the notochord, suggesting the notochord may inhibit neural crest cells in its vicinity. In the cranial region, antibody perturbation experiments suggest that multiple cell-matrix interactions are required for proper in vivo migration of neural crest cells. Neural crest cells utilize integrin receptors to bind to a number of extracellular matrix molecules. Substrate selective inhibition of neural crest cell attachment in vitro by integrin antibodies and antisense oligonucleotides has demonstrated that they possess at least three integrins, one being an alpha 1 beta 1 integrin which functions in the absence of divalent cations. Thus, neural crest cells utilize complex sets of interactions which may differ at different axial levels.
Geographical pattern analysis of income migration in the United States.
"How one conceptualises the impacts of migration depends on whether one takes the viewpoint of aggregate area-level income change, of per capita change, or of longer-term (future earnings) change. Several empirical analytical measures are proposed in order to conceptualise the various income impacts of migration.... [A] decomposition procedure is developed for examining how the changes in per capita income of states reflect three different income differentials: those between (a) in-migrants and 'stayers', (b) out-migrants and 'stayers', and (c) in-migrants and out-migrants. Examination of these measures, and of typologies based on them, highlights how income migration significantly and differentially impacts upon U.S. states. The methods are illustrated here in the context of an important new American data source: the 1993-94 migrant income data released by the U.S. Internal Revenue Service."
An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat.
The dentate gyrus of the rat contains about 600,000 granule cells. These small neurons are generated over a prolonged period from the 14th day of gestation until some time after the second postnatal week. The majority of the cells pass through their last phase of DNA synthesis in the postnatal period, and during the peak period of cell generation, between the fifth and seventh days after birth, up to 50,000 granule cells are formed each day. Contrary to earlier reports, most of the cells pass through their last mitotic division either within the stratum granulosum itself, or within the hilar region of the developing gyrus. The precursor population of cells in the hilar region must therefore constitute a pool of true neuroblasts. The origin of this pool of cells has not been definitely established but it seems probable that its cells are derived from the neuroepithelium lining the lateral ventricle adjacent to the region from which the hippocampal pyramidal cells are generated. Examination of the final location of granule cells labeled at different stages reveals three distinct morphogenetic gradients in the gyrus. The cells in the dorsal blade tend to be formed earlier than those in the ventral blade; cells in the more caudal (or temporal) portions of the gyrus are generated earlier than those in more rostral (or septal) regions; and in all regions the more superficial neurons in the stratum granulosum are formed earlier than the deeper granule cells. The bearing of some of these findings on the development and organization of the connections of the dentate gyrus is discussed.