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PubMed2001

The generation, migration, and differentiation of olfactory neurons in the adult primate brain.

In adult rodents, neural progenitor cells in the subependymal (SZ) zone of the lateral cerebral ventricle generate neuroblasts that migrate in chains via the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into interneurons. However, the existence of this neurogenic migratory system in other mammals has remained unknown. Here, we report the presence of a homologue of the rodent SZ/RMS in the adult macaque monkey, a nonhuman Old World primate with a relatively smaller OB. Our results-obtained by using combined immunohistochemical detection of a marker for DNA replication (5-bromodeoxyuridine) and several cell type-specific markers-indicate that dividing cells in the adult monkey SZ generate neuroblasts that undergo restricted chain migration over an extended distance of more than 2 cm to the OB and differentiate into granule interneurons. These findings in a nonhuman primate extend and support the use of the SZ/RMS as a model system for studying neural regenerative mechanisms in the human brain.

Animals↗

PubMed1995

Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice.

In the brain of adult mice, cell division persists in the subventricular zone (SVZ) of the lateral ventricles. These SVZ cells migrate rostrally 3-5 mm to the olfactory bulb, where they differentiate into neurons. We have investigated the distribution of PSA-N-CAM in the adult mouse forebrain. Immunoreactivity for PSA-N-CAM precisely reveals the migratory pathway of SVZ cells. This pathway of PSA-N-CAM positive cells starts in the lateral wall of the lateral ventricle, where immunopositive cells form weblike patterns. The PSA-N-CAM positive pathway extends rostrally between the corpus callosum and the striatum into the anterior ventral telencephalon, and then into the core of the olfactory bulb. Experiments in which [3H]-thymidine was injected systemically indicated that the majority of the dividing cells on the SVZ of the lateral ventricle and along the migratory pathway are positive to PSA-N-CAM or closely associated with PSA-N-CAM. Microinjection of [3H]-thymidine into the SVZ of the lateral ventricle to label a small patch of dividing SVZ cells shows that neuroblasts that migrated away from the injection site are positive or are closely associated with other cells that are positive for PSA-N-CAM. Migrating cells are tethered together, forming long chains of immunopositive cells. The migratory pathway is formed by 30-40 of these immunopositive chains. Radially oriented individual PSA-N-CAM positive cells were observed in the olfactory bulb. These cells seem to have broken away from chains of immunopositive cells in the core of the olfactory bulb and to be migrating to more superficial layers. Little is known about the mechanisms of tangential migration during development and in adulthood. The cell-cell arrangement revealed by PSA-N-CAM staining suggests new models for this form of neuronal migration. PSA-N-CAM localization along the migratory pathway to the olfactory bulb suggests that in the adult brain this molecule plays a role in migration of neuronal precursors.

Animals↗

PubMed2005

Germinal matrix cells associate with veins and a glial scaffold in the human fetal brain.

Germinal matrix (GM) in the subventricular zone (SVZ) includes progenitor cells of neurons and glia, which migrate from the SVZ to regions where they become integrated into the developing brain. In the human fetal brain, GM cells pack into high density clusters that encircle GM veins producing a profile we describe as a venous cuff. Venous cuffs are, in turn, encircled by GFAP-positive astrocytes that project processes through the cuff to the venous wall. The high cell density exhibited by cuffs, as well as their association with astrocytes, are reminiscent of features associated with chain migration. However, chain migration has not been associated previously with veins. We suggest that the GM cuff cells may represent a distinct subset of GM cells that migrate away from the GM on a pathway consisting of a vein and its associated astrocytic scaffold.

Astrocytes↗

PubMed1978

Murine Ia and human DR antigens: homology of amino-terminal sequences.

Murine Ia and human DR antigens were isolated and purified by immunoprecipitation and sodium dodecyl sulfate/polyacrylamide gel electrophoresis with allo- and xenoantisera, respectively. The I-A subregion antigen consists of two chains, designated Aalpha and Abeta, with molecular weights of 35,000 and 26,000, respectively. The I-C subregion antigen likewise consists of two chains, designated Calpha and Cbeta, with molecular weights of 32,000 and 29,000, respectively. Under nonreducing conditions, the Cbeta chain migrates appreciably more rapidly on sodium dodecyl sulfate/polyacrylamide gels than the reduced Cbeta chain, reflecting the presence of an intrachain disulfide bond. The human DR antigen is also a two-chain unit and contains DRalpha and DRbeta components with molecular weights of 34,000 and 28,000, respectively. The DRbeta chain migrates more rapidly before reduction than afterward, like the murine Cbeta chain. The DRbeta and Cbeta chains are also strikingly homologous if a single amino acid shift is imposed on one of those chains. Thus, human DR antigens strongly resemble the murine I-C subregion antigens.

Amino Acid Sequence↗

PubMedDate not supplied

[A critical approach to endogamy: considerations resulting from the reconstruction of French families (Tandil, 1850-1914)].

"Marriage patterns of French immigrants in Tandil [Argentina] are analyzed on the basis of birth and wedding data obtained from local registers using the Louis Henry model to establish the pattern for the whole immigrant group and not restricted to legally wed couples. The study of marital choices is not fully valid unless also the continuity of practices developed at origin as well as composition of the group and patterns of arrival are taken into account. Two main conclusions are presented: the link between [endo-]/exogamic behaviour and the type of migration (individual or chain migration) and the higher exogamy in rural areas." (SUMMARY IN ENG)

Americas↗

PubMed2004

4-Hydroxyphenylpyruvate dioxygenase: a hybrid density functional study of the catalytic reaction mechanism.

Density functional calculations using the B3LYP functional has been used to study the reaction mechanism of 4-hydroxyphenylpyruvate dioxygenase. The first part of the catalytic reaction, dioxygen activation, is found to have the same mechanism as in alpha-ketoglutarate-dependent enzymes; the ternary enzyme-substrate-dioxygen complex is first decarboxylated to the iron(II)-peracid intermediate, followed by heterolytic cleavage of the O-O bond yielding an iron(IV)-oxo species. This highly reactive intermediate attacks the aromatic ring at the C1 position and forms a radical sigma complex, which can either form an arene oxide or undergo a C1-C2 side-chain migration. The arene oxide is found to have no catalytic relevance. The side-chain migration is a two-step process; the carbon-carbon bond cleavage first affords a biradical intermediate, followed by a decay of this species forming the new C-C bond. The ketone intermediate formed by a 1,2 shift of an acetic acid group rearomatizes either at the active site of the enzyme or in solution. The hypothetical oxidation of the aromatic ring at the C2 position was also studied to shed light on the 4-HPPD product specificity. In addition, the benzylic hydroxylation reaction, catalyzed by 4-hydroxymandelate synthase, was also studied. The results are in good agreement with the experimental findings.

4-Hydroxyphenylpyruvate Dioxygenase↗

PubMed2004

Shear-induced migration in flowing polymer solutions: simulation of long-chain DNA in microchannels [corrected].

We simulate dilute solution dynamics of long flexible polymer molecules in pressure driven flow in channels with widths of roughly 0.1-10 times the polymer bulk radius of gyration. This is done using a self-consistent coarse-grained Langevin description of the polymer dynamics and a numerical simulation of the flow in the confined geometry that is generated by the motions of polymer segments. Results are presented for a model of DNA molecules of approximately 10-100 microm contour length in micron-scale channels. During flow, the chains migrate toward the channel centerline, in agreement with well-known experimental observations. The thickness of the resulting hydrodynamic depletion layer increases with molecular weight at constant flow strength; higher molecular weight chains therefore move with a higher average axial velocity than lower molecular weight chains. In contrast, if the hydrodynamic effects of the confining geometry are neglected, depletion of concentration is observed in the center of the channel rather than at the walls, contradicting experimental observations. The mechanisms for migration are illustrated using a simple kinetic theory dumbbell model of a confined flexible polymer. The simple theory correctly predicts the trends observed in the detailed simulations. We also examine the steady-state stretch of DNA chains as a function of channel width and flow strength. The flow strength needed to stretch a highly confined chain away from its equilibrium length is shown to increase with decreasing channel width, independent of molecular weight; this is fairly well explained using a simple blob picture.

Computer Simulation↗

PubMed2005

Neuronal migration in the murine rostral migratory stream requires serum response factor.

The central nervous system is fundamentally dependent on guided cell migration, both during development and in adulthood. We report an absolute requirement of the transcription factor serum response factor (SRF) for neuronal migration in the mouse forebrain. Conditional, late-prenatal deletion of Srf causes neurons to accumulate ectopically at the subventricular zone (SVZ), a prime neurogenic region in the brain. SRF-deficient cells of the SVZ exhibit impaired tangential chain migration along the rostral migratory stream into the olfactory bulb. SVZ explants display retarded chain migration in vitro. Regarding target genes, SRF deficiency impairs expression of the beta-actin and gelsolin genes, accompanied by reduced cytoskeletal actin fiber density. At the posttranslational level, cofilin, a key regulator of actin dynamics, displays dramatically elevated inhibitory phosphorylation at Ser-3. Our studies indicate that SRF-controlled gene expression directs both the structure and dynamics of the actin microfilament, thereby determining cell-autonomous neuronal migration.

Actins↗

PubMed2004

Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway.

Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1alpha (SDF-1alpha). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1alpha. Exposure of SDF-1alpha to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1alpha/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.

Animals↗

PubMed1989

The process of exempt immediate relative immigration to the United States.

"To examine the chain migration issue [in the United States], this article develops and analyzes a new data base that links information on a sample of exempt immediate relative immigrants in Fiscal Year 1985 with information on the characteristics of their petitioners or sponsors. The analysis generally does not indicate that an explosive increase in future chain migration of exempt immediate relative immigrants is likely in the next ten years." Exempt immediate relative immigrants are defined as those who are exempt from numerical limitations because of their relationship with a U.S. citizen. Data are from the U.S. General Accounting Office.

Americas↗

PubMed1994

A base substitution at IVS-19 3'-end splice junction causes exon 20 skipping in pro alpha 2(I) collagen mRNA and produces mild osteogenesis imperfecta.

Molecular investigations on a young patient and her family were undertaken to identify the molecular defect responsible for a mild form of osteogenesis imperfecta (OI) with blue sclerae, dentinogenesis imperfecta and joint laxity. Analysis of collagenous proteins from the proband's fibroblasts showed the presence of two populations of alpha 2(I) chains, one normal and one migrating faster on SDS gels, thereby suggesting deletion of amino acid sequences. The faster migrating chains were retained mainly in the cell layer and not found in the extracellular matrix deposited by cultured fibroblasts. Chemical cleavage of mismatch (CCM) analysis on the patient's pro alpha 2(I) mRNA: normal cDNA heteroduplexes localized the molecular defect. cDNA sequencing revealed a deletion of exon 20 (54 bp) in about half of the molecules. Genomic DNA sequencing revealed heterozygosity for a G-to-C transversion of the last nucleotide of intron 19, which changed the 3' consensus splicing site. As a consequence pro alpha 2(I)mRNA was abnormally spliced from the last codon of exon 19 to the first codon of exon 21. To our knowledge, this is the first acceptor site mutation so far described in an OI patient. Restriction analysis indicated that the mutation was present also in three other affected family members. The full sequence of COL1A2 introns 19 and 20 are reported.

Base Sequence↗

PubMed1987

Hemoglobin Grange-Blanche [beta 27(B9) Ala----Val], a new variant with normal expression and increased affinity for oxygen.

Hemoglobin Grange-Blanche [beta 27(B9) Ala----Val] is a new variant found in a Portuguese family. The carriers present moderate erythrocytosis. Upon isoelectric focusing, Hb Grange-Blanche was slightly more cathodic than Hb A. beta Grange-Blanche chain migrated like the G gamma chain when submitted to electrophoresis in the presence of urea-Triton X-100. The precentage of Hb Grange-Blanche was about 50% in the heterozygous state. Oxygen affinity was increased (P50 = 22 mmHg), but heme-heme interaction was normal. An abnormal tryptic peptide (beta T3) was isolated using HPLC. Its composition allowed us to deduce unambiguously the amino acid change. The latter is the third mutation found in position 27 of the beta-chain. Because of its normal expression and its elevated affinity for oxygen, Hb Grange-Blanche contrasts with Hb Knossos [beta 27(B9) Ala----Ser], a beta-thalassemic variant with low affinity.

Adult↗

PubMed1977

Molecular properties of T lymphoma immunoglobulin. I. Serological and general physicochemical properties.

Immunoglobulin (Ig) released into the medium by monoclonal continuously cultured murine T lymphoma cells of the lines WEHI-22 and WEHI-7 was isolated by serological precipitation or solid-phase immunoadsorption techniques. The intact immunoglobulin had an electrophoretic mobility on sodium dodecyl-sulphate (SDS) containing polyacrylamide gels comparable to that of IgG (mass 150,000). This mobility was significantly faster than that of '7S' IgM of murine B lymphocyte surfaces. The T lymphoma immunoglobulin consisted of a pair of heavy chains linked by disulphide bonds and light chains non-covalently bound to the heavy chains. The isolated heavy chains migrated slightly faster than the mu chains of MOPC 104E IgM. Some, but not all, antisera directed against mu chains of normal mouse serum IgM bound T lymphoma immunoglobulin apparently via a cross-reaction localized to the Fd fragment. These data indicate that immunoglobulin of T lymphoma cells and, presumably normal T lymphocytes, represents an immunoglobulin isotype which is distinct from those immunoglobulins found on the B cell surface.

Animals↗

PubMed1996

[Italian immigration into Imperial Germany up to World War I].

"A rapid growth, both economic and industrial, of the German Empire during the last decade of the nineteenth century...produced a major switch in Germany's status from that of a country of emigration to a country of immigration.... The essay gives a concise description of the characteristics of Italian migration flows towards Germany, integration processes and chain migration patterns. The impact of immigration on the receiving country is...analyzed, both in terms of economic development and from a social, political and legal point of view." (SUMMARY IN ENG AND FRE)

Acculturation↗

PubMed2006

Cross-stream migration of flexible molecules in a nanochannel.

Molecular dynamics simulations are used to examine the cross-stream chain migration phenomenon in dilute polymer solutions that are flowing in nanochannels. In particular, both uniform planar shear (Couette) and pressure driven (Poiseuille) flows of a dilute polymer solution are studied using a bead-spring representation of polymer chains and a coarse grained model for the solvent. Our results show that three mechanisms govern the migration of deformable molecules in a nanochannel: (1) chain-wall hydrodynamic interactions, (2) thermal diffusion, and (3) gradient in chain mobility. These results are discussed in the context of recent experimental, numerical and theoretical work.

Bacteriophage lambda↗

PubMed1977

Lobster (Homarus americanus) striated muscle myosin.

1. Myosin from the thin-filament regulated flexor muscle of lobster contains 2 moles of each of 2 light chains. 2. The Lb 1 light chain of 19,000 daltons which can be removed by DTNB is heavier than the DTNB light chain of chicken. The Lb 2 light chain of 17,000 daltons can be removed with urea. 3. On electrophoresis in 8 M urea (pH 8.7) the Lb 2 light chain migrates with a mobility similar to that of chicken A2, but the Lb 1 migrates significantly faster than any of the chicken light chains. 4. In lobster, the DTNB treatment destroys the Ca and K-EDTA ATPase activity of lobster myosin.

Animals↗

PubMed1995

Role of two-dimensional electrophoretic analysis in the diagnosis and characterization of IgD monoclonal gammopathy.

Over a period of 5 years, an isolated light chain (kappa = 9, lambda = 12) was detected in 21 sera by immunofixation electrophoresis. Further analysis with anti-delta- and anti-epsilon-specific antisera identified four delta heavy chains, all associated with a lambda light chain, and no epsilon heavy chains. For evaluation of the role of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in the diagnosis of IgD paraproteins, as a possible alternative or complement to immunofixation, IgD paraproteins were retrospectively analyzed by 2D-PAGE. Delta Heavy chains migrated to gel areas clearly distinguishable from other heavy chains alpha, gamma, or mu, and in a wide range of isoelectric points (pI: 5.4-8). In one serum, the monoclonal delta chain had a pI range comparable to that of albumin and was undetectable. However, all four delta chains were easily identified when analyzed from affinity-purified immunoglobulin fractions. These observations showed the following: 1) IgD paraproteins are not rare among apparently isolated monoclonal light chains detected by routine immunofixation, strongly confirming the need for further analysis with anti-delta antisera, before assumption of a light-chain disease. 2) 2D-PAGE analysis of affinity-purified immunoglobulin fractions allowed correct identification of IgD monoclonal gammopathies in all cases. 3) However, although 2D-PAGE analysis is now easy to perform, well standardized, and highly sensitive, this technique remains time-consuming and expensive, and does not appear suitable for routine practice as a first-line diagnostic procedure. 2D-PAGE should find its place as a complement to immunofixation and in the definitive demonstration, in selected ambiguous cases, of the clonal pattern of a suspected gammopathy at immunofixation.

Blotting, Western↗

PubMed1998

The geography of Bangladeshi migration to Rome.

"With reference to the Bangladeshi community in Rome, this paper provides some answers to three key geographical questions: what is the migrants' regional pattern of origin in their home country; what are the mechanisms and routes of their migration to Italy; how are they spatially distributed in Rome?... Chain migration links specific origins in Bangladesh with spatial clusters and economic activities in Rome; the key here is the role of Bangladeshi community leaders in Rome who act both as migration sponsors and entrepreneurs."

Asia↗