Migration Step Research Articles

Energy Collection, Transport, and Trapping by a Supramolecular Organization of Dyes in Hexagonal Zeolite Nanocrystals

AbstractThe incorporation of guest molecules into the cavities of molecular sieves leads to a large variety of highly interesting materials. Zeolite L—an aluminosilicate with one‐dimensional channels of open diameter 7.1 Å—is a very versatile material for building highly organized host–guest systems. We present materials where organic dye molecules have been incorporated into the channels of zeolite L by means of diffusion, to build artificial photonic antenna systems. The channel entrance can be plugged by adding closure molecules that then connect the guest molecules inside with materials or molecules outside of the zeolite channels, since they can act as extensions of the interior of the zeolite crystal. The photophysical processes taking place in such dye‐loaded zeolite L antennae can be studied either on single‐micrometer‐ or submicrometer‐sized crystals or on crystals dispersed in a solvent or coated as thin layers on a support. The energy‐transfer process occurring is of the Förster‐type, and its transfer rate can be tuned by separating the donor dyes and the acceptor dyes locally by varying amounts of spacer molecules. The distribution of the dye molecules and empty sites within a zeolite crystal has been modeled by means of a Monte Carlo simulation. The Förster energy migration and transfer steps are described as a random walk.

Carbon−Fluorine Bond Activation Coupled with Carbon−Hydrogen Bond Formation α to Iridium: Kinetics, Mechanism, and Diastereoselectivity

Reactions of iridium(fluoroalkyl)hydride complexes CpIr(PMe(3))(CF(2)R(F))Y (R(F) = F, CF(3); Y = H, D) with LutHX (Lut = 2,6-dimethylpyridine; X = Cl, I) results in C-F activation coupled with hydride migration to give CpIr(PMe(3))(CYFR(F))X as variable mixtures of diastereomers. Solution conformations and relative diastereomer configurations of the products have been determined by (19)F{(1)H}HOESY NMR to be (S(C), S(Ir))(R(C), R(Ir)) for the kinetic diastereomer and (R(C), S(Ir))(S(C), R(Ir)) for its thermodynamic counterpart. Isotope labeling experiments using LutDCl/CpIr(PMe(3))(CF(2)R(F))H and CpIr(PMe(3))(CF(2)R(F))D/LutHCl) showed that, unlike a previously studied system, H/D exchange is faster than protonation of the alpha-CF bond, giving an identical mixture of product isotopologues from both reaction mixtures. The kinetic rate law shows a first-order dependence on the concentration of iridium substrate, but a half-order dependence on that of LutHCl; this is interpreted to mean that LutHCl dissociates to give HCl as the active protic source for C-F bond activation. Detailed kinetic studies are reported, which demonstrate that lack of complete diastereoselectivity is not a function of the C-F bond activation/H migration steps but that a cationic intermediate plays a double role in loss of diastereoselectivity; the intermediate can undergo epimerization at iridium before being trapped by halide and can also catalyze the epimerization of kinetic diastereomer product to thermodynamic product. A detailed mechanism is proposed and simulations performed to fit the kinetic data.

Study of Pathway of Hydrogen Migration and Desorption on SiGe(100) Surface Using Ab Initio Calculations

Ab initio calculations have been carried out to investigate the pathways of H-atom migration and H2 desorption on a mixed SiGe(100)-2×1 surface using the cluster model. The H2 recombinative desorption is the rate-determining step in hydrogen migration and desorption on SiGe(100) surfaces, since the energy barrier to H-atom migration is generally lower than that of H2 desorption. The energy barriers for H2 desorption from the interdimer, the Si–Ge pair, (52.8 kcal/mol), and the Ge–Ge pair, (45.1 kcal/mol), are lower than that for the Si–Si pair by 7.5 and 15.2 kcal/mol, respectively. Thus, the SiGe(100)-2×1 surface in chemical vapor deposition provides more dangling bonds than the Si(100)-2×1 surface because of Ge inclusion. In contrast, the chemisorbed H tends to stay on the Si-site, since the barrier for H-migration from the Ge-site to the Si-site is lower that in the opposite direction by 5.6 kcal/mol. Hence, a considerably higher percentage of Ge sites are dangling bonds, compared with Si sites on the SiGe(100) surface. Related transition state structures in the migration and desorption steps are also discussed.

Regulators of Endocytosis Maintain Localized Receptor Tyrosine Kinase Signaling in Guided Migration

Guidance receptors detect extracellular cues and instruct migrating cells how to orient in space. Border cells perform a directional invasive migration during Drosophila oogenesis and use two receptor tyrosine kinases (RTKs), EGFR and PVR (PDGF/VEGF Receptor), to read guidance cues. We find that spatial localization of RTK signaling within these migrating cells is actively controlled. Border cells lacking Cbl, an RTK-associated E3 ubiquitin ligase, have delocalized guidance signaling, resulting in severe migration defects. Absence of Sprint, a receptor-recruited, Ras-activated Rab5 guanine exchange factor, gives related defects. In contrast, increasing the level of RTK signaling by receptor overexpression or removing Hrs and thereby decreasing RTK degradation does not perturb migration. Cbl and Sprint both regulate early steps of RTK endocytosis. Thus, a physiological role of RTK endocytosis is to ensure localized intracellular response to guidance cues by stimulating spatial restriction of signaling.

Pleistocene and Holocene distribution of the radiolarian Amphimelissa setosa Cleve in the North Pacific and North Atlantic: Evidence for water mass movement

Abstract The radiolarian Amphimelissa setosa is one of the prominent species of the Pleistocene radiolarian assemblages in the Sea of Okhotsk below the marine isotope stage (MIS) boundary 5/4, and it represents one of the most abundant radiolarian species in Holocene and modern environments of the Nordic Seas. We studied the A. setosa distribution in six cores from the Sea of Okhotsk and established morphometric measurements on A. setosa specimens from two cores of the Sea of Okhotsk and one core from the Labrador Sea. We further compared our data with other available studies from the Subarctic Pacific, the Labrador Sea, the North Atlantic, the Norwegian Sea, and the Iceland/Greenland Seas in order to discuss the possible settling of the species from the North Pacific via the Arctic Ocean into the Iceland/Greenland Seas. A. setosa exhibits a stable abundant population in the Sea of Okhotsk during most of the last ca. 0.7 m.y. and might repeatedly extend its population into the North Atlantic through the Arctic Ocean during the Pleistocene interglacial optima. The species declines from the Sea of Okhotsk and from the Subarctic Pacific at the end of MIS 5. Its final documented settling into the North Atlantic is during MIS 5, when A. setosa appears in low numbers in sediments of the Labrador Sea, however reaching significant percentages at the boundary of MIS 5/4. Based on the available information, we propose that A. setosa could migrate from the North Pacific into the Arctic Ocean during the interglacial optimum MIS 5e and then through the channels of the Canadian Arctic Archipelago into the Baffin Bay and Labrador Sea. A further migration step of A. setosa occurs at the boundary of MIS 5/4, when A. setosa migrated from the Labrador Sea into the North Atlantic, probably related to a southward expansion of cold waters at the end of the MIS 5. During the warming at Termination I, A. setosa moved from the North Atlantic into the Nordic Seas. The abundant occurrence of A. setosa in sediments south of Iceland, the Norwegian and North Seas within the Younger Dryas period points to a marked cooling and a southward movement of polar water masses restricted to this time interval.

Stimulation of cell surface plasminogen activation by membrane-bound melanotransferrin: A key phenomenon for cell invasion

The activation of plasminogen at the cell surface is a crucial step in cell migration and invasion. In the present study, the effect of membrane-bound melanotransferrin (mMTf), also known as human melanoma antigen p97, on cell surface plasminogen binding and activation was investigated by using Chinese Hamster Ovary (CHO) cells transfected with full-length melanotransferrin (MTf) cDNA and SK-MeL-28 melanoma cells. The expression of mMTf in CHO increased cell surface plasminogen binding by about 2-fold. In addition, application of the monoclonal antibody L235 against MTf as well as truncated, soluble MTf (sMTf) abolished plasminogen binding to MTf-transfected and SK-MeL-28 cells, indicating that mMTf is a potential cell surface plasminogen receptor. Moreover, mMTf expression in CHO cells stimulates plasminogen activation at the cell surface by about 2.5-fold. In addition to the induced binding and activation of plasminogen, cell motility, migration and invasion were about 3-fold higher in CHO cells expressing mMTf. Both monoclonal antibody L235 and truncated sMTf inhibited mMTf-stimulated CHO cell motility, migration and invasion. Overall, our results indicate a key role for mMTf in cell surface plasminogen binding and in activation processes involved during cell migration and invasion.

Observing spontaneous branch migration of Holliday junctions one step at a time

Genetic recombination occurs between homologous DNA molecules via a four-way (Holliday) junction intermediate. This ancient and ubiquitous process is important for the repair of double-stranded breaks, the restart of stalled replication forks, and the creation of genetic diversity. Once formed, the four-way junction alone can undergo the stepwise exchange of base pairs known as spontaneous branch migration. Conventional ensemble assays, useful for finding average migration rates over long sequences, have been unable to examine the affect of sequence and structure on the migration process. Here, we present a single-molecule spontaneous branch migration assay with single-base pair resolution in a study of individual DNA junctions that can undergo one step of migration. Junctions exhibit markedly different dynamics of exchange between stacking conformers depending on the point of strand exchange, allowing the moment at which branch migration occurs to be detected. The free energy landscape of spontaneous branch migration is found to be highly nonuniform and governed by two types of sequence-dependent barriers, with unmediated local migration being up to 10 times more rapid than the previously deduced average rate.

Differential expression of matrix metalloproteinases and interleukin‐8 during regeneration of human airway epithelium in vivo

In many airway diseases, the airway epithelium is severely damaged and has to regenerate rapidly to restore its function. The regeneration process involves chronological steps of epithelial cell migration, proliferation, stratification, and differentiation. The present study has used an in vivo humanized airway xenograft model in nude mice that mimics the regeneration dynamics of human airway epithelium after severe injury, and human-specific molecular tools, to study the expression profiles of epithelial matrix metalloproteinases (MMPs)-7 and -9, of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and of the pro-inflammatory cytokine interleukin-8 (IL-8) during the different steps of human airway epithelium regeneration. It was found that during the cell migration and proliferation steps, airway epithelial cells expressed IL-8 at a high level, whereas airway epithelial pseudo-stratification and surface airway epithelial differentiation were associated with increased expression of MMPs and a progressive decrease in IL-8. Interestingly, immunohistochemical analysis revealed exclusive expression of MMPs at the apical part of the well-differentiated regenerated airway epithelium, and incubation of the regenerating epithelial cells with MMP inhibitors led to abnormal epithelial differentiation. These data provide new insight into the temporal expression of MMPs and IL-8 during the regeneration of airway epithelium and demonstrate the involvement of these factors during the different steps that lead to restoration of a well-differentiated and functional airway epithelium.

Substituent Effects in the Migration Step of the Baeyer−Villiger Rearrangement. A Theoretical Study

Quantum mechanical calculations have been performed on the migration step of the Baeyer-Villiger (BV) rearrangements of some acetophenones, p-RC6H4COCH3 (R = CN, Cl, H, CH3, CH3O) with m-chloroperbenzoic acid. The energy barriers, charge distributions, and frontier molecular orbitals determined for the aryl migration step explain the effects of substituents on the reactivity of these ketones. A plot of the log of relative oxidation rates of the ketones versus their corresponding calculated energy barriers of the migration stage showed a downward deviation for the p-OCH3 derivative. This result is consistent with a change in the rate-determining step, from the aryl migration to the carbonyl addition, in the case of p-methoxyacetophenone, according to the suggestion that the rate-determining step of the BV oxidation can change with variations in the substituent group.

Six1 and Six4 homeoproteins are required for Pax3 and Mrf expression during myogenesis in the mouse embryo

In mammals, Six5, Six4 and Six1 genes are co-expressed during mouse myogenesis. Six4 and Six5 single knockout (KO) mice have no developmental defects, while Six1 KO mice die at birth and show multiple organ developmental defects. We have generated Six1Six4 double KO mice and show an aggravation of the phenotype previously reported for the single Six1 KO. Six1Six4 double KO mice are characterized by severe craniofacial and rib defects, and general muscle hypoplasia. At the limb bud level, Six1 and Six4 homeogenes control early steps of myogenic cell delamination and migration from the somite through the control of Pax3 gene expression. Impaired in their migratory pathway, cells of the somitic ventrolateral dermomyotome are rerouted, lose their identity and die by apoptosis. At the interlimb level, epaxial Met expression is abolished, while it is preserved in Pax3-deficient embryos. Within the myotome, absence of Six1 and Six4 impairs the expression of the myogenic regulatory factors myogenin and Myod1, and Mrf4 expression becomes undetectable. Myf5 expression is correctly initiated but becomes restricted to the caudal region of each somite. Early syndetomal expression of scleraxis is reduced in the Six1Six4 embryo, while the myotomal expression of Fgfr4 and Fgf8 but not Fgf4 and Fgf6 is maintained. These results highlight the different roles played by Six proteins during skeletal myogenesis.

Dioxygen reduction by multi-copper oxidases; a structural perspective

The multi-copper oxidases oxidise substrate molecules by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear centre. Dioxygen binds to the trinuclear centre and, following the transfer of four electrons, is reduced to two molecules of water. The precise mechanism of this reduction has been unclear, but recent X-ray structural studies using the CotA endospore coat protein from Bacillus subtilis have given further insights into the principal stages. It is proposed that the mechanism involves binding of the dioxygen into the trinuclear centre so that it is sited approximately symmetrically between the two type 3 copper ions with one oxygen atom close to the type 2 copper ion. Further stages involve the formation of a peroxide intermediate and following the splitting of this intermediate, the migration of the hydroxide moieties towards the solvent exit channel. The migration steps are likely to involve a movement of the type 2 copper ion and its environment. Details of a putative mechanism are described herein based both on structures already reported in the literature and on structures of the CotA protein in the oxidised and reduced states and with the addition of peroxide and the inhibitor, azide.

The biosynthesis of 8-phenylphenalenones from Eichhornia crassipes involves a putative aryl migration step

The first compounds of the novel 8-phenylphenalenone type were isolated from roots and leaves of Eichhornia crassipes (Pontederiaceae). The structures were elucidated by spectrometric methods including 1D and 2D NMR analysis. The incorporation of two molecules of [1- 13C]phenylalanine provides experimental evidence for the biosynthesis of the 8-phenylphenalenones. A biosynthetic pathway via diarylheptanoid and 9-phenylphenalenone intermediates, including a 1,2-aryl migration, is proposed.

Catalytic Roles of Active-Site Amino Acid Residues of Coenzyme B12-Dependent Diol Dehydratase: Protonation State of Histidine and Pull Effect of Glutamate

The hydrogen abstraction and the OH migration processes catalyzed by diol dehydratase are discussed by means of a quantum mechanical/molecular mechanical method. To evaluate the push effect of His143 and the pull effect of Glu170, we considered three kinds of whole-enzyme model, the protonated and two unprotonated His143 models. A calculated activation energy for the hydrogen abstraction by the adenosyl radical is 15.6 (13.6) kcal/mol in the protonated (unprotonated) His143 model. QM/MM calculational results show that the mechanism of the OH migration is significantly changed by the protonation of His143. In the protonated His143 model, the OH group migration triggered by the full proton donation from the imidazolium to the migrating OH group occurs by a stepwise OH abstraction/re-addition process in which the water production reduces the barrier for the C-O bond cleavage. On the other hand, the OH migration in the unprotonated His143 model proceeds in a concerted manner, as we previously proposed using a simple model including only K+ ion and substrate. The latter mechanism seems to be kinetically more favorable from the calculated energy profiles and is consistent with experimental results. The activation barrier of the OH group migration step is only 1.6 kcal/mol reduced by the hydrogen-bonding interaction between the O2 of the substrate and unprotonated His143. Thus, it is predicted that His143 is not protonated, and therefore the main active-site amino acid residue that lowers the energy of the transition state for the OH group migration is determined to be Glu170.

SUCCESS: a next-generation hybrid WDM/TDM optical access network architecture

In this paper, the authors propose a next-generation hybrid WDM/TDM optical access network architecture called Stanford University aCCESS or SUCCESS. This architecture provides practical migration steps from current-generation time-division multiplexing (TDM)-passive optical network (PONs) to future WDM optical access networks. The architecture is backward compatible for users on existing TDM-PONs, while simultaneously capable of providing upgraded high-bandwidth services to new users on DWDM-PONs through advanced WDM techniques. The SUCCESS architecture is based on a collector ring and several distribution stars connecting the CO and the users. A semipassive configuration of the Remote Nodes (RNs) enables protection and restoration, making the network resilient to power failures. A novel design of the OLT and DWDM-PON ONUs minimizes the system cost considerably: 1) tunable lasers and receivers at the OLT are shared by all ONUs on the network to reduce the transceiver count and 2) the fast tunable lasers not only generate downstream data traffic but also provide DWDM-PON ONUs with optical CW bursts for their upstream data transmission. Results from an experimental system testbed support the feasibility of the proposed SUCCESS architecture. Also, simulation results of the first SUCCESS DWDM-PON MAC protocol verify that it can efficiently provide bidirectional transmission between the OLT and ONUs over multiple wavelengths with a small number of tunable transmitters and receivers.

Defend mobile agent against malicious hosts in migration itineraries

Agent integrity verification and fault-tolerance are the two prevalent methods among the solutions to the Problem of Malicious Hosts in Mobile agent system. Agent integrity verification enables the owner of the agent to detect upon its return whether a visited host has maliciously altered the state of the agent based on agent integrity verification [6]. A known drawback of such method is that it cannot detect the tampering of agent immediately, and the tampering can be detected only when the agent returned. Agent fault-tolerance is one method that achieves agent fault-tolerance in migration itineraries by agent replication and majority voting [11]. The drawback of such method is that the agent replication and majority voting can produce many agent replicas in every agent migration step, which may cost significant resource and time. Aiming at those drawbacks, the paper incorporates the two methods, and presents a novel agent migration fault-tolerance model based on integrity verification, which can defend mobile agent against malicious hosts in migration itineraries effectively. The novel agent fault-tolerance model cannot only realize the fault-tolerant execution, but also reduce the complexity and resource cost of agent migration communication.

Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis.

In acute pancreatitis, ICAM-1 is upregulated in various organs and contributes to the development of organ injury. To investigate the effects of pancreatic proteases on ICAM-1 expression and their role in the early process of leukocyte migration, human umbilical vein endothelial cells (HUVECs) were incubated with serum subjected to limited trypsin digestion and Wistar rats were injected with trypsin. Significant upregulation of membrane-bound ICAM-1 was seen on HUVECs incubated with trypsinated serum. Likewise, soluble ICAM-1 increased in the supernatant of HUVECs. Changes of membrane-bound ICAM-1 and soluble ICAM-1 were maximal with high concentrations of trypsin. HUVECs incubated with TNF-alpha (positive control) showed similar changes. In the pancreas and lungs of animals infused with trypsin, ICAM-1 and leukocyte sequestration were increased compared with controls. Reflecting the relevance of protease-induced ICAM-1 expression in leukocyte migration, leukocyte-endothelium interaction, as assessed by intravital microscopy, was markedly increased by trypsin. Inhibition of ICAM-1 ameliorated these changes significantly. In conclusion, trypsinated serum induces the upregulation of both membrane-bound ICAM-1 on endothelial cells and soluble ICAM-1. These changes contribute to the early steps of leukocyte migration in acute pancreatitis. The role of soluble ICAM-1 remains to be investigated.

Reconstitution of human airway tissue in the humanized xenograft model

Normal human airway epithelial tissue may be reconstituted in the humanized xenograft model in immunodeficient NUDE mice. Epithelial cells dissociated from human fetal or adult tissue are seeded on a denuded rat trachea and implanted in the NUDE mice. After a first step of dedifferentiation, the human epithelial cells adhere on the denuded basal lamina of the rat host trachea and progressively reconstitute a normal well-differentiated epithelium after several steps of migration, proliferation, stratification and redifferentiation.

The closely related species Candida albicans and Candida dubliniensis can mate.

Because Candida dubliniensis is closely related to Candida albicans, we tested whether it underwent white-opaque switching and mating and whether white-opaque switching depended on MTL homozygosity and mating depended on switching, as they do in C. albicans. We also tested whether C. dubliniensis could mate with C. albicans. Sequencing revealed that the MTLalpha locus of C. dubliniensis was highly similar to that of C. albicans. Hybridization with the MTLa1, MTLa2, MTLalpha1, and MTLalpha2 open reading frames of C. albicans further revealed that, as in C. albicans, natural strains of C. dubliniensis exist as a/alpha, a/a, and alpha/alpha, but the proportion of MTL homozygotes is 33%, 10 times the frequency of natural C. albicans strains. C. dubliniensis underwent white-opaque switching, and, as in C. albicans, the switching was dependent on MTL homozygosis. C. dubliniensis a/a and alpha/alpha cells also mated, and, as in C. albicans, mating was dependent on a switch from white to opaque. However, white-opaque switching occurred at unusually high frequencies, opaque cell growth was frequently aberrant, and white-opaque switching in many strains was camouflaged by an additional switching system. Mating of C. dubliniensis was far less frequent in suspension cultures, due to the absence of mating-dependent clumping. Mating did occur, however, at higher frequencies on agar or on the skin of newborn mice. The increases in MTL homozygosity, the increase in switching frequencies, the decrease in the quality of switching, and the decrease in mating efficiency all reflected a general deterioration in the regulation of developmental processes, very probably due to the very high frequency of recombination and genomic reorganization characteristic of C. dubliniensis. Finally, interspecies mating readily occurred between opaque C. dubliniensis and C. albicans strains of opposite mating type in suspension, on agar, and on mouse skin. Remarkably, the efficiency of interspecies mating was higher than intraspecies C. dubliniensis mating, and interspecies karyogamy occurred readily with apparently the same sequence of nuclear migration, fusion, and division steps observed during intraspecies C. albicans and C. dubliniensis mating and Saccharomyces cerevisiae mating.

Primordial germ cell migration in the chick and mouse embryo: the role of the chemokine SDF-1/CXCL12

As in many other animals, the primordial germ cells (PGCs) in avian and reptile embryos are specified in positions distinct from the positions where they differentiate into sperm and egg. Unlike in other organism however, in these embryos, the PGCs use the vascular system as a vehicle to transport them to the region of the gonad where they exit the blood vessels and reach their target. To determine the molecular mechanisms governing PGC migration in these species, we have investigated the role of the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) in guiding the cells towards their target in the chick embryo. We show that sdf-1 mRNA is expressed in locations where PGCs are found and towards which they migrate at the time they leave the blood vessels. Ectopically expressed chicken SDF-1α led to accumulation of PGCs at those positions. This analysis, as well as analysis of gene expression and PGC behavior in the mouse embryo, suggest that in both organisms, SDF-1 functions during the second phase of PGC migration, and not at earlier phases. These findings suggest that SDF-1 is required for the PGCs to execute the final migration steps as they transmigrate through the blood vessel endothelium of the chick or the gut epithelium of the mouse.

Downstream-of-FGFR is a fibroblast growth factor-specific scaffolding protein and recruits Corkscrew upon receptor activation.

Fibroblast growth factor (FGF) receptor (FGFR) signaling controls the migration of glial, mesodermal, and tracheal cells in Drosophila melanogaster. Little is known about the molecular events linking receptor activation to cytoskeletal rearrangements during cell migration. We have performed a functional characterization of Downstream-of-FGFR (Dof), a putative adapter protein that acts specifically in FGFR signal transduction in Drosophila. By combining reverse genetic, cell culture, and biochemical approaches, we demonstrate that Dof is a specific substrate for the two Drosophila FGFRs. After defining a minimal Dof rescue protein, we identify two regions important for Dof function in mesodermal and tracheal cell migration. The N-terminal 484 amino acids are strictly required for the interaction of Dof with the FGFRs. Upon receptor activation, tyrosine residue 515 becomes phosphorylated and recruits the phosphatase Corkscrew (Csw). Csw recruitment represents an essential step in FGF-induced cell migration and in the activation of the Ras/MAPK pathway. However, our results also indicate that the activation of Ras is not sufficient to activate the migration machinery in tracheal and mesodermal cells. Additional proteins binding either to the FGFRs, to Dof, or to Csw appear to be crucial for a chemotactic response.