Correlates of frequent gambling and gambling-related chasing behaviors in individuals with schizophrenia-spectrum disorders.

PubMed

Yakovenko, Igor; Fortgang, Rebecca; Prentice, Jennifer; Hoff, Rani A; Potenza, Marc N

2018-05-23

Background and aims Published research on the relationship between disordered gambling and schizophrenia is limited. However, existing data suggest that individuals with schizophrenia/schizoaffective disorder may have a high prevalence of co-occurring disordered gambling. As such, effective strategies for screening and assessing gambling-related problems in individuals with psychosis are needed. The goal of this study was to explore the correlates of increased gambling frequency and chasing behavior, a hallmark feature of gambling disorder, in a sample of individuals with schizophrenia and schizoaffective disorders. Methods Data from 336 participants who met DSM-IV criteria for schizophrenia or schizoaffective disorder were used to examine differences between non-gamblers, infrequent gamblers, frequent gamblers who do not report chasing, and frequent gamblers who report chasing on a variety of associated features and symptoms of schizophrenia and disordered gambling. Results and discussion The results of the study support the conclusion that chasing behavior in individuals with schizophrenia/schizoaffective disorder lies on a continuum of severity, with more frequent gamblers endorsing greater chasing. Chasing was also associated with indicators of lower functioning across co-occurring disorders, such as greater problems with alcohol and drugs, greater gambling involvement, and a family history of gambling problems. The findings from the study suggest the utility of screening for chasing behavior as a brief and efficient strategy for assessing risk of gambling problems in individuals with psychotic-spectrum disorders.

Systemic administration of 8-OH-DPAT and eticlopride, but not SCH23390, alters loss-chasing behavior in the rat.

PubMed

Rogers, Robert D; Wong, Adeline; McKinnon, Chris; Winstanley, Catharine A

2013-05-01

Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards ('quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally ('chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT1A receptor agonist, 8-OH-DPAT, the D2 receptor antagonist, eticlopride, and the D1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT1A and D2, but not D1, receptor activity influence a behavioral analog of loss-chasing in rats.

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

PubMed Central

Rogers, Robert D; Wong, Adeline; McKinnon, Chris; Winstanley, Catharine A

2013-01-01

Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards (‘quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally (‘chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT1A receptor agonist, 8-OH-DPAT, the D2 receptor antagonist, eticlopride, and the D1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT1A and D2, but not D1, receptor activity influence a behavioral analog of loss-chasing in rats. PMID:23303072

What are the underlying units of perceived animacy? Chasing detection is intrinsically object-based.

PubMed

van Buren, Benjamin; Gao, Tao; Scholl, Brian J

2017-10-01

One of the most foundational questions that can be asked about any visual process is the nature of the underlying 'units' over which it operates (e.g., features, objects, or spatial regions). Here we address this question-for the first time, to our knowledge-in the context of the perception of animacy. Even simple geometric shapes appear animate when they move in certain ways. Do such percepts arise whenever any visual feature moves appropriately, or do they require that the relevant features first be individuated as discrete objects? Observers viewed displays in which one disc (the "wolf") chased another (the "sheep") among several moving distractor discs. Critically, two pairs of discs were also connected by visible lines. In the Unconnected condition, both lines connected pairs of distractors; but in the Connected condition, one connected the wolf to a distractor, and the other connected the sheep to a different distractor. Observers in the Connected condition were much less likely to describe such displays using mental state terms. Furthermore, signal detection analyses were used to explore the objective ability to discriminate chasing displays from inanimate control displays in which the wolf moved toward the sheep's mirror-image. Chasing detection was severely impaired on Connected trials: observers could readily detect an object chasing another object, but not a line-end chasing another line-end, a line-end chasing an object, or an object chasing a line-end. We conclude that the underlying units of perceived animacy are discrete visual objects.

Chasing losses in online poker and casino games: characteristics and game play of Internet gamblers at risk of disordered gambling.

PubMed

Gainsbury, Sally M; Suhonen, Niko; Saastamoinen, Jani

2014-07-30

Disordered Internet gambling is a psychological disorder that represents an important public health issue due to the increase in highly available and conveniently accessible Internet gambling sites. Chasing losses is one of the few observable markers of at-risk and problem gambling that may be used to detect early signs of disordered Internet gambling. This study examined loss chasing behaviour in a sample of Internet casino and poker players and the socio-demographic variables, irrational beliefs, and gambling behaviours associated with chasing losses. An online survey was completed by 10,838 Internet gamblers (58% male) from 96 countries. The results showed that Internet casino players had a greater tendency to report chasing losses than poker players and gamblers who reported chasing losses were more likely to hold irrational beliefs about gambling and spend more time and money gambling than those who reported that they were unaffected by previous losses. Gamblers who played for excitement and to win money were more likely to report chasing losses. This study is one of the largest ever studies of Internet gamblers and the results are highly significant as they provide insight into the characteristics and behaviours of gamblers using this mode of access. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position.

PubMed

Harris, J; Honigberg, L; Robinson, N; Kenyon, C

1996-10-01

In C. elegans, the Hox gene mab-5, which specifies the fates of cells in the posterior body region, has been shown to direct the migrations of certain cells within its domain of function. mab-5 expression switches on in the neuroblast QL as it migrates into the posterior body region. mab-5 activity is then required for the descendants of QL to migrate to posterior rather than anterior positions. What information activates Hox gene expression during this cell migration? How are these cells subsequently guided to their final positions? We address these questions by describing four genes, egl-20, mig-14, mig-1 and lin-17, that are required to activate expression of mab-5 during migration of the QL neuroblast. We find that two of these genes, egl-20 and mig-14, also act in a mab-5-independent way to determine the final stopping points of the migrating Q descendants. The Q descendants do not migrate toward any obvious physical targets in wild-type or mutant animals. Therefore, these genes appear to be part of a system that positions the migrating Q descendants along the anteroposterior axis.

Pursuit tracks chase: exploring the role of eye movements in the detection of chasing

PubMed Central

Träuble, Birgit

2015-01-01

We explore the role of eye movements in a chase detection task. Unlike the previous studies, which focused on overall performance as indicated by response speed and chase detection accuracy, we decompose the search process into gaze events such as smooth eye movements and use a data-driven approach to separately describe these gaze events. We measured eye movements of four human subjects engaged in a chase detection task displayed on a computer screen. The subjects were asked to detect two chasing rings among twelve other randomly moving rings. Using principal component analysis and support vector machines, we looked at the template and classification images that describe various stages of the detection process. We showed that the subjects mostly search for pairs of rings that move one after another in the same direction with a distance of 3.5–3.8 degrees. To find such pairs, the subjects first looked for regions with a high ring density and then pursued the rings in this region. Most of these groups consisted of two rings. Three subjects preferred to pursue the pair as a single object, while the remaining subject pursued the group by alternating the gaze between the two individual rings. In the discussion, we argue that subjects do not compare the movement of the pursued pair to a singular preformed template that describes a chasing motion. Rather, subjects bring certain hypotheses about what motion may qualify as chase and then, through feedback, they learn to look for a motion pattern that maximizes their performance. PMID:26401454

Paper Chase and the Socratic Method of Teaching Law.

ERIC Educational Resources Information Center

Dillon, J. T.

1980-01-01

It is argued that the Socratic method of teaching law as depicted in the book, movie, and TV series "Paper Chase" is not really the Socratic method at all. The genuine Socratic method and the questioning technique used in "Paper Chase" are examined and their appropriateness and effectiveness as methods for teaching contract law…

A Vicious Cycle: A Cross-Sectional Study of Canine Tail-Chasing and Human Responses to It, Using a Free Video-Sharing Website

PubMed Central

Burn, Charlotte C.

2011-01-01

Tail-chasing is widely celebrated as normal canine behaviour in cultural references. However, all previous scientific studies of tail-chasing or ‘spinning’ have comprised small clinical populations of dogs with neurological, compulsive or other pathological conditions; most were ultimately euthanased. Thus, there is great disparity between scientific and public information on tail-chasing. I gathered data on the first large (n = 400), non-clinical tail-chasing population, made possible through a vast, free, online video repository, YouTube™. The demographics of this online population are described and discussed. Approximately one third of tail-chasing dogs showed clinical signs, including habitual (daily or ‘all the time’) or perseverative (difficult to distract) performance of the behaviour. These signs were observed across diverse breeds. Clinical signs appeared virtually unrecognised by the video owners and commenting viewers; laughter was recorded in 55% of videos, encouragement in 43%, and the commonest viewer descriptors were that the behaviour was ‘funny’ (46%) or ‘cute’ (42%). Habitual tail-chasers had 6.5+/−2.3 times the odds of being described as ‘Stupid’ than other dogs, and perseverative dogs were 6.8+/−2.1 times more frequently described as ‘Funny’ than distractible ones were. Compared with breed- and age-matched control videos, tail-chasing videos were significantly more often indoors and with a computer/television screen switched on. These findings highlight that tail-chasing is sometimes pathological, but can remain untreated, or even be encouraged, because of an assumption that it is ‘normal’ dog behaviour. The enormous viewing figures that YouTube™ attracts (mean+/−s.e. = 863+/−197 viewings per tail-chasing video) suggest that this perception will be further reinforced, without effective intervention. PMID:22096487

78 FR 69663 - Jonathan and Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption 1. By letter filed October 15, 2013, Jonathan Chase informed the Commission that the exemption from licensing for the Troy Hydroelectric Project, FERC No. 13381, originally issued December 2, 2011,\\1\\ has been transferred to Troy Mills...

On the role of PDZ domain-encoding genes in Drosophila border cell migration.

PubMed

Aranjuez, George; Kudlaty, Elizabeth; Longworth, Michelle S; McDonald, Jocelyn A

2012-11-01

Cells often move as collective groups during normal embryonic development and wound healing, although the mechanisms governing this type of migration are poorly understood. The Drosophila melanogaster border cells migrate as a cluster during late oogenesis and serve as a powerful in vivo genetic model for collective cell migration. To discover new genes that participate in border cell migration, 64 out of 66 genes that encode PDZ domain-containing proteins were systematically targeted by in vivo RNAi knockdown. The PDZ domain is one of the largest families of protein-protein interaction domains found in eukaryotes. Proteins that contain PDZ domains participate in a variety of biological processes, including signal transduction and establishment of epithelial apical-basal polarity. Targeting PDZ proteins effectively assesses a larger number of genes via the protein complexes and pathways through which these proteins function. par-6, a known regulator of border cell migration, was a positive hit and thus validated the approach. Knockdown of 14 PDZ domain genes disrupted migration with multiple RNAi lines. The candidate genes have diverse predicted cellular functions and are anticipated to provide new insights into the mechanisms that control border cell movement. As a test of this concept, two genes that disrupted migration were characterized in more detail: big bang and the Dlg5 homolog CG6509. We present evidence that Big bang regulates JAK/STAT signaling, whereas Dlg5/CG6509 maintains cluster cohesion. Moreover, these results demonstrate that targeting a selected class of genes by RNAi can uncover novel regulators of collective cell migration.

Establishment of the Fox Chase Network Breast Cancer Risk Registry

DTIC Science & Technology

1996-10-01

Neurofibromatosis, type I h) Non-insulin dependent diabetes i) Turner Syndrome j) Tay Sachs Disease k) Marfan Syndrome 1) Cancer (tricky!) 2. Human chromosomes are...gastrointestinal and genitourinary cancers (4). Altogether, over 12 genetic-cancer syndromes have been localized to a specific gene (5). Some families suffer...component of the rare help test the best ways to Risk Registry._5, cases of breast cancer tions are likely to result Li-Fraumeni syndrome , only and up to

Attributing intentions to random motion engages the posterior superior temporal sulcus.

PubMed

Lee, Su Mei; Gao, Tao; McCarthy, Gregory

2014-01-01

The right posterior superior temporal sulcus (pSTS) is a neural region involved in assessing the goals and intentions underlying the motion of social agents. Recent research has identified visual cues, such as chasing, that trigger animacy detection and intention attribution. When readily available in a visual display, these cues reliably activate the pSTS. Here, using functional magnetic resonance imaging, we examined if attributing intentions to random motion would likewise engage the pSTS. Participants viewed displays of four moving circles and were instructed to search for chasing or mirror-correlated motion. On chasing trials, one circle chased another circle, invoking the percept of an intentional agent; while on correlated motion trials, one circle's motion was mirror reflected by another. On the remaining trials, all circles moved randomly. As expected, pSTS activation was greater when participants searched for chasing vs correlated motion when these cues were present in the displays. Of critical importance, pSTS activation was also greater when participants searched for chasing compared to mirror-correlated motion when the displays in both search conditions were statistically identical random motion. We conclude that pSTS activity associated with intention attribution can be invoked by top-down processes in the absence of reliable visual cues for intentionality.

Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration.

PubMed

Salser, S J; Kenyon, C

1992-01-16

Anterior-posterior patterning in insects, vertebrates and nematodes involves members of conserved Antennapedia-class homeobox gene clusters (HOM-C) that are thought to give specific body regions their identities. The effects of these genes on region-specific body structures have been described extensively, particularly in Drosophila, but little is known about how HOM-C genes affect the behaviours of cells that migrate into their domains of function. In Caenorhabditis elegans, the Antennapedia-like HOM-C gene mab-5 not only specifies postembryonic fates of cells in a posterior body region, but also influences the migration of mesodermal and neural cells that move through this region. Here we show that as one neuroblast migrates into this posterior region, it switches on mab-5 gene expression; mab-5 then acts as a developmental switch to control the migratory behaviour of the neuroblast descendants. HOM-C genes can therefore not only direct region-specific patterns of cell division and differentiation, but can also act within migrating cells to programme region-specific migratory behaviour.

Differential gene expression in migratory streams of cortical interneurons

PubMed Central

Antypa, Mary; Faux, Clare; Eichele, Gregor; Parnavelas, John G; Andrews, William D

2011-01-01

Cortical interneurons originate in the ganglionic eminences of the subpallium and migrate into the cortex in well-defined tangential streams. At the start of corticogenesis, two streams of migrating neurons are evident: a superficial one at the level of the preplate (PPL), and a deeper one at the level of the intermediate zone (IZ). Currently, little is known about the signalling mechanisms that regulate interneuron migration, and almost nothing is known about the molecules that may be involved in their choice of migratory stream. Here, we performed a microarray analysis, comparing the changes in gene expression between cells migrating in the PPL and those migrating in the IZ at embryonic day 13.5. This analysis identified genes, many of them novel, that were upregulated in one of the two streams. Moreover, polymerase chain reaction, in situ hybridization experiments and immunohistochemistry showed the expression of these genes in interneurons migrating within the PPL or IZ, suggesting that they play a role in their migration and choice of stream. PMID:22103416

New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

PubMed

Qi, Jingjing; Yu, Yong; Akilli Öztürk, Özlem; Holland, Jane D; Besser, Daniel; Fritzmann, Johannes; Wulf-Goldenberg, Annika; Eckert, Klaus; Fichtner, Iduna; Birchmeier, Walter

2016-10-01

We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Post-translational modification of Rauscher leukemia virus precursor polyproteins encoded by the gag gene.

PubMed Central

Schultz, A M; Rabin, E H; Oroszlan, S

1979-01-01

Post-translational modifications of retrovirus gag gene-encoded polyproteins include proteolytic cleavage, phosphorylation, and glycosylation. To study the sequence of these events, we labeled JLS-V9 cells chronically infected with Rauscher murine leukemia virus in pulse-chase experiments with the radioactive precursors [35S]methionine, [14C]mannose, [3H]glucosamine, and [32P]phosphate. Newly synthesized gag polyproteins which incorporated label, and the modified products derived from them, were identified by immunoprecipitation of cell lysates with anti-p30 rabbit serum, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Pulse-chase experiments were carried out in the presence as well as in the absence of tunicamycin, an inhibitor of glycosylation. Among the three major polyproteins synthesized in the absence of tunicamycin, two were found to be glycosylated but not phosphorylated. These were designated gPr80gag and gP94gag. Both shared identical [35S]methionine peptides with Pr65gag and p30. Of the two nonglycosylated precursors, Pr65gag and Pr75gag, only Pr65gag was found to be detectably phosphorylated, and Pr75gag could be readily identified only when glycosylation was inhibited. On the basis of these results, a scheme for the post-translational modification of gag polyproteins is proposed. According to this scheme the gag gene-encoded polyproteins are processed from a common precursor, Pr75gag, by two divergent pathways: one leading through the intermediate Pr65gag to internal virion components via cleavage and phosphorylation and the other via tunicamycin-sensitive mannosylation to the intermediate gPr80gag, which is further glycosylated to yield cell surface polyprotein gP94gag. Images PMID:480454

Gaze maintenance and autism spectrum disorder.

PubMed

Kaye, Leah; Kurtz, Marie; Tierney, Cheryl; Soni, Ajay; Augustyn, Marilyn

2014-01-01

Chase is a 5½-year-old boy whom you have followed in your primary care practice since age 26 months. He was born full-term vaginal delivery weighing 6 pounds 15 ounces. His biological mother used heroin, tobacco, and cocaine during pregnancy. From 8 weeks to 18 months, he spent time in a foster home where he was provided limited attention and nurturing. At age 18 months, he entered a loving foster home; at 26 months, he was adopted. There is maternal history of attention-deficit hyperactivity disorder, learning disability, depression, bipolar disorder, and substance abuse but no history of autism or cognitive disability. Chase received early intervention before adoption. Specific concerns are unknown. At the time of his adoption, he had delays in gross motor and fine motor skills, nonverbal communication, and speech production. Familiar listeners find Chase to be 100% intelligible but unfamiliar listeners understand about 70% of what Chase says. He enjoys being with his adopted mother and imitating her. He has demonstrated significant anxiety during his play therapy. He has difficulty in paying attention to multistep directions. Chase can point and wave but has difficulty following someone's eyes to see where another person is looking. Chase enjoys a variety of interests but has a special fixation on Toy Story characters. Chase does initiate social interactions but can be aggressive toward his siblings and oppositional toward his parents. He is not aggressive at school. Teachers note hyperactivity and impulsivity. Chase is bothered by bright lights and by others making loud noises but has no difficulty with crowds. Chase is reported to have difficulty in transitioning between activities. At his 5-year-old visit, you as well as his mother and therapists note that he has trouble following with his eyes so he is referred to a neuro-ophthalmologist. Evaluation showed Chase was able to fix on and follow objects and light, his peripheral vision was normal, his pupils were equal and reactive without afferent pupillary defect, and normal visual tracking as assessed through pursuit and saccades. There were some head jerking motions observed which were not thought to be part of Chase's attempts to view objects. Gaze impersistence was noted, although it was not clear if this was due to a lack of attention or a true inability to maintain a gaze in the direction instructed. On review of the school's speech and language report, they state that he is >90% intelligible. He has occasional lip trills. Testing with the Clinical Evaluation of Language Fundamentals shows mild delays in receptive language, especially those that require visual attention. Verbal Motor Production Assessment for Children reveals focal oromotor control and sequencing skills that are below average, with groping when asked to imitate single oromotor nonspeech movements and sequenced double oromotor nonspeech movements. At 5½ years, he returns for follow-up, and he is outgoing and imaginative, eager to play and socialize. He makes eye contact but does not always maintain it. He asks and responds to questions appropriately, and he is able to follow verbal directions and verbal redirection. He is very interested in Toy Story characters but willing to share them and plays with other toys. Chase's speech has predictable, easy to decode sound substitutions. On interview with him, you feel that he has borderline cognitive abilities. He also demonstrates good eye contact but lack of visual gaze maintenance; this is the opposite of the pattern you are accustomed to in patients with autism spectrum disorder. What do you do next?

Migration of cochlear lateral wall cells.

PubMed

Dunaway, George; Mhaskar, Yashanad; Armour, Gary; Whitworth, Craig; Rybak, Leonard

2003-03-01

The role of apoptosis and proliferation in maintenance of cochlear lateral wall cells was examined. The methods employed for detection of apoptosis were the Hoechst fluorescence stain and TUNEL (TdT-mediated dUTP-biotin nick-end-labeling) assay, and proliferations were 5-bromo-2'-deoxyuridine (BrdU) incorporation and presence of the proliferating cell nuclear antigen. The incidence of apoptosis in the strial marginal cell was 50% greater (32.9+/-3.7%) than strial intermediate and basal cells but similar to spiral ligament cells. Although division of marginal strial cells was rarely detected, a significant number of proliferating cells in the remaining stria vascularis and spiral ligament were observed. These data implied that replacement of marginal cells arose elsewhere and could be followed by a BrdU-deoxythymidine pulse-chase study. At 2 h post injection, nuclear BrdU in marginal cells was not detected; however, by 24 h post injection, 20-25% of marginal cell nuclei were BrdU-positive. These observations are consistent with the hypothesis that marginal cells were replaced by underlying cells. Cell migration appears to be an important mechanism for preserving the function and structure of the stria vascularis.

Energy cost and return for hunting in African wild dogs and cheetahs.

PubMed

Hubel, Tatjana Y; Myatt, Julia P; Jordan, Neil R; Dewhirst, Oliver P; McNutt, J Weldon; Wilson, Alan M

2016-03-29

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs.

The CHASE laboratory search for chameleon dark energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steffen, Jason H.; /Fermilab

2010-11-01

A scalar field is a favorite candidate for the particle responsible for dark energy. However, few theoretical means exist that can simultaneously explain the observed acceleration of the Universe and evade tests of gravity. The chameleon mechanism, whereby the properties of a particle depend upon the local environment, is one possible avenue. We present the results of the Chameleon Afterglow Search (CHASE) experiment, a laboratory probe for chameleon dark energy. CHASE marks a significant improvement other searches for chameleons both in terms of its sensitivity to the photon/chameleon coupling as well as its sensitivity to the classes of chameleon darkmore » energy models and standard power-law models. Since chameleon dark energy is virtually indistinguishable from a cosmological constant, CHASE tests dark energy models in a manner not accessible to astronomical surveys.« less

Bobcat attack on a cottontail rabbit

USGS Publications Warehouse

Biggins, D.E.; Biggins, D.M.

2006-01-01

We observed an attack by a bobcat (Lynx rufus) on a cottontail rabbit (Sylvilagus) that involved stealthy approach by the cat for >1 h, followed by a 12.3-s chase covering 116.0 m for the cat and 128.4 m for the rabbit. During the chase, the route of the cat from starting point to kill site was more direct than the semi-circular route of the rabbit. Stride lengths for the cat and total distance covered by the chase were longer than those previously reported for bobcats.

78 FR 42777 - Formations of, Acquisitions by, and Mergers of Bank Holding Companies

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-17

... President) 100 North 6th Street, Philadelphia, Pennsylvania 19105-1521: 1. Fox Chase Bancorp Inc., Hatboro, Pennsylvania; to become a bank holding company upon the conversion of Fox Chase Bank, Hatboro, Pennsylvania...

Energy cost and return for hunting in African wild dogs and cheetahs

PubMed Central

Hubel, Tatjana Y.; Myatt, Julia P.; Jordan, Neil R.; Dewhirst, Oliver P.; McNutt, J. Weldon; Wilson, Alan M.

2016-01-01

African wild dogs (Lycaon pictus) are reported to hunt with energetically costly long chase distances. We used high-resolution GPS and inertial technology to record 1,119 high-speed chases of all members of a pack of six adult African wild dogs in northern Botswana. Dogs performed multiple short, high-speed, mostly unsuccessful chases to capture prey, while cheetahs (Acinonyx jubatus) undertook even shorter, higher-speed hunts. We used an energy balance model to show that the energy return from group hunting and feeding substantially outweighs the cost of multiple short chases, which indicates that African wild dogs are more energetically robust than previously believed. Comparison with cheetah illustrates the trade-off between sheer athleticism and high individual kill rate characteristic of cheetahs, and the energetic robustness of frequent opportunistic group hunting and feeding by African wild dogs. PMID:27023457

T-34C back seat instrument panel

NASA Image and Video Library

1997-05-15

The back seat instrument panel on the NASA T-34C chase plane. In its role as a military trainer, the instructor pilot would ride in the back seat, while the student would be in the front seat. As a chase plane, the back seat would be occupied by a photographer. The aircraft was previously used at the Lewis Research Center in propulsion experiments involving turboprop engines, and was used as a chase aircraft at Dryden for smaller and slower research projects. Chase aircraft accompany research flights for photography and video purposes, and also as support for safety and research. At Dryden, the T-34 is used mainly for smaller remotely piloted vehicles which fly slower than NASA's F-18's, used for larger scale projects. This aircraft was returned to the U.S. Navy in May of 2002. The T-34C, built by Beech, carries a crew of 2 and is nicknamed the Mentor.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rohde, Magdalena; Sievers, Elisabeth; Janzer, Andreas

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, immune responses and invasive tumors all require the orchestrated movement of cells to specific locations. Histone demethylase proteins alter transcription by regulating the chromatin state at specific gene loci. FBXL10 is a conserved and ubiquitously expressed member of the JmjC domain-containing histone demethylase family and is implicated in the demethylation of H3K4me3 and H3K36me2 and thereby removing active chromatin marks. However, the physiological role of FBXL10 in vivo remains largely unknown. Therefore, we established an inducible gain of functionmore » model to analyze the role of Fbxl10 and compared wild-type with Fbxl10 overexpressing mouse embryonic fibroblasts (MEFs). Our study shows that overexpression of Fbxl10 in MEFs doesn’t influence the proliferation capability but leads to an enhanced migration capacity in comparison to wild-type MEFs. Transcriptome and ChIP-seq experiments demonstrated that Fbxl10 binds to genes involved in migration like Areg, Mdk, Lmnb1, Thbs1, Mgp and Cxcl12. Taken together, our results strongly suggest that Fbxl10 plays a critical role in migration by binding to the promoter region of migration-associated genes and thereby might influences cell behaviour to a possibly more aggressive phenotype. - Highlights: • Migration capability of MEFs is enhanced after Fbxl10 upregulation. • Overexpression of Fbxl10 induced migration-associated genes. • Fbxl10 binds directly to migration-associated genes.« less

Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration

PubMed Central

Wang, Xiangming; Zhou, Fanli; Lv, Sijing; Yi, Peishan; Zhu, Zhiwen; Yang, Yihong; Feng, Guoxin; Li, Wei; Ou, Guangshuo

2013-01-01

Directional cell migration is a fundamental process in neural development. In Caenorhabditis elegans, Q neuroblasts on the left (QL) and right (QR) sides of the animal generate cells that migrate in opposite directions along the anteroposterior body axis. The homeobox (Hox) gene lin-39 promotes the anterior migration of QR descendants (QR.x), whereas the canonical Wnt signaling pathway activates another Hox gene, mab-5, to ensure the QL descendants’ (QL.x) posterior migration. However, the regulatory targets of LIN-39 and MAB-5 remain elusive. Here, we showed that MIG-13, an evolutionarily conserved transmembrane protein, cell-autonomously regulates the asymmetric distribution of the actin cytoskeleton in the leading migratory edge. We identified mig-13 as a cellular target of LIN-39 and MAB-5. LIN-39 establishes QR.x anterior polarity by binding to the mig-13 promoter and promoting mig-13 expression, whereas MAB-5 inhibits QL.x anterior polarity by associating with the lin-39 promoter and downregulating lin-39 and mig-13 expression. Thus, MIG-13 links the Wnt signaling and Hox genes that guide migrations, to the actin cytoskeleton, which executes the motility response in neuronal migration. PMID:23784779

Tornado Chasing.

ERIC Educational Resources Information Center

Faidley, Warren

1991-01-01

Presents the rationale and purposes behind the phenomenon known as storm chasing, as well as the contributions that tornado chasers have made to both scientific knowledge and public safety. Provides statistical information on tornado frequencies and locations and contact addresses for storm chasers. (JJK)

A gene delivery system with a human artificial chromosome vector based on migration of mesenchymal stem cells towards human glioblastoma HTB14 cells.

PubMed

Kinoshita, Yusuke; Kamitani, Hideki; Mamun, Mahabub Hasan; Wasita, Brian; Kazuki, Yasuhiro; Hiratsuka, Masaharu; Oshimura, Mitsuo; Watanabe, Takashi

2010-05-01

Mesenchymal stem cells (MSCs) have been expected to become useful gene delivery vehicles against human malignant gliomas when coupled with an appropriate vector system, because they migrate towards the lesion. Human artificial chromosomes (HACs) are non-integrating vectors with several advantages for gene therapy, namely, no limitations on the size and number of genes that can be inserted. We investigated the migration of human immortalized MSCs bearing a HAC vector containing the herpes simplex virus thymidine kinase gene (HAC-tk-hiMSCs) towards malignant gliomas in vivo. Red fluorescence protein-labeled human glioblastoma HTB14 cells were implanted into a subcortical region in nude mice. Four days later, green fluorescence protein-labeled HAC-tk-hiMSCs were injected into a contralateral subcortical region (the HTB14/HAC-tk-hiMSC injection model). Tropism to the glioma mass and the route of migration were visualized by fluorescence microscopy and immunohistochemical staining. HAC-tk-hiMSCs began to migrate toward the HTB14 glioma area via the corpus callosum on day 4, and gathered around the HTB14 glioma mass on day 7. To test whether the delivered gene could effectively treat glioblastoma in vivo, HTB14/HAC-tk-hiMSC injected mice were treated with ganciclovir (GCV) or PBS. The HTB14 glioma mass was significantly reduced by GCV treatment in mice injected with HAC-tk-hiMSCs. It was confirmed that gene delivery by our HAC-hiMSC system was effective after migration of MSCs to the glioma mass in vivo. Therefore, MSCs containing HACs carrying an anticancer gene or genes may provide a new tool for the treatment of malignant gliomas and possibly of other tumor types.

Amyloid precursor protein regulates migration and metalloproteinase gene expression in prostate cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyazaki, Toshiaki; Ikeda, Kazuhiro; Horie-Inoue, Kuniko

Highlights: • APP knockdown reduced proliferation and migration of prostate cancer cells. • APP knockdown reduced expression of metalloproteinase and EMT-related genes. • APP overexpression promoted LNCaP cell migration. • APP overexpression increased expression of metalloproteinase and EMT-related genes. - Abstract: Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer’s disease. We previously showed that APP is a primary androgen-responsive gene in prostate cancer and that its increased expression is correlated with poor prognosis for patients with prostate cancer. APPmore » has also been implicated in several human malignancies. Nevertheless, the mechanism underlying the pro-proliferative effects of APP on cancers is still not well-understood. In the present study, we explored a pathophysiological role for APP in prostate cancer cells using siRNA targeting APP (siAPP). The proliferation and migration of LNCaP and DU145 prostate cancer cells were significantly suppressed by siAPP. Differentially expressed genes in siAPP-treated cells compared to control siRNA-treated cells were identified by microarray analysis. Notably, several metalloproteinase genes, such as ADAM10 and ADAM17, and epithelial–mesenchymal transition (EMT)-related genes, such as VIM, and SNAI2, were downregulated in siAPP-treated cells as compared to control cells. The expression of these genes was upregulated in LNCaP cells stably expressing APP when compared with control cells. APP-overexpressing LNCaP cells exhibited enhanced migration in comparison to control cells. These results suggest that APP may contribute to the proliferation and migration of prostate cancer cells by modulating the expression of metalloproteinase and EMT-related genes.« less

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells.

PubMed

Demirci, Selami; Doğan, Ayşegül; Apdik, Hüseyin; Tuysuz, Emre Can; Gulluoglu, Sukru; Bayrak, Omer Faruk; Şahin, Fikrettin

2018-01-01

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblast cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment.

AMF/PGI transactivates the MMP-3 gene through the activation of Src-RhoA-phosphatidylinositol 3-kinase signaling to induce hepatoma cell migration.

PubMed

Shih, Wen-Ling; Liao, Ming-Huei; Yu, Feng-Ling; Lin, Ping-Yuan; Hsu, Hsue-Yin; Chiu, Shu-Jun

2008-11-08

We have previously shown that AMF/PGI induces hepatoma cell migration through the induction of MMP-3. This work investigates how AMF/PGI activates the MMP-3 gene. We demonstrated that AMF/PGI transactivates the MMP-3 gene promoter through AP-1. The transactivation and induction of cell migration effect of AMF/PGI directly correlates with its enzymatic activity. Various analyses showed that AMF/PGI stimulated the Src-RhoA-PI3-kinase signaling pathway, and these three signaling molecules could form a complex. Our results demonstrate a new mechanism of AMF/PGI-induced cell migration and a link between Src-RhoA-PI3-kinase, AP-1, MMP-3 and hepatoma cell migration.

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant.

PubMed

van Roosmalen, Wies; Le Dévédec, Sylvia E; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M; Look, Maxime P; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A C 't; Martens, John W M; Foekens, John A; Geiger, Benjamin; van de Water, Bob

2015-04-01

Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3-binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis.

76 FR 24912 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-03

... DEPARTMENT OF JUSTICE Parole Commission Sunshine Act Meeting TIME AND DATE: 11 a.m., Tuesday, May 10, 2011. PLACE: U.S. Parole Commission, 5550 Friendship Boulevard, Chevy Chase, Maryland. STATUS... the Chairman, U.S. Parole Commission, 5550 Friendship Boulevard, Chevy Chase, Maryland 20815, (301...

Validity of chase car data used in developing emissions cycles

DOT National Transportation Integrated Search

2000-09-01

Air quality policies, driving cycles and profiles of average driving behavior have been constructed to characterize the driving behavior of the overall fleet in an effort to ensure vehicle compliance. Chase car data and speed-time profiles of in-use ...

Balancing Cell Migration with Matrix Degradation Enhances Gene Delivery to Cells Cultured Three-Dimensionally Within Hydrogels

PubMed Central

Shepard, Jaclyn A.; Huang, Alyssa; Shikanova, Ariella; Shea, Lonnie D.

2010-01-01

In regenerative medicine, hydrogels are employed to fill defects and support the infiltration of cells that can ultimately regenerate tissue. Gene delivery within hydrogels targeting infiltrating cells has the potential to promote tissue formation, but the delivery efficiency of nonviral vectors within hydrogels is low hindering their applicability in tissue regeneration. To improve their functionality, we have conducted a mechanistic study to investigate the contribution of cell migration and matrix degradation on gene delivery. In this report, lipoplexes were entrapped within hydrogels based on poly(ethylene glycol) (PEG) crosslinked with peptides containing matrix metalloproteinase degradable sequences. The mesh size of these hydrogels is substantially less than the size of the entrapped lipoplexes, which can function to retain vectors. Cell migration and transfection were simultaneously measured within hydrogels with varying density of cell adhesion sites (Arg-Gly-Asp peptides) and solids content. Increasing RGD density increased expression levels up to 100-fold, while greater solids content sustained expression levels for 16 days. Increasing RGD density and decreasing solids content increased cell migration, which indicates expression levels increase with increased cell migration. Initially exposing cells to vector resulted in transient expression that declined after 2 days, verifying the requirement of migration to sustain expression. Transfected cells were predominantly located within the population of migrating cells for hydrogels that supported cell migration. Although the small mesh size retained at least 70% of the lipoplexes in the absence of cells after 32 days, the presence of cells decreased retention to 10% after 16 days. These results indicate that vectors retained within hydrogels contact migrating cells, and that persistent cell migration can maintain elevated expression levels. Thus matrix degradation and cell migration are fundamental design parameters for maximizing gene delivery from hydrogels. PMID:20450944

Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

PubMed

Shimada, Masaki

2006-10-01

Social object play (SOP), i.e., social play using portable object(s), among young Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was studied using a modified sequence sampling method from July to October 2000. SOP was a relatively common activity for most of the young macaques and often continued for long periods. Participants used many kinds of object, including edible natural objects and artificial objects, such as plastic bottles, but they never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts (>/=0.5 min) revealed the following interactive SOP features: (1) at any given time, participants used only one object, and only one participant held the object; (2) during SOP play-chasing, the object holder was likely to be chased by others; (3) during long bouts, the object changed hands frequently; and (4) agonistic competition for an object among young macaques was rare. Combinations of sexes, ages, relative ranks, or matrilines of the object holder and non-holder did not affect the tendency that the holder was chased by non-holder(s) during play-chasing. Even when there was a change in object holders, the repetitiveness of this interactive pattern, i.e., that the holder would be chased during SOP bouts, distinguished the SOP structure from that of other types of social play without object(s). General proximate social play mechanisms, such as self-handicapping or role taking, were associated with SOP. Other mechanisms that affected SOP included the following: (1) young macaques treated an object as a target in play competition, and (2) 'being the holder of a target object' was associated with the 'role of the chasee.'

Gene expression profiling and environmental contaminant assessment of migrating Pacific salmon in the Fraser River watershed of British Columbia.

PubMed

Veldhoen, Nik; Ikonomou, Michael G; Dubetz, Cory; Macpherson, Nancy; Sampson, Tracy; Kelly, Barry C; Helbing, Caren C

2010-05-05

The health and physiological condition of anadromous salmon is of concern as their upriver migration requires navigation of human-impacted waterways and metabolism of stored energy reserves containing anthropogenic contaminants. Such factors may affect reproductive success of fish stocks. This study investigates chemical contaminant burdens and select gene expression profiles in Pacific Sockeye (Oncorhynchus nerka) and Chinook (Oncorhynchus tshawytscha) salmon which traverse the Fraser River watershed during their spawning migration. Chemical analyses of muscle tissue and eggs of salmon collected from the lower Fraser River (pre-migration) and from upstream spawning grounds (post-migration) during the 2007 migration revealed the presence of numerous chemical contaminants, including PCBs, dioxins/furans, pesticides, and heavy metals. However, muscle tissue residue concentrations were well below human health consumption guidelines and 2,3,7,8 TCDD toxic equivalents (SigmaTEQs) in salmon eggs, calculated using WHO toxic equivalency factors (WHO-TEFs) for fish health, did not exceed the 0.3pgg(-1) wet weight toxicological threshold level previously associated with 30% egg mortality in salmon populations. Quantitative real-time PCR probes were generated and used to assess differences in abundance of key mRNA transcripts encoding nine gene products associated with reproduction, stress, metal toxicity, and exposure to environmental contaminants. Gene expression profiles were characterized in liver and muscle tissue of pre- and post-migration Sockeye and Chinook salmon. The results of stock-matched animals indicate that dynamic changes in mRNA levels occur for a number of genes in both species during migration and suggest that Sockeye salmon exhibit a greater level of biological stress compared to the Chinook salmon population. Using a male-specific genotypic marker, we found that out of the 154 animals examined, one Sockeye was genotypically male but phenotypically female. This individual's gene expression profile in liver and muscle was reminiscent of, but not identical to, the female expression profile. These studies provide the first glimpse of the dynamic yet common nature of changes in the transcriptome that are shared between species during in-migration and highlight differences that may relate to population success. Continued longitudinal assessment will further define the association between contaminant burden, physiological stress, and modulation of gene expression in migrating Pacific salmon.

6. CONSTRUCTION PROGRESS VIEW (EXTERIOR) OF TANK, CABLE CHASE, AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. CONSTRUCTION PROGRESS VIEW (EXTERIOR) OF TANK, CABLE CHASE, AND MOUNDED BUNKER. CONSTRUCTION WAS 99 PERCENT COMPLETE. CAMERA IS FACING WEST. INEL PHOTO NUMBER 65-5435, TAKEN OCTOBER 20, 1965. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

A compilation of chase work characterizes this image, looking south, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

A compilation of chase work characterizes this image, looking south, in the niche which slightly separates E Building form R Building, on the north side - Department of Energy, Mound Facility, Electronics Laboratory Building (E Building), One Mound Road, Miamisburg, Montgomery County, OH

Stare and chase of space debris targets using real-time derived pointing data

NASA Astrophysics Data System (ADS)

Steindorfer, Michael A.; Kirchner, Georg; Koidl, Franz; Wang, Peiyuan; Antón, Alfredo; Fernández Sánchez, Jaime; Merz, Klaus

2017-09-01

We successfully demonstrate Stare & Chase: Space debris laser ranging to uncooperative targets has been achieved without a priori knowledge of any orbital information. An analog astronomy CCD with a standard objective, piggyback mounted on our 50 cm Graz SLR receive telescope, 'stares' into the sky in a fixed direction. The CCD records the stellar background within a field of view of approx. 7°. From the stellar X/Y positions on the sensor a plate solving algorithm determines the pointing data of the image center with an accuracy of approx. 15 arc seconds. If a sunlit target passes through this field of view, its equatorial coordinates are calculated, stored and a Consolidated Prediction Format (CPF) file is created in near real time. The derived CPF data is used to start laser ranging ('chase' the object) within the same pass to retrieve highly accurate distance information. A comparison of Stare & Chase CPFs with standard TLE predictions shows the possibilities and limits of this method.

Lower levels of interleukin-1β gene expression are associated with impaired Langerhans' cell migration in aged human skin.

PubMed

Pilkington, Suzanne M; Ogden, Stephanie; Eaton, Laura H; Dearman, Rebecca J; Kimber, Ian; Griffiths, Christopher E M

2018-01-01

Langerhans' cells (LC) play pivotal roles in skin immune responses, linking innate and adaptive immunity. In aged skin there are fewer LC and migration is impaired compared with young skin. These changes may contribute to declining skin immunity in the elderly, including increased skin infections and skin cancer. Interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) are mandatory signals for LC migration and previous studies suggest that IL-1β signalling may be dysregulated in aged skin. Therefore, we sought to explore the mechanisms underlying these phenomena. In skin biopsies of photoprotected young (< 30 years) and aged (> 70 years) human skin ex vivo, we assessed the impact of trauma, and mandatory LC mobilizing signals on LC migration and gene expression. Biopsy-related trauma induced LC migration from young epidermis, whereas in aged skin, migration was greatly reduced. Interleukin-1β treatment restored LC migration in aged epidermis whereas TNF-α was without effect. In uncultured, aged skin IL-1β gene expression was lower compared with young skin; following culture, IL-1βmRNA remained lower in aged skin under control and TNF-α conditions but was elevated after culture with IL-1β. Interleukin-1 receptor type 2 (IL1R2) gene expression was significantly increased in aged, but not young skin, after cytokine treatment. Keratinocyte-derived factors secreted from young and aged primary cells did not restore or inhibit LC migration from aged and young epidermis, respectively. These data suggest that in aged skin, IL-1β signalling is diminished due to altered expression of IL1B and decoy receptor gene IL1R2. © 2017 The Authors. Immunology Published by John Wiley & Sons Ltd., Immunology.

Solution or suspension - Does it matter for lipid based systems? In vivo studies of chase dosing lipid vehicles with aqueous suspensions of a poorly soluble drug.

PubMed

Larsen, A T; Holm, R; Müllertz, A

2017-08-01

In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension. For halofantrine the chase dosed group had a tendency towards a low bioavailability relative to the Labrafil M2125CS solution, but still a significant higher bioavailability relative to the aqueous suspension. This could be due to factors such as a slower dissolution rate in the intestinal phase of halofantrine or a lower solubility in the colloidal structures formed during digestion, but other mechanisms may also be involved. The study thereby supported the potential of chase dosing as a potential dosing regimen in situations where it is beneficial to have a drug in the solid state, e.g. due to chemical stability issues in the lipid vehicle. Copyright © 2017 Elsevier B.V. All rights reserved.

Swimming activity in marine fish.

PubMed

Wardle, C S

1985-01-01

Marine fish are capable of swimming long distances in annual migrations; they are also capable of high-speed dashes of short duration, and they can occupy small home territories for long periods with little activity. There is a large effect of fish size on the distance fish migrate at slow swimming speeds. When chased by a fishing trawl the effect of fish size on swimming performance can decide their fate. The identity and thickness of muscle used at each speed and evidence for the timing of myotomes used during the body movement cycle can be detected using electromyogram (EMG) electrodes. The cross-sectional area of muscle needed to maintain different swimming speeds can be predicted by relating the swimming drag force to the muscle force. At maximum swimming speed one completed cycle of swimming force is derived in sequence from the whole cross-sectional area of the muscles along the two sides of the fish. This and other aspects of the swimming cycle suggest that each myotome might be responsible for generating forces involved in particular stages of the tail sweep. The thick myotomes at the head end shorten during the peak thrust of the tail blade whereas the thinner myotomes nearer the tail generate stiffness appropriate for transmission of these forces and reposition the tail for the next cycle.

Tumor cell migration screen identifies SRPK1 as breast cancer metastasis determinant

PubMed Central

van Roosmalen, Wies; Le Dévédec, Sylvia E.; Golani, Ofra; Smid, Marcel; Pulyakhina, Irina; Timmermans, Annemieke M.; Look, Maxime P.; Zi, Di; Pont, Chantal; de Graauw, Marjo; Naffar-Abu-Amara, Suha; Kirsanova, Catherine; Rustici, Gabriella; Hoen, Peter A.C. ‘t; Martens, John W.M.; Foekens, John A.; Geiger, Benjamin; van de Water, Bob

2015-01-01

Tumor cell migration is a key process for cancer cell dissemination and metastasis that is controlled by signal-mediated cytoskeletal and cell matrix adhesion remodeling. Using a phagokinetic track assay with migratory H1299 cells, we performed an siRNA screen of almost 1,500 genes encoding kinases/phosphatases and adhesome- and migration-related proteins to identify genes that affect tumor cell migration speed and persistence. Thirty candidate genes that altered cell migration were validated in live tumor cell migration assays. Eight were associated with metastasis-free survival in breast cancer patients, with integrin β3–binding protein (ITGB3BP), MAP3K8, NIMA-related kinase (NEK2), and SHC-transforming protein 1 (SHC1) being the most predictive. Examination of genes that modulate migration indicated that SRPK1, encoding the splicing factor kinase SRSF protein kinase 1, is relevant to breast cancer outcomes, as it was highly expressed in basal breast cancer. Furthermore, high SRPK1 expression correlated with poor breast cancer disease outcome and preferential metastasis to the lungs and brain. In 2 independent murine models of breast tumor metastasis, stable shRNA-based SRPK1 knockdown suppressed metastasis to distant organs, including lung, liver, and spleen, and inhibited focal adhesion reorganization. Our study provides comprehensive information on the molecular determinants of tumor cell migration and suggests that SRPK1 has potential as a drug target for limiting breast cancer metastasis. PMID:25774502

Divergence hitchhiking and the spread of genomic isolation during ecological speciation-with-gene-flow

PubMed Central

Via, Sara

2012-01-01

In allopatric populations, geographical separation simultaneously isolates the entire genome, allowing genetic divergence to accumulate virtually anywhere in the genome. In sympatric populations, however, the strong divergent selection required to overcome migration produces a genetic mosaic of divergent and non-divergent genomic regions. In some recent genome scans, each divergent genomic region has been interpreted as an independent incidence of migration/selection balance, such that the reduction of gene exchange is restricted to a few kilobases around each divergently selected gene. I propose an alternative mechanism, ‘divergence hitchhiking’ (DH), in which divergent selection can reduce gene exchange for several megabases around a gene under strong divergent selection. Not all genes/markers within a DH region are divergently selected, yet the entire region is protected to some degree from gene exchange, permitting genetic divergence from mechanisms other than divergent selection to accumulate secondarily. After contrasting DH and multilocus migration/selection balance (MM/SB), I outline a model in which genomic isolation at a given genomic location is jointly determined by DH and genome-wide effects of the progressive reduction in realized migration, then illustrate DH using data from several pairs of incipient species in the wild. PMID:22201174

Chinese Learning Journeys: Chasing the Dream

ERIC Educational Resources Information Center

Su, Feng, Ed.

2011-01-01

Eight students from mainland China chart their learning journeys across national and continental boundaries and socio-cultural contexts. The five women and three men structure their experiences of studying in China and the West around the turning points and life changing choices they made in chasing their dreams. They embody its emergent…

What Do Tag Games Teach?

ERIC Educational Resources Information Center

Belka, David

2006-01-01

Tag games have been described as "Chasing, fleeing, and dodging" type activities. Most "fleeing" activities involve dramatic play, use of movement concepts (such as quick and light), or movement changes without a partner, while many of the chasing and dodging activities utilize dodging concepts between partners or within small groups and are…

78 FR 18801 - Establishment of Class E Airspace; Beeville, TX

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... Instrument Approach Procedures at Chase Field Industrial Airport. The FAA is taking this action to enhance the safety and management of Instrument Flight Rule (IFR) operations at the airport. DATES: Effective... Federal Register a notice of proposed rulemaking (NPRM) to establish Class E airspace at Chase Industrial...

adrift, a novel bnl-induced Drosophila gene, required for tracheal pathfinding into the CNS.

PubMed

Englund, C; Uv, A E; Cantera, R; Mathies, L D; Krasnow, M A; Samakovlis, C

1999-04-01

Neurons and glial cells provide guidance cues for migrating neurons. We show here that migrating epithelial cells also contact specific neurons and glia during their pathfinding, and we describe the first gene required in the process. In wild-type Drosophila embryos, the ganglionic tracheal branch navigates a remarkably complex path along specific neural and glial substrata, switching substrata five times before reaching its ultimate target in the CNS. In adrift mutants, ganglionic branches migrate normally along the intersegmental nerve, but sporadically fail to switch to the segmental nerve and enter the CNS; they wind up meandering along the ventral epidermis instead. adrift encodes a novel nuclear protein with an evolutionarily conserved motif. The gene is required in the trachea and is expressed in the leading cells of migrating ganglionic branches where it is induced by the branchless FGF pathway. We propose that Adrift regulates expression of tracheal genes required for pathfinding on the segmental nerve, and FGF induction of adrift expression in migrating tracheal cells promotes the switch from the intersegmental to the segmental nerve.

American white pelicans breeding in the northern plains: productivity, behavior, movements, and migration

USGS Publications Warehouse

Sovada, Marsha A.; Pietz, Pamela J.; Woodward, Robert O.; Bartos, Alisa J.; Buhl, Deborah A.; Assenmacher, Michael J.

2013-01-01

Nearly half of American white pelicans (Pelecanus erythrorhynchos; hereafter pelicans) are believed to nest in several large colonies in the northern plains, yet few studies had been conducted on pelicans in this region until research began in 2004 to investigate the impact of West Nile virus (WNV) on their chicks. The work reported here focused on two of the largest colonies in the region, at Bitter Lake, South Dakota, and Chase Lake, North Dakota, during 2005–10. Pelicans usually began arriving at these two breeding colonies in early April. Egg-laying began during mid-April and nest initiations continued through May. The number of nests documented at these colonies reached a high of about 15,400 at Bitter Lake and 17,300 at Chase Lake, both in 2006. During 2006–8, annual variation in hatching success was high (40 to 100 percent) at video-monitored nests, averaging 61 percent for 82 nests at Bitter Lake and 57 percent for 88 nests at Chase Lake. Although most nests contained two eggs, of those where two chicks hatched, both chicks survived to the crèche stage (about 15 days old) at only two nests. Severe weather events, disturbance, and siblicide were documented causes of early season (before mid-July) mortalities. In the late season (mid-July to fledging), WNV was the most important factor contributing to chick mortality. Nests were nearly always attended by one adult during incubation and brooding. Adults typically exchanged places at the nest around mid-day in all 3 years, apparently taking advantage of thermals to gain altitude for travel to and from foraging areas. The mean time of exchange differed by about an hour between Bitter Lake (1328 central standard time, CST) and Chase Lake (1434 CST) colonies. During incubation, nearly 3 days often passed between adult nest exchanges; after chicks hatched, exchanges usually occurred daily. Exchanges were more frequent and chicks were fed more often at successful nests than at failed nests. Adult pelicans with satellite transmitters that incorporated a Global Positioning System (GPS) foraged primarily in shallow areas of lakes and semipermanent wetlands. These areas coincide with typical habitats of crayfish, salamanders, and rough fish, which were also the foods most commonly seen in pelican regurgitates at the colonies. Several satellite-tracked pelicans made frequent round trips between their breeding colony and foraging areas, most likely to provision their chicks. Typical distances travelled to foraging sites ranged from 30 kilometers to over 90 kilometers. Return times to the colonies (about 1300 and 1500 CST at Bitter Lake and Chase Lake, respectively) supported the colony difference documented at video-monitored nests. Of 28 pelicans tagged with GPS satellite transmitters in 2005–6, 26 survived the first summer and migrated south during fall. Nineteen of these returned to the breeding region (defined as north of the latitude of South Dakota’s southern border) in at least 1 year during 2006–9; collectively, they returned to the breeding region 33 times. Very few pelicans returned to the colony where they had been tagged; many did not breed and concentrated their activities at wetland complexes in South Dakota and North Dakota, but few tagged pelicans temporally overlapped at specific sites. During 2005–9, tagged pelicans collectively made 56 migratory trips south in the fall. Most wintered in Mexico, near the gulf coast and elsewhere; others wintered in Texas, Louisiana, Mississippi, and Florida. Individuals typically returned to the same general areas each winter. Individuals rarely followed the same migratory path on their way south and north, but they often roughly repeated southerly or northerly routes among years. Ensuring a sustainable population of American white pelicans requires identification and mitigation of known threats. The work described herein has identified WNV and severe weather as important factors that potentially limit reproductive success and recruitment in the northern plains. Managers in this region could assess the influence of such factors on productivity at key colonies by annually obtaining aerial photographs during peak nesting, and estimating numbers of chicks fledged from aerial photographs or ground counts. Banding a subsample of chicks in late June or early July, followed by a sweep for bands at the end of the season, would allow estimation of mortality rates of older chicks (that normally would fledge) and help track the influence of WNV or other mortality factors over time and varying environmental conditions.

On the anomalous afterglow seen in a chameleon afterglow search

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steffen, Jason H.; Baumbaugh, Alan; Chou, Aaron S.

2012-05-01

We present data from our investigation of the anomalous orange-colored afterglow that was seen in the GammeV Chameleon Afterglow Search (CHASE). These data include information about the broadband color of the observed glow, the relationship between the glow and the temperature of the apparatus, and other data taken prior to, and during the science operations of CHASE. While differing in several details, the generic properties of the afterglow from CHASE are similar to luminescence seen in some vacuum compounds. Contamination from this, or similar, luminescent signatures will likely impact the design of implementation of future experiments involving single photon detectorsmore » and high intensity light sources in a cryogenic environment.« less

Aggregation increases prey survival time in group chase and escape

NASA Astrophysics Data System (ADS)

Yang, Sicong; Jiang, Shijie; Jiang, Li; Li, Geng; Han, Zhangang

2014-08-01

Recently developed chase-and-escape models have addressed a fascinating pursuit-and-evasion problem that may have both theoretical significance and potential applications. We introduce three aggregation strategies for the prey in a group chase model on a lattice. Simulation results show that aggregation dramatically increases the group survival time, even allowing immortal prey. The average survival time τ and the aggregation probability P have a power-law dependence of \\tau \\sim {{(1-P)}^{-1}} for P\\in [0.9,0.997]. With increasing numbers of predators, there is still a phase transition. When the number of predators is less than the critical point value, the prey group survival time increases significantly.

A comparative study of the response to repeated chasing stress in Atlantic salmon (Salmo salar L.) parr and post-smolts.

PubMed

Madaro, Angelico; Olsen, Rolf Erik; Kristiansen, Tore S; Ebbesson, Lars O E; Flik, Gert; Gorissen, Marnix

2016-02-01

When Atlantic salmon parr migrate from fresh water towards the sea, they undergo extensive morphological, neural, physiological and behavioural changes. Such changes have the potential to affect their responsiveness to various environmental factors that impose stress. In this study we compared the stress responses in parr and post-smolt salmon following exposure to repeated chasing stress (RCS) for three weeks. At the end of this period, all fish were challenged with a novel stressor and sampled before (T0) and after 1h (T1). Parr had a higher growth rate than post-smolts. Plasma cortisol declined in the RCS groups within the first week suggesting a rapid habituation/desensitisation of the endocrine stress axis. As a result of the desensitised HPI axis, RCS groups showed a reduced cortisol response when exposed to the novel stressor. In preoptic area (POA) crf mRNA levels were higher in all post-smolt groups compared to parr. 11βhsd2 decreased by RCS and by the novel stressor in post-smolt controls (T1), whereas no effect of either stress was seen in parr. The grs were low in all groups except for parr controls. In pituitary, parr controls had higher levels of crf1r mRNA than the other parr and post-smolt groups, whilst pomcb was higher in post-smolt control groups. Overall, 11βhsd2 transcript abundance in parr was lower than post-smolt groups; after the novel stressor pomcs, grs and mr were up-regulated in parr control (T1). In summary, we highlight differences in the central stress response between parr and post-smolt salmon following RCS. Copyright © 2015 Elsevier Inc. All rights reserved.

Chase and NYANA: A Partnership To Remove Barriers to Job Performance 1993-94. Final Report.

ERIC Educational Resources Information Center

Auerbach, Charles

A workplace literacy program implemented cooperatively by the New York Association for New Americans, Inc. (NYANA) and Chase Manhattan Bank is reported. The federally-funded project provided individualized communication workplace behavior and skills training in English as a Second Language for 30 limited-English-proficient bank employees working…

Motivations and sensation seeking characteristics of recreational storm chasers

Treesearch

Shuangyu Xu; Sonja Wilhelm Stanis; Carla Barbieri; Jiawen Chen

2012-01-01

Little is known about recreational storm chasing, a type of risk recreation that has increased in popularity since the 1990s. This study was conducted to understand factors associated with participation in recreational storm chasing in the United States. Particularly, this study assessed the motivations and sensation seeking attributes of recreational storm chasers, as...

Maximum Likelihood Implementation of an Isolation-with-Migration Model for Three Species.

PubMed

Dalquen, Daniel A; Zhu, Tianqi; Yang, Ziheng

2017-05-01

We develop a maximum likelihood (ML) method for estimating migration rates between species using genomic sequence data. A species tree is used to accommodate the phylogenetic relationships among three species, allowing for migration between the two sister species, while the third species is used as an out-group. A Markov chain characterization of the genealogical process of coalescence and migration is used to integrate out the migration histories at each locus analytically, whereas Gaussian quadrature is used to integrate over the coalescent times on each genealogical tree numerically. This is an extension of our early implementation of the symmetrical isolation-with-migration model for three species to accommodate arbitrary loci with two or three sequences per locus and to allow asymmetrical migration rates. Our implementation can accommodate tens of thousands of loci, making it feasible to analyze genome-scale data sets to test for gene flow. We calculate the posterior probabilities of gene trees at individual loci to identify genomic regions that are likely to have been transferred between species due to gene flow. We conduct a simulation study to examine the statistical properties of the likelihood ratio test for gene flow between the two in-group species and of the ML estimates of model parameters such as the migration rate. Inclusion of data from a third out-group species is found to increase dramatically the power of the test and the precision of parameter estimation. We compiled and analyzed several genomic data sets from the Drosophila fruit flies. Our analyses suggest no migration from D. melanogaster to D. simulans, and a significant amount of gene flow from D. simulans to D. melanogaster, at the rate of ~0.02 migrant individuals per generation. We discuss the utility of the multispecies coalescent model for species tree estimation, accounting for incomplete lineage sorting and migration. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High-resolution gadolinium-enhanced 3D MRA of the infrapopliteal arteries. Lessons for improving bolus-chase peripheral MRA.

PubMed

Hood, Maureen N; Ho, Vincent B; Foo, Thomas K F; Marcos, Hani B; Hess, Sandra L; Choyke, Peter L

2002-09-01

Peripheral magnetic resonance angiography (MRA) is growing in use. However, methods of performing peripheral MRA vary widely and continue to be optimized, especially for improvement in illustration of infrapopliteal arteries. The main purpose of this project was to identify imaging factors that can improve arterial visualization in the lower leg using bolus chase peripheral MRA. Eighteen healthy adults were imaged on a 1.5T MR scanner. The calf was imaged using conventional three-station bolus chase three-dimensional (3D) MRA, two dimensional (2D) time-of-flight (TOF) MRA and single-station Gadolinium (Gd)-enhanced 3D MRA. Observer comparisons of vessel visualization, signal to noise ratios (SNR), contrast to noise ratios (CNR) and spatial resolution comparisons were performed. Arterial SNR and CNR were similar for all three techniques. However, arterial visualization was dramatically improved on dedicated, arterial-phase Gd-enhanced 3D MRA compared with the multi-station bolus chase MRA and 2D TOF MRA. This improvement was related to optimization of Gd-enhanced 3D MRA parameters (fast injection rate of 2 mL/sec, high spatial resolution imaging, the use of dedicated phased array coils, elliptical centric k-space sampling and accurate arterial phase timing for image acquisition). The visualization of the infrapopliteal arteries can be substantially improved in bolus chase peripheral MRA if voxel size, contrast delivery, and central k-space data acquisition for arterial enhancement are optimized. Improvements in peripheral MRA should be directed at these parameters.

Predator evasion by white-tailed deer fawns

USGS Publications Warehouse

Grovenburg, Troy W.; Monteith, Kevin L.; Klaver, Robert W.; Jenks, Jonathan A.

2012-01-01

Despite their importance for understanding predator–prey interactions, factors that affect predator evasion behaviours of offspring of large ungulates are poorly understood. Our objective was to characterize the influence of selection and availability of escape cover and maternal presence on predator evasion by white-tailed deer, Odocoileus virginianus, fawns in the northern Great Plains, U.S.A. We observed 45 coyote, Canis latrans, chases of fawns, and we participated in 83 human chases of fawns during 2007–2009, of which, 19 and 42 chases, respectively, ended with capture of the fawn. Evasive techniques used by fawns were similar for human and coyote chases. Likelihood of a white-tailed deer fawn escaping capture, however, was influenced by deer group size and a number of antipredator behaviours, including aggressive defence by females, initial habitat and selection of escape cover, all of which were modified by the presence of parturient females. At the initiation of a chase, fawns in grasslands were more likely to escape, whereas fawns in forested cover, cultivated land or wheat were more likely to be captured by a coyote or human. Fawns fleeing to wetlands and grasslands also were less likely to be captured compared with those choosing forested cover, wheat and cultivated land. Increased probability of capture was associated with greater distance to wetland and grassland habitats and decreased distance to wheat. Use of wetland habitat as a successful antipredator strategy highlights the need for a greater understanding of the importance of habitat complexity in predator avoidance.

Sexually dimorphic aggression indicates male gray wolves specialize in pack defense against conspecific groups

USGS Publications Warehouse

Cassidy, Kira A.; Mech, L. David; MacNulty, Daniel R; Stahler, Daniel R.; Smith, Douglas W.

2017-01-01

Aggression directed at conspecific groups is common among gregarious, territorial species, and for some species such as gray wolves (Canis lupus) intraspecific strife is the leading cause of natural mortality. Each individual in a group likely has different measures of the costs and benefits associated with a group task, such as an aggressive attack on another group, which can alter motivation and behavior. We observed 292 inter-pack aggressive interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300 days of observation) in order to determine the role of both sexes, and the influence of pack, age, and other traits on aggression. We recorded the behaviors and characteristics of all individuals present during the interactions (n = 534 individuals) and which individuals participated in each step (i.e. chase, attack, kill, flight) of the interaction. Overall, all wolves were more likely to chase rivals if they outnumbered their opponent, suggesting packs accurately assess their opponent’s size during encounters and individuals adjust their behavior based on relative pack size. Males were more likely than females to chase rival packs and gray-colored wolves were more aggressive than black-colored wolves. Male wolves and gray-colored wolves also recorded higher cortisol levels than females and black-colored wolves, indicating hormonal support for more intense aggressive behavior. Further, we found a positive correlation between male age and probability of chasing, while age-specific participation for females remained constant. Chasing behavior was influenced by the sex of lone intruders, with males more likely to chase male intruders. This difference in behavior suggests male and female wolves may have different strategies and motivations during inter-pack aggressive interactions related to gray wolf mating systems. A division of labor between pack members concerning resource and territory defense suggests selection for specific traits related to aggression is an adaptive response to intense competition between groups of conspecifics.

Sexually dimorphic aggression indicates male gray wolves specialize in pack defense against conspecific groups.

PubMed

Cassidy, Kira A; Mech, L David; MacNulty, Daniel R; Stahler, Daniel R; Smith, Douglas W

2017-03-01

Aggression directed at conspecific groups is common among gregarious, territorial species, and for some species such as gray wolves (Canis lupus) intraspecific strife is the leading cause of natural mortality. Each individual in a group likely has different measures of the costs and benefits associated with a group task, such as an aggressive attack on another group, which can alter motivation and behavior. We observed 292 inter-pack aggressive interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300days of observation) in order to determine the role of both sexes, and the influence of pack, age, and other traits on aggression. We recorded the behaviors and characteristics of all individuals present during the interactions (n=534 individuals) and which individuals participated in each step (i.e. chase, attack, kill, flight) of the interaction. Overall, all wolves were more likely to chase rivals if they outnumbered their opponent, suggesting packs accurately assess their opponent's size during encounters and individuals adjust their behavior based on relative pack size. Males were more likely than females to chase rival packs and gray-colored wolves were more aggressive than black-colored wolves. Male wolves and gray-colored wolves also recorded higher cortisol levels than females and black-colored wolves, indicating hormonal support for more intense aggressive behavior. Further, we found a positive correlation between male age and probability of chasing, while age-specific participation for females remained constant. Chasing behavior was influenced by the sex of lone intruders, with males more likely to chase male intruders. This difference in behavior suggests male and female wolves may have different strategies and motivations during inter-pack aggressive interactions related to gray wolf mating systems. A division of labor between pack members concerning resource and territory defense suggests selection for specific traits related to aggression is an adaptive response to intense competition between groups of conspecifics. Copyright © 2017 Elsevier B.V. All rights reserved.

CCDC-55 is required for larval development and distal tip cell migration in Caenorhabditis elegans.

PubMed

Kovacevic, Ismar; Ho, Richard; Cram, Erin J

2012-01-01

The Caenorhabditis elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study, we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

CCDC-55 is required for larval development and distal tip cell migration in C. elegans

PubMed Central

Kovacevic, Ismar; Ho, Richard; Cram, Erin J.

2012-01-01

The C. elegans distal tip cells (DTCs) are an in vivo model for the study of developmentally regulated cell migration. In this study we characterize a novel role for CCDC-55, a conserved coiled-coil domain containing protein, in DTC migration and larval development in C. elegans. Although animals homozygous for a probable null allele, ccdc-55(ok2851), display an early larval arrest, RNAi depletion experiments allow the analysis of later phenotypes and suggest that CCDC-55 is needed within the DTC for migration to cease at the end of larval morphogenesis. The ccdc-55 gene is found in an operon with rnf-121 and rnf-5, E3 ubiquitin ligases that target cell migration genes such as the β-integrin PAT-3. Genetic interaction studies using RNAi depletion and the deletion alleles rnf-121(ok848) and rnf-5(tm794) indicate that CCDC-55 and the RNF genes act at least partially in parallel to promote termination of cell migration in the adult DTC. PMID:22285439

Tumor-specific detection of an optically targeted antibody combined with a quencher-conjugated neutravidin "quencher-chaser": a dual "quench and chase" strategy to improve target to nontarget ratios for molecular imaging of cancer.

PubMed

Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L; Kobayashi, Hisataka

2009-01-01

In vivo molecular cancer imaging with monoclonal antibodies has great potential not only for cancer detection, but also for cancer characterization. However, the prolonged retention of intravenously injected antibody in the blood causes low target tumor-to-background ratio (TBR). Avidin has been used as a "chase" to clear the unbound, circulating biotinylated antibody and decrease the background signal. Here, we utilize a combined approach of a fluorescence resonance energy transfer (FRET) quenched antibody with an "avidin chase" to increase TBR. Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type 2 (HER2), was biotinylated and conjugated with the near-infrared (NIR) fluorophore Alexa680 to synthesize Tra-Alexa680-biotin. Next, the FRET quencher, QSY-21, was conjugated to avidin, neutravidin (nAv), or streptavidin (sAv), thus creating Av-QSY21, nAv-QSY21, or sAv-QSY21 as "chasers". The fluorescence was quenched in vitro by binding Tra-Alexa680-biotin to Av-QSY21, nAv-QSY21, or sAv-QSY21. To evaluate if the injection of quencher-conjugated avidin derivatives can improve target TBR by using a dual "quench and chase" strategy, both target (3T3/HER2+) and nontarget (Balb3T3/ZsGreen) tumor-bearing mice were employed. The "FRET quench" effect induced by all the QSY21 avidin-based conjugates reduced but did not totally eliminate background signal from the blood pool. The addition of nAv-QSY21 administration increased target TBR mainly because of the "chase" effect where unbound conjugated antibody was preferentially cleared to the liver. The relatively slow clearance of unbound nAv-QSY21 leads to further reductions in background signal by leaking out of the vascular space and binding to unbound antibodies in the extravascular space of tumors, resulting in decreased nontarget tumor-to-background ratios but increased target TBR due to the "FRET quench" effect, because target-bound antibodies were internalized and could not bind to nAv-QSY21. In conclusion, the proposed "quench-and-chase" system combines two strategies, fluorescent quenching and avidin chasing, to improve target TBR and reduce nontarget TBR, which should result in both improved tumor sensitivity and improved specificity.

Neural crest specification and migration independently require NSD3-related lysine methyltransferase activity

PubMed Central

Jacques-Fricke, Bridget T.; Gammill, Laura S.

2014-01-01

Neural crest precursors express genes that cause them to become migratory, multipotent cells, distinguishing them from adjacent stationary neural progenitors in the neurepithelium. Histone methylation spatiotemporally regulates neural crest gene expression; however, the protein methyltransferases active in neural crest precursors are unknown. Moreover, the regulation of methylation during the dynamic process of neural crest migration is unclear. Here we show that the lysine methyltransferase NSD3 is abundantly and specifically expressed in premigratory and migratory neural crest cells. NSD3 expression commences before up-regulation of neural crest genes, and NSD3 is necessary for expression of the neural plate border gene Msx1, as well as the key neural crest transcription factors Sox10, Snail2, Sox9, and FoxD3, but not gene expression generally. Nevertheless, only Sox10 histone H3 lysine 36 dimethylation requires NSD3, revealing unexpected complexity in NSD3-dependent neural crest gene regulation. In addition, by temporally limiting expression of a dominant negative to migratory stages, we identify a novel, direct requirement for NSD3-related methyltransferase activity in neural crest migration. These results identify NSD3 as the first protein methyltransferase essential for neural crest gene expression during specification and show that NSD3-related methyltransferase activity independently regulates migration. PMID:25318671

Animal tracking meets migration genomics: transcriptomic analysis of a partially migratory bird species.

PubMed

Franchini, Paolo; Irisarri, Iker; Fudickar, Adam; Schmidt, Andreas; Meyer, Axel; Wikelski, Martin; Partecke, Jesko

2017-06-01

Seasonal migration is a widespread phenomenon, which is found in many different lineages of animals. This spectacular behaviour allows animals to avoid seasonally adverse environmental conditions to exploit more favourable habitats. Migration has been intensively studied in birds, which display astonishing variation in migration strategies, thus providing a powerful system for studying the ecological and evolutionary processes that shape migratory behaviour. Despite intensive research, the genetic basis of migration remains largely unknown. Here, we used state-of-the-art radio-tracking technology to characterize the migratory behaviour of a partially migratory population of European blackbirds (Turdus merula) in southern Germany. We compared gene expression of resident and migrant individuals using high-throughput transcriptomics in blood samples. Analyses of sequence variation revealed a nonsignificant genetic structure between blackbirds differing by their migratory phenotype. We detected only four differentially expressed genes between migrants and residents, which might be associated with hyperphagia, moulting and enhanced DNA replication and transcription. The most pronounced changes in gene expression occurred between migratory birds depending on when, in relation to their date of departure, blood was collected. Overall, the differentially expressed genes detected in this analysis may play crucial roles in determining the decision to migrate, or in controlling the physiological processes required for the onset of migration. These results provide new insights into, and testable hypotheses for, the molecular mechanisms controlling the migratory phenotype and its underlying physiological mechanisms in blackbirds and other migratory bird species. © 2017 John Wiley & Sons Ltd.

Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.

PubMed

Bett, N N; Hinch, S G; Kaukinen, K H; Li, S; Miller, K M

2018-04-16

Expression of 12 olfactory genes was analysed in adult sockeye salmon Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from their natal migration route. Variation was found in six of these genes, all of which were olfc olfactory receptors and had lower expression levels in salmon nearing spawning grounds. The results may reflect decreased sensitivity to natal water olfactory cues as these fish are no longer seeking the correct migratory route. The expression of olfactory genes during the olfactory-mediated spawning migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these findings demonstrate a link between migratory behaviours and olfactory plasticity that provides a basis for future molecular research on salmon homing. © 2018 The Fisheries Society of the British Isles.

Anticancer effects of the engineered stem cells transduced with therapeutic genes via a selective tumor tropism caused by vascular endothelial growth factor toward HeLa cervical cancer cells.

PubMed

Kim, Hye-Sun; Yi, Bo-Rim; Hwang, Kyung-A; Kim, Seung U; Choi, Kyung-Chul

2013-10-01

The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/or human interferon-beta (IFN-β) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTECs. These GESTECs transduced with CD gene and IFN-β may provide a potential of a novel gene therapy for anticervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration.

PubMed

Josephson, Matthew P; Miltner, Adam M; Lundquist, Erik A

2016-08-01

Nervous system development and circuit formation requires neurons to migrate from their birthplaces to specific destinations.Migrating neurons detect extracellular cues that provide guidance information. In Caenorhabditis elegans, the Q right (QR) and Q left (QL) neuroblast descendants migrate long distances in opposite directions. The Hox gene lin-39 cell autonomously promotes anterior QR descendant migration, and mab-5/Hox cell autonomously promotes posterior QL descendant migration. Here we describe a nonautonomous role of mab-5 in regulating both QR and QL descendant migrations, a role masked by redundancy with lin-39 A third Hox gene, egl-5/Abdominal-B, also likely nonautonomously regulates Q descendant migrations. In the lin-39 mab-5 egl-5 triple mutant, little if any QR and QL descendant migration occurs. In addition to well-described roles of lin-39 and mab-5 in the Q descendants, our results suggest that lin-39, mab-5, and egl-5 might also pattern the posterior region of the animal for Q descendant migration. Previous studies showed that the spon-1 gene might be a target of MAB-5 in Q descendant migration. spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin. Here we show that spon-1 acts nonautonomously to control Q descendant migration, and might function as a permissive rather than instructive signal for cell migration. We find that increased levels of MAB-5 in body wall muscle (BWM) can drive the spon-1 promoter adjacent to the Q cells, and loss of spon-1 suppresses mab-5 gain of function. Thus, MAB-5 might nonautonomously control Q descendant migrations by patterning the posterior region of the animal to which Q cells respond. spon-1 expression from BWMs might be part of the posterior patterning necessary for directed Q descendant migration. Copyright © 2016 by the Genetics Society of America.

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration

PubMed Central

Josephson, Matthew P.; Miltner, Adam M.; Lundquist, Erik A.

2016-01-01

Nervous system development and circuit formation requires neurons to migrate from their birthplaces to specific destinations.Migrating neurons detect extracellular cues that provide guidance information. In Caenorhabditis elegans, the Q right (QR) and Q left (QL) neuroblast descendants migrate long distances in opposite directions. The Hox gene lin-39 cell autonomously promotes anterior QR descendant migration, and mab-5/Hox cell autonomously promotes posterior QL descendant migration. Here we describe a nonautonomous role of mab-5 in regulating both QR and QL descendant migrations, a role masked by redundancy with lin-39. A third Hox gene, egl-5/Abdominal-B, also likely nonautonomously regulates Q descendant migrations. In the lin-39mab-5egl-5 triple mutant, little if any QR and QL descendant migration occurs. In addition to well-described roles of lin-39 and mab-5 in the Q descendants, our results suggest that lin-39, mab-5, and egl-5 might also pattern the posterior region of the animal for Q descendant migration. Previous studies showed that the spon-1 gene might be a target of MAB-5 in Q descendant migration. spon-1 encodes a secreted basement membrane molecule similar to vertebrate F-spondin. Here we show that spon-1 acts nonautonomously to control Q descendant migration, and might function as a permissive rather than instructive signal for cell migration. We find that increased levels of MAB-5 in body wall muscle (BWM) can drive the spon-1 promoter adjacent to the Q cells, and loss of spon-1 suppresses mab-5 gain of function. Thus, MAB-5 might nonautonomously control Q descendant migrations by patterning the posterior region of the animal to which Q cells respond. spon-1 expression from BWMs might be part of the posterior patterning necessary for directed Q descendant migration. PMID:27225683

77 FR 45690 - Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... is made by a Plan fiduciary or Plan participant or IRA owner who is independent (as defined in... process; (d) A person is ``independent'' of JPMorgan Chase if the person is: (1) Not JPMorgan Chase or an... independent act of SPF as a corporate entity for business reasons which did not involve the Plan. As such, all...

Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus | Hawaii Public

Science.gov Websites

Scenes of Devastation: Chasing Hawaii's Deadly Ohia Fungus By Molly Solomon * Mar 25, 2016 TweetShareGoogle+Email Molly Solomon Rapid Ohia Death has devastated native forests on Hawaii Island, especially in Lower Puna subdivisions like Leilani Estates. Credit Molly Solomon One of Hawai'i's oldest and most

76 FR 31955 - Jonathan and Jayne Chase; Notice of Application Accepted for Filing With the Commission, Intent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

.... c. Date filed: July 23, 2010. d. Applicant: Jonathan and Jayne Chase. e. Name of Project: Troy Hydropower Project. f. Location: On the Missisquoi River, in the Town of Troy, Orleans County, Vermont. The... filing and is now ready for environmental analysis. l. Project Description: The Troy Project would...

The Psychophysics of Chasing: A Case Study in the Perception of Animacy

ERIC Educational Resources Information Center

Gao, Tao; Newman, George E.; Scholl, Brian J.

2009-01-01

Psychologists have long been captivated by the perception of animacy--the fact that even simple moving shapes may appear to engage in animate, intentional, and goal-directed movements. Here we report several new types of studies of a particularly salient form of perceived animacy: "chasing", in which one shape (the "wolf") pursues another shape…

Observations and reinterpretation of kingfisher-raptor interactions

USGS Publications Warehouse

Kirby, Ronald E.; Fuller, Mark R.

1978-01-01

Reported observations of Belted Kingfisher (Megaceryle alcyon)-raptor interactions have ranged from brief encounters where the kingfisher escaped the raptor and the hawk subsequently flew away to repeated chases (Johnson 1925, McCabe and McCabe 1928, Skinner 1928, Smith 1963). In some repetitive chases, kingfishers appeared to initiate the interaction (McCabe and McCabe 1928, Skinner 1928).

Engaging Experiential Service Learning through a Co-Curricular Club: The Chase Charlie Races

ERIC Educational Resources Information Center

Judge, Lawrence W.; Pierce, David; Petersen, Jeffrey; Bellar, David; Wanless, Elizabeth; Gilreath, Erin; Simon, Laura

2011-01-01

The efficacy of the "Chase Charlie Races" (an experiential learning activity) was demonstrated via program assessment. This was achieved via post-event evaluations of race participants and student club members, and with fitness assessments of 76 elementary students who participated in an eight-week training program. Paired sample t-tests revealed…

Impact of transgene genome location on gene migration from herbicide-resistant wheat (Triticum aestivum L.) to jointed goatgrass (Aegilops cylindrica Host).

PubMed

Rehman, Maqsood; Hansen, Jennifer L; Mallory-Smith, Carol A; Zemetra, Robert S

2017-08-01

Wheat (Triticum aestivum) (ABD) and jointed goatgrass (Aegilops cylindrica) (CD) can cross and produce hybrids that can backcross to either parent. Such backcrosses can result in progeny with chromosomes and/or chromosome segments retained from wheat. Thus, a herbicide resistance gene could migrate from wheat to jointed goatgrass. In theory, the risk of gene migration from herbicide-resistant wheat to jointed goatgrass is more likely if the gene is located on the D genome and less likely if the gene is located on the A or B genome of wheat. BC 1 populations (jointed goatgrass as a recurrent parent) were analyzed for chromosome numbers and transgene transmission rates under sprayed and non-sprayed conditions. Transgene retention in the non-sprayed BC 1 generation for the A, B and D genomes was 84, 60 and 64% respectively. In the sprayed populations, the retention was 81, 59 and 74% respectively. The gene transmission rates were higher than the expected 50% or less under sprayed and non-sprayed conditions, possibly owing to meiotic chromosome restitution and/or chromosome non-disjunction. Such high transmission rates in the BC 1 generation negates the benefits of gene placement for reducing the potential of gene migration from wheat to jointed goatgrass. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

T-34C in flight

NASA Image and Video Library

1997-03-21

A NASA T-34C aircraft, used for safety chase, is shown flying above the Dryden Flight Research Center, Edwards, California in March 1997. The aircraft was previously used at the Lewis Research Center in propulsion experiments involving turboprop engines, and was used as a chase aircraft at Dryden for smaller and slower research projects. Chase aircraft accompany research flights for photography and video purposes, and also as support for safety and research. At Dryden, the T-34 is used mainly for smaller remotely piloted vehicles which fly slower than NASA's F-18's, used for larger scale projects. This aircraft was returned to the U.S. Navy in May of 2002. The T-34C, built by Beech, carries a crew of 2 and is nicknamed the Mentor.

Matrix metalloproteinase-9 plays a role in protecting zebrafish from lethal infection with Listeria monocytogenes by enhancing macrophage migration.

PubMed

Shan, Ying; Zhang, Yikai; Zhuo, Xunhui; Li, Xiaoliang; Peng, Jinrong; Fang, Weihuan

2016-07-01

Zebrafish could serve as an alternative animal model for pathogenic bacteria in multiple infectious routes. Our previous study showed that immersion infection in zebrafish with Listeria monocytogenes did not cause lethality but induced transient expression of several immune response genes. We used an Affymetrix gene chip to examine the expression profiles of genes of zebrafish immersion-infected with L. monocytogenes. A total of 239 genes were up-regulated and 56 genes down-regulated compared with uninfected fish. Highest expression (>20-fold) was seen with the mmp-9 gene encoding the matrix metalloproteinase-9 (Mmp-9) known to degrade the extracellular matrix proteins. By morpholino knockdown of mmp-9, we found that the morphants showed rapid death with much higher bacterial load after intravenous or intraventricular (brain ventricle) infection with L. monocytogenes. Macrophages in mmp-9-knockdown morphants had significant defect in migrating to the brain cavity upon intraventricular infection. Decreased migration of murine macrophages with knockdown of mmp-9 and cd44 was also seen in transwell inserts with 8-μm pore polycarbonate membrane, as compared with the scrambled RNA. These findings suggest that Mmp-9 is a protective molecule against infection by L. monocytogenes by engaging in migration of zebrafish macrophages to the site of infection via a non-proteolytic role. Further work is required on the molecular mechanisms governing Mmp-9-driven macrophage migration in zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcriptomics of environmental acclimatization and survival in wild adult Pacific sockeye salmon (Oncorhynchus nerka) during spawning migration.

PubMed

Evans, Tyler G; Hammill, Edd; Kaukinen, Karia; Schulze, Angela D; Patterson, David A; English, Karl K; Curtis, Janelle M R; Miller, Kristina M

2011-11-01

Environmental shifts accompanying salmon spawning migrations from ocean feeding grounds to natal freshwater streams can be severe, with the underlying stress often cited as a cause of increased mortality. Here, a salmonid microarray was used to characterize changes in gene expression occurring between ocean and river habitats in gill and liver tissues of wild migrating sockeye salmon (Oncorhynchus nerka Walbaum) returning to spawn in the Fraser River, British Columbia, Canada. Expression profiles indicate that the transcriptome of migrating salmon is strongly affected by shifting abiotic and biotic conditions encountered along migration routes. Conspicuous shifts in gene expression associated with changing salinity, temperature, pathogen exposure and dissolved oxygen indicate that these environmental variables most strongly impact physiology during spawning migrations. Notably, transcriptional changes related to osmoregulation were largely preparatory and occurred well before salmon encountered freshwater. In the river environment, differential expression of genes linked with elevated temperatures indicated that thermal regimes within the Fraser River are approaching tolerance limits for adult salmon. To empirically correlate gene expression with survival, biopsy sampling of gill tissue and transcriptomic profiling were combined with telemetry. Many genes correlated with environmental variables were differentially expressed between premature mortalities and successful migrants. Parametric survival analyses demonstrated a broad-scale transcriptional regulator, cofactor required for Sp1 transcriptional activation (CRSP), to be significantly predictive of survival. As the environmental characteristics of salmon habitats continue to change, establishing how current environmental conditions influence salmon physiology under natural conditions is critical to conserving this ecologically and economically important fish species. © 2011 Blackwell Publishing Ltd.

Substance-specific importance of EGFR for vascular smooth muscle cells motility in primary culture.

PubMed

Schreier, Barbara; Schwerdt, Gerald; Heise, Christian; Bethmann, Daniel; Rabe, Sindy; Mildenberger, Sigrid; Gekle, Michael

2016-07-01

Besides their importance for the vascular tone, vascular smooth muscle cells (VSMC) also contribute to pathophysiological vessel alterations. Various G-protein coupled receptor ligands involved in vascular dysfunction and remodeling can transactivate the epidermal growth factor receptor (EGFR) of VSMC, yet the importance of EGFR transactivation for the VSMC phenotype is incompletely understood. The aims of this study were (i) to characterize further the importance of the VSMC-EGFR for proliferation, migration and marker gene expression for inflammation, fibrosis and reactive oxygen species (ROS) homeostasis and (ii) to test the hypothesis that vasoactive substances (endothelin-1, phenylephrine, thrombin, vasopressin and ATP) rely differentially on the EGFR with respect to the abovementioned phenotypic alterations. In primary, aortic VSMC from mice without conditional deletion of the EGFR, proliferation, migration, marker gene expression (inflammation, fibrosis and ROS homeostasis) and cell signaling (ERK 1/2, intracellular calcium) were analyzed. VSMC-EGFR loss reduced collective cell migration and single cell migration probability, while no difference between the genotypes in single cell velocity, chemotaxis or marker gene expression could be observed under control conditions. EGF promoted proliferation, collective cell migration, chemokinesis and chemotaxis and leads to a proinflammatory gene expression profile in wildtype but not in knockout VSMC. Comparing the impact of five vasoactive substances (all reported to transactivate EGFR and all leading to an EGFR dependent increase in ERK1/2 phosphorylation), we demonstrate that the importance of EGFR for their action is substance-dependent and most apparent for crowd migration but plays a minor role for gene expression regulation. Copyright © 2016 Elsevier B.V. All rights reserved.

CHASE Survey of Technology Needs

DTIC Science & Technology

2017-03-01

CHASE Survey of Technology Needs Shahed Enamul Quadir ECE Department University of Connecticut Storrs, CT, USA Daniel DiMase Honeywell, Inc...based on a survey conducted in late 2015. Counterfeits and Hardware Trojans have been identified as areas needing continued research and focus... survey of its advisory board and industry professionals to determine the technology needs in the area of IC counterfeits, hardware assurance

Saying the Right Word at the Right Time: Syntagmatic and Paradigmatic Interference in Sentence Production

ERIC Educational Resources Information Center

Dell, Gary S.; Oppenheim, Gary M.; Kittredge, Audrey K.

2008-01-01

Retrieving a word in a sentence requires speakers to overcome syntagmatic, as well as paradigmatic interference. When accessing "cat" in "The cat chased the string", not only are similar competitors such as "dog" and "cap" activated, but also other words in the planned sentence, such as "chase" and "string". We hypothesise that both types of…

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

PubMed Central

Wilson, John W.; Mills, Michael G. L.; Wilson, Rory P.; Peters, Gerrit; Mills, Margaret E. J.; Speakman, John R.; Durant, Sarah M.; Bennett, Nigel C.; Marks, Nikki J.; Scantlebury, Michael

2013-01-01

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s−1 and accelerated up to 7.5 m s−2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival. PMID:24004493

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey.

PubMed

Wilson, John W; Mills, Michael G L; Wilson, Rory P; Peters, Gerrit; Mills, Margaret E J; Speakman, John R; Durant, Sarah M; Bennett, Nigel C; Marks, Nikki J; Scantlebury, Michael

2013-10-23

Predator-prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s(-1) and accelerated up to 7.5 m s(-2) with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5-8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

A open loop guidance architecture for navigationally robust on-orbit docking

NASA Technical Reports Server (NTRS)

Chern, Hung-Sheng

1995-01-01

The development of an open-hop guidance architecture is outlined for autonomous rendezvous and docking (AR&D) missions to determine whether the Global Positioning System (GPS) can be used in place of optical sensors for relative initial position determination of the chase vehicle. Feasible command trajectories for one, two, and three impulse AR&D maneuvers are determined using constrained trajectory optimization. Early AR&D command trajectory results suggest that docking accuracies are most sensitive to vertical position errors at the initial conduction of the chase vehicle. Thus, a feasible command trajectory is based on maximizing the size of the locus of initial vertical positions for which a fixed sequence of impulses will translate the chase vehicle into the target while satisfying docking accuracy requirements. Documented accuracies are used to determine whether relative GPS can achieve the vertical position error requirements of the impulsive command trajectories. Preliminary development of a thruster management system for the Cargo Transfer Vehicle (CTV) based on optimal throttle settings is presented to complete the guidance architecture. Results show that a guidance architecture based on a two impulse maneuvers generated the best performance in terms of initial position error and total velocity change for the chase vehicle.

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard T. (Inventor); Book, Michael L. (Inventor); Bryan, Thomas C. (Inventor); Bell, Joseph L. (Inventor)

1996-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprising at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard (Inventor)

1994-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprises at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Turnover of galactans and other cell wall polysaccharides during development of flax plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorshkova, T.A.; Chemikosova, S.B.; Lozovaya, V.V.

1997-06-01

We investigated the synthesis and turnover of cell wall polysaccharides of the flax (Linum usitatissimum L.) plant during development of the phloem fibers. One-month-old flax plants were exposed to a 40-min pulse with {sup 14}CO{sub 2} followed by 8-h, 24-h, and 1-month periods of chase with ambient CO{sub 2}, and radioactivity in cell wall sugars was determined in various plant parts. The relative radioactivity of glucose in noncellulosic polysaccharides was the highest compared with all other cell wall sugars immediately after the pulse and decreased substantially during the subsequent chase. The relative radioactivities of the other cell wall sugars changedmore » with differing rates, indicating turnover of specific polysaccharides. Notably, after 1 month of chase there was a marked decrease in the proportional mass and total radioactivity in cell wall galactose, indicating a long-term turnover of the galactans enriched in the fiber-containing tissues. The ratio of radiolabeled xylose to arabinose also increased during the chase, indicating a turnover of arabinose-containing polymers and interconversion to xylose. The pattern of label redistribution differed between organs, indicating that the cell wall turnover processes are tissue- and cell-specific.« less

Wound Healing Activity of Extracts and Formulations of Aloe vera, Henna, Adiantum capillus-veneris, and Myrrh on Mouse Dermal Fibroblast Cells.

PubMed

Negahdari, Samira; Galehdari, Hamid; Kesmati, Mahnaz; Rezaie, Anahita; Shariati, Gholamreza

2017-01-01

Among the most important factors in wound healing pathways are transforming growth factor beta1 and vascular endothelial growth factor. Fibroblasts are the main cell in all phases wound closure. In this study, the extracts of plant materials such as Adiantum capillus-veneris , Commiphora molmol , Aloe vera , and henna and one mixture of them were used to treatment of normal mouse skin fibroblasts. Cytotoxic effects of each extract and their mixture were assessed on mouse skin fibroblasts cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. We performed migration assays to assess migration properties of mouse skin fibroblasts cells in response to the extracts. Changes in the gene expression of the Tgf β1 and Vegf-A genes were monitored by real-time polymerase chain reaction. A. capillus-veneris , C. molmol and henna extract improved the expression of Tgfβ1 gene. All used extracts upregulated the expression of Vegf-A gene and promoted the migration of mouse fibroblast cells in vitro . The present study demonstrated that the mentioned herbal extracts might be effective in wound healing, through the improvement in the migration of fibroblast cells and regulating the gene expression of Tgfβ1 and Vegf-A genes in fibroblast cells treated with extracts.

Identification of Novel Pro-Migratory, Cancer-Associated Genes Using Quantitative, Microscopy-Based Screening

PubMed Central

Naffar-Abu-Amara, Suha; Shay, Tal; Galun, Meirav; Cohen, Naomi; Isakoff, Steven J.; Kam, Zvi; Geiger, Benjamin

2008-01-01

Background Cell migration is a highly complex process, regulated by multiple genes, signaling pathways and external stimuli. To discover genes or pharmacological agents that can modulate the migratory activity of cells, screening strategies that enable the monitoring of diverse migratory parameters in a large number of samples are necessary. Methodology In the present study, we describe the development of a quantitative, high-throughput cell migration assay, based on a modified phagokinetic tracks (PKT) procedure, and apply it for identifying novel pro-migratory genes in a cancer-related gene library. In brief, cells are seeded on fibronectin-coated 96-well plates, covered with a monolayer of carboxylated latex beads. Motile cells clear the beads, located along their migratory paths, forming tracks that are visualized using an automated, transmitted-light screening microscope. The tracks are then segmented and characterized by multi-parametric, morphometric analysis, resolving a variety of morphological and kinetic features. Conclusions In this screen we identified 4 novel genes derived from breast carcinoma related cDNA library, whose over-expression induces major alteration in the migration of the stationary MCF7 cells. This approach can serve for high throughput screening for novel ways to modulate cellular migration in pathological states such as tumor metastasis and invasion. PMID:18213366

Tectonic-1 contributes to the growth and migration of prostate cancer cells in vitro

PubMed Central

WANG, ZHIJUN; GAO, YI; LIU, YUSHAN; CHEN, JIE; WANG, JUNKAI; GAN, SISHUN; XU, DANFENG; CUI, XINGANG

2015-01-01

Tectonic-1 (TCTN1) is an upstream gene involved in embryonic development. The aim of the present study was to investigate the effect of the TCTN1 gene on the viability and migration of prostate cancer cells. Lentivirus-mediated short hairpin RNA (shRNA) was constructed to silence the expression of TCTN1 in PC-3 and DU145 prostate cancer cells. Cell viability and proliferation were measured using MTT and colony formation assays, and the distribution of cells in phases of the cell cycle was determined using flow cytometry. Cell migration was detected using a Transwell assay. The results demonstrated that TCTN1 was widely expressed in several human prostate cancer cell lines. Knockdown of the TCTN1 gene by RNA interference markedly suppressed cell viability and colony formation in the PC-3 and DU145 cell lines. Cell cycle progression was also arrested by TCTN1 silencing. In addition, knockdown of the TCTN1 gene led to the inhibition of cell migration in the two cell lines. These findings confirmed the direct association between the TCTN1 gene and prostate cancer growth in vitro. With further understanding and clinical investigation, this indicates the potential for future development of a novel marker for early detection and gene therapy for prostate cancer. PMID:26310786

Analysis of nuclear accumulation of influenza NP antigen in von Magnus virus-infected cells.

PubMed

Maeno, K; Aoki, H; Hamaguchi, M; Iinuma, M; Nagai, Y; Matsumoto, T; Takeura, S; Shibata, M

1981-01-01

When 1-5C-4 cells were infected with von Magnus virus derived from influenza A/RI/5+ virus by successive undiluted passages in chick embryos, virus-specific proteins were synthesized but production of infectious virus was inhibited. In these cells the synthesis of viral RNA was suppressed and the nucleoprotein (NP) antigen was found predominantly in the nucleus in contrast to standard virus-infected cells in which the antigen was distributed throughout the whole cell. The intracellular location and migration of NP were determined by isotope labeling and sucrose gradient centrifugation of subcellular fractions. In standard virus-infected cell NP polypeptide was present predominantly in the cytoplasm in the form of viral ribonucleoprotein (RNP) and intranuclear RNP was detected in reduced amounts. In contrast, in von Magnus virus-infected cells NP polypeptide was present predominantly in the nucleus in a nonassembled, soluble from and the amount of cytoplasmic RNP was considerably reduced. After short-pulse labeling NP was detected exclusively in the cytoplasm in a soluble form and after a chase a large proportion of such soluble NP was seen in the nucleus. It is suggested that a large proportion of the NP synthesized in von Magnus virus-infected cells in not assembled into cytoplasmic RNP because of the lack of available RNA and the NP migrated into the nucleus and remained there.

History Run Wild: The Alternate World of Joan Aiken's "The Wolves of Willoughby Chase" Series

ERIC Educational Resources Information Center

Dams, Isobel

2005-01-01

This article examines the historical fantasy world created by Joan Aiken in the eleven volumes of her "Wolves of Willoughby Chase" series. In particular it looks at her subversion of historical reality by the creation of an alternative yet recognisable representation of our own world, using a wide range of events, and the remoulding of aspects of…

The Effect of Laziness in Group Chase and Escape

NASA Astrophysics Data System (ADS)

Masuko, Makoto; Hiraoka, Takayuki; Ito, Nobuyasu; Shimada, Takashi

2017-08-01

The effect of laziness in the group chase and escape problem is studied using a simple model. Laziness is introduced as random walks in two ways: uniformly and in a "division of labor" way. It is shown that while the former is always ineffective, the latter can improve the efficiency of catching, through the formation of pincer attack configuration by diligent and lazy chasers.

The identification of N-linked oligosaccharides on the human CR2/Epstein-Barr virus receptor and their function in receptor metabolism, plasma membrane expression, and ligand binding.

PubMed

Weis, J J; Fearon, D T

1985-11-05

Human complement receptor type 2 (CR2) was biosynthetically labeled by pulsing SB B lymphoblastoid cells for 25 min with [35S]methionine followed by chase in the presence of excess unlabeled methionine. An Mr 134,000 polypeptide represented the major form of the receptor at the end of the pulse period, and within 1 h of chase this disappeared coincident with the appearance of the Mr 145,000 mature form of CR2. Precursor, but not mature, CR2 was sensitive to endoglycosidase H, indicating that maturation of CR2 represented processing of N-linked high mannose oligosaccharides to the complex type. The processing of precursor CR2 was impaired by monensin. In the presence of tunicamycin an Mr 111,000 form of CR2 was synthesized by SB cells, and this did not chase into either precursor or mature CR2. This Mr 111,000 form of CR2 did not incorporate [3H]glucosamine, indicating that it lacked both N- and O-linked oligosaccharide. The half-lives of mature CR2 and nonglycosylated CR2 pulse-labeled in the presence of tunicamycin were 13.8 and 2.8 h, respectively; the turnover rate of B1, a membrane protein normally lacking carbohydrate, was unaffected by the presence of the antibiotic. The percentage of pulse-labeled, nonglycosylated CR2 that was expressed at the cell surface after 1 h of chase in the presence of tunicamycin was 30%, identical to that of mature CR2 in cells chased in the absence of the antibiotic. However, after 6 h of chase there was no additional net accumulation of nonglycosylated CR2 at the plasma membrane, while the proportion of pulse-labeled mature CR2 at this site had risen to 81%. Therefore, N-linked oligosaccharides are essential for the stability of CR2 and have some role in its plasma membrane expression. In contrast, the observation that all three forms of CR2 bound to Sepharose C3 indicates that oligosaccharides are not necessary for the interaction between CR2 and its complement ligand.

Overexpression of HER2 signaling to WAVE2-Arp2/3 complex activates MMP-independent migration in breast cancer.

PubMed

Yokotsuka, Mayumi; Iwaya, Keiichi; Saito, Tsuyoshi; Pandiella, Atanasio; Tsuboi, Ryoji; Kohno, Norio; Matsubara, Osamu; Mukai, Kiyoshi

2011-04-01

The final signal for triggering the formation of lamellipodia that initiate directional migration of mammalian cells is binding of the Wiskott-Aldrich syndrome (WASP)/WASP family verproline-homologous protein 2 (WAVE2) to the actin-related protein 2 and 3 (Arp2/3) complex. This WAVE2-Arp2/3 signal is suggested to be enhanced in some breast cancers, facilitating invasion, and/or metastasis. Here, we demonstrated one cause of the enhanced signal using four breast cancer cell lines (SKBR3, AU565, MCF7, and MDA-MB-231). The WAVE2-Arp2/3 signal was estimated semi-quantitatively by counting the number of lamellipodia expressing both WAVE2 and Arp2 using high-power confocal laser microscopy. Higher expression of the WAVE2-Arp2/3 signal was detected in SKBR3 and AU565, which have HER2 gene amplification, than in the other two cell lines that lack HER2 gene amplification. Trastuzumab suppressed both the formation of lamellipodia and migration in a Boyden chamber experiment in SKBR3 and AU565. When the HER2 gene was transfected into MCF7, the number of both lamellipodia and migrated cells was increased. This enhancement of migration did not occur in the presence of extracellular matrix, and zymographic analysis showed no clear difference between HER2 gene-transfected cells and MCF7 cells. Immunohistochemical analysis of 115 cases of breast cancer revealed that coexpression of WAVE2 and Arp2 was significantly correlated with HER2-overexpression (P < 0.0001). These data indicate that an abnormal signal resulting from HER2 gene amplification activates lamellipodia formation in breast cancer cells, which initiates their metalloproteinase-independent migration.

Detecting the existence of gene flow between Spanish and North African goats through a coalescent approach.

PubMed

Martínez, Amparo; Manunza, Arianna; Delgado, Juan Vicente; Landi, Vincenzo; Adebambo, Ayotunde; Ismaila, Muritala; Capote, Juan; El Ouni, Mabrouk; Elbeltagy, Ahmed; Abushady, Asmaa M; Galal, Salah; Ferrando, Ainhoa; Gómez, Mariano; Pons, Agueda; Badaoui, Bouabid; Jordana, Jordi; Vidal, Oriol; Amills, Marcel

2016-12-14

Human-driven migrations are one of the main processes shaping the genetic diversity and population structure of domestic species. However, their magnitude and direction have been rarely analysed in a statistical framework. We aimed to estimate the impact of migration on the population structure of Spanish and African goats. To achieve this goal, we analysed a dataset of 1,472 individuals typed with 23 microsatellites. Population structure of African and Spanish goats was moderate (mean F ST  = 0.07), with the exception of the Canarian and South African breeds that displayed a significant differentiation when compared to goats from North Africa and Nigeria. Measurement of gene flow with Migrate-n and IMa coalescent genealogy samplers supported the existence of a bidirectional gene flow between African and Spanish goats. Moreover, IMa estimates of the effective number of migrants were remarkably lower than those calculated with Migrate-n and classical approaches. Such discrepancies suggest that recent divergence, rather than extensive gene flow, is the main cause of the weak population structure observed in caprine breeds.

Detecting the existence of gene flow between Spanish and North African goats through a coalescent approach

PubMed Central

Martínez, Amparo; Manunza, Arianna; Delgado, Juan Vicente; Landi, Vincenzo; Adebambo, Ayotunde; Ismaila, Muritala; Capote, Juan; El Ouni, Mabrouk; Elbeltagy, Ahmed; Abushady, Asmaa M.; Galal, Salah; Ferrando, Ainhoa; Gómez, Mariano; Pons, Agueda; Badaoui, Bouabid; Jordana, Jordi; Vidal, Oriol; Amills, Marcel

2016-01-01

Human-driven migrations are one of the main processes shaping the genetic diversity and population structure of domestic species. However, their magnitude and direction have been rarely analysed in a statistical framework. We aimed to estimate the impact of migration on the population structure of Spanish and African goats. To achieve this goal, we analysed a dataset of 1,472 individuals typed with 23 microsatellites. Population structure of African and Spanish goats was moderate (mean FST = 0.07), with the exception of the Canarian and South African breeds that displayed a significant differentiation when compared to goats from North Africa and Nigeria. Measurement of gene flow with Migrate-n and IMa coalescent genealogy samplers supported the existence of a bidirectional gene flow between African and Spanish goats. Moreover, IMa estimates of the effective number of migrants were remarkably lower than those calculated with Migrate-n and classical approaches. Such discrepancies suggest that recent divergence, rather than extensive gene flow, is the main cause of the weak population structure observed in caprine breeds. PMID:27966592

A Continuous Method for Gene Flow

PubMed Central

Palczewski, Michal; Beerli, Peter

2013-01-01

Most modern population genetics inference methods are based on the coalescence framework. Methods that allow estimating parameters of structured populations commonly insert migration events into the genealogies. For these methods the calculation of the coalescence probability density of a genealogy requires a product over all time periods between events. Data sets that contain populations with high rates of gene flow among them require an enormous number of calculations. A new method, transition probability-structured coalescence (TPSC), replaces the discrete migration events with probability statements. Because the speed of calculation is independent of the amount of gene flow, this method allows calculating the coalescence densities efficiently. The current implementation of TPSC uses an approximation simplifying the interaction among lineages. Simulations and coverage comparisons of TPSC vs. MIGRATE show that TPSC allows estimation of high migration rates more precisely, but because of the approximation the estimation of low migration rates is biased. The implementation of TPSC into programs that calculate quantities on phylogenetic tree structures is straightforward, so the TPSC approach will facilitate more general inferences in many computer programs. PMID:23666937

Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata.

PubMed

Bradshaw, Brian; Thompson, Kerry; Frank, Uri

2015-04-17

Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1(+) stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology.

Patterning C. elegans: homeotic cluster genes, cell fates and cell migrations.

PubMed

Salser, S J; Kenyon, C

1994-05-01

Despite its simple body form, the nematode C. elegans expresses homeotic cluster genes similar to those of insects and vertebrates in the patterning of many cell types and tissues along the anteroposterior axis. In the ventral nerve cord, these genes program spatial patterns of cell death, fusion, division and neurotransmitter production; in migrating cells they regulate the direction and extent of movement. Nematode development permits an analysis at the cellular level of how homeotic cluster genes interact to specify cell fates, and how cell behavior can be regulated to assemble an organism.

Adeno-associated virus rep protein synthesis during productive infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Redemann, B.E.; Mendelson, E.; Carter, B.J.

1989-02-01

Adeno-associated virus (AAV) Rep proteins mediate viral DNA replication and can regulate expression from AAV genes. The authors studied the kinetics of synthesis of the four Rep proteins, Rep78, Rep68, Rep52, and Rep40, during infection of human 293 or KB cells with AAV and helper adenovirus by in vivo labeling with (/sup 35/S)methionine, immunoprecipitation, and immunoblotting analyses. Rep78 and Rep52 were readily detected concomitantly with detection of viral monomer duplex DNA replicating about 10 to 12 h after infection, and Rep68 and Rep40 were detected 2 h later. Rep78 and Rep52 were more abundant than Rep68 and Rep40 owing tomore » a higher synthesis rate throughout the infectious cycle. In some experiments, very low levels of Rep78 could be detected as early as 4 h after infection. The synthesis rates of Rep proteins were maximal between 14 and 24 h and then decreased later after infection. Isotopic pulse-chase experiments showed that each of the Rep proteins was synthesized independently and was stable for at least 15 h. A slower-migrating, modified form of Rep78 was identified late after infection. AAV capsid protein synthesis was detected at 10 to 12 h after infection and also exhibited synthesis kinetics similar to those of the Rep proteins. AAV DNA replication showed at least two clearly defined stages. Bulk duplex replicating DNA accumulation began around 10 to 12 h and reached a maximum level at about 20 h when Rep and capsid protein synthesis was maximal. Progeny single-stranded DNA accumulation began about 12 to 13 h, but most of this DNA accumulated after 24 h when Rep and capsid protein synthesis had decreased.« less

Effect of body temperature on chondroitinase ABC's ability to cleave chondroitin sulfate glycosaminoglycans.

PubMed

Tester, Nicole J; Plaas, Anna H; Howland, Dena R

2007-04-01

Chondroitinase ABC (Ch'ase ABC) is a bacterial lyase that degrades chondroitin sulfate (CS), dermatan sulfate, and hyaluronan glycosaminoglycans (GAGs). This enzyme has received significant attention as a potential therapy for promoting central nervous system and peripheral nervous system repair based on its degradation of CS GAGs. Determination of the stability of Ch'ase ABC activity at temperatures equivalent to normal (37 degrees C) and elevated (39 degrees C) body temperatures is important for optimizing its clinical usage. We report here data obtained from examining enzymatic activity at these temperatures across nine lots of commercially available protease-free Ch'ase ABC. CS GAG degrading activity was assayed by using 1) immunohistochemical detection of unsaturated disaccharide stubs generated by digestion of proteoglycans in tissue sections and 2) fluorophore-assisted carbohydrate electrophoresis (FACE) and/or high-performance liquid chromatography (HPLC) to separate and quantify unsaturated disaccharide digestion products. Our results indicate that there is a significant effect of lot and time on enzymatic thermostability. Average enzymatic activity is significantly decreased at 1 and 3 days at 39 degrees C and 37 degrees C, respectively. Furthermore, the average activity seen after 1 day was significantly different between the two temperatures. Addition of bovine serum albumin as a stabilizer significantly preserved enzymatic activity at 1 day, but not 3 days, at 39 degrees C. These results show that the CS GAG degrading activity of Ch'ase ABC is significantly decreased with incubation at body temperature over time and that all lots do not show equal thermostability. These findings are important for the design and interpretation of experimental and potential clinical studies involving Ch'ase ABC. (c) 2007 Wiley-Liss, Inc.

Following isotopes in pulse-chase enriched aspen seedlings

NASA Astrophysics Data System (ADS)

Norris, C. E.; Wasylishen, R. E.; Landhäusser, S.; Quideau, S. A.

2011-12-01

One method to quantitatively trace biogeochemical fluxes through ecosystems, such as organic matter decomposition, is to use plant material enriched with stable isotopes. However, as plant macromolecules are known to vary in their rate of formation and decomposition, both the enrichment levels and the location of enrichment within the plant material should be characterized prior to decomposition and tracing studies. Aspen (Populus tremuloides Michx.) is a common tree species with a diverse organic matter chemical structure found in the western Canadian boreal forest. This study used a multi pulse and multi chase enrichment of stable isotopes (15N and 13C) on aspen seedlings to determine the seedling enrichment, isotope movement among plant tissues and translocation of isotopes within plant macromolecules e.g., carbohydrates and lignin. As expected, all tissues experienced increased enrichment with multiple pulses. An initial enrichment with 13C was observed in the leaves followed by translocation to the stems and roots while the 15N moved upward from the roots to leaves. The macromolecular chemistry of the organic carbon was further characterized using 13C solid state nuclear magnetic resonance spectroscopy. After the initial two hour chase period enrichment of the O-alkyl type (carbohydrate) carbon within the leaves was identified, followed by redistribution to more complex carbon compounds after the one week chase period. Root and stem tissues did not show the same pattern. Rather, changes in 13C enrichment were observed in shifting ethyl and methyl alkyl (lipid) carbon peak intensities for the stem samples while roots did not preferentially allocate 13C to a specific macromolecule. These results confirm that stable isotope enrichment of plants was non-uniform across macromolecules and tissue types. Enrichment of aspen seedlings was therefore dependant on the pulse-chase sequence used.

Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

PubMed Central

Lafyatis, Robert; Burkly, Linda C.

2017-01-01

Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. PMID:28662216

Normal radial migration and lamination are maintained in dyslexia-susceptibility candidate gene homolog Kiaa0319 knockout mice.

PubMed

Martinez-Garay, Isabel; Guidi, Luiz G; Holloway, Zoe G; Bailey, Melissa A G; Lyngholm, Daniel; Schneider, Tomasz; Donnison, Timothy; Butt, Simon J B; Monaco, Anthony P; Molnár, Zoltán; Velayos-Baeza, Antonio

2017-04-01

Developmental dyslexia is a common disorder with a strong genetic component, but the underlying molecular mechanisms are still unknown. Several candidate dyslexia-susceptibility genes, including KIAA0319, DYX1C1, and DCDC2, have been identified in humans. RNA interference experiments targeting these genes in rat embryos have shown impairments in neuronal migration, suggesting that defects in radial cortical migration could be involved in the disease mechanism of dyslexia. Here we present the first characterisation of a Kiaa0319 knockout mouse line. Animals lacking KIAA0319 protein do not show anatomical abnormalities in any of the layered structures of the brain. Neurogenesis and radial migration of cortical projection neurons are not altered, and the intrinsic electrophysiological properties of Kiaa0319-deficient neurons do not differ from those of wild-type neurons. Kiaa0319 overexpression in cortex delays radial migration, but does not affect final neuronal position. However, knockout animals show subtle differences suggesting possible alterations in anxiety-related behaviour and in sensorimotor gating. Our results do not reveal a migration disorder in the mouse model, adding to the body of evidence available for Dcdc2 and Dyx1c1 that, unlike in the rat in utero knockdown models, the dyslexia-susceptibility candidate mouse homolog genes do not play an evident role in neuronal migration. However, KIAA0319 protein expression seems to be restricted to the brain, not only in early developmental stages but also in adult mice, indicative of a role of this protein in brain function. The constitutive and conditional knockout lines reported here will be useful tools for further functional analyses of Kiaa0319.

Cheetah do not abandon hunts because they overheat.

PubMed

Hetem, Robyn S; Mitchell, Duncan; de Witt, Brenda A; Fick, Linda G; Meyer, Leith C R; Maloney, Shane K; Fuller, Andrea

2013-10-23

Hunting cheetah reportedly store metabolic heat during the chase and abandon chases because they overheat. Using biologging to remotely measure the body temperature (every minute) and locomotor activity (every 5 min) of four free-living cheetah, hunting spontaneously, we found that cheetah abandoned hunts, but not because they overheated. Body temperature averaged 38.4°C when the chase was terminated. Storage of metabolic heat did not compromise hunts. The increase in body temperature following a successful hunt was double that of an unsuccessful hunt (1.3°C ± 0.2°C versus 0.5°C ± 0.1°C), even though the level of activity during the hunts was similar. We propose that the increase in body temperature following a successful hunt is a stress hyperthermia, rather than an exercise-induced hyperthermia.

Cheetah do not abandon hunts because they overheat

PubMed Central

Hetem, Robyn S.; Mitchell, Duncan; de Witt, Brenda A.; Fick, Linda G.; Meyer, Leith C. R.; Maloney, Shane K.; Fuller, Andrea

2013-01-01

Hunting cheetah reportedly store metabolic heat during the chase and abandon chases because they overheat. Using biologging to remotely measure the body temperature (every minute) and locomotor activity (every 5 min) of four free-living cheetah, hunting spontaneously, we found that cheetah abandoned hunts, but not because they overheated. Body temperature averaged 38.4°C when the chase was terminated. Storage of metabolic heat did not compromise hunts. The increase in body temperature following a successful hunt was double that of an unsuccessful hunt (1.3°C ± 0.2°C versus 0.5°C ± 0.1°C), even though the level of activity during the hunts was similar. We propose that the increase in body temperature following a successful hunt is a stress hyperthermia, rather than an exercise-induced hyperthermia. PMID:23883578

Douglas Lowy and Nirali Shah discuss advancements in cancer treatment at the second annual Chasing Cancer Summit | Center for Cancer Research

Cancer.gov

On Monday, September 18, 2017, the second annual Chasing Cancer Summit was held at the Washington Post headquarters in downtown Washington, D.C. The live event brought together a group of experts, including CCR’s Douglas Lowy, M.D., and Nirali Shah, M.D., for discussions on the latest developments in cancer detection and treatment.  Read more...

The influence of complex and threatening environments in early life on brain size and behaviour.

PubMed

DePasquale, C; Neuberger, T; Hirrlinger, A M; Braithwaite, V A

2016-01-27

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. © 2016 The Authors.

The influence of complex and threatening environments in early life on brain size and behaviour

PubMed Central

Neuberger, T.; Hirrlinger, A. M.; Braithwaite, V. A.

2016-01-01

The ways in which challenging environments during development shape the brain and behaviour are increasingly being addressed. To date, studies typically consider only single variables, but the real world is more complex. Many factors simultaneously affect the brain and behaviour, and whether these work independently or interact remains untested. To address this, zebrafish (Danio rerio) were reared in a two-by-two design in housing that varied in structural complexity and/or exposure to a stressor. Fish experiencing both complexity (enrichment objects changed over time) and mild stress (daily net chasing) exhibited enhanced learning and were less anxious when tested as juveniles (between 77 and 90 days). Adults tested (aged 1 year) were also less anxious even though fish were kept in standard housing after three months of age (i.e. no chasing or enrichment). Volumetric measures of the brain using magnetic resonance imaging (MRI) showed that complexity alone generated fish with a larger brain, but this increase in size was not seen in fish that experienced both complexity and chasing, or chasing alone. The results highlight the importance of looking at multiple variables simultaneously, and reveal differential effects of complexity and stressful experiences during development of the brain and behaviour. PMID:26817780

PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells

PubMed Central

Jilg, Cordula A.; Ketscher, Anett; Metzger, Eric; Hummel, Barbara; Willmann, Dominica; Rüsseler, Vanessa; Drendel, Vanessa; Imhof, Axel; Jung, Manfred; Franz, Henriette; Hölz, Stefanie; Krönig, Malte; Müller, Judith M.; Schüle, Roland

2014-01-01

The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation. Transcriptome and interactome analyses uncover that PRK1 regulates expression of migration-relevant genes by interacting with the scaffold protein sperm-associated antigen 9 (SPAG9/JIP4). SPAG9 and PRK1 colocalize in human cancer tissue and are required for p38-phosphorylation and cell migration. Accordingly, depletion of either ETS domain-containing protein Elk-1 (ELK1), an effector of p38-signalling or p38 depletion hinders cell migration and changes expression of migration-relevant genes as observed upon PRK1-depletion. Importantly, a PRK1 inhibitor prevents metastases in mice, showing that the PRK1-pathway is a promising target to hamper prostate cancer metastases in vivo. Statement of significance Here we describe a novel mechanism controlling the metastatic behavior of PCa cells and identify PRK1 as a promising therapeutic target to treat androgen-independent metastatic prostate cancer. PMID:25504435

Candidate genes have sex-specific effects on timing of spring migration and moult speed in a long-distance migratory bird.

PubMed

Bazzi, Gaia; Podofillini, Stefano; Gatti, Emanuele; Gianfranceschi, Luca; Cecere, Jacopo G; Spina, Fernando; Saino, Nicola; Rubolini, Diego

2017-10-01

The timing of major life-history events, such as migration and moult, is set by endogenous circadian and circannual clocks, that have been well characterized at the molecular level. Conversely, the genetic sources of variation in phenology and in other behavioral traits have been sparsely addressed. It has been proposed that inter-individual variability in the timing of seasonal events may arise from allelic polymorphism at phenological candidate genes involved in the signaling cascade of the endogenous clocks. In this study of a long-distance migratory passerine bird, the willow warbler Phylloscopus trochilus , we investigated whether allelic variation at 5 polymorphic loci of 4 candidate genes ( Adcyap1 , Clock , Creb1 , and Npas2 ), predicted 2 major components of the annual schedule, namely timing of spring migration across the central Mediterranean sea and moult speed, the latter gauged from ptilochronological analyses of tail feathers moulted in the African winter quarters. We identified a novel Clock gene locus ( Clock region 3) showing polyQ polymorphism, which was however not significantly associated with any phenotypic trait. Npas2 allele size predicted male (but not female) spring migration date, with males bearing longer alleles migrating significantly earlier than those bearing shorter alleles. Creb1 allele size significantly predicted male (but not female) moult speed, longer alleles being associated with faster moult. All other genotype-phenotype associations were statistically non-significant. These findings provide new evidence for a role of candidate genes in modulating the phenology of different circannual activities in long-distance migratory birds, and for the occurrence of sex-specific candidate gene effects.

The Pseudomonas aeruginosa quorum sensing signal molecule N-(3-oxododecanoyl) homoserine lactone enhances keratinocyte migration and induces Mmp13 gene expression in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paes, Camila, E-mail: camilaquinetti@gmail.com; Nakagami, Gojiro, E-mail: gojiron-tky@umin.ac.jp; Minematsu, Takeo, E-mail: tminematsu-tky@umin.ac.jp

2012-10-19

Highlights: Black-Right-Pointing-Pointer An evidence of the positive effect of AHL on epithelialization process is provided. Black-Right-Pointing-Pointer AHL enhances keratinocyte's ability to migrate in an in vitro scratch wound model. Black-Right-Pointing-Pointer AHL induces the expression of Mmp13. Black-Right-Pointing-Pointer Topical application of AHL represents a possible strategy to treat chronic wounds. -- Abstract: Re-epithelialization is an essential step of wound healing involving three overlapping keratinocyte functions: migration, proliferation and differentiation. While quorum sensing (QS) is a cell density-dependent signaling system that enables bacteria to regulate the expression of certain genes, the QS molecule N-(3-oxododecanoyl) homoserine lactone (AHL) exerts effects also on mammalianmore » cells in a process called inter-kingdom signaling. Recent studies have shown that AHL improves epithelialization in in vivo wound healing models but detailed understanding of the molecular and cellular mechanisms are needed. The present study focused on the AHL as a candidate reagent to improve wound healing through direct modulation of keratinocyte's activity in the re-epithelialization process. Results indicated that AHL enhances the keratinocyte's ability to migrate in an in vitro scratch wound healing model probably due to the high Mmp13 gene expression analysis after AHL treatment that was revealed by real-time RT-PCR. Inhibition of activator protein 1 (AP-1) signaling pathway completely prevented the migration of keratinocytes, and also resulted in a diminished Mmp13 gene expression, suggesting that AP-1 might be essential in the AHL-induced migration. Taken together, these results imply that AHL is a promising candidate molecule to improve re-epithelialization through the induction of migration of keratinocytes. Further investigation is needed to clarify the mechanism of action and molecular pathway of AHL on the keratinocyte migration process.« less

Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway

PubMed Central

Xie, Weiwei; Zheng, Rongliang; Gan, Yu; Chang, Jianhua

2016-01-01

The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors. PMID:27494860

Apatinib inhibits cellular invasion and migration by fusion kinase KIF5B-RET via suppressing RET/Src signaling pathway.

PubMed

Lin, Chen; Wang, Shanshan; Xie, Weiwei; Zheng, Rongliang; Gan, Yu; Chang, Jianhua

2016-09-13

The Rearranged during transfection (RET) fusion gene is a newly identified oncogenic mutation in non-small cell lung cancer (NSCLC). The aim of this study is to explore the biological functions of the gene in tumorigenesis and metastasis in RET gene fusion-driven preclinical models. We also investigate the anti-tumor activity of Apatinib, a potent inhibitor of VEGFR-2, PDGFR-β, c-Src and RET, in RET-rearranged lung adenocarcinoma, together with the mechanisms underlying. Our results suggested that KIF5B-RET fusion gene promoted cell invasion and migration, which were probably mediated through Src signaling pathway. Apatinib exerted its anti-cancer effect not only via cytotoxicity, but also via inhibition of migration and invasion by suppressing RET/Src signaling pathway, supporting a potential role for Apatinib in the treatment of KIF5B-RET driven tumors.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Zhong Xin; Sun, Cong Cong; Wenzhou People's Hospital, Wenzhou, Zhejiang

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Westernmore » blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

Synthesis of Globulins in Maize Embryos 1

PubMed Central

Kriz, Alan L.; Schwartz, Drew

1986-01-01

The two major components of the globulin fraction in Zea mays embryos are specified by the Prot gene. Pulse-chase analysis of protein synthesis in cultured, immature embryos indicates that the smaller Prot-specific polypeptide, PROT, is derived from the larger polypeptide, PROT'. These experiments also demonstrate that PROT' is derived from a short-lived precursor polypeptide, prePROT'. The primary Prot-specific translation product, as detected by in vitro translation of immature embryo RNA, is of a lower apparent molecular weight than pre-PROT', suggesting the involvement of co- and/or post-translational modification in the production of prePROT'. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:16665136

Genome engineering for microbial natural product discovery.

PubMed

Choi, Si-Sun; Katsuyama, Yohei; Bai, Linquan; Deng, Zixin; Ohnishi, Yasuo; Kim, Eung-Soo

2018-03-03

The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transcriptional and post-transcriptional regulation of the ionizing radiation response by ATM and p53

PubMed Central

Venkata Narayanan, Ishwarya; Paulsen, Michelle T.; Bedi, Karan; Berg, Nathan; Ljungman, Emily A.; Francia, Sofia; Veloso, Artur; Magnuson, Brian; di Fagagna, Fabrizio d’Adda; Wilson, Thomas E.; Ljungman, Mats

2017-01-01

In response to ionizing radiation (IR), cells activate a DNA damage response (DDR) pathway to re-program gene expression. Previous studies using total cellular RNA analyses have shown that the stress kinase ATM and the transcription factor p53 are integral components required for induction of IR-induced gene expression. These studies did not distinguish between changes in RNA synthesis and RNA turnover and did not address the role of enhancer elements in DDR-mediated transcriptional regulation. To determine the contribution of synthesis and degradation of RNA and monitor the activity of enhancer elements following exposure to IR, we used the recently developed Bru-seq, BruChase-seq and BruUV-seq techniques. Our results show that ATM and p53 regulate both RNA synthesis and stability as well as enhancer element activity following exposure to IR. Importantly, many genes in the p53-signaling pathway were coordinately up-regulated by both increased synthesis and RNA stability while down-regulated genes were suppressed either by reduced synthesis or stability. Our study is the first of its kind that independently assessed the effects of ionizing radiation on transcription and post-transcriptional regulation in normal human cells. PMID:28256581

Role of the p55-gamma subunit of PI3K in ALK-induced cell migration: RNAi-based selection of cell migration regulators.

PubMed

Seo, Minchul; Kim, Jong-Heon; Suk, Kyoungho

2017-05-04

Recently, unbiased functional genetic selection identified novel cell migration-regulating genes. This RNAi-based functional selection was performed using 63,996 pooled lentiviral shRNAs targeting 21,332 mouse genes. After five rounds of selection using cells with accelerated or impaired migration, shRNAs were retrieved and identified by half-hairpin barcode sequencing using cells with the selected phenotypes. This selection process led to the identification of 29 novel cell migration regulators. One of these candidates, anaplastic lymphoma kinase (ALK), was further investigated. Subsequent studies revealed that ALK promoted cell migration through the PI3K-AKT pathway via the p55γ regulatory subunit of PI3K, rather than more commonly used p85 subunit. Western blot and immunohistochemistry studies using mouse brain tissues revealed similar temporal expression patterns of ALK, phospho-p55γ, and phospho-AKT during different stages of development. These data support an important role for the p55γ subunit of PI3K in ALK-induced cell migration during brain development.

Stanniocalcin-1 regulates re-epithelialization in human keratinocytes.

PubMed

Yeung, Bonnie H Y; Wong, Chris K C

2011-01-01

Stanniocalcin-1 (STC1), a glycoprotein hormone, is believed to be involved in various biological processes such as inflammation, oxidative responses and cell migration. Riding on these emerging evidences, we hypothesized that STC1 may participate in the re-epithelialization during wound healing. Re-epithelialization is a critical step that involves keratinocyte lamellipodia (e-lam) formation, followed by cell migration. In this study, staurosporine (STS) treatment induced human keratinocyte (HaCaT) e-lam formation on fibronectin matrix and migration via the activation of focal adhesion kinase (FAK), the surge of intracellular calcium level [Ca²⁺]i and the inactivation of Akt. In accompanied with these migratory features, a time- and dose-dependent increase in STC1 expression was detected. STC1 gene expression was found not the downstream target of FAK-signaling as illustrated by FAK inhibition using PF573228. The reduction of [Ca²⁺]i by BAPTA/AM blocked the STS-mediated keratinocyte migration and STC1 gene expression. Alternatively the increase of [Ca²⁺]i by ionomycin exerted promotional effect on STS-induced STC1 gene expression. The inhibition of Akt by SH6 and GSK3β by lithium chloride (LiCl) could respectively induce and inhibit the STS-mediated e-lam formation, cell migration and STC1 gene expression. The STS-mediated e-lam formation and cell migration were notably hindered or induced respectively by STC1 knockdown or overexpression. This notion was further supported by the scratched wound assay. Collectively the findings provide the first evidence that STC1 promotes re-epithelialization in wound healing.

Fox Chase Cancer Center's Genitourinary Division: a national resource for research, innovation and patient care.

PubMed

Uzzo, Robert G; Horwitz, Eric M; Plimack, Elizabeth R

2016-04-01

Founded in 1904, Fox Chase Cancer Center remains committed to its mission. It is one of 41 centers in the country designated as a Comprehensive Cancer Center by the National Cancer Institute, is a founding member of the National Comprehensive Cancer Network, holds the magnet designation for nursing excellence, is one of the first to establish a family cancer risk assessment program, and has achieved national distinction because of the scientific discoveries made there that have advanced clinical care. Two of its researchers have won Nobel prizes. The Genitourinary Division is nationally recognized and viewed as one of the top driving forces behind the growth of Fox Chase due to its commitment to initiating and participating in clinical trials, its prolific contributions to peer-reviewed publications and presentations at scientific meetings, its innovations in therapies and treatment strategies, and its commitment to bringing cutting-edge therapies to patients.

A Factor Increasing Venous Contamination on Bolus Chase Three-dimensional Magnetic Resonance Imaging: Charcot Neuroarthropathy.

PubMed

Çildağ, Mehmet B; Ertuğrul, Mustafa B; Köseoğlu, Ömer Fk; Armstrong, David G

2018-01-01

The study aimed to evaluate the ratio of venous contamination in diabetic cases without foot lesion, with foot lesion and with Charcot neuroarthropathy (CN). Bolus-chase three-dimensional magnetic resonance (MR) of 396 extremities of patients with diabetes mellitus was analyzed, retrospectively. Extremities were divided into three groups as follows: diabetic patients without foot ulcer or Charcot arthropathy (Group A), patients with diabetic foot ulcers (Group B) and patients with CN accompanying diabetic foot ulcers (Group C). Furthermore, amount of venous contamination classified as no venous contamination, mild venous contamination, and severe venous contamination. The relationship between venous contamination and extremity groups was investigated. Severe venous contamination was seen in Group A, Group B, and Group C, 5.6%, 15.2%, and 34.1%, respectively. Statistically significant difference was seen between groups with regard to venous contamination. Venous contamination following bolus chase MR was higher in patients with CN.

STS-4 landing at Edwards Air Foce Base, California

NASA Technical Reports Server (NTRS)

1982-01-01

STS-4 landing at Edwards Air Foce Base, California. Actor Roy Rogers with Astronauts Jerry L. Ross, left, and Guy S. Gardner at Edwards for the STS-4 landing on July 1, 1982. Also present (behind Gardner at extreme right) was former Astronaut Edwin E. Aldrin, Jr. (33226); President Ronald Reagan and First Lady Nancy Reagan meet Astronauts Thomas K. Mattingly, II., right, and Henry W. Hartsfield, Jr., after the landing of the Columbia at Edwards (33227,33230); Space Shuttle Columbia, followed by two T-38 chase planes, touches down on Edwards Air Force Base's Runway 22 to complete mission. In this view, one chase plane appears to be directly above and behind the Columbia, whose nose wheels have not yet touched ground. The other plane appears to be further up front (33228); The rear wheels of the Columbia touch down on the Edwards AFB runway. There are no chase planes in sight in this photo (33229).

Technology Solutions Case Study: Duct in Conditioned Space in a Dropped Ceiling or Fur-down, Gainesville, Florida

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2014-09-01

Forced-air distribution systems (duct systems) typically are installed out of sight for aesthetic reasons, most often in unconditioned areas such as attics or crawlspaces. Any leakage of air to or from the duct system in unconditioned space not only loses energy, but impacts home and equipment durability and indoor air quality. An obvious solution is to bring the duct system into the interior of the house, either by sealing the area where the ducts are installed (attic or crawlspace) or by building an interior cavity or chase above the ceiling plane (raised ceiling or fur-up chase) or below the ceilingmore » plane (dropped ceiling or fur-down) for the duct system. In this project, Building America Partnership for Improved Residential Construction team partnered with Tommy Williams Homes to implement an inexpensive, quick, and effective method of building a fur-down chase.« less

Defective neuronal migration and inhibition of bipolar to multipolar transition of migrating neural cells by Mesoderm-Specific Transcript, Mest, in the developing mouse neocortex.

PubMed

Ji, Liting; Bishayee, Kausik; Sadra, Ali; Choi, Seunghyuk; Choi, Wooyul; Moon, Sungho; Jho, Eek-Hoon; Huh, Sung-Oh

2017-07-04

Brain developmental disorders such as lissencephaly can result from faulty neuronal migration and differentiation during the formation of the mammalian neocortex. The cerebral cortex is a modular structure, where developmentally, newborn neurons are generated as a neuro-epithelial sheet and subsequently differentiate, migrate and organize into their final positions in the cerebral cortical plate via a process involving both tangential and radial migration. The specific role of Mest, an imprinted gene, in neuronal migration has not been previously studied. In this work, we reduced expression of Mest with in utero electroporation of neuronal progenitors in the developing embryonic mouse neocortex. Reduction of Mest levels by shRNA significantly reduced the number of neurons migrating to the cortical plate. Also, Mest-knockdown disrupted the transition of bipolar neurons into multipolar neurons migrating out of the sub-ventricular zone region. The migrating neurons also adopted a more tangential migration pattern upon knockdown of the Mest message, losing their potential to attach to radial glia cells, required for radial migration. The differentiation and migration properties of neurons via Wnt-Akt signaling were affected by Mest changes. In addition, miR-335, encoded in a Mest gene intron, was identified as being responsible for blocking the default tangential migration of the neurons. Our results suggest that Mest and its intron product, miR-335, play important roles in neuronal migration with Mest regulating the morphological transition of primary neurons required in the formation of the mammalian neocortex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Nectin-like molecule 1 inhibits the migration and invasion of U251 glioma cells by regulating the expression of an extracellular matrix protein osteopontin.

PubMed

Yin, Bin; Li, Ke-han; An, Tai; Chen, Tao; Peng, Xiao-zhong

2010-06-01

To investigate the molecular mechanism of nectin-like molecule 1 (NECL1) inhibiting the migration and invasion of U251 glioma cells. We infected U251 glioma cells with adeno-nectin-like molecule 1 (Ad-NECL1) or empty adenovirus (Ad). Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells. DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines. The differential expression of osteopontin (OPN), a gene related to migration and invasion, was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry. The restoration of NECL1 inhibited migration of U251 cells significantly (P<0.05). Altogether 195 genes were found differentially expressed by microarray, in which 175 were up-regulated and 20 down-regulated, including 9 extracellular matrix proteins involved in the migration of cells. Both mRNA and protein expressions of OPN, the most markedly reduced extracellular matrix protein, were found decreased in U251 cells after restoration of NECL1. Immunohistochemical assay also detected an increase of OPN in glioma tissues, related with the progressing of malignant grade. A link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.

Systematic Analysis of the Transcriptional Switch Inducing Migration of Border Cells

PubMed Central

Borghese, Lodovica; Fletcher, Georgina; Mathieu, Juliette; Atzberger, Ann; Eades, William C.; Cagan, Ross L.; Rørth, Pernille

2010-01-01

Summary Cell migration within a natural context is tightly controlled, often by specific transcription factors. However, the switch from stationary to migratory behavior is poorly understood. Border cells perform a spatially and temporally controlled invasive migration during Drosophila oogenesis. Slbo, a C/EBP family transcriptional activator, is required for them to become migratory. We purified wild-type and slbo mutant border cells as well as nonmigratory follicle cells and performed comparative whole-genome expression profiling, followed by functional tests of the contributions of identified targets to migration. About 300 genes were significantly upregulated in border cells, many dependent on Slbo. Among these, the microtubule regulator Stathmin was strongly upregulated and was required for normal migration. Actin cytoskeleton regulators were also induced, including, surprisingly, a large cluster of “muscle-specific” genes. We conclude that Slbo induces multiple cytoskeletal effectors, and that each contributes to the behavioral changes in border cells. PMID:16580994

Retention Kinetics of the 18F-Labeled Sympathetic Nerve PET Tracer LMI1195: Comparison with 11C-Hydroxyephedrine and 123I-MIBG.

PubMed

Werner, Rudolf A; Rischpler, Christoph; Onthank, David; Lapa, Constantin; Robinson, Simon; Samnick, Samuel; Javadi, Mehrbod; Schwaiger, Markus; Nekolla, Stephan G; Higuchi, Takahiro

2015-09-01

(18)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine ((18)F-LMI1195) is a new PET tracer designed for noninvasive assessment of sympathetic innervation of the heart. The (18)F label facilitates the imaging advantages of PET over SPECT technology while allowing centralized manufacturing. Highly specific neural uptake of (18)F-LMI1195 has previously been established, but the retention kinetics are not yet fully understood. Healthy New Zealand White rabbits were studied with (18)F-LMI1195 using a small-animal PET system. Dynamic 40-min chest scans were started just before intravenous bolus injection of (18)F-LMI1195. Imaging was performed under norepinephrine transport inhibition with desipramine pretreatment, a 1.5 mg/kg desipramine chase administered 10 min after tracer injection, and saline treatment of controls. As a reference, cardiac uptake of (11)C-hydroxyephedrine and (123)I-metaiodobenzylguanidine ((123)I-MIBG) was examined by PET and planar scintigraphy, respectively. Cardiac uptake of all 3 tracers was inhibited by pretreatment with desipramine. Stable cardiac tracer retention was delineated by dynamic PET in control rabbits for (11)C-hydroxyephedrine (washout rate, 0.42% ± 0.57%/min) and (18)F-LMI1195 (washout rate, 0.058% ± 0.28%/min). A desipramine chase increased (11)C-hydroxyephedrine washout from the heart (2.43% ± 0.15%/min, P < 0.001), whereas (18)F-LMI1195 washout was not influenced (0.059% ± 0.11%/min, not statistically significant). Additionally, a desipramine chase did not change the cardiac (123)I-MIBG uptake (delayed heart-to-mediastinum ratio, 1.99 ± 0.12 (desipramine chase) vs. 2.05 ± 0.16 (controls), not statistically significant). In vivo norepinephrine transporter (NET) blockade with desipramine confirmed specific neural uptake of (18)F-LMI1195, (11)C-hydroxyephedrine, and (123)I-MIBG in rabbit hearts. (11)C-hydroxyephedrine cardiac retention was sensitive to a NET inhibitor chase, indicating a cycle of continuous NET uptake and release at the nerve terminals. In contrast, (18)F-LMI1195 and (123)I-MIBG demonstrated stable storage at the nerve terminal with resistance to a NET inhibitor chase, mimicking physiologic norepinephrine turnover. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

An analysis of equine round pen training videos posted online: Differences between amateur and professional trainers

PubMed Central

Kydd, Erin; Padalino, Barbara; Henshall, Cathrynne; McGreevy, Paul

2017-01-01

Natural Horsemanship is popular among many amateur and professional trainers and as such, has been the subject of recent scientific enquiry. One method commonly adopted by Natural Horsemanship (NH) trainers is that of round pen training (RPT). RPT sessions are usually split into a series of bouts; each including two phases: chasing/flight and chasing offset/flight offset. However, NH training styles are heterogeneous. This study investigated online videos of RPT to explore the characteristics of RPT sessions and test for differences in techniques and outcomes between amateurs and professionals (the latter being defined as those with accompanying online materials that promote clinics, merchandise or a service to the public). From more than 300 candidate videos, we selected sample files for individual amateur (n = 24) and professional (n = 21) trainers. Inclusion criteria were: training at liberty in a Round Pen; more than one bout and good quality video. Sessions or portions of sessions were excluded if the trainer attached equipment, such as a lunge line, directly to the horse or the horse was saddled, mounted or ridden. The number of bouts and duration of each chasing and non-chasing phase were recorded, and the duration of each RPT session was calculated. General weighted regression analysis revealed that, when compared with amateurs, professionals showed fewer arm movements per bout (p<0.05). Poisson regression analysis showed that professionals spent more time looking up at their horses, when transitioning between gaits, than amateurs did (p<0.05). The probability of horses following the trainer was not significantly associated with amount of chasing, regardless of category. Given that, according to some practitioners, the following response is a goal of RPT, this result may prompt caution in those inclined to give chase. The horses handled by professionals showed fewer conflict behaviours (e.g. kicking, biting, stomping, head-tossing, defecating, bucking and attempting to escape), and fewer oral and head movements (e.g. head-lowering, licking and chewing) than those horses handled by amateurs Overall, these findings highlight the need for selectivity when using the internet as an educational source and the importance of trainer skill and excellent timing when using negative reinforcement in horse training. PMID:28922395

An analysis of equine round pen training videos posted online: Differences between amateur and professional trainers.

PubMed

Kydd, Erin; Padalino, Barbara; Henshall, Cathrynne; McGreevy, Paul

2017-01-01

Natural Horsemanship is popular among many amateur and professional trainers and as such, has been the subject of recent scientific enquiry. One method commonly adopted by Natural Horsemanship (NH) trainers is that of round pen training (RPT). RPT sessions are usually split into a series of bouts; each including two phases: chasing/flight and chasing offset/flight offset. However, NH training styles are heterogeneous. This study investigated online videos of RPT to explore the characteristics of RPT sessions and test for differences in techniques and outcomes between amateurs and professionals (the latter being defined as those with accompanying online materials that promote clinics, merchandise or a service to the public). From more than 300 candidate videos, we selected sample files for individual amateur (n = 24) and professional (n = 21) trainers. Inclusion criteria were: training at liberty in a Round Pen; more than one bout and good quality video. Sessions or portions of sessions were excluded if the trainer attached equipment, such as a lunge line, directly to the horse or the horse was saddled, mounted or ridden. The number of bouts and duration of each chasing and non-chasing phase were recorded, and the duration of each RPT session was calculated. General weighted regression analysis revealed that, when compared with amateurs, professionals showed fewer arm movements per bout (p<0.05). Poisson regression analysis showed that professionals spent more time looking up at their horses, when transitioning between gaits, than amateurs did (p<0.05). The probability of horses following the trainer was not significantly associated with amount of chasing, regardless of category. Given that, according to some practitioners, the following response is a goal of RPT, this result may prompt caution in those inclined to give chase. The horses handled by professionals showed fewer conflict behaviours (e.g. kicking, biting, stomping, head-tossing, defecating, bucking and attempting to escape), and fewer oral and head movements (e.g. head-lowering, licking and chewing) than those horses handled by amateurs Overall, these findings highlight the need for selectivity when using the internet as an educational source and the importance of trainer skill and excellent timing when using negative reinforcement in horse training.

Effect of non-thermal air atmospheric pressure plasma jet treatment on gingival wound healing

NASA Astrophysics Data System (ADS)

Lee, Jung-Hwan; Choi, Eun-Ha; Kim, Kwang-Mahn; Kim, Kyoung-Nam

2016-02-01

Non-thermal atmospheric pressure plasmas have been applied in the biomedical field for the improvement of various cellular activities. In dentistry, the healing of gingival soft tissue plays an important role in health and aesthetic outcomes. While the biomedical application of plasma has been thoroughly studied in dentistry, a detailed investigation of plasma-mediated human gingival fibroblast (HGF) migration for wound healing and its underlying biological mechanism is still pending. Therefore, the aim of this study is to apply a non-thermal air atmospheric pressure plasma jet (NTAAPPJ) to HGF to measure the migration and to reveal the underlying biological mechanisms involved in the migration. After the characterization of NTAAPPJ by optical emission spectroscopy, the adherent HGF was treated with NTAAPPJ or air with a different flow rate. Cell viability, lipid peroxidation, migration, intracellular reactive oxygen species (ROS), and the expression of migration-related genes (EGFR, PAK1, and MAPK3) were investigated. The level of statistical significance was set at 0.05. NTAAPPJ and air treatment with a flow rate of 250-1000 standard cubic centimetres per minute (sccm) for up to 30 s did not induce significant decreases in cell viability or membrane damage. A significant increase in the migration of mitomycin C-treated HGF was observed after 30 s of NTAAPPJ treatment compared to 30 s air-only treatment, which was induced by high levels of intracellular reactive oxygen species (ROS). An increase in migration-related gene expression and EGFR activation was observed following NTAAPPJ treatment in an air flow rate-dependent manner. This is the first report that NTAAPPJ treatment induces an increase in HGF migration without changing cell viability or causing membrane damage. HGF migration was related to an increase in intracellular ROS, changes in the expression of three of the migration-related genes (EGFR, PAK1, and MAPK1), and EGFR activation. Therefore, NTAAPPJ for gingival tissue healing is a promising method for health and aesthetic outcomes.

Spatial pattern analysis of nuclear migration in remodelled muscles during Drosophila metamorphosis.

PubMed

Kuleesha; Feng, Lin; Wasser, Martin

2017-07-10

Many human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration. Previously, we showed that loss of Cathepsin-L inhibited anti-polar movements, while knockdown of autophagy-related genes affected nuclear positioning along the medial axis in late metamorphosis. To compare the phenotypic effects of gene perturbations on nuclear migration more objectively, we developed new descriptors of myonuclear distribution. To obtain nuclear pattern features, we designed an algorithm to detect and track nuclear regions inside live muscles. Nuclear tracks were used to distinguish between fast moving nuclei associated with fragments of dead muscles (sarcolytes) and slow-moving nuclei inside remodelled muscles. Nuclear spatial pattern features, such as longitudinal (lonNS) and lateral nuclear spread (latNS), allowed us to compare nuclear migration during muscle remodelling in different genetic backgrounds. Anti-polar migration leads to a lonNS decrease. As expected, lack of myonuclear migration caused by the loss of Cp1 was correlated with a significantly lower lonNS decrease. Unexpectedly, the decrease in lonNS was significantly enhanced by Atg9, Atg5 and Atg18 silencing, indicating that the loss of autophagy promotes the migration and clustering of nuclei. Loss of autophagy also caused a scattering of nuclei along the lateral axis, leading to a two-row as opposed to single row distribution in control muscles. Increased latNS resulting from knockdown of Atg9 and Atg18 was correlated with increased muscle diameter, suggesting that the wider muscle fibre promotes lateral displacement of nuclei from the medial axis during polar migration. We developed new nuclear features to characterize the dynamics of nuclear distribution in time-lapse images of Drosophila metamorphosis. Image quantification improved our understanding of phenotypic abnormalities in nuclear distribution resulting from gene perturbations. Therefore, in vivo imaging and quantitative image analysis of Drosophila metamorphosis promise to provide novel insights into the relationship between muscle wasting and myonuclear positioning.

Functional characterization of the turkey macrophage migration inhibitory factor

USDA-ARS?s Scientific Manuscript database

Macrophage migration inhibitory factor (MIF) is a soluble protein that inhibits the random migration of macrophages and plays a pivotal immunoregulatory function in innate and adaptive immunity. The aim of this study was to clone the turkey MIF (TkMIF) gene, express the active protein, and characte...

Migration features of Ips typographus in the Tatra Mountains: using a genetic method

Treesearch

Ferenc Lakatos

2003-01-01

The genetic structure of Ips typographus populations in the Tatra Mountains was studied based on the observed differences of gene flow and migration rate. It was a highlighted question as to what extent different natural barriers influence the migration potential of the species.

Knockout Mice for Dyslexia Susceptibility Gene Homologs KIAA0319 and KIAA0319L have Unaffected Neuronal Migration but Display Abnormal Auditory Processing

PubMed Central

Guidi, Luiz G; Mattley, Jane; Martinez-Garay, Isabel; Monaco, Anthony P; Linden, Jennifer F; Velayos-Baeza, Antonio

2017-01-01

Abstract Developmental dyslexia is a neurodevelopmental disorder that affects reading ability caused by genetic and non-genetic factors. Amongst the susceptibility genes identified to date, KIAA0319 is a prime candidate. RNA-interference experiments in rats suggested its involvement in cortical migration but we could not confirm these findings in Kiaa0319-mutant mice. Given its homologous gene Kiaa0319L (AU040320) has also been proposed to play a role in neuronal migration, we interrogated whether absence of AU040320 alone or together with KIAA0319 affects migration in the developing brain. Analyses of AU040320 and double Kiaa0319;AU040320 knockouts (dKO) revealed no evidence for impaired cortical lamination, neuronal migration, neurogenesis or other anatomical abnormalities. However, dKO mice displayed an auditory deficit in a behavioral gap-in-noise detection task. In addition, recordings of click-evoked auditory brainstem responses revealed suprathreshold deficits in wave III amplitude in AU040320-KO mice, and more general deficits in dKOs. These findings suggest that absence of AU040320 disrupts firing and/or synchrony of activity in the auditory brainstem, while loss of both proteins might affect both peripheral and central auditory function. Overall, these results stand against the proposed role of KIAA0319 and AU040320 in neuronal migration and outline their relationship with deficits in the auditory system. PMID:29045729

Strategic Studies Quarterly. Volume 6, Number 2. Summer 2012

DTIC Science & Technology

2012-06-01

Jr . Forging an Indian Partnership Capt Craig H. Neuman II, USAF Chasing Its Tail: Nuclear Deterrence in the Information Age? Stephen J. Cimbala Commentary Our Brick Moon William H. Gerstenmaier ...Su m m er 2012 SUMMER 2012 Vol. 6, No. 2 Commentary Our Brick Moon William H. Gerstenmaier Chasing Its Tail: Nuclear Deterrence in...Extended Deterrence: How Much Strategic Force Is Too Little? David J. Trachtenberg The Common Sense of Small Nuclear Arsenals James Wood Forsyth

Modeling Syntax for Parsing and Translation

DTIC Science & Technology

2003-12-15

20 CHAPTER 2. MONOLINGUAL PROBABILISTIC PARSING a the D cat snake D S O chased S O ran SS Mary O Figure 2.1: Part of a dictionary . the cat S chased S O...along with their training algorithms: a monolingual gen- erative model of sentence structure, and a model of the relationship between the structure of a...tasks of monolingual parsing and word-level bilingual corpus alignment, they are demonstrated in two additional applications. First, a new statistical

New periodic solutions for some planar N + 3-body problems with Newtonian potentials

NASA Astrophysics Data System (ADS)

Yuan, Pengfei; Zhang, Shiqing

2018-03-01

For some planar Newtonian N + 3-body problems, we use variational minimization methods to prove the existence of new periodic solutions satisfying that N bodies chase each other on a curve, and the other 3 bodies chase each other on another curve. From the definition of orbit spaces in our paper, we can find that they are new solutions which are also different from all the examples of Ferrario and Terracini (2004).

Effects of repeated simulated removal activities on feral swine movements and space use

USGS Publications Warehouse

Fischer, Justin W.; McMurtry , Dan; Blass, Chad R.; Walter, W. David; Beringer, Jeff; VerCauterren, Kurt C.

2016-01-01

Abundance and distribution of feral swine (Sus scrofa) in the USA have increased dramatically during the last 30 years. Effective measures are needed to control and eradicate feral swine populations without displacing animals over wider areas. Our objective was to investigate effects of repeated simulated removal activities on feral swine movements and space use. We analyzed location data from 21 feral swine that we fitted with Global Positioning System harnesses in southern MO, USA. Various removal activities were applied over time to eight feral swine before lethal removal, including trapped-and-released, chased with dogs, chased with hunter, and chased with helicopter. We found that core space-use areas were reduced following the first removal activity, whereas overall space-use areas and diurnal movement distances increased following the second removal activity. Mean geographic centroid shifts did not differ between pre- and post-periods for either the first or second removal activities. Our information on feral swine movements and space use precipitated by human removal activities, such as hunting, trapping, and chasing with dogs, helps fill a knowledge void and will aid wildlife managers. Strategies to optimize management are needed to reduce feral swine populations while preventing enlarged home ranges and displacing individuals, which could lead to increased disease transmission risk and human-feral swine conflict in adjacent areas.

Overexpression of the growth arrest-specific homeobox gene Gax inhibits proliferation, migration, cell cycle progression, and apoptosis in serum-induced vascular smooth muscle cells.

PubMed

Zheng, H; Xue, S; Hu, Z L; Shan, J G; Yang, W G

2014-03-24

The Gax gene has been implicated in a variety of cell-developmental and biological processes, and aberrant Gax expression is linked to many diseases. In this study, to provide important insights for Gax-based gene therapy in vein graft restenosis and its anti-restenotic mechanism, we used rabbit vascular smooth muscle cells (VSMCs) to investigate the effects of Gax overexpression on proliferation, migration, cell cycle, and apoptosis in a serum-stimulated culture. Rabbit VSMC lines that stably overexpressed Gax were established by transfection with recombinant adenoviral vector Ad5-Gax. The effect of Gax overexpression on in vitro serum-induced VSMCs proliferation, migration, cell cycle, and apoptosis was assessed by MTT, wound healing, and flow cytometry assays, respectively. To investigate the effect of Gax overexpression on PCNA and MMP-2 in serum-induced VSMCs, immunocytochemistry, RT-PCR, and gelatin zymography were performed. The results clearly showed that Gax overexpression decreases PCNA expression in serum-induced VSMCs. Gax overexpression also significantly inhibited cell proliferation by blocking entry into the S-phase of the cell cycle, promoted cell apoptosis, and reduced cell migration activity by downregulating MMP-2 release and activity. These findings indicate that Gax would be an optimal target gene for gene therapy to treat vein graft restenosis.

Glycosylation and processing of high-mannose oligosaccharides of thyroid-stimulating hormone subunits: comparison to nonsecretory cell glycoproteins.

PubMed

Ronin, C; Stannard, B S; Rosenbloom, I L; Magner, J A; Weintraub, B D

1984-09-25

Thyroid-stimulating hormone (TSH) subunit glycosylation was compared to that of total cell glycoproteins in mouse thyrotropic tumors. Lipid-linked oligosaccharides, total cell glycoproteins, and TSH subunits were labeled with either [3H]mannose, [3H]galactose, or [3H]glucose in pulse and pulse-chase experiments. The various oligosaccharides were isolated respectively by lipid extraction and mild acid hydrolysis, by selective immunoprecipitation, or by acid precipitation followed by trypsin and endoglycosidase H treatment. The nature of the oligosaccharides was assessed by their migration in paper chromatography, their relative incorporation of different precursors, and also their resistance to alpha-mannosidase. At 60 min, lipid-linked oligosaccharides were found to be composed of Glc3-2Man9GlcNAc2, Man9-8GlcNAc2, and Man5GlcNAc2. At 10 or 60 min of labeling, total cell proteins contained Glc3Man9GlcNAc2, Glc1Man9GlcNAc2, Man9GlcNAc2, Glc1Man8GlcNAc2, Man8GlcNAc2, and Man7GlcNAc2. The largest oligosaccharide, Glc3Man9GlcNAc2, had an unusually long half-life of about 2 h. In contrast, no Glc3Man9GlcNAc2 was found either on TSH + alpha subunits or on free beta subunits isolated either by immunoprecipitation or by sodium dodecyl sulfate gel electrophoresis. Instead, primarily Man9GlcNAc2 was found after a 10-min pulse both on TSH + alpha subunits and on beta subunits. When the pulse was followed by a chase up to 2 h, there was a progressive increase in Man8GlcNAc2 in higher amounts on TSH + alpha-subunit carbohydrate chains than on beta subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

Standardized Cannabis sativa extract attenuates tau and stathmin gene expression in the melanoma cell line.

PubMed

Vaseghi, Golnaz; Taki, Mohamad Javad; Javanmard, Shaghayegh Haghjooy

2017-10-01

Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C. sativa extract. Cells with no treatment were considered as the control group, then study was followed by Quantitative RT-Real Time PCR assay. Relative gene expression was calculated by the ΔΔct method. Migration assay was used to evaluate cancer metastasis. Tau and stathmin gene expression was significantly decreased compared to the control group. Cell migration was also significantly reduced compared to controls. C. sativa decreased tau and stathmin gene expression and cancer metastasis. The results may have some clinical relevance for the use of cannabis-based medicines in patients with metastatic melanoma.

Genetic Structure and Demographic History Reveal Migration of the Diamondback Moth Plutella xylostella (Lepidoptera: Plutellidae) from the Southern to Northern Regions of China

PubMed Central

Wei, Shu-Jun; Shi, Bao-Cai; Gong, Ya-Jun; Jin, Gui-Hua; Chen, Xue-Xin; Meng, Xiang-Feng

2013-01-01

The diamondback moth Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae) is one of the most destructive insect pests of cruciferous plants worldwide. Biological, ecological and genetic studies have indicated that this moth is migratory in many regions around the world. Although outbreaks of this pest occur annually in China and cause heavy damage, little is known concerning its migration. To better understand its migration pattern, we investigated the population genetic structure and demographic history of the diamondback moth by analyzing 27 geographical populations across China using four mitochondrial genes and nine microsatellite loci. The results showed that high haplotype diversity and low nucleotide diversity occurred in the diamondback moth populations, a finding that is typical for migratory species. No genetic differentiation among all populations and no correlation between genetic and geographical distance were found. However, pairwise analysis of the mitochondrial genes has indicated that populations from the southern region were more differentiated than those from the northern region. Gene flow analysis revealed that the effective number of migrants per generation into populations of the northern region is very high, whereas that into populations of the southern region is quite low. Neutrality testing, mismatch distribution and Bayesian Skyline Plot analyses based on mitochondrial genes all revealed that deviation from Hardy-Weinberg equilibrium and sudden expansion of the effective population size were present in populations from the northern region but not in those from the southern region. In conclusion, all our analyses strongly demonstrated that the diamondback moth migrates within China from the southern to northern regions with rare effective migration in the reverse direction. Our research provides a successful example of using population genetic approaches to resolve the seasonal migration of insects. PMID:23565158

MicroRNA-29 regulates myocardial microvascular endothelial cells proliferation and migration in association with IGF1 in type 2 diabetes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhenjie; Jiang, Runxia; Yue, Qingcai

Background: In our study, we investigated the expression and function of microRNA-29 in myocardial microvascular endothelial cells (MMEVC) in type 2 diabetic Goto-Kakizaki (GK) rats. Methods: MiR-29 gene expression was compared, by qRT-PCR between diabetic GK rat MMEVC and non-diabetic Wistar rat MMEVC. MiR-29 was downregulated in GK MMEVC and its effect on angiogenic properties of proliferation and migration was examined. Potential downstream target gene of miR-29, insulin growth factor 1 (IGF1), was assessed by dual-luciferase reporter assay, qRT-PCR and western blot in GK MMEVC. IGF1 was also downregulated by siRNA in miR-29-downregulated GK MMEVC. Its effect on miR-29-associated angiogenicmore » regulation on MMEVC proliferation and migration was further investigated. Results: MiR-29 was substantially upregulated in GK MMEVC than in Wistar MMEVC. Transfection of synthetic miR-29 inhibitor successfully downregulate endogenous miR-29 in GK MMEVC, and subsequently promoted angiogenesis by increasing cell proliferation and migration. IGF1 was confirmed to be downstream target gene of miR-29 in GK MMEVC, with its gene and protein expressions both upregulated in miR-29-downregualted GK MMEVC. Conversely, siRNA-mediated IGF1 downregulation reversed the pro-angiogenic effect of miR-29 downregulation in GK MMEVC, as it decreased cell proliferation and migration. Conclusion: Our study suggests that miR-29 downregulation, through its inverse regulation on downstream target of IGF1 gene, is a pro-angiogenic factor in MMEVC in type 2 diabetic rats.« less

CoCl2 , a mimic of hypoxia, enhances bone marrow mesenchymal stem cells migration and osteogenic differentiation via STAT3 signaling pathway.

PubMed

Yu, Xin; Wan, Qilong; Cheng, Gu; Cheng, Xin; Zhang, Jing; Pathak, Janak L; Li, Zubing

2018-06-16

Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl 2 ) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression i.e., metal-loproteinase (MMP) 7, MMP9 and C-X-C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c-jun n-terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hy-poxia-induced BMSCs migration, cell migration related signaling molecules phos-phorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia-induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK and MMP9 signaling pathways. This article is protected by copyright. All rights reserved.

Myth-free space advocacy part I-The myth of innate exploratory and migratory urges

NASA Astrophysics Data System (ADS)

Schwartz, James S. J.

2017-08-01

This paper discusses the ;myth; that we have an innate drive to explore or to migrate into space. Three interpretations of the claim are considered. According to the ;mystical interpretation,; it is part of our ;destiny; as humans to explore and migrate into space. Such a claim has no rational basis and should play no role in rationally- or evidence-based space advocacy. According to the ;cultural interpretation,; exploration and migration are essential features of human culture and society. These are not universal features because there are cultures and societies that have not encouraged exploration and migration. Moreover, the cultures that have explored have seldom conducted exploration for its own sake. According to the ;biological interpretation; there is a psychological or genetic basis for exploration or migration. While there is limited genetic evidence for such a claim, that evidence suggests that genes associated with exploratory behavior were selected for subsequent to migration, making it unlikely that these genes played a role in causing migration. In none of these senses is it clearly true that we have an innate drive to explore or migrate into space; and even if we did it would be fallacious to argue that the existence of such a drive justified spaceflight activities.

Thermal Stress Limit Rafting Migration of Seahorses: Prediction Based on Physiological and Behavioral Responses to Thermal Stress

NASA Astrophysics Data System (ADS)

Qin, G.; Li, C.; Lin, Q.

2017-12-01

Marine fish species escape from harmful environment by migration. Seahorses, with upright posture and low mobility, could migrate from unfavorable environment by rafting with their prehensile tail. The present study was designed to examine the tolerance of lined seahorse Hippocampus erectus to thermal stress and evaluate the effects of temperature on seahorse migration. The results figured that seahorses' tolerance to thermal stress was time dependent. Acute thermal stress (30°C) increased breathing rate and HSP genes expression significantly, but didn't affect seahorse feeding behavior. Chronic thermal treatment lead to persistent high expression of HSP genes, higher breathing rate, and decreasing feeding, and final higher mortality, suggesting that seahorse cannot adapt to thermal stress by acclimation. No significant negative effects were found in seahorse reproduction in response to chronic thermal stress. Given that seahorses make much slower migration by rafting on sea surface compared to other fishes, we suggest that thermal stress might limit seahorse migration range. and the influence might be magnified by global warming in future.

Machine Learning

DTIC Science & Technology

1990-04-01

DTIC i.LE COPY RADC-TR-90-25 Final Technical Report April 1990 MACHINE LEARNING The MITRE Corporation Melissa P. Chase Cs) CTIC ’- CT E 71 IN 2 11990...S. FUNDING NUMBERS MACHINE LEARNING C - F19628-89-C-0001 PE - 62702F PR - MOlE S. AUTHO(S) TA - 79 Melissa P. Chase WUT - 80 S. PERFORMING...341.280.5500 pm I " Aw Sig rill Ia 2110-01 SECTION 1 INTRODUCTION 1.1 BACKGROUND Research in machine learning has taken two directions in the problem of

National Program for Inspection of Non-Federal Dams. Chase Pond Dam (NH 00255), NHWRB Number 253.02, Merrimack River Basin, Wilmot, New Hampshire. Phase I Inspection Report.

DTIC Science & Technology

1980-03-01

STANDAROS-1963-A L ~.°.. o...... 1....MERRIMACK RIVER BASIN -!. WILMOT , NEW HAMPSHIRE ’,- CHASE POND DAM NH 00255 NHWRB NO. 253.02 r PHASE I...Continue on fewsorsp side #0 .o..oemay and Ientify by black Muthot) - DAMS, NSPECTION, PAM S’AFETY, Merrimack River Basin. * Wilmot , New Hampshire...MERRIMACK RIVER BASIN R WILMOT , NEW HAMPSHIRE - - PHASE I INSPECTION REPORT NATIONAL DAM INSPECTION PROGRAM :: : I

Application of curative therapy in the ward. 1920.

PubMed

Marble, Henry Chase

2009-06-01

This Classic article is a reprint of the original work by Henry Chase Marble, Application of Curative Therapy in the Ward. An accompanying biographical sketch on Henry Chase Marble, MD, is available at DOI 10.1007/s11999-009-0789-7 . The Classic Article is (c)1920 by the Journal of Bone and Joint Surgery, Inc. and is reprinted with permission from Marble HC. Application of curative therapy in the ward. J Bone Joint Surg Am. 1920;2:136-138.

The F-18 simulator at NASA's Dryden Flight Research Center, Edwards, California

NASA Image and Video Library

2004-10-04

The F-18 simulator at NASA's Dryden Flight Research Center, Edwards, California. Simulators offer a safe and economical alternative to actual flights to gather data, as well as being excellent facilities for pilot practice and training. The F-18 Hornet is used primarily as a safety chase and mission support aircraft at NASA's Dryden Flight Research Center, Edwards, California. As support aircraft, the F-18's are used for safety chase, pilot proficiency, aerial photography and other mission support functions.

The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells.

PubMed

Okusha, Yuka; Eguchi, Takanori; Sogawa, Chiharu; Okui, Tatsuo; Nakano, Keisuke; Okamoto, Kuniaki; Kozaki, Ken-Ichi

2018-05-15

Members of matrix metalloproteinase (MMP) family promote cancer cell migration, invasion, and metastasis through alteration of the tumor milieu, intracellular signaling pathways, and transcription. We examined gene expression signatures of colon adenocarcinoma cell lines with different metastatic potentials and found that rapidly metastatic cells powerfully expressed genes encoding MMP3 and MMP9. The non-proteolytic PEX isoform and proteolytic isoforms of MMPs were significantly expressed in the metastatic cells in vitro. Knockdown of MMP3 attenuated cancer cell migration and invasion in vitro and lung metastasis in vivo. Profound nuclear localization of MMP3/PEX was found in tumor-stroma marginal area. In contrast, MMP9 was localized in central area of subcutaneous tumors. Overexpression of the PEX isoform of MMP3 promoted proliferation and migration of the rapidly metastatic cells in vitro. Taken together, the non-proteolytic PEX isoform of MMPs locating in cell nuclei involves proliferation, migration, and subsequent metastasis of aggressive adenocarcinoma cells. © 2018 Wiley Periodicals, Inc.

Social grouping: perceptual grouping of objects by cooperative but not competitive relationships in dynamic chase.

PubMed

Yin, Jun; Ding, Xiaowei; Zhou, Jifan; Shui, Rende; Li, Xinyu; Shen, Mowei

2013-10-01

Historically, perceptual grouping is associated with physical principles. This article reports a novel finding that social information-cooperative but not competitive relationships-can drive perceptual grouping of objects in dynamic chase. Particularly, each relationship was constructed with human-generated chasing motions (i.e., two predators and one prey), and its role on perceptual grouping was examined by grouping-induced effect-attentional consequences. The results showed that: (1) Predators can be perceived as a group due to their cooperative relationship, causing attention to automatically spread within grouped predators, thus the response to target appearing on uncued predator is also facilitated; and (2) The attentional effect on competitive predators has no difference from any condition which controls low-level motion patterns, even including the random-motion condition wherein no grouping factor was contained. These findings extend perceptual grouping into the social field, implying that social information gets involved in visual cognition at an early perceptual stage. Copyright © 2013 Elsevier B.V. All rights reserved.

Building America Case Study: Duct in Conditioned Space in a Dropped Ceiling or Fur-down, Gainesville, Florida (Fact Sheet)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

2014-09-01

Forced air distribution systems (duct systems) typically are installed out of sight for aesthetic reasons, most often in unconditioned areas such as an attic or crawlspace. Any leakage of air to or from the duct system (duct leakage) in unconditioned space not only loses energy, but impacts home and equipment durability and indoor air quality. An obvious solution to this problem is to bring the duct system into the interior of the house, either by sealing the area where the ducts are installed (sealed attic or crawlspace) or by building an interior cavity or chase above the ceiling plane (raisedmore » ceiling or fur-up chase) or below the ceiling plane (dropped ceiling or fur-down) for the duct system. This case study examines one Building America builder partner's implementation of an inexpensive, quick and effective method of building a fur-down or dropped ceiling chase.« less

Pattern production through a chiral chasing mechanism

NASA Astrophysics Data System (ADS)

Woolley, Thomas E.

2017-09-01

Recent experiments on zebrafish pigmentation suggests that their typical black and white striped skin pattern is made up of a number of interacting chromatophore families. Specifically, two of these cell families have been shown to interact through a nonlocal chasing mechanism, which has previously been modeled using integro-differential equations. We extend this framework to include the experimentally observed fact that the cells often exhibit chiral movement, in that the cells chase, and run away, at angles different to the line connecting their centers. This framework is simplified through the use of multiple small limits leading to a coupled set of partial differential equations which are amenable to Fourier analysis. This analysis results in the production of dispersion relations and necessary conditions for a patterning instability to occur. Beyond the theoretical development and the production of new pattern planiforms we are able to corroborate the experimental hypothesis that the global pigmentation patterns can be dependent on the chirality of the chromatophores.

Goal attribution to inanimate moving objects by Japanese macaques (Macaca fuscata)

PubMed Central

Atsumi, Takeshi; Koda, Hiroki; Masataka, Nobuo

2017-01-01

Humans interpret others’ goals based on motion information, and this capacity contributes to our mental reasoning. The present study sought to determine whether Japanese macaques (Macaca fuscata) perceive goal-directedness in chasing events depicted by two geometric particles. In Experiment 1, two monkeys and adult humans were trained to discriminate between Chasing and Random sequences. We then introduced probe stimuli with various levels of correlation between the particle trajectories to examine whether participants performed the task using higher correlation. Participants chose stimuli with the highest correlations by chance, suggesting that correlations were not the discriminative cue. Experiment 2 examined whether participants focused on particle proximity. Participants differentiated between Chasing and Control sequences; the distance between two particles was identical in both. Results indicated that, like humans, the Japanese macaques did not use physical cues alone to perform the discrimination task and integrated the cues spontaneously. This suggests that goal attribution resulting from motion information is a widespread cognitive phenotype in primate species. PMID:28053305

Circadian locomotor output cycles kaput affects the proliferation and migration of breast cancer cells by regulating the expression of E-cadherin via IQ motif containing GTPase activating protein 1.

PubMed

Li, Xiaoxue; Wang, Siyang; Yang, Shuhong; Ying, Junjie; Yu, Hang; Yang, Chunlei; Liu, Yanyou; Wang, Yuhui; Cheng, Shuting; Xiao, Jing; Guo, Huiling; Jiang, Zhou; Wang, Zhengrong

2018-05-01

The circadian rhythm regulates numerous physiological activities, including sleep and wakefulness, behavior, immunity and metabolism. Previous studies have demonstrated that circadian rhythm disorder is associated with the occurrence of tumors. Responsible for regulating a number of functions, the Circadian locomotor output cycles kaput ( Clock ) gene is one of the core regulatory genes of circadian rhythm. The Clock gene has also been implicated in the occurrence and development of tumors in previously studies. The present study evaluated the role of the Clock gene in the proliferation and migration of mouse breast cancer 4T1 cells, and investigated its possible regulatory pathways and mechanisms. It was reported that downregulation of Clock facilitated the proliferation and migration of breast cancer cells. Further investigation revealed the involvement of IQ motif containing GTPase activating protein 1 (IQGAP1) protein expression in the Clock regulatory pathway, further influencing the expression of E-cadherin, a known proprietor of tumor cell migration and invasion. To the best of our knowledge, the present study is the first to report that Clock , acting through the regulation of the scaffolding protein IQGAP1, regulates the downstream expression of E-cadherin, thereby affecting tumor cell structure and motility. These results confirmed the role of Clock in breast cancer tumor etiology and provide insight regarding the molecular avenues of its regulatory nature, which may translate beyond breast cancer into other known functions of the gene.

Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells.

PubMed

Asghar, Muhammad Yasir; Viitanen, Tero; Kemppainen, Kati; Törnquist, Kid

2012-10-01

Anaplastic thyroid cancer (ATC) is the most aggressive form of human thyroid cancer, lacking any effective treatment. Sphingosine 1-phosphate (S1P) receptors and human ether-a'-go-go-related gene (HERG (KCNH2)) potassium channels are important modulators of cell migration. In this study, we have shown that the S1P(1-3) receptors are expressed in C643 and THJ-16T human ATC cell lines, both at mRNA and protein level. S1P inhibited migration of these cells and of follicular FTC-133 thyroid cancer cells. Using the S1P(1,3) inhibitor VPC-23019, the S1P(2) inhibitor JTE-013, and the S1P(2) receptor siRNA, we showed that the effect was mediated through S1P(2). Treatment of the cells with the Rho inhibitor C3 transferase abolished the effect of S1P on migration. S1P attenuated Rac activity, and inhibiting Rac decreased migration. Sphingosine kinase inhibitor enhanced basal migration of cells, and addition of exogenous S1P inhibited migration. C643 cells expressed a nonconducting HERG protein, and S1P decreased HERG protein expression. The HERG blocker E-4031 decreased migration. Interestingly, downregulating HERG protein with siRNA decreased the basal migration. In experiments using HEK cells overexpressing HERG, we showed that S1P decreased channel protein expression and current and that S1P attenuated migration of the cells. We conclude that S1P attenuates migration of C643 ATC cells by activating S1P(2) and the Rho pathway. The attenuated migration is also, in part, dependent on a S1P-induced decrease of HERG protein.

Maintenance of Tissue Pluripotency by Epigenetic Factors Acting at Multiple Levels

PubMed Central

Sadasivam, Devendran A.; Huang, Der-Hwa

2016-01-01

Pluripotent stem cells often adopt a unique developmental program while retaining certain flexibility. The molecular basis of such properties remains unclear. Using differentiation of pluripotent Drosophila imaginal tissues as assays, we examined the contribution of epigenetic factors in ectopic activation of Hox genes. We found that over-expression of Trithorax H3K4 methyltransferase can induce ectopic adult appendages by selectively activating the Hox genes Ultrabithorax and Sex comb reduced in wing and leg discs, respectively. This tissue-specific inducibility correlates with the presence of paused RNA polymerase II in the promoter-proximal region of these genes. Although the Antennapedia promoter is paused in eye-antenna discs, it cannot be induced by Trx without a reduction in histone variants or their chaperones, suggesting additional control by the nucleosomal architecture. Lineage tracing and pulse-chase experiments revealed that the active state of Hox genes is maintained substantially longer in mutants deficient for HIRA, a chaperone for the H3.3 variant. In addition, both HIRA and H3.3 appeared to act cooperatively with the Polycomb group of epigenetic repressors. These results support the involvement of H3.3-mediated nucleosome turnover in restoring the repressed state. We propose a regulatory framework integrating transcriptional pausing, histone modification, nucleosome architecture and turnover for cell lineage maintenance. PMID:26926299

Catalysis-dependent selenium incorporation and migration in the nitrogenase active site iron-molybdenum cofactor.

PubMed

Spatzal, Thomas; Perez, Kathryn A; Howard, James B; Rees, Douglas C

2015-12-16

Dinitrogen reduction in the biological nitrogen cycle is catalyzed by nitrogenase, a two-component metalloenzyme. Understanding of the transformation of the inert resting state of the active site FeMo-cofactor into an activated state capable of reducing dinitrogen remains elusive. Here we report the catalysis dependent, site-selective incorporation of selenium into the FeMo-cofactor from selenocyanate as a newly identified substrate and inhibitor. The 1.60 Å resolution structure reveals selenium occupying the S2B site of FeMo-cofactor in the Azotobacter vinelandii MoFe-protein, a position that was recently identified as the CO-binding site. The Se2B-labeled enzyme retains substrate reduction activity and marks the starting point for a crystallographic pulse-chase experiment of the active site during turnover. Through a series of crystal structures obtained at resolutions of 1.32-1.66 Å, including the CO-inhibited form of Av1-Se2B, the exchangeability of all three belt-sulfur sites is demonstrated, providing direct insights into unforeseen rearrangements of the metal center during catalysis.

Cell tracking supports secondary gastrulation in the moon jellyfish Aurelia.

PubMed

Gold, David A; Nakanishi, Nagayasu; Hensley, Nicholai M; Hartenstein, Volker; Jacobs, David K

2016-11-01

The moon jellyfish Aurelia exhibits a dramatic reorganization of tissue during its metamorphosis from planula larva to polyp. There are currently two competing hypotheses regarding the fate of embryonic germ layers during this metamorphosis. In one scenario, the original endoderm undergoes apoptosis and is replaced by a secondary endoderm derived from ectodermal cells. In the second scenario, both ectoderm and endoderm remain intact through development. In this study, we performed a pulse-chase experiment to trace the fate of larval ectodermal cells. We observed that prior to metamorphosis, ectodermal cells that proliferated early in larval development concentrate at the future oral end of the polyp. During metamorphosis, these cells migrate into the endoderm, extending all the way to the aboral portion of the gut. We therefore reject the hypothesis that larval endoderm remains intact during metamorphosis and provide additional support for the "secondary gastrulation" hypothesis. Aurelia appears to offer the first and only described case where a cnidarian derives its endoderm twice during normal development, adding to a growing body of evidence that germ layers can be dramatically reorganized in cnidarian life cycles.

Migration in Afro-Brazilian rural communities: crossing demographic and genetic data.

PubMed

Amorim, Carlos Eduardo G; Gontijo, Carolina C; Falcão-Alencar, Gabriel; Godinho, Neide M O; Toledo, Rafaela C P; Pedrosa, Maria Angélica F; Luizon, Marcelo R; Simões, Aguinaldo L; Klautau-Guimãres, Maria N; Oliveira, Silviene F

2011-08-01

Many studies have used genetic markers to understand global migration patterns of our species. However, there are only few studies of human migration on a local scale. We, therefore, researched migration dynamics in three Afro-Brazilian rural communities, using demographic data and ten Ancestry Informative Markers. In addition to the description of migration and marriage structures, we carried out genetic comparisons between the three populations, as well as between locals and migrants from each community. Genetic admixture analyses were conducted according to the gene-identity method, with Sub-Saharan Africans, Amerindians, and Europeans as parental populations. The three analyzed Afro-Brazilian rural communities consisted of 16% to 30% of migrants, most of them women. The age pyramid revealed a gap in the segment of men aged between 20 to 30 yrs. While endogamous marriages predominated, exogamous marriages were mainly patrilocal. Migration dynamics are apparently associated with matrimonial customs and other social practices of such communities. The impact of migration upon the populations' genetic composition was low but showed an increase in European alleles with a concomitant decrease in the Amerindian contribution. Admixture analysis evidenced a higher African contribution to the gene pool of the studied populations, followed by the contribution of Europeans and Amerindians, respectively.

Possible Source Populations of the White-backed Planthopper in the Greater Mekong Subregion Revealed by Mitochondrial DNA Analysis

NASA Astrophysics Data System (ADS)

Li, Xiang-Yong; Chu, Dong; Yin, Yan-Qiong; Zhao, Xue-Qing; Chen, Ai-Dong; Khay, Sathya; Douangboupha, Bounneuang; Kyaw, Mu Mu; Kongchuensin, Manita; Ngo, Vien Vinh; Nguyen, Chung Huy

2016-12-01

The white-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera: Delphacidae), is a serious pest of rice in Asia. However, little is known regarding the migration of this pest insect from the Greater Mekong Subregion (GMS) including Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, into China’s Yunnan Province. To determine the migration patterns of S. furcifera in the GMS and putative secondary immigration inside China’s Yunnan Province, we investigated the population genetic diversity, genetic structure, and gene flow of 42 S. furcifera populations across the six countries in the GMS by intensive sampling using mitochondrial genes. Our study revealed the potential emigration of S. furcifera from the GMS consists primarily of three major sources: 1) the S. furcifera from Laos and Vietnam migrate into south and southeast Yunnan, where they proceed to further migrate into northeast and central Yunnan; 2) the S. furcifera from Myanmar migrate into west Yunnan, and/or central Yunnan, and/or northeast Yunnan; 3) the S. furcifera from Cambodia migrate into southwest Yunnan, where the populations can migrate further into central Yunnan. The new data will not only be helpful in predicting population dynamics of the planthopper, but will also aid in regional control programs for this economically important pest insect.

Redox sensor CtBP mediates hypoxia-induced tumor cell migration

PubMed Central

Zhang, Qinghong; Wang, Su-Yan; Nottke, Amanda C.; Rocheleau, Jonathan V.; Piston, David W.; Goodman, Richard H.

2006-01-01

The rapid growth and poor vascularization of solid tumors expose cancer cells to hypoxia, which promotes the metastatic phenotype by reducing intercellular adhesion and increasing cell motility and invasiveness. In this study, we found that hypoxia increased free NADH levels in cancer cells, promoting CtBP recruitment to the E-cadherin promoter. This effect was blocked by pyruvate, which prevents the NADH increase. Furthermore, hypoxia repressed E-cadherin gene expression and increased tumor cell migration, effects that were blocked by CtBP knockdown. We propose that CtBP senses levels of free NADH to control expression of cell adhesion genes, thereby promoting tumor cell migration under hypoxic stress. PMID:16740659

Interactions of UNC-34 Enabled With Rac GTPases and the NIK Kinase MIG-15 in Caenorhabditis elegans Axon Pathfinding and Neuronal Migration

PubMed Central

Shakir, M. Afaq; Gill, Jason S.; Lundquist, Erik A.

2006-01-01

Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating axon pathfinding and cell migration. Here we present evidence that, in Caenorhabditis elegans, three Rac GTPases, CED-10, RAC-2, and MIG-2, define three redundant pathways that each control axon pathfinding, and that the NIK kinase MIG-15 acts in each Rac pathway. Furthermore, we show that the Enabled molecule UNC-34 defines a fourth partially redundant pathway that acts in parallel to Rac/MIG-15 signaling in axon pathfinding. Enabled and the three Racs also act redundantly to mediate AQR and PQR neuronal cell migration. The Racs and UNC-34 Ena might all control the formation of actin-based protrusive structures (lamellipodia and filopodia) that mediate growth cone outgrowth and cell migration. MIG-15 does not act with the three Racs in execution of cell migration. Rather, MIG-15 affects direction of PQR neuronal migration, similar to UNC-40 and DPY-19, which control initial Q cell polarity, and Wnt signaling, which acts later to control Q cell-directed migration. MIG-2 Rac, which acts with CED-10 Rac, RAC-2 Rac, and UNC-34 Ena in axon pathfinding and cell migration, also acts with MIG-15 in PQR directional migration. PMID:16204220

Long-term US energy outlook

DOE Office of Scientific and Technical Information (OSTI.GOV)

Friesen, G.

Chase Econometrics summarizes the assumptions underlying long-term US energy forecasts. To illustrate the uncertainty involved in forecasting for the period to the year 2000, they compare Chase Econometrics forecasts with some recent projections prepared by the DOE Office of Policy, Planning and Analysis for the annual National Energy Policy Plan supplement. Scenario B, the mid-range reference case, is emphasized. The purpose of providing Scenario B as well as Scenarios A and C as alternate cases is to show the sensitivity of oil price projections to small swings in energy demand. 4 tables.

Combat History Analysis Study Effort (CHASE) Data Enhancement Study (CDES). Volume 1. Introductory Materials and Bioliography.

DTIC Science & Technology

1986-01-31

Operations, France and Belgium, 1914: Mons, the Retreat to the Seine , the Marne , the Aisne, August-October 1914. London, 1922. Edmonds, Brig. Gen...7-175 712 COMBAT HISTORY ANAL YSIS STUDY EFFORT (CHASE) DATA l/f ENHANCEMENT STUDY CDES (U) DATA MEMORY SYSTEMS INC FAIRFAX VA HERO DIV B R BADER ET ...Fleville 350 Noyon-Montdidier 378 Hill 212 351 Champagne- Marne 379 Bois de Boyon- 352 Aisne- Marne I Montrefagne 353 Missy aux Bois Ravine 380 Hill 272 354

Chicken HOXA3 Gene: Its Expression Pattern and Role in Branchial Nerve Precursor Cell Migration

PubMed Central

Watari-Goshima, Natsuko; Chisaka, Osamu

2011-01-01

In vertebrates, the proximal and distal sensory ganglia of the branchial nerves are derived from neural crest cells (NCCs) and placodes, respectively. We previously reported that in Hoxa3 knockout mouse embryos, NCCs and placode-derived cells of the glossopharyngeal nerve were defective in their migration. In this report, to determine the cell-type origin for this Hoxa3 knockout phenotype, we blocked the expression of the gene with antisense morpholino oligonucleotides (MO) specifically in either NCCs/neural tube or placodal cells of chicken embryos. Our results showed that HOXA3 function was required for the migration of the epibranchial placode-derived cells and that HOXA3 regulated this cell migration in both NCCs/neural tube and placodal cells. We also report that the expression pattern of chicken HOXA3 was slightly different from that of mouse Hoxa3. PMID:21278919

ΔNp63α induces the expression of FAT2 and Slug to promote tumor invasion

PubMed Central

Dang, Tuyen T.; Westcott, Jill M.; Maine, Erin A.; Kanchwala, Mohammed; Xing, Chao; Pearson, Gray W.

2016-01-01

Tumor invasion can be induced by changes in gene expression that alter cell phenotype. The transcription factor ΔNp63α promotes basal-like breast cancer (BLBC) migration by inducing the expression of the mesenchymal genes Slug and Axl, which confers cells with a hybrid epithelial/mesenchymal state. However, the extent of the ΔNp63α regulated genes that support invasive behavior is not known. Here, using gene expression analysis, ChIP-seq, and functional testing, we find that ΔNp63α promotes BLBC motility by inducing the expression of the atypical cadherin FAT2, the vesicular binding protein SNCA, the carbonic anhydrase CA12, the lipid binding protein CPNE8 and the kinase NEK1, along with Slug and Axl. Notably, lung squamous cell carcinoma migration also required ΔNp63α dependent FAT2 and Slug expression, demonstrating that ΔNp63α promotes migration in multiple tumor types by inducing mesenchymal and non-mesenchymal genes. ΔNp63α activation of FAT2 and Slug influenced E-cadherin localization to cell-cell contacts, which can restrict spontaneous cell movement. Moreover, live-imaging of spheroids in organotypic culture demonstrated that ΔNp63α, FAT2 and Slug were essential for the extension of cellular protrusions that initiate collective invasion. Importantly, ΔNp63α is co-expressed with FAT2 and Slug in patient tumors and the elevated expression of ΔNp63α, FAT2 and Slug correlated with poor patient outcome. Together, these results reveal how ΔNp63α promotes cell migration by directly inducing the expression of a cohort of genes with distinct cellular functions and suggest that FAT2 is a new regulator of collective invasion that may influence patient outcome. PMID:27081041

Putting on the brakes: Bacterial impediment of wound healing

PubMed Central

Brothers, Kimberly M.; Stella, Nicholas A.; Hunt, Kristin M.; Romanowski, Eric G.; Liu, Xinyu; Klarlund, Jes K.; Shanks, Robert M. Q.

2015-01-01

The epithelium provides a crucial barrier to infection, and its integrity requires efficient wound healing. Bacterial cells and secretomes from a subset of tested species of bacteria inhibited human and porcine corneal epithelial cell migration in vitro and ex vivo. Secretomes from 95% of Serratia marcescens, 71% of Pseudomonas aeruginosa, 29% of Staphylococcus aureus strains, and other bacterial species inhibited epithelial cell migration. Migration of human foreskin fibroblasts was also inhibited by S. marcescens secretomes indicating that the effect is not cornea specific. Transposon mutagenesis implicated lipopolysaccharide (LPS) core biosynthetic genes as being required to inhibit corneal epithelial cell migration. LPS depletion of S. marcescens secretomes with polymyxin B agarose rendered secretomes unable to inhibit epithelial cell migration. Purified LPS from S. marcescens, but not from Escherichia coli or S. marcescens strains with mutations in the waaG and waaC genes, inhibited epithelial cell migration in vitro and wound healing ex vivo. Together these data suggest that S. marcescens LPS is sufficient for inhibition of epithelial wound healing. This study presents a novel host-pathogen interaction with implications for infections where bacteria impact wound healing and provides evidence that secreted LPS is a key factor in the inhibitory mechanism. PMID:26365869

Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

PubMed Central

Aquino, Jorge B.; Malvicini, Mariana; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G.; Mazzolini, Guillermo

2014-01-01

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC. PMID:25147818

Human umbilical cord perivascular cells exhibited enhanced migration capacity towards hepatocellular carcinoma in comparison with bone marrow mesenchymal stromal cells: a role for autocrine motility factor receptor.

PubMed

Bayo, Juan; Fiore, Esteban; Aquino, Jorge B; Malvicini, Mariana; Rizzo, Manglio; Peixoto, Estanislao; Alaniz, Laura; Piccioni, Flavia; Bolontrade, Marcela; Podhajcer, Osvaldo; Garcia, Mariana G; Mazzolini, Guillermo

2014-01-01

Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs) as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs) and human umbilical cord perivascular cells (HUCPVCs) towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF) receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2) and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

Identification of olfactory receptor genes in the Japanese grenadier anchovy Coilia nasus.

PubMed

Zhu, Guoli; Wang, Liangjiang; Tang, Wenqiao; Wang, Xiaomei; Wang, Cong

2017-01-01

Olfaction is essential for fish to detect odorant elements in the environment and plays a critical role in navigating, locating food and detecting predators. Olfactory function is produced by the olfactory transduction pathway and is activated by olfactory receptors (ORs) through the binding of odorant elements. Recently, four types of olfactory receptors have been identified in vertebrate olfactory epithelium, including main odorant receptors (MORs), vomeronasal type receptors (VRs), trace-amine associated receptors (TAARs) and formyl peptide receptors (FPRs). It has been hypothesized that migratory fish, which have the ability to perform spawning migration, use olfactory cues to return to natal rivers. Therefore, obtaining OR genes from migratory fish will provide a resource for the study of molecular mechanisms that underlie fish spawning migration behaviors. Previous studies of OR genes have mainly focused on genomic data, however little information has been gained at the transcript level. In this study, we identified the OR genes of an economically important commercial fish Coilia nasus through searching for olfactory epithelium transcriptomes. A total of 142 candidate MOR, 52 V2R/OlfC, 32 TAAR and two FPR putative genes were identified. In addition, through genomic analysis we identified several MOR genes containing introns, which is unusual for vertebrate MOR genes. The transcriptome-scale mining strategy proved to be fruitful in identifying large sets of OR genes from species whose genome information is unavailable. Our findings lay the foundation for further research into the possible molecular mechanisms underlying the spawning migration behavior in C. nasus .

Transcription Factor SOX5 Promotes the Migration and Invasion of Fibroblast-Like Synoviocytes in Part by Regulating MMP-9 Expression in Collagen-Induced Arthritis.

PubMed

Shi, Yumeng; Wu, Qin; Xuan, Wenhua; Feng, Xiaoke; Wang, Fang; Tsao, Betty P; Zhang, Miaojia; Tan, Wenfeng

2018-01-01

Fibroblast-like synoviocytes (FLS) exhibit a unique aggressive phenotype in rheumatoid arthritis (RA). Increased FLS migration and subsequent invasion of the extracellular matrix are essential to joint destruction in RA. Our previous research reported that transcription factor SOX5 was highly expressed in RA-FLS. Here, the effects of SOX5 in RA-FLS migration and invasion will be investigated. The migration and invasion of RA-FLS were evaluated using a transwell chamber assay. The expression of several potential SOX5-targeted genes, including matrix metalloproteinases (MMP-1, 2, 3 and 9), chemokines (CCL4, CCL2, CCR5 and CCR2), and pro-inflammatory cytokines (TNF-α and IL-6), were examined in RA-FLS using SOX5 gain- and loss-of-function study. The molecular mechanisms of SOX5-mediated MMP-9 expressions were assayed by luciferase reporter gene and chromatin immunoprecipitation (ChIP) studies. The in vivo effect of SOX5 on FLS migration and invasion was examined using collagen-induced arthritis (CIA) in DBA/1J mice. Knockdown SOX5 decreased lamellipodium formation, migration, and invasion of RA-FLS. The expression of MMP-9 was the only gene tested to be concomitantly affected by silencing or overexpressing SOX5. ChIP assay revealed that SOX5 was bound to the MMP-9 promoter in RA-FLS. The overexpression of SOX5 markedly enhanced the MMP-9 promoter activity, and specific deletion of a putative SOX5-binding site in MMP-9 promoter diminished this promoter-driven transcription in FLS. Locally knocked down SOX5 inhibited MMP-9 expression in the joint tissue and reduced pannus migration and invasion into the cartilage in CIA mice. SOX5 plays a novel role in mediating migration and invasion of FLS in part by regulating MMP-9 expression in RA.

Mesenchymal stem cells induce dermal fibroblast responses to injury

PubMed Central

Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2009-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury. PMID:19666021

Gene flow from domesticated species to wild relatives: migration load in a model of multivariate selection.

PubMed

Tufto, Jarle

2010-01-01

Domesticated species frequently spread their genes into populations of wild relatives through interbreeding. The domestication process often involves artificial selection for economically desirable traits. This can lead to an indirect response in unknown correlated traits and a reduction in fitness of domesticated individuals in the wild. Previous models for the effect of gene flow from domesticated species to wild relatives have assumed that evolution occurs in one dimension. Here, I develop a quantitative genetic model for the balance between migration and multivariate stabilizing selection. Different forms of correlational selection consistent with a given observed ratio between average fitness of domesticated and wild individuals offsets the phenotypic means at migration-selection balance away from predictions based on simpler one-dimensional models. For almost all parameter values, correlational selection leads to a reduction in the migration load. For ridge selection, this reduction arises because the distance the immigrants deviates from the local optimum in effect is reduced. For realistic parameter values, however, the effect of correlational selection on the load is small, suggesting that simpler one-dimensional models may still be adequate in terms of predicting mean population fitness and viability.

In Vivo MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture.

PubMed

Guo, Ruomi; Li, Qingling; Yang, Fei; Hu, Xiaojun; Jiao, Ju; Guo, Yu; Wang, Jin; Zhang, Yong

2018-06-01

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF). Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology. The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology. The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation.

PubMed

Pohl, Sandra; Hasilik, Andrej

2015-01-01

Incorporation of radioactive precursors of amino acids and/or modifier groups into proteins, isolation and sizing of polypeptide species of interest, and finally their detection and characterization provide a robust handle to examine the life cycle and varied modifications of any protein. A prerequisite in application of these techniques to lysosomal enzymes is the availability of an avid and specific antibody, because lysosomal proteins represent a very minor fraction of the cellular protein and must be purified without a significant loss many 1000-fold as conveniently as possible. Pulse-chase labeling and good knowledge on organelle-specific modifications of lysosomal proteins may enhance the information that can be obtained from such experiments. We describe procedures for pulse-chase labeling experiments that have proven to work with a commercially available antibody against a mouse and a human lysosomal protease and can be used as a reference in establishing the technique in any laboratory that has an access to a certified isotope facility and the knowledge to handle radioactivity safely. We discuss the crucial steps and refer to alternatives described in the literature. The present model protein cathepsin Z is synthesized as a larger proenzyme that contains two N-linked oligosaccharides and matures to a shorter single chain enzyme retaining the processed oligosaccharides. A pulse-chase experiment demonstrates the conversion of the precursor into the mature form. In addition, results on deglycosylation of metabolically labeled cathepsin Z are shown and the alterations in the apparent size of the glycopeptides are explained. Copyright © 2015 Elsevier Inc. All rights reserved.

Duration of effects of acute environmental changes on food anticipatory behaviour, feed intake, oxygen consumption, and cortisol release in Atlantic salmon parr.

PubMed

Folkedal, Ole; Torgersen, Thomas; Olsen, Rolf Erik; Fernö, Anders; Nilsson, Jonatan; Oppedal, Frode; Stien, Lars H; Kristiansen, Tore S

2012-01-18

We compared behavioural and physiological responses and recovery time after different acute environmental challenges in groups of salmon parr. The fish were prior to the study conditioned to a flashing light signalling arrival of food 30 s later to study if the strength of Pavlovian conditioned food anticipatory behaviour can be used to assess how salmon parr cope with various challenges. The effect on anticipatory behaviour was compared to the effect on feed intake and physiological responses of oxygen hyper-consumption and cortisol excretion. The challenges were temperature fluctuation (6.5C° over 4 h), hyperoxia (up to 380% O(2) saturation over 4 h), and intense chasing for 10 min. Cortisol excretion was only elevated after hyperoxia and chasing, and returned to baseline levels after around 3 h or less. Oxygen hyper-consumption persisted for even shorter periods. Feed intake was reduced the first feeding after all challenges and recovered within 3 h after temperature and hyperoxia, but was reduced for days after chasing. Food anticipatory behaviour was reduced for a longer period than feed intake after hyperoxia and was low at least 6 h after chasing. Our findings suggest that a recovery of challenged Atlantic salmon parr to baseline levels of cortisol excretion and oxygen consumption does not mean full recovery of all psychological and physiological effects of environmental challenges, and emphasise the need for measuring several factors including behavioural parameters when assessing fish welfare. Copyright © 2011 Elsevier Inc. All rights reserved.

Measure Guideline: Summary of Interior Ducts in New Construction, Including an Efficient, Affordable Method to Install Fur-Down Interior Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beal, D.; McIlvaine , J.; Fonorow, K.

2011-11-01

This document illustrates guidelines for the efficient installation of interior duct systems in new housing, including the fur-up chase method, the fur-down chase method, and interior ducts positioned in sealed attics or sealed crawl spaces. This document illustrates guidelines for the efficient installation of interior duct systems in new housing. Interior ducts result from bringing the duct work inside a home's thermal and air barrier. Architects, designers, builders, and new home buyers should thoroughly investigate any opportunity for energy savings that is as easy to implement during construction, such as the opportunity to construct interior duct work. In addition tomore » enhanced energy efficiency, interior ductwork results in other important advantages, such as improved indoor air quality, increased system durability and increased homeowner comfort. While the advantages of well-designed and constructed interior duct systems are recognized, the implementation of this approach has not gained a significant market acceptance. This guideline describes a variety of methods to create interior ducts including the fur-up chase method, the fur-down chase method, and interior ducts positioned in sealed attics or sealed crawl spaces. As communication of the intent of an interior duct system, and collaboration on its construction are paramount to success, this guideline details the critical design, planning, construction, inspection, and verification steps that must be taken. Involved in this process are individuals from the design team; sales/marketing team; and mechanical, insulation, plumbing, electrical, framing, drywall and solar contractors.« less

MiR-661 inhibits glioma cell proliferation, migration and invasion by targeting hTERT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhen, E-mail: lizhen7111@163.com; Liu, Yun-hui; Diao, Hong-yu

In this study, we analyzed the functional role of miR-661 in glioma cell proliferation, migration and invasion. We found that overexpression of miR-661 obviously suppressed the proliferation, migration and invasion of glioma cells. MiRNA target prediction algorithms implied that hTERT is a candidate target gene for miR-661. A fluorescent reporter assay confirmed that miR-661 could lead to hTERT gene silencing by recognizing and specifically binding to the predicted site of the hTERT mRNA 3′ untranslated region (3′UTR) specifically. Furthermore, hTERT knockdown significantly decreased the growth and viability of glioma cells. These results indicate that miR-661 can inhibit glioma cell proliferation,more » migration and invasion by targeting hTERT. - Highlights: • MiR-661 was downregulated in glioma tissues and functional as a tumor suppressor. • MiR-661 modulates cell proliferation, invasion and migration of glioma cells. • MiR-661 directly target hTERT in glioma cells. • MiR-661 inhibits glioma cell tumorgenesis by targeting hTERT.« less

Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee

2006-12-08

Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPKmore » signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.« less

The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis

PubMed Central

Sechler, Marybeth; Parrish, Janet K.; Birks, Diane K.; Jedlicka, Paul

2017-01-01

Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. However, the mechanisms underpinning Ewing Sarcoma metastasis are currently not well understood. In the present study, we identify and characterize a novel metastasis-promotional pathway in Ewing Sarcoma, involving the histone demethylase KDM3A, previously identified by our laboratory as a new cancer-promoting gene in this disease. Using global gene expression profiling, we show that KDM3A positively regulates genes and pathways implicated in cell migration and metastasis, and demonstrate, using functional assays, that KDM3A promotes migration in vitro and experimental, post-intravasation, metastasis in vivo. We further identify the Melanoma Cell Adhesion Molecule (MCAM) as a novel KDM3A target gene in Ewing Sarcoma, and an important effector of KDM3A pro-metastatic action. Specifically, we demonstrate that MCAM depletion, like KDM3A depletion, inhibits cell migration in vitro and experimental metastasis in vivo, and that MCAM partially rescues impaired migration due to KDM3A knock-down. Mechanistically, we show that KDM3A regulates MCAM expression both through a direct mechanism, involving modulation of H3K9 methylation at the MCAM promoter, and an indirect mechanism, via the Ets1 transcription factor. Lastly, we identify an association between high MCAM levels in patient tumors and poor survival, in two different Ewing Sarcoma clinical cohorts. Taken together, our studies uncover a new metastasis-promoting pathway in Ewing Sarcoma, with therapeutically targetable components. PMID:28319067

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics.

PubMed

Langabeer, Stephen E

2016-01-01

The majority of patients with classical myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia, and primary myelofibrosis harbor distinct disease-driving mutations within the JAK2 , CALR , or MPL genes. The term triple-negative has been recently applied to those MPN without evidence of these consistent mutations, prompting whole or targeted exome sequencing approaches to determine the driver mutational status of this subgroup. These strategies have identified numerous novel mutations that occur in alternative exons of both JAK2 and MPL , the majority of which result in functional activation. Current molecular diagnostic approaches may possess insufficient coverage to detect these alternative mutations, prompting further consideration of targeted exon sequencing into routine diagnostic practice. How to incorporate these illuminating findings into the expanding molecular diagnostic algorithm for MPN requires continual attention.

Artificial selection for food colour preferences.

PubMed

Cole, Gemma L; Endler, John A

2015-04-07

Colour is an important factor in food detection and acquisition by animals using visually based foraging. Colour can be used to identify the suitability of a food source or improve the efficiency of food detection, and can even be linked to mate choice. Food colour preferences are known to exist, but whether these preferences are heritable and how these preferences evolve is unknown. Using the freshwater fish Poecilia reticulata, we artificially selected for chase behaviour towards two different-coloured moving stimuli: red and blue spots. A response to selection was only seen for chase behaviours towards the red, with realized heritabilities ranging from 0.25 to 0.30. Despite intense selection, no significant chase response was recorded for the blue-selected lines. This lack of response may be due to the motion-detection mechanism in the guppy visual system and may have novel implications for the evolvability of responses to colour-related signals. The behavioural response to several colours after five generations of selection suggests that the colour opponency system of the fish may regulate the response to selection. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Geology and hydrogeology of Naval Air Station Chase Field and Naval Auxiliary Landing Field Goliad, Bee and Goliad counties, Texas

USGS Publications Warehouse

Snyder, G.L.

1995-01-01

Large vertical hydraulic-head gradients are present between the unconfined Evangeline aquifer and confined Fleming aquifers at Naval Air Station Chase Field and Naval Auxiliary Landing Field Goliad. These gradients, together with the results of the aquifer test at Naval Air Station Chase Field and assumed characteristics of the confining units, indicate that downward flow of ground water probably occurs from the water-table aquifer to the underlying aquifers. The rate of downward flow between the two confined Fleming aquifers (from A-sand to B-sand) can be approximated using an estimate of vertical hydraulic conductivity of the intervening confining unit obtained from assumed storage characteristics and data from the aquifer test. Under the relatively high vertical hydraulic-head gradient induced by the aquifer test, ground-water movement from the A-sand aquifer to the B-sand aquifer could require about 490 years; and about 730 years under the natural gradient. Future increases in ground-water withdrawals from the B-sand aquifer might increase downward flow in the aquifer system of the study area.

Magnetic state selected by magnetic dipole interaction in the kagome antiferromagnet NaBa2Mn3F11

NASA Astrophysics Data System (ADS)

Hayashida, Shohei; Ishikawa, Hajime; Okamoto, Yoshihiko; Okubo, Tsuyoshi; Hiroi, Zenji; Avdeev, Maxim; Manuel, Pascal; Hagihala, Masato; Soda, Minoru; Masuda, Takatsugu

2018-02-01

We haved studied the ground state of the classical kagome antiferromagnet NaBa2Mn3F11 . Strong magnetic Bragg peaks observed for d spacings shorter than 6.0 Å were indexed by the propagation vector of k0=(0 ,0 ,0 ) . Additional peaks with weak intensities in the d -spacing range above 8.0 Å were indexed by the incommensurate vector of k1=[0.3209 (2 ) ,0.3209 (2 ) ,0 ] and k2=[0.3338 (4 ) ,0.3338 (4 ) ,0 ] . Magnetic structure analysis unveils a 120∘ structure with the tail-chase geometry having k0 modulated by the incommensurate vector. A classical calculation of the Heisenberg kagome antiferromagnet with antiferromagnetic second-neighbor interaction, for which the ground state a k0120∘ degenerated structure, reveals that the magnetic dipole-dipole (MDD) interaction including up to the fourth neighbor terms selects the tail-chase structure. The observed modulation of the tail-chase structure is attributed to a small perturbation such as the long-range MDD interaction or the interlayer interaction.

Artificial selection for food colour preferences

PubMed Central

Cole, Gemma L.; Endler, John A.

2015-01-01

Colour is an important factor in food detection and acquisition by animals using visually based foraging. Colour can be used to identify the suitability of a food source or improve the efficiency of food detection, and can even be linked to mate choice. Food colour preferences are known to exist, but whether these preferences are heritable and how these preferences evolve is unknown. Using the freshwater fish Poecilia reticulata, we artificially selected for chase behaviour towards two different-coloured moving stimuli: red and blue spots. A response to selection was only seen for chase behaviours towards the red, with realized heritabilities ranging from 0.25 to 0.30. Despite intense selection, no significant chase response was recorded for the blue-selected lines. This lack of response may be due to the motion-detection mechanism in the guppy visual system and may have novel implications for the evolvability of responses to colour-related signals. The behavioural response to several colours after five generations of selection suggests that the colour opponency system of the fish may regulate the response to selection. PMID:25740894

The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.

PubMed

Itou, Junji; Tanaka, Sunao; Li, Wenzhao; Iida, Atsuo; Sehara-Fujisawa, Atsuko; Sato, Fumiaki; Toi, Masakazu

2017-01-01

During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells. Loss-of-function studies of SALL4 showed that this transcription factor is required for the spindle-shaped morphology and the enhanced migration of cancer cells. SALL4 also up-regulated integrin gene expression. The impaired cell migration observed in SALL4 knockdown cells was restored by overexpression of integrin α6 and β1. In addition, we clarified that integrin α6 and β1 formed a heterodimer. At the molecular level, loss of the SALL4 - integrin α6β1 network lost focal adhesion dynamics, which impairs cell migration. Over-activation of Rho is known to inhibit focal adhesion dynamics. We observed that SALL4 knockdown cells exhibited over-activation of Rho. Aberrant Rho activation was suppressed by integrin α6β1 expression, and pharmacological inhibition of Rho activity restored cell migration in SALL4 knockdown cells. These results indicated that the SALL4 - integrin α6β1 network promotes cell migration via modulation of Rho activity. Moreover, our zebrafish metastasis assays demonstrated that this gene network enhances cell migration in vivo. Our findings identify a potential new therapeutic target for the prevention of metastasis, and provide an improved understanding of cancer cell migration. Copyright © 2016 Elsevier B.V. All rights reserved.

Hox paralog group 2 genes control the migration of mouse pontine neurons through slit-robo signaling.

PubMed

Geisen, Marc J; Di Meglio, Thomas; Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

2008-06-10

The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain.

Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling

PubMed Central

Pasqualetti, Massimo; Ducret, Sebastien; Brunet, Jean-François; Chedotal, Alain; Rijli, Filippo M

2008-01-01

The pontine neurons (PN) represent a major source of mossy fiber projections to the cerebellum. During mouse hindbrain development, PN migrate tangentially and sequentially along both the anteroposterior (AP) and dorsoventral (DV) axes. Unlike DV migration, which is controlled by the Netrin-1/Dcc attractive pathway, little is known about the molecular mechanisms guiding PN migration along the AP axis. Here, we show that Hoxa2 and Hoxb2 are required both intrinsically and extrinsically to maintain normal AP migration of subsets of PN, by preventing their premature ventral attraction towards the midline. Moreover, the migration defects observed in Hoxa2 and Hoxb2 mutant mice were phenocopied in compound Robo1;Robo2, Slit1;Slit2, and Robo2;Slit2 knockout animals, indicating that these guidance molecules act downstream of Hox genes to control PN migration. Indeed, using chromatin immunoprecipitation assays, we further demonstrated that Robo2 is a direct target of Hoxa2 in vivo and that maintenance of high Robo and Slit expression levels was impaired in Hoxa2 mutant mice. Lastly, the analysis of Phox2b-deficient mice indicated that the facial motor nucleus is a major Slit signaling source required to prevent premature ventral migration of PN. These findings provide novel insights into the molecular control of neuronal migration from transcription factor to regulation of guidance receptor and ligand expression. Specifically, they address the question of how exposure to multiple guidance cues along the AP and DV axes is regulated at the transcriptional level and in turn translated into stereotyped migratory responses during tangential migration of neurons in the developing mammalian brain. PMID:18547144

Metastatic potential of melanoma cells is not affected by electrochemotherapy.

PubMed

Todorovic, Vesna; Sersa, Gregor; Mlakar, Vid; Glavac, Damjan; Flisar, Karel; Cemazar, Maja

2011-06-01

Electrochemotherapy is a local treatment combining chemotherapy and application of electric pulses to the tumour. Electrochemotherapy with bleomycin and cisplatin has shown its effectiveness in controlling local tumour growth in the treatment of malignant melanoma. However, the effect of electrochemotherapy on the metastatic potential of tumour cells is not known. Prevention of metastasis is an important aspect of successful treatment; however, it is known that metastasis can be induced by different treatment modalities. Therefore, the aim of this study was to evaluate the effect of electrochemotherapy with cisplatin on the metastatic potential of human malignant melanoma cells. Cells treated by electrochemotherapy with cisplatin were tested for their ability to migrate and invade through Matrigel-coated porous membrane. In addition, RNA was isolated from cells after treatment and differentially expressed genes were investigated by microarray analysis to evaluate the effect of electrochemotherapy with cisplatin on gene expression. There were no significant changes observed in cell migration and invasion of melanoma cells after electrochemotherapy. In addition, there were no changes observed in cell adhesion on Matrigel. Gene expression analysis showed that a very low number of genes were differentially expressed after electrochemotherapy with cisplatin. Two genes, LAMB3 and CD63 involved in cell migration, were both downregulated after electrochemotherapy with cisplatin and the expression of metastasis promoting genes was not increased after electrochemotherapy. Our data suggest that electrochemotherapy does not increase the metastatic behaviour of human melanoma cells.

Identifying Loci Under Selection Against Gene Flow in Isolation-with-Migration Models

PubMed Central

Sousa, Vitor C.; Carneiro, Miguel; Ferrand, Nuno; Hey, Jody

2013-01-01

When divergence occurs in the presence of gene flow, there can arise an interesting dynamic in which selection against gene flow, at sites associated with population-specific adaptations or genetic incompatibilities, can cause net gene flow to vary across the genome. Loci linked to sites under selection may experience reduced gene flow and may experience genetic bottlenecks by the action of nearby selective sweeps. Data from histories such as these may be poorly fitted by conventional neutral model approaches to demographic inference, which treat all loci as equally subject to forces of genetic drift and gene flow. To allow for demographic inference in the face of such histories, as well as the identification of loci affected by selection, we developed an isolation-with-migration model that explicitly provides for variation among genomic regions in migration rates and/or rates of genetic drift. The method allows for loci to fall into any of multiple groups, each characterized by a different set of parameters, thus relaxing the assumption that all loci share the same demography. By grouping loci, the method can be applied to data with multiple loci and still have tractable dimensionality and statistical power. We studied the performance of the method using simulated data, and we applied the method to study the divergence of two subspecies of European rabbits (Oryctolagus cuniculus). PMID:23457232

Orbiter "Enterprise" rides "piggy-back" atop NASA 747 carrier

NASA Image and Video Library

1977-09-23

S77-28649 (23 Sept 1977) --- The shuttle Orbiter 101 "Enterprise" sits atop the NASA 747 carrier aircraft in a piggy-back configuration prior to separation for the third free flight of the Shuttle Approach and Landing Tests (ALT) conducted on September 23, 1977, at the Dryden Flight Research Center (DFRC) in Southern California. The crew of the "enterprise" consisted of astronauts Fred W. Haise Jr., commander, and C. Gordon Fullerton, pilot. This photo was shot from one of the T-38 chase planes accompanying the ALT craft. Three other T-38 chase planes are pictured.

Involvement of hormones in olfactory imprinting and homing in chum salmon.

PubMed

Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

2016-02-16

The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration

PubMed Central

Abbruzzese, Genevieve; Cousin, Hélène; Salicioni, Ana Maria; Alfandari, Dominique

2014-01-01

ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13. PMID:25298404

Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

PubMed

Oviedo, Pilar J; Sobrino, Agua; Laguna-Fernandez, Andrés; Novella, Susana; Tarín, Juan J; García-Pérez, Miguel-Angel; Sanchís, Juan; Cano, Antonio; Hermenegildo, Carlos

2011-03-30

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

SDN-1/syndecan regulates growth factor signaling in distal tip cell migrations in C. elegans.

PubMed

Schwabiuk, Megan; Coudiere, Ludivine; Merz, David C

2009-10-01

Mutations in the sdn-1/syndecan gene act as genetic enhancers of the ventral-to-dorsal distal tip cell (DTC) migration defects caused by a weak allele of the netrin receptor gene unc-5. The sdn-1(ev697) allele was identified in a genetic screen for enhancers of unc-5 DTC migration defects, and carried a nonsense mutation predicted to truncate the SDN-1 protein prior to the transmembrane domain. The enhancement of unc-5 caused by an sdn-1 mutation was rescued by expression of wild-type sdn-1 in the hypodermis or nervous system rather than the DTCs, indicating a cell non-autonomous function of sdn-1. The enhancement was also partially reversed by mutations in the egl-17/FGF or egl-20/Wnt genes, suggesting that sdn-1 affects UNC-5 function through a mis-regulation of signaling in growth factor pathways. egl-20 reporter constructs exhibited increased and mis-localized EGL-20 distribution in sdn-1 mutants compared to wild-type animals. Finally, using loss of function mutations, we show that egl-17/Fgf and egl-20/Wnt are partially redundant in regulating the migration pattern of the posterior DTC, as double mutants exhibit significant frequencies of defects in migration phases along both the anteroposterior and dorsoventral axes. Together these results suggest that SDN-1 affects UNC-5 function by regulating the proper extracellular distribution of growth factors.

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

PubMed Central

Zhang, Yue; Sun, Bin; Huang, Zhi

2018-01-01

Background Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. Material/Methods The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN. Results Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown. Conclusions Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration. PMID:29389913

The giant mottled eel, Anguilla marmorata, uses blue-shifted rod photoreceptors during upstream migration.

PubMed

Wang, Feng-Yu; Fu, Wen-Chun; Wang, I-Li; Yan, Hong Young; Wang, Tzi-Yuan

2014-01-01

Catadromous fishes migrate between ocean and freshwater during particular phases of their life cycle. The dramatic environmental changes shape their physiological features, e.g. visual sensitivity, olfactory ability, and salinity tolerance. Anguilla marmorata, a catadromous eel, migrates upstream on dark nights, following the lunar cycle. Such behavior may be correlated with ontogenetic changes in sensory systems. Therefore, this study was designed to identify changes in spectral sensitivity and opsin gene expression of A. marmorata during upstream migration. Microspectrophotometry analysis revealed that the tropical eel possesses a duplex retina with rod and cone photoreceptors. The λmax of rod cells are 493, 489, and 489 nm in glass, yellow, and wild eels, while those of cone cells are 508, and 517 nm in yellow, and wild eels, respectively. Unlike European and American eels, Asian eels exhibited a blue-shifted pattern of rod photoreceptors during upstream migration. Quantitative gene expression analyses of four cloned opsin genes (Rh1f, Rh1d, Rh2, and SWS2) revealed that Rh1f expression is dominant at all three stages, while Rh1d is expressed only in older yellow eel. Furthermore, sequence comparison and protein modeling studies implied that a blue shift in Rh1d opsin may be induced by two known (N83, S292) and four putative (S124, V189, V286, I290) tuning sites adjacent to the retinal binding sites. Finally, expression of blue-shifted Rh1d opsin resulted in a spectral shift in rod photoreceptors. Our observations indicate that the giant mottled eel is color-blind, and its blue-shifted scotopic vision may influence its upstream migration behavior and habitat choice.

JC Virus Mediates Invasion and Migration in Colorectal Metastasis

PubMed Central

Link, Alexander; Shin, Sung Kwan; Nagasaka, Takeshi; Balaguer, Francesc; Koi, Minoru; Jung, Barbara; Boland, C. Richard; Goel, Ajay

2009-01-01

Introduction JC Virus (JCV), a human polyomavirus, is frequently present in colorectal cancers (CRCs). JCV large T-Ag (T-Ag) expressed in approximately half of all CRC's, however, its functional role in CRC is poorly understood. We hypothesized that JCV T-Ag may mediate metastasis in CRC cells through increased migration and invasion. Material and Methods CRC cell lines (HCT116 and SW837) were stably transfected with JCV early transcript sequences cloned into pCR3 or empty vectors. Migration and invasion assays were performed using Boyden chambers. Global gene expression analysis was performed to identify genetic targets and pathways altered by T-Ag expression. Microarray results were validated by qRT-PCR, protein expression analyses and immunohistochemistry. Matching primary CRCs and liver metastases from 33 patients were analyzed for T-Ag expression by immunohistochemistry. Results T-Ag expressing cell lines showed 2 to 3-fold increase in migration and invasion compared to controls. JCV T-Ag expression resulted in differential expression of several genetic targets, including genes that mediate cell migration and invasion. Pathway analysis suggested a significant involvement of these genes with AKT and MAPK signaling. Treatment with selective PI3K/AKT and MAPK pathway inhibitors resulted in reduced migration and invasion. In support of our in-vitro results, immunohistochemical staining of the advanced stage tumors revealed frequent JCV T-Ag expression in metastatic primary tumors (92%) as well as in their matching liver metastasis (73%). Conclusion These data suggest that JCV T-Ag expression in CRC associates with a metastatic phenotype, which may partly be mediated through the AKT/MAPK signaling pathway. Frequent expression of JCV T-Ag in CRC liver metastasis provides further clues supporting a mechanistic role for JCV as a possible mediator of cellular motility and invasion in CRC. PMID:19997600

β-Globin gene sequencing of hemoglobin Austin revises the historically reported electrophoretic migration pattern.

PubMed

Racsa, Lori D; Luu, Hung S; Park, Jason Y; Mitui, Midori; Timmons, Charles F

2014-06-01

Hemoglobin (Hb) Austin was defined in 1977, using amino acid sequencing of samples from 3 unrelated Mexican-Americans, as a substitution of serine for arginine at position 40 of the β-globin chain (Arg40Ser). Its electrophoretic migration on both cellulose acetate (pH 8.4) and citrate agar (pH 6.2) was reported between Hb F and Hb A, and this description persists in reference literature. OBJECTIVES.-To review the clinical features and redefine the diagnostic characteristics of Hb Austin. Eight samples from 6 unrelated individuals and 2 siblings, all with Hispanic surnames, were submitted for abnormal Hb identification between June 2010 and September 2011. High-performance liquid chromatography, isoelectric focusing (IEF), citrate agar electrophoresis, and bidirectional DNA sequencing of the entire β-globin gene were performed. DNA sequencing confirmed all 8 individuals to be heterozygous for Hb Austin (Arg40Ser). Retention time on high-performance liquid chromatography and migration on citrate agar electrophoresis were consistent with that identification. Migration on IEF, however, was not between Hb F and Hb A, as predicted from the report of cellulose acetate electrophoresis. By IEF, Hb Austin migrated anodal to ("faster than") Hb A. Hemoglobin Austin (Arg40Ser) appears on IEF as a "fast," anodally migrating, Hb variant, just as would be expected from its amino acid substitution. The cited historic report is, at best, not applicable to IEF and is probably erroneous. Our observation of 8 cases in 16 months suggests that this variant may be relatively common in some Hispanic populations, making its recognition important. Furthermore, gene sequencing is proving itself a powerful and reliable tool for definitive identification of Hb variants.

Annotating novel genes by integrating synthetic lethals and genomic information

PubMed Central

Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

2008-01-01

Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

The effects of old and recent migration waves in the distribution of HBB*S globin gene haplotypes

PubMed Central

Lindenau, Juliana D.; Wagner, Sandrine C.; de Castro, Simone M.; Hutz, Mara H.

2016-01-01

Abstract Sickle cell hemoglobin is the result of a mutation at the sixth amino acid position of the beta (β) globin chain. The HBB*S gene is in linkage disequilibrium with five main haplotypes in the β-globin-like gene cluster named according to their ethnic and geographic origins: Bantu (CAR), Benin (BEN), Senegal (SEN), Cameroon (CAM) and Arabian-Indian (ARAB). These haplotypes demonstrated that the sickle cell mutation arose independently at least five times in human history. The distribution of βS haplotypes among Brazilian populations showed a predominance of the CAR haplotype. American populations were clustered in two groups defined by CAR or BEN haplotype frequencies. This scenario is compatible with historical records about the slave trade in the Americas. When all world populations where the sickle cell gene occurs were analyzed, three clusters were disclosed based on CAR, BEN or ARAB haplotype predominance. These patterns may change in the next decades due to recent migrations waves. Since these haplotypes show different clinical characteristics, these recent migrations events raise the necessity to develop optimized public health programs for sickle cell disease screening and management. PMID:27706371

Probability of identity by descent in metapopulations.

PubMed Central

Kaj, I; Lascoux, M

1999-01-01

Equilibrium probabilities of identity by descent (IBD), for pairs of genes within individuals, for genes between individuals within subpopulations, and for genes between subpopulations are calculated in metapopulation models with fixed or varying colony sizes. A continuous-time analog to the Moran model was used in either case. For fixed-colony size both propagule and migrant pool models were considered. The varying population size model is based on a birth-death-immigration (BDI) process, to which migration between colonies is added. Wright's F statistics are calculated and compared to previous results. Adding between-island migration to the BDI model can have an important effect on the equilibrium probabilities of IBD and on Wright's index. PMID:10388835

MicroRNA-137 Affects Proliferation and Migration of Placenta Trophoblast Cells in Preeclampsia by Targeting ERRα.

PubMed

Lu, Tan-Min; Lu, Wei; Zhao, Long-Jun

2016-06-06

To investigate the effects of microRNA-137 (miRNA-137) in proliferation and migration of placenta trophoblast cells of preeclampsia and the targeting gene of miRNA-137. A total of 134 cases of puerperants were divided into normal pregnancy (n = 50), mild preeclampsia (n = 38), and severe preeclampsia groups (n = 46). MiRNA-137, estrogen-related receptor α (ERRα), and wingless INT (WNT)11 messenger RNAs (mRNAs) were measured in placental tissue and trophoblast cells after transfection, and ERRα protein in placental tissues was detected by immunohistochemistry. The target genes of miRNA-137, trophoblast cell proliferation, migration, and invasion abilities were detected. Both ERRα and WNT11 proteins in the trophoblast cells were measured after transfection. Relative expressions of miRNA-137 were higher, and positive expression rates and relative expression levels of ERRα protein were lower in mild and severe preeclampsia and early- and late-onset preeclampsia than in normal pregnancy group (all P < .05). MiRNA-137 in the placental tissues was negatively correlated with ERRα protein (P < .05). Luciferase reporter gene assay analysis showed that ERRα was a direct target gene of miRNA-137. Absorbance values, relative scratch-covered areas, cell membrane permeable rate, ERRα, and WNT11 mRNA and protein relative expressions were significantly lower, while cells at G1/G0 phase were higher in miRNA-137 mimic group than those in the blank, negative control, and miRNA-137 inhibitor group. MiRNA-137 significantly reduced the proliferation and migration of placenta trophoblast cells of preeclampsia by targeting ERRα, which might be a potential target for gene therapy. © The Author(s) 2016.

Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

PubMed Central

Lin, Hong Reng; Heish, Chao-Wen; Liu, Cheng-Hui; Muduli, Saradaprasan; Li, Hsing-Fen; Higuchi, Akon; Kumar, S. Suresh; Alarfaj, Abdullah A.; Munusamy, Murugan A.; Hsu, Shih-Tien; Chen, Da-Chung; Benelli, Giovanni; Murugan, Kadarkarai; Cheng, Nai-Chen; Wang, Han-Chow; Wu, Gwo-Jang

2017-01-01

Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not. PMID:28071738

Dcdc2 knockout mice display exacerbated developmental disruptions following knockdown of Dcx

PubMed Central

Wang, Yu; Yin, Xiuyin; Rosen, Glenn; Gabel, Lisa; Guadiana, Sarah M.; Sarkisian, Matthew R; Galaburda, Albert M.; LoTurco, Joseph J.

2011-01-01

The dyslexia-associated gene DCDC2 is a member of the DCX family of genes known to play roles in neurogenesis, neuronal migration and differentiation. Here we report the first phenotypic analysis of a Dcdc2 knockout mouse. Comparisons between Dcdc2 knockout mice and wild type littermates revealed no significant differences in neuronal migration, neocortical lamination, neuronal cilliogenesis or dendritic differentiation. Considering previous studies showing genetic interactions and potential functional redundancy among members of the DCX family, we tested whether decreasing Dcx expression by RNAi would differentially impair neurodevelopment in Dcdc2 knockouts and wild type mice. Consistent with this hypothesis, we found that deficits in neuronal migration, and dendritic growth caused by RNAi of Dcx were more severe in Dcdc2 knockouts than in wild type mice with the same transfection. These results indicate that Dcdc2 is not required for neurogenesis, neuronal migration or differentiation in mice, but may have partial functional redundancy with Dcx. PMID:21689730

MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis.

PubMed

Wang, Yingmei; Wen, Jing; Zhang, Wei

2011-02-01

The migration and invasion inhibitory protein (MIIP) was initially discovered in a yeast two-hybrid screen for proteins that interact and inhibit the migration and invasion-promoting protein insulin-like growth factor binding protein 2 (IGFBP2). Recent studies have shown that MIIP not only modulates IGFBP2 but also regulates microtubule by binding to and inhibiting HDAC6, a class 2 histone deacetylase that deacetylates α-tubulin, heat-shock protein 90 (HSP90), and cortactin. In addition, MIIP also regulates the mitosis checkpoint, another microtubule-associated process. The location of the MIIP gene in chromosomal region 1p36, a commonly deleted region in a broad spectrum of human cancers, and the observation that MIIP attenuates tumorigenesis in a mouse model suggest that it functions as a tumor-suppressor gene. This review summarizes the recent progress in characterizing this novel protein, which regulates cell migration and mitosis, two processes that rely on the highly coordinated dynamics of the microtubule and cytoskeleton systems.

Insight into the Migration Routes of Plutella xylostella in China Using mtCOI and ISSR Markers

PubMed Central

Tian, Lixia; Xu, Baoyun; Xie, Wen; Wang, Shaoli; Zhang, Youjun; Wang, Xiangjing; Wu, Qingjun

2015-01-01

The larvae of the diamondback moth, Plutella xylostella, cause major economic losses to cruciferous crops, including cabbage, which is an important vegetable crop in China. In this study, we used the mitochondrial COI gene and 11 ISSR markers to characterize the genetic structure and seasonal migration routes of 23 P. xylostella populations in China. Both the mitochondrial and nuclear markers revealed high haplotype diversity and gene flow among the populations, although some degree of genetic isolation was evident between the populations of Hainan Island and other sampling sites. The dominant haplotypes, LX1 and LX2, differed significantly from all other haplotypes both in terms of the number of individuals with those haplotypes and their distributions. Haplotypes that were shared among populations revealed that P. xylostella migrates from the lower reaches of the Yangtze River to northern China and then to northeastern China. Our results also revealed another potential migration route for P. xylostella, i.e., from southwestern China to both northwestern and southern China. PMID:26098353

Platelets Inhibit Migration of Canine Osteosarcoma Cells.

PubMed

Bulla, S C; Badial, P R; Silva, R C; Lunsford, K; Bulla, C

2017-01-01

The interaction between platelets and tumour cells is important for tumour growth and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on cancer metastasis, demonstrating potentially important roles for platelets in tumour progression. To our knowledge, there is no information regarding the role of platelets in cancer progression in dogs. This study was designed to test whether canine platelets affected the migratory behaviour of three canine osteosarcoma cell lines and to give insights of molecular mechanisms. Intact platelets, platelet lysate and platelet releasate inhibited the migration of canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet samples did not alter the inhibitory effect on migration. Platelet treatment also significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes. The interaction between canine platelets or molecules released during platelet activation and these tumour cell lines inhibits their migration, which suggests that canine platelets might antagonize metastasis of canine osteosarcoma. This effect is probably due to, at least in part, downregulation of genes related to epithelial-mesenchymal transition. Copyright © 2016. Published by Elsevier Ltd.

Mesenchymal stem cells induce dermal fibroblast responses to injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Andria N., E-mail: snosmith@u.washington.edu; Willis, Elise, E-mail: elise.willis@gmail.com; Chan, Vincent T.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. Whenmore » co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.« less

Methyl-CpG-binding protein 2 mediates antifibrotic effects in scleroderma fibroblasts.

PubMed

He, Ye; Tsou, Pei-Suen; Khanna, Dinesh; Sawalha, Amr H

2018-05-14

Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro. Fibroblast proliferation was analysed by ki67 immunofluorescence staining. A wound healing assay in vitro was used to determine fibroblast migration rates. RNA-seq was performed with and without MeCP2 knockdown in dcSSc to identify MeCP2-regulated genes. The expression of MeCP2 and its targets were modulated by siRNA or plasmid. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MeCP2 antibody was performed to assess MeCP2 binding sites within MeCP2-regulated genes. Elevated expression of MeCP2 was detected in dcSSc fibroblasts compared with normal fibroblasts. Overexpressing MeCP2 in normal fibroblasts suppressed myofibroblast differentiation, fibroblast proliferation and fibroblast migration. RNA-seq in MeCP2-deficient dcSSc fibroblasts identified MeCP2-regulated genes involved in fibrosis, including PLAU , NID2 and ADA . Plasminogen activator urokinase (PLAU) overexpression in dcSSc fibroblasts reduced myofibroblast differentiation and fibroblast migration, while nidogen-2 (NID2) knockdown promoted myofibroblast differentiation and fibroblast migration. Adenosine deaminase (ADA) depletion in dcSSc fibroblasts inhibited cell migration rates. Taken together, antifibrotic effects of MeCP2 were mediated, at least partly, through modulating PLAU, NID2 and ADA. ChIP-seq further showed that MeCP2 directly binds regulatory sequences in NID2 and PLAU gene loci. This study demonstrates a novel role for MeCP2 in skin fibrosis and identifies MeCP2-regulated genes associated with fibroblast migration, myofibroblast differentiation and extracellular matrix degradation, which can be potentially targeted for therapy in SSc. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The JNM1 gene in the yeast Saccharomyces cerevisiae is required for nuclear migration and spindle orientation during the mitotic cell cycle

PubMed Central

1994-01-01

JNM1, a novel gene on chromosome XIII in the yeast Saccharomyces cerevisiae, is required for proper nuclear migration. jnm1 null mutants have a temperature-dependent defect in nuclear migration and an accompanying alteration in astral microtubules. At 30 degrees C, a significant proportion of the mitotic spindles is not properly located at the neck between the mother cell and the bud. This defect is more severe at low temperature. At 11 degrees C, 60% of the cells accumulate with large buds, most of which have two DAPI staining regions in the mother cell. Although mitosis is delayed and nuclear migration is defective in jnm1 mutant, we rarely observe more than two nuclei in a cell, nor do we frequently observe anuclear cells. No loss of viability is observed at 11 degrees C and cells continue to grow exponentially with increased doubling time. At low temperature the large budded cells of jnm1 mutants exhibit extremely long astral microtubules that often wind around the periphery of the cell. jnm1 mutants are not defective in chromosome segregation during mitosis, as assayed by the rate of chromosome loss, or nuclear migration during conjugation, as assayed by the rate of mating and cytoduction. The phenotype of a jnm1 mutant is strikingly similar to that for mutants in the dynein heavy chain gene (Eshel, D., L. A. Urrestarazu, S. Vissers, J.-C. Jauniaux, J. C. van Vliet-Reedijk, R. J. Plants, and I. R. Gibbons. 1993. Proc. Natl. Acad. Sci. USA. 90:11172-11176; Li, Y. Y., E. Yeh, T. Hays, and K. Bloom. 1993. Proc. Natl. Acad. Sci. USA. 90:10096-10100). The JNM1 gene product is predicted to encode a 44-kD protein containing three coiled coil domains. A JNM1:lacZ gene fusion is able to complement the cold sensitivity and microtubule phenotype of a jnm1 deletion strain. This hybrid protein localizes to a single spot in the cell, most often near the spindle pole body in unbudded cells and in the bud in large budded cells. Together these results point to a specific role for Jnm1p in spindle migration, possibly as a subunit or accessory protein for yeast dynein. PMID:8138567

Energetics and evasion dynamics of large predators and prey: pumas vs. hounds.

PubMed

Bryce, Caleb M; Wilmers, Christopher C; Williams, Terrie M

2017-01-01

Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs ( Canis lupus familiaris , 26 kg, n  = 4-5 per chase) pursuing simultaneously instrumented solitary pumas ( Puma concolor , 60 kg, n  = 2). We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides) as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns) to increase their escape distance from the overall faster hounds (avg. 2.3× faster). These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg -1  min -1 , respectively). On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted [Formula: see text] and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids.

Directional migration in the Hindu castes: inferences from mitochondrial, autosomal and Y-chromosomal data.

PubMed

Wooding, Stephen; Ostler, Christopher; Prasad, B V Ravi; Watkins, W Scott; Sung, Sandy; Bamshad, Mike; Jorde, Lynn B

2004-08-01

Genetic, ethnographic, and historical evidence suggests that the Hindu castes have been highly endogamous for several thousand years and that, when movement between castes does occur, it typically consists of females joining castes of higher social status. However, little is known about migration rates in these populations or the extent to which migration occurs between caste groups of low, middle, and high social status. To investigate these aspects of migration, we analyzed the largest collection of genetic markers collected to date in Hindu caste populations. These data included 45 newly typed autosomal short tandem repeat polymorphisms (STRPs), 411 bp of mitochondrial DNA sequence, and 43 Y-chromosomal single-nucleotide polymorphisms that were assayed in more than 200 individuals of known caste status sampled in Andrah Pradesh, in South India. Application of recently developed likelihood-based analyses to this dataset enabled us to obtain genetically derived estimates of intercaste migration rates. STRPs indicated migration rates of 1-2% per generation between high-, middle-, and low-status caste groups. We also found support for the hypothesis that rates of gene flow differ between maternally and paternally inherited genes. Migration rates were substantially higher in maternally than in paternally inherited markers. In addition, while prevailing patterns of migration involved movement between castes of similar rank, paternally inherited markers in the low-status castes were most likely to move into high-status castes. Our findings support earlier evidence that the caste system has been a significant, long-term source of population structuring in South Indian Hindu populations, and that patterns of migration differ between males and females. Copyright 2004 Springer-Verlag

Noninvasive electromagnetic fields on keratinocyte growth and migration.

PubMed

Huo, Ran; Ma, Qianli; Wu, James J; Chin-Nuke, Kayla; Jing, Yuqi; Chen, Juan; Miyar, Maria E; Davis, Stephen C; Li, Jie

2010-08-01

Although evidence has shown that very small electrical currents produce a beneficial therapeutic result for wounds, noninvasive electromagnetic field (EMF) therapy has consisted mostly of anecdotal clinical reports, with very few well-controlled laboratory mechanistic studies. In this study, we evaluate the effects and potential mechanisms of a noninvasive EMF device on skin wound repair. The effects of noninvasive EMF on keratinocytes and fibroblasts were assessed via proliferation and incisional wound model migration assays. cDNA microarray and RT-PCR were utilized to assess genetic expression changes in keratinocytes after noninvasive EMF treatment. In vitro analyses with human skin keratinocyte cultures demonstrated that noninvasive EMFs have a strong effect on accelerating keratinocyte migration and a relatively weaker effect on promoting keratinocyte proliferation. The positive effects of noninvasive EMFs on cell migration and proliferation seem keratinocyte-specific without such effects seen on dermal fibroblasts. cDNA microarray and RT-PCR performed revealed increased expression of CRK7 and HOXC8 genes in treated keratinocytes. This study suggests that a noninvasive EMF accelerates wound re-epithelialization through a mechanism of promoting keratinocyte migration and proliferation, possibly due to upregulation of CRK7 and HOXC8 genes. Copyright 2010 Elsevier Inc. All rights reserved.

Curcumin is a potent modulator of microglial gene expression and migration

PubMed Central

2011-01-01

Background Microglial cells are important effectors of the neuronal innate immune system with a major role in chronic neurodegenerative diseases. Curcumin, a major component of tumeric, alleviates pro-inflammatory activities of these cells by inhibiting nuclear factor kappa B (NFkB) signaling. To study the immuno-modulatory effects of curcumin on a transcriptomic level, DNA-microarray analyses were performed with resting and LPS-challenged microglial cells after short-term treatment with curcumin. Methods Resting and LPS-activated BV-2 cells were stimulated with curcumin and genome-wide mRNA expression patterns were determined using DNA-microarrays. Selected qRT-PCR analyses were performed to confirm newly identified curcumin-regulated genes. The migration potential of microglial cells was determined with wound healing assays and transwell migration assays. Microglial neurotoxicity was estimated by morphological analyses and quantification of caspase 3/7 levels in 661W photoreceptors cultured in the presence of microglia-conditioned medium. Results Curcumin treatment markedly changed the microglial transcriptome with 49 differentially expressed transcripts in a combined analysis of resting and activated microglial cells. Curcumin effectively triggered anti-inflammatory signals as shown by induced expression of Interleukin 4 and Peroxisome proliferator activated receptor α. Several novel curcumin-induced genes including Netrin G1, Delta-like 1, Platelet endothelial cell adhesion molecule 1, and Plasma cell endoplasmic reticulum protein 1, have been previously associated with adhesion and cell migration. Consequently, curcumin treatment significantly inhibited basal and activation-induced migration of BV-2 microglia. Curcumin also potently blocked gene expression related to pro-inflammatory activation of resting cells including Toll-like receptor 2 and Prostaglandin-endoperoxide synthase 2. Moreover, transcription of NO synthase 2 and Signal transducer and activator of transcription 1 was reduced in LPS-triggered microglia. These transcriptional changes in curcumin-treated LPS-primed microglia also lead to decreased neurotoxicity with reduced apoptosis of 661W photoreceptor cultures. Conclusions Collectively, our results suggest that curcumin is a potent modulator of the microglial transcriptome. Curcumin attenuates microglial migration and triggers a phenotype with anti-inflammatory and neuroprotective properties. Thus, curcumin could be a nutraceutical compound to develop immuno-modulatory and neuroprotective therapies for the treatment of various neurodegenerative disorders. PMID:21958395

Selection of reference genes for RT-qPCR analysis in the monarch butterfly, Danaus plexippus (L.), a migrating bio-indicator

USDA-ARS?s Scientific Manuscript database

Quantitative real-time PCR (qRT-PCR) is a reliable and reproducible technique for measuring and evaluating changes in gene expression. To facilitate gene expression studies and obtain more accurate qRT-PCR data, normalization relative to stable housekeeping genes is required. In this study, expres...

Wars of the holographic world

NASA Astrophysics Data System (ADS)

Preskill, John

2008-12-01

In the popular imagination, the iconic American theoretical physicist is Richard Feynman, in all his safe-cracking, bongo-thumping, woman-chasing glory. I suspect that many physicists, if asked to name a living colleague who best captures the spirit of Feynman, would give the same answer as me: Leonard Susskind. As far as I know, Susskind does not crack safes, thump bongos, or chase women, yet he shares Feynman's brash cockiness (which in Susskind's case is leavened by occasional redeeming flashes of self-deprecation) and Feynman's gift for spinning fascinating anecdotes. If you are having a group of physicists over for dinner and want to be sure to have a good time, invite Susskind.

Pilot Ed Lewis with T-34C aircraft on ramp

NASA Image and Video Library

1998-03-04

NASA pilot Ed Lewis with the T-34C aircraft on the Dryden Flight Research Center Ramp. The aircraft was previously used at the Lewis Research Center in propulsion experiments involving turboprop engines, and was used as a chase aircraft at Dryden for smaller and slower research projects. Chase aircraft accompany research flights for photography and video purposes, and also as support for safety and research. At Dryden, the T-34 is used mainly for smaller remotely piloted vehicles which fly slower than NASA's F-18's, used for larger scale projects. This aircraft was returned to the U.S. Navy in May of 2002.

Inhibition of processing of plant N-linked oligosaccharides by castanospermine.

PubMed

Hori, H; Pan, Y T; Molyneux, R J; Elbein, A D

1984-02-01

Castanospermine (1,6,7,8-tetrahydroxyoctahydroindolizine) is a plant alkaloid that inhibits lysosomal alpha- and beta-glucosidase. It also inhibits processing of influenza viral glycoproteins by inhibiting glucosidase I and leads to altered glycoproteins with Glc3Man7GlcNAc2 structures. Castanospermine was tested as an inhibitor of glycoprotein processing in suspension-cultured soybean cells. Soybean cells were pulse-labeled with [2-3H]mannose and chased for varying periods in unlabeled medium. In normal cells, the initial glycopeptides contained oligosaccharides having Glc3Man9GlcNAc2 to Glc1Man9GlcNAc2 structures and these were trimmed during the chase to Man9GlcNac2 to Man7GlcNAc2 structures. In the presence of castanospermine, no trimming of glucose residues occurred although some mannose residues were apparently still removed. Thus, the major oligosaccharide in the glycopeptides of castanospermine-incubated cells after a 90-min chase was a Glc3Man7GlcNAc2 structure. Smaller amounts of Glc3Man6GlcNAc2 and Glc3Man5GlcNAc2 were also identified. Thus, in plant cells, castanospermine also prevents the removal of the outermost glucose residue.

Dynamic properties of chasers in a moving queue based on a delayed chasing model

NASA Astrophysics Data System (ADS)

Ning, Guo; Jian-Xun, Ding; Xiang, Ling; Qin, Shi; Reinhart, Kühne

2016-05-01

A delayed chasing model is proposed to simulate the chase behavior in the queue, where each member regards the closest one ahead as the target, and the leader is attracted to a target point with slight fluctuation. When the initial distances between neighbors possess an identical low value, the fluctuating target of the leader can cause an amplified disturbance in the queue. After a long period of time, the queue recovers the stable state from the disturbance, forming a straight-line-like pattern again, but distances between neighbors grow. Whether the queue can keep stable or not depends on initial distance, desired velocity, and relaxation time. Furthermore, we carry out convergence analysis to explain the divergence transformation behavior and confirm the convergence conditions, which is in approximate agreement with simulations. Project supported by the National Natural Science Foundation of China (Grant Nos. 71071044, 71001001, 71201041, and 11247291), the Doctoral Program of the Ministry of Education of China (Grant Nos. 20110111120023 and 20120111120022), the Postdoctoral Fund Project of China (Grant No. 2013M530295), the National Basic Research Program of China (Grant No. 2012CB725404), and 1000 Plan for Foreign Talent, China (Grant No. WQ20123400070).

Steering a virtual blowfly: simulation of visual pursuit.

PubMed

Boeddeker, Norbert; Egelhaaf, Martin

2003-09-22

The behavioural repertoire of male flies includes visually guided chasing after moving targets. The visuomotor control system for these pursuits belongs to the fastest found in the animal kingdom. We simulated a virtual fly, to test whether or not experimentally established hypotheses on the underlying control system are sufficient to explain chasing behaviour. Two operating instructions for steering the chasing virtual fly were derived from behavioural experiments: (i) the retinal size of the target controls the fly's forward speed and, thus, indirectly its distance to the target; and (ii) a smooth pursuit system uses the retinal position of the target to regulate the fly's flight direction. Low-pass filters implement neuronal processing time. Treating the virtual fly as a point mass, its kinematics are modelled in consideration of the effects of translatory inertia and air friction. Despite its simplicity, the model shows behaviour similar to that of real flies. Depending on its starting position and orientation as well as on target size and speed, the virtual fly either catches the target or follows it indefinitely without capture. These two behavioural modes of the virtual fly emerge from the control system for flight steering without implementation of an explicit decision maker.

Design of the LBNF Beamline Target Station

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tariq, S.; Ammigan, K.; Anderson, K.

2016-10-01

The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding inmore » a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.« less

A Novel Pulse-Chase Paradigm to Visualize the Trafficking of Transport Vesicles in Neurons

NASA Astrophysics Data System (ADS)

Al-Bassam, Sarmad

In neurons transmembrane proteins are targeted to dendrites in vesicles that traffic solely within the somatodendritic compartment. How these vesicles are retained within the somatodendritic domain is unknown. Here we adapt a novel pulse chase system that allows synchronous release of exogenous transmembrane proteins from the endoplasmic reticulum using FKBP12 and Rapamycin. We demonstrate proof-of-concept and establish protein trafficking controls in incremental steps. We demonstrate the utility of this approach in studying protein trafficking and establish parameters for analysis of time-lapse images. We implement this novel pulse-chase strategy to track the movements of post-Golgi transport vesicles. Surprisingly, we found that post-Golgi vesicles carrying dendritic proteins were equally likely to enter axons and dendrites. However, once such vesicles entered the axon they very rarely moved beyond the axon initial segment, but instead either halted or reversed direction in an actin and Myosin Va-dependent manner. In contrast, vesicles carrying either an axonal or a nonspecifically localized protein only rarely halted or reversed and instead generally proceeded to the distal axon. Thus, our results are consistent with the axon initial segment behaving as a vesicle filter that mediates the differential trafficking of transport vesicles.

Stepped leaders observed in ground operations of ADELE

NASA Astrophysics Data System (ADS)

Smith, D. M.; Kelley, N.; Lowell, A.; Martinez-McKinney, F.; Dwyer, J. R.; Splitt, M. E.; Lazarus, S. M.; Cramer, E. S.; Levine, S.; Cummer, S. A.; Lu, G.; Shao, X.; Ho, C.; Eastvedt, E. M.; Trueblood, J.; Edens, H. E.; Hunyady, S. J.; Winn, W. P.; Rassoul, H. K.

2010-12-01

While the Airborne Detector for Energetic Lightning Emissions (ADELE) was designed primarily to study high-energy radiation associated with thunderstorms at aircraft altitude, it can also be used as a mobile ground-based instrument when mounted in a van. ADELE contains scintillation detectors optimized for faint and bright events and a flat-plate antenna measuring dE/dt. In July and August 2010, ADELE was brought to Langmuir Laboratory in New Mexico as a stationary detector and to the Florida peninsula (based at the Florida Institute of Technology in Melbourne) for rapid-response (storm-chasing) operations. In ten days of chasing, stepped-leader x-ray emission was observed from at least four close CG flashes, a much higher rate of success than can be achieved from a stationary detector or array. We will present these four events as well as the results of a study of candidate events of lesser statistical significance. We will also discuss the optimization of lightning-chasing strategies, science goals for future ground campaigns, and what additional instrumentation would be most scientifically beneficial. In the latter category, a proximity sensor (comparing flash and thunder arrival times) and a field mill are particularly important.

Gene Flow within and between Catchments in the Threatened Riparian Plant Myricaria germanica

PubMed Central

Werth, Silke; Scheidegger, Christoph

2014-01-01

One of the major distinctions of riparian habitats is their linearity. In linear habitats, gene flow is predicted to follow a one-dimensional stepping stone model, characterized by bidirectional gene flow between neighboring populations. Here, we studied the genetic structure of Myricaria germanica, a threatened riparian shrub which is capable of both wind and water dispersal. Our data led us to reject the ‘one catchment – one gene pool’ hypothesis as we found support for two gene pools, rather than four as expected in a study area including four catchments. This result also implies that in the history of the studied populations, dispersal across catchments has occurred. Two contemporary catchment-crossing migration events were detected, albeit between spatially proximate catchments. Allelic richness and inbreeding coefficients differed substantially between gene pools. There was significant isolation by distance, and our data confirmed the one-dimensional stepping-stone model of gene flow. Contemporary migration was bidirectional within the studied catchments, implying that dispersal vectors other than water are important for M. germanica. PMID:24932520

Automated Monitoring and Analysis of Social Behavior in Drosophila

PubMed Central

Dankert, Heiko; Wang, Liming; Hoopfer, Eric D.; Anderson, David J.; Perona, Pietro

2009-01-01

We introduce a method based on machine vision for automatically measuring aggression and courtship in Drosophila melanogaster. The genetic and neural circuit bases of these innate social behaviors are poorly understood. High-throughput behavioral screening in this genetically tractable model organism is a potentially powerful approach, but it is currently very laborious. Our system monitors interacting pairs of flies, and computes their location, orientation and wing posture. These features are used for detecting behaviors exhibited during aggression and courtship. Among these, wing threat, lunging and tussling are specific to aggression; circling, wing extension (courtship “song”) and copulation are specific to courtship; locomotion and chasing are common to both. Ethograms may be constructed automatically from these measurements, saving considerable time and effort. This technology should enable large-scale screens for genes and neural circuits controlling courtship and aggression. PMID:19270697

The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration

PubMed Central

Elsen, Gina E.; Choi, Louis Y.; Prince, Victoria E.; Ho, Robert K.

2009-01-01

During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders. PMID:19732764

Lasp1 gene disruption is linked to enhanced cell migration and tumor formation Address for reprint requests and other correspondence: C. S. Chew, Inst. of Molecular Medicine and Genetics, Sanders R&E Bldg., Rm. CB 2803, Medical College of Georgia, Augusta, GA 30912-3175 (e-mail: cchew@mcg.edu).

PubMed Central

Zhang, Han; Chen, Xunsheng; Bollag, Wendy B.; Bollag, Roni J.; Sheehan, Daniel J.; Chew, Catherine S.

2009-01-01

Lasp1 is an actin-binding, signaling pathway-regulated phosphoprotein that is overexpressed in several cancers. siRNA knockdown in cell lines retards cell migration, suggesting the possibility that Lasp1 upregulation influences cancer metastasis. Herein, we utilized a recently developed gene knockout model to assess the role of Lasp1 in modulating nontransformed cell functions. Wound healing and tumor initiation progressed more rapidly in Lasp1−/− mice compared with Lasp1+/+ controls. Embryonic fibroblasts (MEFs) derived from Lasp1−/− mice also migrated more rapidly in vitro. These MEFs characteristically possessed increased focal adhesion numbers and displayed more rapid attachment compared with wild-type MEFs. Differential microarray analyses revealed alterations in message expression for proteins implicated in cell migration, adhesion, and cytoskeletal organization. Notably, the focal adhesion protein, lipoma preferred partner (LPP), a zyxin family member and putative Lasp1 binding protein, was increased about twofold. Because LPP gene disruption reduces cell migration, we hypothesize that LPP plays a role in enhancing the migratory capacity of Lasp1−/− MEFs, perhaps by modifying the subcellular localization of other motility-associated proteins. The striking contrast in the functional effects of loss of Lasp1 in innate cells compared with cell lines reveals distinct differences in mechanisms of motility and attachment in these models. PMID:19531578

Knockdown endogenous CypA with siRNA in U2OS cells results in disruption of F-actin structure and alters tumor phenotype.

PubMed

Calhoun, Colonya C; Lu, Ying-Chun; Song, Jun; Chiu, Robert

2009-01-01

Cyclophilin A (CypA) was originally identified as a cytosolic protein possessing peptidyl-prolyl isomerase activity. CypA has been shown to play a pivotal role in the immune response, but little is known about other molecular mechanisms of CypA-mediated biologic events. In our present study, we demonstrate that knockdown CypA expression using RNAi in U2OS cells resulted in disruption of the F-actin structure, as well as decreased anchorage-independent growth, proliferation, and migration. Wild-type U2OS cells treated with cyclosporine A (CsA), a peptidyl-prolyl isomerase inhibitor, displayed the same phenotype as knockdown CypA cells, suggesting that the isomerase activity of CypA is required to maintain a normal phenotype. In vitro and in vivo binding assays revealed that CypA binds to N-WASP, which functions in the nucleation of actin via the Arp2/3 complex. Pulse-chase labeling study indicated an enhanced degradation of N-WASP in cell lacking CypA, suggesting that CypA is required for stabilizing N-WASP to form a N-WASP/Arp2/3 complex for the nucleation/initiation of F-actin polymerization.

Temperature-induced physiological stress and reproductive characteristics of the migratory seahorse Hippocampus erectus during a thermal stress simulation.

PubMed

Qin, Geng; Johnson, Cara; Zhang, Yuan; Zhang, Huixian; Yin, Jianping; Miller, Glen; Turingan, Ralph G; Guisbert, Eric; Lin, Qiang

2018-05-15

Inshore-offshore migration occurs frequently in seahorse species either because of prey opportunities or because it is driven by reproduction, and variations in water temperature may dramatically change migratory seahorse behavior and physiology. The present study investigated the behavioral and physiological responses of the lined seahorse Hippocampus erectus under thermal stress and evaluated the potential effects of different temperatures on its reproduction. The results showed that the thermal tolerance of the seahorses was time dependent. Acute thermal stress (30°C, 2-10 hours) increased the basal metabolic rate (breathing rate) and the expression of stress response genes ( Hsp genes) significantly and further stimulated seahorse appetite. Chronic thermal treatment (30°C, 4 weeks) led to a persistently higher basal metabolic rate, higher stress response gene expression, and higher mortality, indicating that the seahorses could not acclimate to chronic thermal stress and might experience massive mortality due to excessive basal metabolic rates and stress damage. Additionally, no significant negative effects on gonad development or reproductive endocrine regulation genes were observed in response to chronic thermal stress, suggesting that seahorse reproductive behavior could adapt to higher-temperature conditions during migration and within seahorse breeding grounds. In conclusion, this simulation experiment indicated that temperature variations during inshore-offshore migration have no effect on reproduction but promote basal metabolic rates and stress responses significantly. Therefore, we suggest that the high observed tolerance of seahorse reproduction was in line with the inshore-offshore reproductive migration pattern of lined seahorse. © 2018. Published by The Company of Biologists Ltd.

Genetics Home Reference: craniofacial-deafness-hand syndrome

MedlinePlus

... the PAX3 gene is active in cells called neural crest cells. These cells migrate from the developing ... directs the activity of other genes that signal neural crest cells to form specialized tissues or cell ...

Considering Plants.

ERIC Educational Resources Information Center

Flannery, Maura C.

1991-01-01

Examples from research that incorporate plants to illustrate biological principles are presented. Topics include dried pea shape, homeotic genes, gene transcription in plants that are touched or wounded, production of grasslands, seaweed defenses, migrating plants, camouflage, and family rivalry. (KR)

RNase L Suppresses Androgen Receptor Signaling, Cell Migration and Matrix Metalloproteinase Activity in Prostate Cancer Cells

PubMed Central

Dayal, Shubham; Zhou, Jun; Manivannan, Praveen; Siddiqui, Mohammad Adnan; Ahmad, Omaima Farid; Clark, Matthew; Awadia, Sahezeel; Garcia-Mata, Rafael; Shemshedini, Lirim; Malathi, Krishnamurthy

2017-01-01

The interferon antiviral pathways and prostate cancer genetics converge on a regulated endoribonuclease, RNase L. Positional cloning and linkage studies mapped Hereditary Prostate Cancer 1 (HPC1) to RNASEL. To date, there is no correlation of viral infections with prostate cancer, suggesting that RNase L may play additional roles in tumor suppression. Here, we demonstrate a role of RNase L as a suppressor of androgen receptor (AR) signaling, cell migration and matrix metalloproteinase activity. Using RNase L mutants, we show that its nucleolytic activity is dispensable for both AR signaling and migration. The most prevalent HPC1-associated mutations in RNase L, R462Q and E265X, enhance AR signaling and cell migration. RNase L negatively regulates cell migration and attachment on various extracellular matrices. We demonstrate that RNase L knockdown cells promote increased cell surface expression of integrin β1 which activates Focal Adhesion Kinase-Sarcoma (FAK-Src) pathway and Ras-related C3 botulinum toxin substrate 1-guanosine triphosphatase (Rac1-GTPase) activity to increase cell migration. Activity of matrix metalloproteinase (MMP)-2 and -9 is significantly increased in cells where RNase L levels are ablated. We show that mutations in RNase L found in HPC patients may promote prostate cancer by increasing expression of AR-responsive genes and cell motility and identify novel roles of RNase L as a prostate cancer susceptibility gene. PMID:28257035

Human migration activities drive the fluctuation of ARGs: Case study of landfills in Nanjing, eastern China.

PubMed

Sun, Mingming; Ye, Mao; Schwab, Arthur P; Li, Xu; Wan, Jinzhong; Wei, Zhong; Wu, Jun; Friman, Ville-Petri; Liu, Kuan; Tian, Da; Liu, Manqiang; Li, Huixin; Hu, Feng; Jiang, Xin

2016-09-05

Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination. Copyright © 2016 Elsevier B.V. All rights reserved.

Trypanosoma cruzi Calreticulin Is a Lectin That Binds Monoglucosylated Oligosaccharides but Not Protein Moieties of Glycoproteins

PubMed Central

Labriola, Carlos; Cazzulo, Juan J.; Parodi, Armando J.

1999-01-01

Trypanosoma cruzi is a protozoan parasite that belongs to an early branch in evolution. Although it lacks several features of the pathway of protein N-glycosylation and oligosaccharide processing present in the endoplasmic reticulum of higher eukaryotes, it displays UDP-Glc:glycoprotein glucosyltransferase and glucosidase II activities. It is herewith reported that this protozoan also expresses a calreticulin-like molecule, the third component of the quality control of glycoprotein folding. No calnexin-encoding gene was detected. Recombinant T. cruzi calreticulin specifically recognized free monoglucosylated high-mannose-type oligosaccharides. Addition of anti-calreticulin serum to extracts obtained from cells pulse–chased with [35S]Met plus [35S]Cys immunoprecipitated two proteins that were identified as calreticulin and the lysosomal proteinase cruzipain (a major soluble glycoprotein). The latter but not the former protein disappeared from immunoprecipitates upon chasing cells. Contrary to what happens in mammalian cells, addition of the glucosidase II inhibitor 1-deoxynojirimycin promoted calreticulin–cruzipain interaction. This result is consistent with the known pathway of protein N-glycosylation and oligosaccharide processing occurring in T. cruzi. A treatment of the calreticulin-cruzipain complexes with endo-β-N-acetylglucosaminidase H either before or after addition of anti-calreticulin serum completely disrupted calreticulin–cruzipain interaction. In addition, mature monoglucosylated but not unglucosylated cruzipain isolated from lysosomes was found to interact with recombinant calreticulin. It was concluded that the quality control of glycoprotein folding appeared early in evolution, and that T. cruzi calreticulin binds monoglucosylated oligosaccharides but not the protein moiety of cruzipain. Furthermore, evidence is presented indicating that glucosyltransferase glucosylated cruzipain at its last folding stages. PMID:10233151

Trypanosoma cruzi calreticulin is a lectin that binds monoglucosylated oligosaccharides but not protein moieties of glycoproteins.

PubMed

Labriola, C; Cazzulo, J J; Parodi, A J

1999-05-01

Trypanosoma cruzi is a protozoan parasite that belongs to an early branch in evolution. Although it lacks several features of the pathway of protein N-glycosylation and oligosaccharide processing present in the endoplasmic reticulum of higher eukaryotes, it displays UDP-Glc:glycoprotein glucosyltransferase and glucosidase II activities. It is herewith reported that this protozoan also expresses a calreticulin-like molecule, the third component of the quality control of glycoprotein folding. No calnexin-encoding gene was detected. Recombinant T. cruzi calreticulin specifically recognized free monoglucosylated high-mannose-type oligosaccharides. Addition of anti-calreticulin serum to extracts obtained from cells pulse-chased with [35S]Met plus [35S]Cys immunoprecipitated two proteins that were identified as calreticulin and the lysosomal proteinase cruzipain (a major soluble glycoprotein). The latter but not the former protein disappeared from immunoprecipitates upon chasing cells. Contrary to what happens in mammalian cells, addition of the glucosidase II inhibitor 1-deoxynojirimycin promoted calreticulin-cruzipain interaction. This result is consistent with the known pathway of protein N-glycosylation and oligosaccharide processing occurring in T. cruzi. A treatment of the calreticulin-cruzipain complexes with endo-beta-N-acetylglucosaminidase H either before or after addition of anti-calreticulin serum completely disrupted calreticulin-cruzipain interaction. In addition, mature monoglucosylated but not unglucosylated cruzipain isolated from lysosomes was found to interact with recombinant calreticulin. It was concluded that the quality control of glycoprotein folding appeared early in evolution, and that T. cruzi calreticulin binds monoglucosylated oligosaccharides but not the protein moiety of cruzipain. Furthermore, evidence is presented indicating that glucosyltransferase glucosylated cruzipain at its last folding stages.

Biological and Clinical Significance of MAD2L1 and BUB1, Genes Frequently Appearing in Expression Signatures for Breast Cancer Prognosis

PubMed Central

Wang, Zhanwei; Katsaros, Dionyssios; Shen, Yi; Fu, Yuanyuan; Canuto, Emilie Marion; Benedetto, Chiara; Lu, Lingeng; Chu, Wen-Ming; Risch, Harvey A.; Yu, Herbert

2015-01-01

To investigate the biologic relevance and clinical implication of genes involved in multiple gene expression signatures for breast cancer prognosis, we identified 16 published gene expression signatures, and selected two genes, MAD2L1 and BUB1. These genes appeared in 5 signatures and were involved in cell-cycle regulation. We analyzed the expression of these genes in relation to tumor features and disease outcomes. In vitro experiments were also performed in two breast cancer cell lines, MDA-MB-231 and MDA-MB-468, to assess cell proliferation, migration and invasion after knocking down the expression of these genes. High expression of these genes was found to be associated with aggressive tumors and poor disease-free survival of 203 breast cancer patients in our study, and the association with survival was confirmed in an online database consisting of 914 patients. In vitro experiments demonstrated that lowering the expression of these genes by siRNAs reduced tumor cell growth and inhibited cell migration and invasion. Our investigation suggests that MAD2L1 and BUB1 may play important roles in breast cancer progression, and measuring the expression of these genes may assist the prediction of breast cancer prognosis. PMID:26287798

Suppression of the Epidermal Growth Factor-like Domain 7 and Inhibition of Migration and Epithelial-Mesenchymal Transition in Human Pancreatic Cancer PANC-1 Cells.

PubMed

Wang, Yun-Liang; Dong, Feng-Lin; Yang, Jian; Li, Zhi; Zhi, Qiao-Ming; Zhao, Xin; Yang, Yong; Li, De-Chun; Shen, Xiao-Chun; Zhou, Jin

2015-01-01

Epidermal growth factor-like domain multiple 7 (EGFL7), a secreted protein specifically expressed by endothelial cells during embryogenesis, recently was identified as a critical gene in tumor metastasis. Epithelial-mesenchymal transition (EMT) was found to be closely related with tumor progression. Accordingly, it is important to investigate the migration and EMT change after knock-down of EGFL7 gene expression in human pancreatic cancer cells. EGFL7 expression was firstly testified in 4 pancreatic cancer cell lines by real-time polymerase chain reaction (Real-time PCR) and western blot, and the highest expression of EGFL7 was found in PANC-1 cell line. Then, PANC-1 cells transfected with small interference RNA (siRNA) of EGFL7 using plasmid vector were named si-PANC-1, while transfected with negative control plasmid vector were called NC-PANC-1. Transwell assay was used to analyze the migration of PANC-1 cells. Real-time PCR and western blotting were used to detect the expression change of EGFL7 gene, EMT markers like E-Cadherin, N-Cadherin, Vimentin, Fibronectin and transcription factors like snail, slug in PANC-1, NC- PANC-1, and si-PANC-1 cells, respectively. After successful plasmid transfection, EGFL7 gene were dramatically knock-down by RNA interference in si-PANC-1 group. Meanwhile, migration ability decreased significantly, compared with PANC-1 and NC-PANC-1 group. Meanwhile, the expression of epithelial phenotype marker E-Cadherin increased and that of mesenchymal phenotype markers N-Cadherin, Vimentin, Fibronectin dramatically decreased in si-PANC-1 group, indicating a reversion of EMT. Also, transcription factors snail and slug decreased significantly after RNA interference. Current study suggested that highly-expressed EGFL7 promotes migration of PANC-1 cells and acts through transcription factors snail and slug to induce EMT, and further study is needed to confirm this issue.

LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

PubMed

Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

2015-02-15

Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development. Copyright © 2015 the American Physiological Society.

Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.

PubMed

Leijs, Maarten J C; van Buul, Gerben M; Verhaar, Jan A N; Hoogduijn, Martin J; Bos, Pieter K; van Osch, Gerjo J V M

2017-04-01

Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Controlled laboratory study. We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.

Altruism Can Proliferate through Population Viscosity despite High Random Gene Flow

PubMed Central

Schonmann, Roberto H.; Vicente, Renato; Caticha, Nestor

2013-01-01

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis has led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism through population viscosity in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism that benefits equally all group members, regardless of kinship and without greenbeard effects, can spread when rare under realistic group sizes and levels of migration, due to the assortment of genes resulting only from population viscosity. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton’s rule for the spread of altruistic alleles, applicable under broad conditions. PMID:23991035

The effect of biogeographic and phylogeographic barriers on gene flow in the brown smoothhound shark, Mustelus henlei, in the northeastern Pacific

PubMed Central

Chabot, Chris L; Espinoza, Mario; Mascareñas-Osorio, Ismael; Rocha-Olivares, Axayácatl

2015-01-01

We assessed the effects of the prominent biogeographic (Point Conception and the Peninsula of Baja California) and phylogeographic barriers (Los Angeles Region) of the northeastern Pacific on the population connectivity of the brown smoothhound shark, Mustelus henlei (Triakidae). Data from the mitochondrial control region and six nuclear microsatellite loci revealed significant population structure among three populations: northern (San Francisco), central (Santa Barbara, Santa Catalina, Punta Lobos, and San Felipe), and southern (Costa Rica). Patterns of long-term and contemporary migration were incongruent, with long-term migration being asymmetric and occurring in a north to south direction and a lack of significant contemporary migration observed between localities with the exception of Punta Lobos that contributed migrants to all localities within the central population. Our findings indicate that Point Conception may be restricting gene flow between the northern and central populations whereas barriers to gene flow within the central population would seem to be ineffective; additionally, a contemporary expansion of tropical M. henlei into subtropical and temperate waters may have been observed. PMID:25937903

Stem cells in asexual reproduction of Enchytraeus japonensis (Oligochaeta, Annelid): proliferation and migration of neoblasts.

PubMed

Sugio, Mutsumi; Yoshida-Noro, Chikako; Ozawa, Kaname; Tochinai, Shin

2012-05-01

Enchytraeus japonensis is a small oligochaete that reproduces mainly asexually by fragmentation (autotomy) and regeneration. As sexual reproduction can also be induced, it is a good animal model for the study of both somatic and germline stem cells. To clarify the features of stem cells in regeneration, we investigated the proliferation and lineage of stem cells in E. japonensis. Neoblasts, which have the morphological characteristics of undifferentiated cells, were found to firmly adhere to the posterior surface of septa in each trunk segment. Also, smaller neoblast-like cells, which are designated as N-cells in this study, were located dorsal to the neoblasts on the septa. By conducting 5-bromo-2'-deoxyuridine (BrdU)-labeling-experiments, we have shown that neoblasts are slow-cycling (or quiescent) in intact growing worms, but proliferate rapidly in response to fragmentation. N-cells proliferate more actively than do neoblasts in intact worms. The results of pulse-chase experiments indicated that neoblast and N-cell lineage mesodermal cells that incorporated BrdU early in regeneration migrated toward the autotomized site to form the mesodermal region of the blastema, while the epidermal and intestinal cells also contributed to the blastema locally near the autotomized site. We have also shown that neoblasts have stem cell characteristics by expressing Ej-vlg2 and by the activity of telomerase during regeneration. Telomerase activity was high in the early stage of regeneration and correlated with the proliferation activity in the neoblast lineage of mesodermal stem cells. Taken together, our results indicate that neoblasts are mesodermal stem cells involved in the regeneration of E. japonensis. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells.

PubMed

Yan, Lin-Lin; Huang, Yuan-Jiao; Yi, Xiang; Yan, Xue-Min; Cai, Yan; He, Qin; Han, Zi-Jian

2015-06-01

The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells.

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

PubMed Central

YAN, LIN-LIN; HUANG, YUAN-JIAO; YI, XIANG; YAN, XUE-MIN; CAI, YAN; HE, QIN; HAN, ZI-JIAN

2015-01-01

The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells. PMID:26137102

Soluble vascular endothelial growth factor (VEGF) receptor-1 inhibits migration of human monocytic THP-1 cells in response to VEGF.

PubMed

Zhu, Cansheng; Xiong, Zhaojun; Chen, Xiaohong; Lu, Zhengqi; Zhou, Guoyu; Wang, Dunjing; Bao, Jian; Hu, Xueqiang

2011-08-01

We aimed to investigate the regulation and contribution of vascular endothelial growth factor (VEGF) and sFlt-1(1-3) to human monocytic THP-1 migration. Ad-sFlt-1/FLAG, a recombinant adenovirus carrying the human sFlt-1(1-3) (the first three extracellular domains of FLT-1, the hVEGF receptor-1) gene, was constructed. L929 cells were infected with Ad-sFlt-1/FLAG and the expression of sFlt-1 was detected by immunofluorescent assay and ELISA. Corning(®) Transwell(®) Filter Inserts containing polyethylene terephthalate (PET) membranes with pore sizes of 3 μm were used as an experimental model to simulate THP-1 migration. Five VEGF concentrations (0, 0.1, 1, 10 and 100 ng/ml), four concentrations of sFlt-1(1-3)/FLAG expression supernatants (0.1, 1, 10 and 100 ng/ml), and monocyte chemoattractant protein-1 (MCP-1, 10 ng/ml) were used to test the ability of THP-1 cells to migrate through PET membranes. The sFlt-1(1-3) gene was successfully recombined into Ad-sFlt-1/FLAG. sFlt-1(1-3) was expressed in L929 cells transfected with Ad-sFlt-1/FLAG. THP-1 cell migration increased with increasing concentrations of VEGF, while cell migration decreased with increasing concentrations of sFlt1(1-3)/FLAG. sFlt1(1-3)/FLAG had no effect on MCP-1-induced cell migration. This study demonstrated that VEGF is able to elicit a migratory response in THP-1 cells, and that sFlt-1(1-3) is an effective inhibitor of THP-1 migration towards VEGF.

SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Feng; Jordan, Ashley; Kluz, Thomas

The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealedmore » the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.« less

Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition.

PubMed

Khan, Md Asaduzzaman; Tania, Mousumi; Wei, Chunli; Mei, Zhiqiang; Fu, Shelly; Cheng, Jingliang; Xu, Jianming; Fu, Junjiang

2015-08-14

Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis.

Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition

PubMed Central

Khan, Md. Asaduzzaman; Tania, Mousumi; Wei, Chunli; Mei, Zhiqiang; Fu, Shelly; Cheng, Jingliang; Xu, Jianming; Fu, Junjiang

2015-01-01

Proteins that promote epithelial to mesenchymal transition (EMT) are associated with cancer metastasis. Inhibition of EMT regulators may be a promising approach in cancer therapy. In this study, Thymoquinone (TQ) was used to treat cancer cell lines to investigate its effects on EMT-regulatory proteins and cancer metastasis. We show that TQ inhibited cancer cell growth, migration and invasion in a dose-dependent manner. At the molecular level, TQ treatment decreased the transcriptional activity of the TWIST1 promoter and the mRNA expression of TWIST1, an EMT-promoting transcription factor. Accordingly, TQ treatment also decreased the expression of TWIST1-upregulated genes such as N-Cadherin and increased the expression of TWIST1-repressed genes such as E-Cadherin, resulting in a reduction of cell migration and invasion. TQ treatment also inhibited the growth and metastasis of cancer cell-derived xenograft tumors in mice but partially attenuated the migration and invasion in TWIST1-overexpressed cell lines. Furthermore, we found that TQ treatment enhanced the promoter DNA methylation of the TWIST1 gene in BT 549 cells. Together, these results demonstrate that TQ treatment inhibits TWIST1 promoter activity and decreases its expression, leading to the inhibition of cancer cell migration, invasion and metastasis. These findings suggest TQ as a potential small molecular inhibitor of cancer growth and metastasis. PMID:26023736

Higher impact of female than male migration on population structure in large mammals.

PubMed

Tiedemann, R; Hardy, O; Vekemans, X; Milinkovitch, M C

2000-08-01

We simulated large mammal populations using an individual-based stochastic model under various sex-specific migration schemes and life history parameters from the blue whale and the Asian elephant. Our model predicts that genetic structure at nuclear loci is significantly more influenced by female than by male migration. We identified requisite comigration of mother and offspring during gravidity and lactation as the primary cause of this phenomenon. In addition, our model predicts that the common assumption that geographical patterns of mitochondrial DNA (mtDNA) could be translated into female migration rates (Nmf) will cause biased estimates of maternal gene flow when extensive male migration occurs and male mtDNA haplotypes are included in the analysis.

Increased asthma and adipose tissue inflammatory gene expression with obesity and Inuit migration to a western country.

PubMed

Backer, Vibeke; Baines, Katherine J; Powell, Heather; Porsbjerg, Celeste; Gibson, Peter G

2016-02-01

An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1β) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01). No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

An analysis of the gene interaction networks identifying the role of PARP1 in metastasis of non-small cell lung cancer.

PubMed

Chen, Kai; Li, Yajie; Xu, Hui; Zhang, Chunfeng; Li, Zhiqiang; Wang, Wei; Wang, Baofeng

2017-10-20

Though there were many researches about the effects of cancer cells on non-small cell lung cancer (NSCLC) currently, it has been rarely reported completed oncogene and its mechanism in tumors by far. Here, we used biological methods with known oncogene of NSCLC to find new oncogene and explore its functionary mechanism in NSCLC. The study firstly built NSCLC genetic interaction network based on bioinformatics methods and then combined shortest path algorithm with significance test to confirmed core genes that were closely involved with given genes; real-time qPCR was conducted to detect expression levels between patients with NSCLC and normal people; additionally, detection of PARP1's role in migration and invasion was performed by trans-well assays and wound-healing. Through gene interaction network, it was found that, core genes like PARP1, EGFR and ALK had a direct interaction. TCGA database showed that PARP1 presented strong expression in NSCLC and the expression level of metastatic NSCLC was significantly higher than that of non-metastatic NSCLC. Cell migration of NSCLC in accordance to the scratch test was suppressed by PARP1 silence but stimulated noticeably by PARP1 overexpression. According to Kaplan-meier survival curve, the higher PARP1 expression, the poorer patient survival rate and prognosis. Thus, PARP1 expression had a negative correction with patient survival rate and prognosis. New oncogene PARP1 was found from known NSCLC oncogene in terms of gene interaction network, demonstrating PARP1's impact on NSCLC cell migration.

Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

PubMed

Kennedy, Lisa M; Grishok, Alla

2014-05-01

Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

Neuronal Migration Is Regulated by Endogenous RNAi and Chromatin-Binding Factor ZFP-1/AF10 in Caenorhabditis elegans

PubMed Central

Kennedy, Lisa M.; Grishok, Alla

2014-01-01

Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning. PMID:24558261

Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB.

PubMed

Suboj, Priya; Babykutty, Suboj; Valiyaparambil Gopi, Deepak Roshan; Nair, Rakesh S; Srinivas, Priya; Gopala, Srinivas

2012-04-11

Aloe emodin (AE), a natural anthraquinone, is reported to have antiproliferative activity in various cancer cell lines. In this study we analyzed molecular mechanisms involved in the antimigratory and antiangiogenic activity of this hydroxy anthraquinone in colon cancer cell, WiDr. Our results show that a relatively non toxic concentration of AE suppressed the phorbol-12-myristyl-13-acetate (PMA) induced migration and invasion of tumor cells. On analysis for the molecules involved in the migration/invasion, we found AE downregulated mRNA expression and promoter/gelatinolytic activity of Matrix Metalloproteinase (MMP)-2/9, as well as the RhoB expression at gene and protein level. It was also a strong inhibitor of Vascular Endothelial Growth Factor (VEGF) expression, promoter activity and endothelial cell migration/invasion and in vitro angiogenesis. AE suppressed the nuclear translocation and DNA binding of NF-κB, which is an important transcription factor for controlling MMP-2/9 and VEGF gene expression. Taken together these data indicate that AE target multiple molecules responsible for cellular invasion, migration and angiogenesis. Inhibitory effect on angiogenic and metastatic regulatory processes make AE a sensible candidate as a specific blocker of tumor associated events. Copyright © 2011 Elsevier B.V. All rights reserved.

Cytonuclear Theory for Haplodiploid Species and X-Linked Genes. I. Hardy-Weinberg Dynamics and Continent-Island, Hybrid Zone Models

PubMed Central

Goodisman, MAD.; Asmussen, M. A.

1997-01-01

We develop models that describe the cytonuclear structure for either a cytoplasmic and nuclear marker in a haplodiploid species or a cytoplasmic and X-linked marker in a diploid species. Sex-specific disequilibrium statistics that summarize nonrandom cytonuclear associations in such systems are defined, and their basic Hardy-Weinberg dynamics and admixture formulae are delimited. We focus on the context of hybrid zones and develop continent-island models whereby individuals from two genetically differentiated source populations migrate into and mate within a single zone of admixture. We examine the effects of differential migration of the sexes, assortative mating by pure type females, and census time (relative to mating and migration), as well as special cases of random mating and migration subsumed under the general models. We show that pure type individuals and nonzero cytonuclear disequilibria can be maintained within a hybrid zone if there is continued migration from both source populations, and that females generally have a greater influence over these cytonuclear variables than males. The resulting theoretical framework can be used to estimate the rates of assortative mating and sex-specific gene flow in hybrid zones and other zones of admixture involving haplodiploid or sex-linked cytonuclear data. PMID:9286692

Far infrared promotes wound healing through activation of Notch1 signaling.

PubMed

Hsu, Yung-Ho; Lin, Yuan-Feng; Chen, Cheng-Hsien; Chiu, Yu-Jhe; Chiu, Hui-Wen

2017-11-01

The Notch signaling pathway is critically involved in cell proliferation, differentiation, development, and homeostasis. Far infrared (FIR) has an effect that promotes wound healing. However, the underlying molecular mechanisms are unclear. In the present study, we employed in vivo and HaCaT (a human skin keratinocyte cell line) models to elucidate the role of Notch1 signaling in FIR-promoted wound healing. We found that FIR enhanced keratinocyte migration and proliferation. FIR induced the Notch1 signaling pathway in HaCaT cells and in a microarray dataset from the Gene Expression Omnibus database. We next determined the mRNA levels of NOTCH1 in paired normal and wound skin tissues derived from clinical patients using the microarray dataset and Ingenuity Pathway Analysis software. The result indicated that the Notch1/Twist1 axis plays important roles in wound healing and tissue repair. In addition, inhibiting Notch1 signaling decreased the FIR-enhanced proliferation and migration. In a full-thickness wound model in rats, the wounds healed more rapidly and the scar size was smaller in the FIR group than in the light group. Moreover, FIR could increase Notch1 and Delta1 in skin tissues. The activation of Notch1 signaling may be considered as a possible mechanism for the promoting effect of FIR on wound healing. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model. FIR stimulates keratinocyte migration and proliferation. Notch1 in keratinocytes has an essential role in FIR-induced migration and proliferation. NOTCH1 promotes TWIST1-mediated gene expression to assist wound healing. FIR might promote skin wound healing in a rat model.

NASA HS3 Global Hawk on the Wing

NASA Image and Video Library

2013-08-30

The NASA Wallops T-34 chase aircraft intercepted Global Hawk 872 on its descent to runway 28 at NASA's Wallops Flight Facility in Wallops Island, Va. This photo of the Global Hawk was taken from the chase plane after finishing its third science flight. For more information about NASA's HS3 mission, visit: www.nasa.gov/HS3 Credit: NASA/ Brea Reeves NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

The Chase to Capture Gamma Ray Bursts

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2008-01-01

Gamma-ray bursts are the most powerful explosions in the universe, thought to be the birth cries of black holes. It has taken 40 years of international cooperation and competition to begin to unravel the mystery of their origin. The most recent chapter in this field is being written by the SWIFT mission, a fast-response satellite with 3 power telescopes. An international team from countries all over the world participates in the chase to capture the fading light of bursts detected by SWIFT. This talk will discuss the challenges and excitement of building this space observatory. New results will be presented on our growing understanding of exploding stars and fiery mergers of orbiting stars.

Irc3 is a mitochondrial DNA branch migration enzyme

PubMed Central

Gaidutšik, Ilja; Sedman, Tiina; Sillamaa, Sirelin; Sedman, Juhan

2016-01-01

Integrity of mitochondrial DNA (mtDNA) is essential for cellular energy metabolism. In the budding yeast Saccharomyces cerevisiae, a large number of nuclear genes influence the stability of mitochondrial genome; however, most corresponding gene products act indirectly and the actual molecular mechanisms of mtDNA inheritance remain poorly characterized. Recently, we found that a Superfamily II helicase Irc3 is required for the maintenance of mitochondrial genome integrity. Here we show that Irc3 is a mitochondrial DNA branch migration enzyme. Irc3 modulates mtDNA metabolic intermediates by preferential binding and unwinding Holliday junctions and replication fork structures. Furthermore, we demonstrate that the loss of Irc3 can be complemented with mitochondrially targeted RecG of Escherichia coli. We suggest that Irc3 could support the stability of mtDNA by stimulating fork regression and branch migration or by inhibiting the formation of irregular branched molecules. PMID:27194389

The genetics of monarch butterfly migration and warning colouration.

PubMed

Zhan, Shuai; Zhang, Wei; Niitepõld, Kristjan; Hsu, Jeremy; Haeger, Juan Fernández; Zalucki, Myron P; Altizer, Sonia; de Roode, Jacobus C; Reppert, Steven M; Kronforst, Marcus R

2014-10-16

The monarch butterfly, Danaus plexippus, is famous for its spectacular annual migration across North America, recent worldwide dispersal, and orange warning colouration. Despite decades of study and broad public interest, we know little about the genetic basis of these hallmark traits. Here we uncover the history of the monarch's evolutionary origin and global dispersal, characterize the genes and pathways associated with migratory behaviour, and identify the discrete genetic basis of warning colouration by sequencing 101 Danaus genomes from around the globe. The results rewrite our understanding of this classic system, showing that D. plexippus was ancestrally migratory and dispersed out of North America to occupy its broad distribution. We find the strongest signatures of selection associated with migration centre on flight muscle function, resulting in greater flight efficiency among migratory monarchs, and that variation in monarch warning colouration is controlled by a single myosin gene not previously implicated in insect pigmentation.

Role of NADPH Oxidase-4 in Human Endothelial Progenitor Cells

PubMed Central

Hakami, Nora Y.; Ranjan, Amaresh K.; Hardikar, Anandwardhan A.; Dusting, Greg J.; Peshavariya, Hitesh M.

2017-01-01

Introduction: Endothelial progenitor cells (EPCs) display a unique ability to promote angiogenesis and restore endothelial function in injured blood vessels. NADPH oxidase 4 (NOX4)-derived hydrogen peroxide (H2O2) serves as a signaling molecule and promotes endothelial cell proliferation and migration as well as protecting against cell death. However, the role of NOX4 in EPC function is not completely understood. Methods: EPCs were isolated from human saphenous vein and mammary artery discarded during bypass surgery. NOX4 gene and protein expression in EPCs were measured by real time-PCR and Western blot analysis respectively. NOX4 gene expression was inhibited using an adenoviral vector expressing human NOX4 shRNA (Ad-NOX4i). H2O2 production was measured by Amplex red assay. EPC migration was evaluated using a transwell migration assay. EPC proliferation and viability were measured using trypan blue counts. Results: Inhibition of NOX4 using Ad-NOX4i reduced Nox4 gene and protein expression as well as H2O2 formation in EPCs. Inhibition of NOX4-derived H2O2 decreased both proliferation and migration of EPCs. Interestingly, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) decreased NOX4 expression and reduced survival of EPCs. However, the survival of EPCs was further diminished by TNF-α in NOX4-knockdown cells, suggesting that NOX4 has a protective role in EPCs. Conclusion: These findings suggest that NOX4-type NADPH oxidase is important for proliferation and migration functions of EPCs and protects against pro-inflammatory cytokine induced EPC death. These properties of NOX4 may facilitate the efficient function of EPCs which is vital for successful neovascularization. PMID:28386230

PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer.

PubMed

Juang, Yu-Lin; Jeng, Yung-Ming; Chen, Chi-Long; Lien, Huang-Chun

2016-12-01

TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-β-induced invasion and EMT in breast cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery.

PubMed

Larifla, Laurent; Déprez, Isabelle; Pham, Isabelle; Rideau, Dominique; Louzier, Vanessa; Adam, Micheline; Eloit, Marc; Foucan, Lydia; Adnot, Serge; Teiger, Emmanuel

2012-07-01

Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled β-galactosidase gene (Ad-RSV-β-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury. Copyright © 2012 John Wiley & Sons, Ltd.

Ecological Trade-offs between Migration and Reproduction Are Mediated by the Nutrition-Sensitive Insulin-Signaling Pathway.

PubMed

Lin, Xinda; Yao, Yun; Wang, Bo; Emlen, Douglas J; Lavine, Laura Corley

2016-01-01

Crowding and changes in food availability are two critical environmental conditions that impact an animal's trajectory toward either migration or reproduction. Many insects facing this challenge have evolved wing polyphenisms. When conditions favor reproduction, wing polyphenic species produce adults that either have no wings or short, non-functional wings. Facultative wing growth reflects a physiological and evolutionary trade-off between migration and reproduction, triggered by environmental conditions. How environmental cues are transduced to produce these alternative forms, and their associated ecological shift from migration to reproduction, remains an important unsolved problem in evolutionary ecology. The brown planthopper, a wing polymorphic insect exhibiting strong trade-offs in investment between migration and reproduction, is one of the most serious rice pests in Asia. In this study, we investigated the function of four genes in the insulin-signaling pathway known to couple nutrition with growth, PI3 Kinase (PI3K), PDK1, Akt (Protein Kinase B), and the forkhead gene FOXO. Using a combination of RNA interference and pharmacological inhibitor treatment, we show that all four genes contribute to tissue level regulation of wing polymorphic development in this insect. As predicted, silencing of the NlPI3K, NlAkt and NlPDK1 through dsRNA and with the pharmacological inhibitor Perifosine resulted in short-winged brown planthoppers, whereas knockdown of NlFOXO resulted in long-winged planthoppers. Morphometric analyses confirm that phenotypes from our manipulations mimic what would be found in nature, i.e., major parameters such as bristle number, wing area and body weight are not significantly different from non-experimental animals. Taken together, these data implicate the insulin-signaling pathway in the transduction of environmental factors into condition-dependent patterns of wing growth in insects.

Promotive Effect of Zinc Ions on the Vitality, Migration, and Osteogenic Differentiation of Human Dental Pulp Cells.

PubMed

An, Shaofeng; Gong, Qimei; Huang, Yihua

2017-01-01

Zinc is an essential trace element for proper cellular function and bone formation. However, its exact role in the osteogenic differentiation of human dental pulp cells (hDPCs) has not been fully clarified before. Here, we speculated that zinc may be effective to regulate their growth and osteogenic differentiation properties. To test this hypothesis, different concentrations (1 × 10 -5 , 4 × 10 -5 , and 8 × 10 -5  M) of zinc ions (Zn 2+ ) were added to the basic growth culture medium and osteogenic inductive medium. Cell viability and migration were measured by cell counting kit-8 (CCK-8) and transwell migration assay in the basic growth culture medium, respectively. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expression levels of selective osteogenic differentiation markers and zinc transporters. Alkaline phosphatase (ALP) activity analysis and alizarin red S staining were used to investigate the mineralization of hDPCs. Exposure of hDPCs to Zn 2+ stimulated their viability and migration capacity in a dose- and time-dependent manner. RT-qPCR assay revealed elevated expression levels of osteogenic differentiation-related genes and zinc transporters genes in various degrees. ALP activity was also increased with elevated Zn 2+ concentrations and extended culture periods, but enhanced matrix nodules formation were observed only in 4 × 10 -5 and 8 × 10 -5  M Zn 2+ groups. These findings suggest that specific concentrations of Zn 2+ could potentiate the vitality, migration, and osteogenic differentiation of hDPCs. We may combine optimum zinc element into pulp capping materials to improve their biological performance.

[Regulation of microRNA-199a on adhesion, migration and invasion ability of human endometrial stromal cells].

PubMed

Dai, Lan; Gu, Li-ying; Zhu, Jie; Shi, Jun; Wang, Yao; Ji, Fang; Di, Wen

2011-11-01

To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKβ was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKβ), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P < 0.01). (2) Migration and invasion: in the scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKβ, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKβ is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKβ gene.

Consequences of high temperatures and premature mortality on the transcriptome and blood physiology of wild adult sockeye salmon (Oncorhynchus nerka)

PubMed Central

Jeffries, Ken M; Hinch, Scott G; Sierocinski, Thomas; Clark, Timothy D; Eliason, Erika J; Donaldson, Michael R; Li, Shaorong; Pavlidis, Paul; Miller, Kristi M

2012-01-01

Elevated river water temperature in the Fraser River, British Columbia, Canada, has been associated with enhanced mortality of adult sockeye salmon (Oncorhynchus nerka) during their upriver migration to spawning grounds. We undertook a study to assess the effects of elevated water temperatures on the gill transcriptome and blood plasma variables in wild-caught sockeye salmon. Naturally migrating sockeye salmon returning to the Fraser River were collected and held at ecologically relevant temperatures of 14°C and 19°C for seven days, a period representing a significant portion of their upstream migration. After seven days, sockeye salmon held at 19°C stimulated heat shock response genes as well as many genes associated with an immune response when compared with fish held at 14°C. Additionally, fish at 19°C had elevated plasma chloride and lactate, suggestive of a disturbance in osmoregulatory homeostasis and a stress response detectable in the blood plasma. Fish that died prematurely over the course of the holding study were compared with time-matched surviving fish; the former fish were characterized by an upregulation of several transcription factors associated with apoptosis and downregulation of genes involved in immune function and antioxidant activity. Ornithine decarboxylase (ODC1) was the most significantly upregulated gene in dying salmon, which suggests an association with cellular apoptosis. We hypothesize that the observed decrease in plasma ions and increases in plasma cortisol that occur in dying fish may be linked to the increase in ODC1. By highlighting these underlying physiological mechanisms, this study enhances our understanding of the processes involved in premature mortality and temperature stress in Pacific salmon during migration to spawning grounds. PMID:22957178

Consequences of high temperatures and premature mortality on the transcriptome and blood physiology of wild adult sockeye salmon (Oncorhynchus nerka).

PubMed

Jeffries, Ken M; Hinch, Scott G; Sierocinski, Thomas; Clark, Timothy D; Eliason, Erika J; Donaldson, Michael R; Li, Shaorong; Pavlidis, Paul; Miller, Kristi M

2012-07-01

Elevated river water temperature in the Fraser River, British Columbia, Canada, has been associated with enhanced mortality of adult sockeye salmon (Oncorhynchus nerka) during their upriver migration to spawning grounds. We undertook a study to assess the effects of elevated water temperatures on the gill transcriptome and blood plasma variables in wild-caught sockeye salmon. Naturally migrating sockeye salmon returning to the Fraser River were collected and held at ecologically relevant temperatures of 14°C and 19°C for seven days, a period representing a significant portion of their upstream migration. After seven days, sockeye salmon held at 19°C stimulated heat shock response genes as well as many genes associated with an immune response when compared with fish held at 14°C. Additionally, fish at 19°C had elevated plasma chloride and lactate, suggestive of a disturbance in osmoregulatory homeostasis and a stress response detectable in the blood plasma. Fish that died prematurely over the course of the holding study were compared with time-matched surviving fish; the former fish were characterized by an upregulation of several transcription factors associated with apoptosis and downregulation of genes involved in immune function and antioxidant activity. Ornithine decarboxylase (ODC1) was the most significantly upregulated gene in dying salmon, which suggests an association with cellular apoptosis. We hypothesize that the observed decrease in plasma ions and increases in plasma cortisol that occur in dying fish may be linked to the increase in ODC1. By highlighting these underlying physiological mechanisms, this study enhances our understanding of the processes involved in premature mortality and temperature stress in Pacific salmon during migration to spawning grounds.

Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an "eye open at birth" phenotype.

PubMed

Wu, L C; Liu, C; Jiang, M R; Jiang, Y M; Wang, Q H; Lu, Z Y; Wang, S J; Yang, W L; Shao, Y X

2016-08-26

Development of the eyelid requires coordination of the cellular processes involved in proliferation, cell size alteration, migration, and cell death. C57BL/6J-corneal opacity (B6-Co) mice are mutant mice generated by the administration of N-ethyl-N-nitrosourea (100 mg/kg). They exhibit the eyelids open at birth phenotype, abnormal round cell shape from tightened F-actin bundles in leading edge keratinocytes at E16.5, and gradual corneal opacity with neovessels. The tip of the leading edge in B6-Co mice did not move forward, and demonstrated a sharp peak shape without obvious directionality. Analysis of the biological characteristics of B6-Co mice demonstrated that abnormal migration of keratinocytes could affect eyelid development, but proliferation and apoptosis in B6-Co mice had no effect. Mutant gene mapping and sequence analysis demonstrated that in B6-Co mice, adenosine was inserted into the untranslated regions, between 3030 and 3031, in the mRNA 3'-terminal of Fgf10. In addition, guanine 7112 was substituted by adenine in the Mtap1B mRNA, and an A2333T mutation was identified in Mtap1B. Quantitative real-time polymerase chain reaction analysis showed that expression of the Hbegf gene was significantly down-regulated in the eyelids of B6- Co mice at E16.5, compared to B6 mice. However, the expression of Rock1, Map3k1, and Jnk1 genes did not show any significant changes. Abnormal keratinocyte migration and down-regulated expression of the Hbegf gene might be associated with impaired eyelid development in B6-Co mice.

Vitamin K2 improves proliferation and migration of bovine skeletal muscle cells in vitro.

PubMed

Rønning, Sissel Beate; Pedersen, Mona Elisabeth; Berg, Ragnhild Stenberg; Kirkhus, Bente; Rødbotten, Rune

2018-01-01

Skeletal muscle function is highly dependent on the ability to regenerate, however, during ageing or disease, the proliferative capacity is reduced, leading to loss of muscle function. We have previously demonstrated the presence of vitamin K2 in bovine skeletal muscles, but whether vitamin K has a role in muscle regulation and function is unknown. In this study, we used primary bovine skeletal muscle cells, cultured in monolayers in vitro, to assess a potential effect of vitamin K2 (MK-4) during myogenesis of muscle cells. Cell viability experiments demonstrate that the amount of ATP produced by the cells was unchanged when MK-4 was added, indicating viable cells. Cytotoxicity analysis show that MK-4 reduced the lactate dehydrogenase (LDH) released into the media, suggesting that MK-4 was beneficial to the muscle cells. Cell migration, proliferation and differentiation was characterised after MK-4 incubation using wound scratch analysis, immunocytochemistry and real-time PCR analysis. Adding MK-4 to the cells led to an increased muscle proliferation, increased gene expression of the myogenic transcription factor myod as well as increased cell migration. In addition, we observed a reduction in the fusion index and relative gene expression of muscle differentiation markers, with fewer complex myotubes formed in MK-4 stimulated cells compared to control cells, indicating that the MK-4 plays a significant role during the early phases of muscle proliferation. Likewise, we see the same pattern for the relative gene expression of collagen 1A, showing increased gene expression in proliferating cells, and reduced expression in differentiating cells. Our results also suggest that MK-4 incubation affect low density lipoprotein receptor-related protein 1 (LRP1) and the low-density lipoprotein receptor (LDLR) with a peak in gene expression after 45 min of MK-4 incubation. Altogether, our experiments show that MK-4 has a positive effect on muscle cell migration and proliferation, which are two important steps during early myogenesis.

Small heat shock proteins are necessary for heart migration and laterality determination in zebrafish

PubMed Central

Lahvic, Jamie L.; Ji, Yongchang; Marin, Paloma; Zuflacht, Jonah P.; Springel, Mark W.; Wosen, Jonathan E.; Davis, Leigh; Hutson, Lara D.; Amack, Jeffrey D.; Marvin, Martha J.

2013-01-01

Small heat shock proteins (sHsps) regulate cellular functions not only under stress, but also during normal development, when they are expressed in organ-specific patterns. Here we demonstrate that two small heat shock proteins expressed in embryonic zebrafish heart, hspb7 and hspb12, have roles in the development of left-right asymmetry. In zebrafish, laterality is determined by the motility of cilia in Kupffer’s vesicle (KV), where hspb7 is expressed; knockdown of hspb7 causes laterality defects by disrupting the motility of these cilia. In embryos with reduced hspb7, the axonemes of KV cilia have a 9+0 structure, while control embyros have a predominately 9+2 structure. Reduction of either hspb7 or hspb12 alters the expression pattern of genes that propagate the signals that establish left-right asymmetry: the nodal-related gene southpaw (spaw) in the lateral plate mesoderm, and its downstream targets pitx2, lefty1 and lefty2. Partial depletion of hspb7 causes concordant heart, brain and visceral laterality defects, indicating that loss of KV cilia motility leads causes coordinated but randomized laterality. Reducing hspb12 leads to similar alterations in the expression of downstream laterality genes, but at a lower penetrance. Simultaneous reduction of hspb7 and hspb12 randomizes heart, brain and visceral laterality, suggesting that these two genes have partially redundant functions in the establishment of left-right asymmetry. In addition, both hspb7 and hspb12 are expressed in the precardiac mesoderm and in the yolk syncytial layer, which supports the migration and fusion of mesodermal cardiac precursors. In embryos in which the reduction of hspb7 or hspb12 was limited to the yolk, migration defects predominated, suggesting that the yolk expression of these genes rather than heart expression is responsible for the migration defects. PMID:24140541

Silencing heat shock protein 27 (HSP27) inhibits the proliferation and migration of vascular smooth muscle cells in vitro.

PubMed

Huang, Jie; Xie, Liang-di; Luo, Li; Zheng, Su-Li; Wang, Hua-Jun; Xu, Chang-Sheng

2014-05-01

The objective of this study was to examine the role of heat shock protein 27 (HSP27) in proliferation and migration of vascular smooth muscle cells (VSMCs). Three complementary DNA sequences targeting rat HSP27 gene were designed, synthesized, and subcloned into lentiviral vector. The interfering efficiency was detected by reverse transcriptase-polymerase chain reaction and Western blot. Methyl thiazolyl tetrazolium bromide assay was used for examining cell proliferation. F-actin polymerization was detected by FITC-Phalloidin staining using confocal microscopy. Modified Boyden chamber technique was used to assess VSMCs migration. The recombinant lentivirus containing RNAi targeting HSP27 gene significantly inhibited expression of HSP27 at both mRNA and protein levels. The interfering efficiencies of pNL-HSP27-EGFP-1, pNL-HSP27-EGFP-2, and pNL-HSP27-EGFP-3 were 71 %, 77 %, and 43 %, respectively. Reorganization of actin stimulated by PDGF-BB was markedly blocked by pretreatment with pNL-HSP27-EGFP-2. Proliferation and migration rates of VSMCs induced by PDGF-BB were inhibited by 30.8 % and 45.6 %, respectively, by pNL-HSP27-EGFP-2 (all P < 0.01). To conclude, these data indicate that HSP27 may regulate the proliferation, actin reorganization, and the migration of VSMCs. RNAi targeting at HSP27 may be a potential approach for inhibition of cell migration involved in pathogenesis of proliferative vascular diseases.

Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.

PubMed

Yang, Jilong; Annala, Matti; Ji, Ping; Wang, Guowen; Zheng, Hong; Codgell, David; Du, Xiaoling; Fang, Zhiwei; Sun, Baocun; Nykter, Matti; Chen, Kexin; Zhang, Wei

2014-10-10

The identification of fusion genes such as SYT-SSX1/SSX2, PAX3-FOXO1, TPM3/TPM4-ALK and EWS-FLI1 in human sarcomas has provided important insight into the diagnosis and targeted therapy of sarcomas. No recurrent fusion has been reported in human osteosarcoma. Transcriptome sequencing was used to characterize the gene fusions and mutations in 11 human osteosarcomas. Nine of 11 samples were found to harbor genetic inactivating alterations in the TP53 pathway. Two recurrent fusion genes associated with the 12q locus, LRP1-SNRNP25 and KCNMB4-CCND3, were identified and validated by RT-PCR, Sanger sequencing and fluorescence in situ hybridization, and were found to be osteosarcoma specific in a validation cohort of 240 other sarcomas. Expression of LRP1-SNRNP25 fusion gene promoted SAOS-2 osteosarcoma cell migration and invasion. Expression of KCNMB4-CCND3 fusion gene promoted SAOS-2 cell migration. Our study represents the first whole transcriptome analysis of untreated human osteosarcoma. Our discovery of two osteosarcoma specific fusion genes associated with osteosarcoma cellular motility highlights the heterogeneity of osteosarcoma and provides opportunities for new treatment modalities.

Digital data sets that describe aquifer characteristics of the Central Oklahoma Aquifer in central Oklahoma

USGS Publications Warehouse

Runkle, D.L.; Christenson, S.C.; Rea, Alan

1997-01-01

ARC/INFO export files The data sets in this report include digitized aquifer boundaries and maps of hydraulic conductivity, recharge, and ground-water level elevation contours for the Central Oklahoma aquifer in central Oklahoma. This area encompasses all or part of Cleveland, Lincoln, Logan, Oklahoma, Payne, and Pottawatomie Counties. The Central Oklahoma aquifer includes the alluvial and terrace deposits along major streams, the Garber Sandstone and Wellington Formations, and the Chase, Council Grove, and Admire Groups. The Quaternary-age alluvial and terrace deposits consist of unconsolidated clay, silt, sand, and gravel. The Permian-age Garber Sandstone and Wellington Formations consist of sandstone with interbedded siltstone and mudstone. The Permian-age Chase, Council Grove, and Admire Groups consist of sandstone, shale, and thin limestone. The Central Oklahoma aquifer underlies about 3,000 square miles of central Oklahoma where the aquifer is used extensively for municipal, industrial, commercial, and domestic water supplies. Most of the usable ground water within the aquifer is from the Garber Sandstone and Wellington Formations. Substantial quantities of usable ground water also are present in the Chase, Council Grove, and Admire Groups, and in alluvial and terrace deposits associated with the major streams. The aquifer boundaries, hydraulic conductivity and recharge values, and ground-water level elevation contours are from previously published reports.

Real-time measurements of nitrogen oxide emissions from in-use New York City transit buses using a chase vehicle.

PubMed

Shorter, Joanne H; Herndon, Scott; Zahniser, Mark S; Nelson, David D; Wormhoudt, Joda; Demerjian, Kenneth L; Kolb, Charles E

2005-10-15

New diesel engine technologies and alternative fuel engines are being introduced into fleets of mass transit buses to try to meet stricter emission regulations of nitrogen oxides and particulates: Real-time instruments including an Aerodyne Research tunable infrared laser differential absorption spectrometer (TILDAS) were deployed in a mobile laboratory to assess the impact of the implementation of the new technologies on nitrogen oxide emissions in real world driving conditions. Using a "chase" vehicle sampling strategy, the mobile laboratory followed target vehicles, repeatedly sampling their exhaust. Nitrogen oxides from approximately 170 in-use New York City mass transit buses were sampled during the field campaigns. Emissions from conventional diesel buses, diesel buses with continuously regenerating technology (CRT), diesel hybrid electric buses, and compressed natural gas (CNG) buses were compared. The chase vehicle sampling method yields real world emissions that can be included in more realistic emission inventories. The NO, emissions from the diesel and CNG buses were comparable. The hybrid electric buses had approximately one-half the NOx emissions. In CRT diesels, NO2 accounts for about one-third of the NOx emitted in the exhaust, while for non-CRT buses the NO2 fraction is less than 10%.

Dynamical behaviour of a discrete selection-migration model with arbitrary dominance

Treesearch

James F. Selgrade; Jordan West Bostic; James H. Roberds

2009-01-01

To study the effects of immigration of genes (possibly transgenic) into a natural population, a one-island selection-migration model with density-dependent regulation is used to track allele frequency and population size. The existence and uniqueness of a polymorphic genetic equilibrium is proved under a general assumption about dominance in fitnesses. Also, conditions...

Detection of BrdU-label Retaining Cells in the Lacrimal Gland: Implications for Tissue Repair

PubMed Central

You, Samantha; Tariq, Ayesha; Kublin, Claire L.; Zoukhri, Driss

2011-01-01

The purpose of the present study was to determine if the lacrimal gland contains 5-bromo-2’-deoxyuridine (BrdU)-label retaining cells and if they are involved in tissue repair. Animals were pulsed daily with BrdU injections for 7 consecutive days. After a chase period of 2, 4, or 12 weeks, the animals were sacrificed and the lacrimal glands were removed and processed for BrdU immunostaining. In another series of experiments, the lacrimal glands of 12-week chased animals were either left untreated or were injected with interleukin 1 (IL-1) to induce injury. Two and half day post-injection, the lacrimal glands were removed and processed for BrdU immunostaining. After 2 and 4 week of chase period, a substantial number of lacrimal gland cells were BrdU+ (11.98 ± 1.84 and 7.95 ± 1.83 BrdU+ cells/mm2, respectively). After 12 weeks of chase, there was a 97% decline in the number of BrdU+ cells (0.38 ± 0.06 BrdU+ cells/mm2), suggesting that these BrdU-label retaining cells may represent slow-cycling adult stem/progenitor cells. In support of this hypothesis, the number of BrdU labeled cells increased over 7-fold during repair of the lacrimal gland (control: 0.41 ± 0.09 BrdU+ cells/mm2, injured: 2.91 ± 0.62 BrdU+ cells/mm2). Furthermore, during repair, among BrdU+ cells 58.2 ± 3.6 % were acinar cells, 26.4 ± 4.1% were myoepithelial cells, 0.4 ± 0.4% were ductal cells, and 15.0 ± 3.0% were stromal cells. We conclude that the murine lacrimal gland contains BrdU-label retaining cells that are mobilized following injury to generate acinar, myoepithelial and ductal cells. PMID:22101331

Energetics and evasion dynamics of large predators and prey: pumas vs. hounds

PubMed Central

Wilmers, Christopher C.; Williams, Terrie M.

2017-01-01

Quantification of fine-scale movement, performance, and energetics of hunting by large carnivores is critical for understanding the physiological underpinnings of trophic interactions. This is particularly challenging for wide-ranging terrestrial canid and felid predators, which can each affect ecosystem structure through distinct hunting modes. To compare free-ranging pursuit and escape performance from group-hunting and solitary predators in unprecedented detail, we calibrated and deployed accelerometer-GPS collars during predator-prey chase sequences using packs of hound dogs (Canis lupus familiaris, 26 kg, n = 4–5 per chase) pursuing simultaneously instrumented solitary pumas (Puma concolor, 60 kg, n = 2). We then reconstructed chase paths, speed and turning angle profiles, and energy demands for hounds and pumas to examine performance and physiological constraints associated with cursorial and cryptic hunting modes, respectively. Interaction dynamics revealed how pumas successfully utilized terrain (e.g., fleeing up steep, wooded hillsides) as well as evasive maneuvers (e.g., jumping into trees, running in figure-8 patterns) to increase their escape distance from the overall faster hounds (avg. 2.3× faster). These adaptive strategies were essential to evasion in light of the mean 1.6× higher mass-specific energetic costs of the chase for pumas compared to hounds (mean: 0.76 vs. 1.29 kJ kg−1 min−1, respectively). On an instantaneous basis, escapes were more costly for pumas, requiring exercise at ≥90% of predicted \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\dot {\\mathrm{V }}{\\mathrm{O}}_{2\\mathrm{MAX}}$\\end{document}V ˙O2MAX and consuming as much energy per minute as approximately 5 min of active hunting. Our results demonstrate the marked investment of energy for evasion by a large, solitary carnivore and the advantage of dynamic maneuvers to postpone being overtaken by group-hunting canids. PMID:28828280

Pilots' Attention Distributions Between Chasing a Moving Target and a Stationary Target.

PubMed

Li, Wen-Chin; Yu, Chung-San; Braithwaite, Graham; Greaves, Matthew

2016-12-01

Attention plays a central role in cognitive processing; ineffective attention may induce accidents in flight operations. The objective of the current research was to examine military pilots' attention distributions between chasing a moving target and a stationary target. In the current research, 37 mission-ready F-16 pilots participated. Subjects' eye movements were collected by a portable head-mounted eye-tracker during tactical training in a flight simulator. The scenarios of chasing a moving target (air-to-air) and a stationary target (air-to-surface) consist of three operational phases: searching, aiming, and lock-on to the targets. The findings demonstrated significant differences in pilots' percentage of fixation during the searching phase between air-to-air (M = 37.57, SD = 5.72) and air-to-surface (M = 33.54, SD = 4.68). Fixation duration can indicate pilots' sustained attention to the trajectory of a dynamic target during air combat maneuvers. Aiming at the stationary target resulted in larger pupil size (M = 27,105, SD = 6565), reflecting higher cognitive loading than aiming at the dynamic target (M = 23,864, SD = 8762). Pilots' visual behavior is not only closely related to attention distribution, but also significantly associated with task characteristics. Military pilots demonstrated various visual scan patterns for searching and aiming at different types of targets based on the research settings of a flight simulator. The findings will facilitate system designers' understanding of military pilots' cognitive processes during tactical operations. They will assist human-centered interface design to improve pilots' situational awareness. The application of an eye-tracking device integrated with a flight simulator is a feasible and cost-effective intervention to improve the efficiency and safety of tactical training.Li W-C, Yu C-S, Braithwaite G, Greaves M. Pilots' attention distributions between chasing a moving target and a stationary target. Aerosp Med Hum Perform. 2016; 87(12):989-995.

Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

PubMed

Lim, Lynette; Pakan, Janelle M P; Selten, Martijn M; Marques-Smith, André; Llorca, Alfredo; Bae, Sung Eun; Rochefort, Nathalie L; Marín, Oscar

2018-06-18

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.

Lipid phosphate phosphatase activity regulates dispersal and bilateral sorting of embryonic germ cells in Drosophila

PubMed Central

Renault, Andrew D.; Kunwar, Prabhat S.; Lehmann, Ruth

2010-01-01

In Drosophila, germ cell survival and directionality of migration are controlled by two lipid phosphate phosphatases (LPP), wunen (wun) and wunen-2 (wun2). wun wun2 double mutant analysis reveals that the two genes, hereafter collectively called wunens, act redundantly in primordial germ cells. We find that wunens mediate germ cell-germ cell repulsion and that this repulsion is necessary for germ cell dispersal and proper transepithelial migration at the onset of migration and for the equal sorting of the germ cells between the two embryonic gonads during their migration. We propose that this dispersal function optimizes adult fecundity by assuring maximal germ cell occupancy of both gonads. Furthermore, we find that the requirement for wunens in germ cell survival can be eliminated by blocking germ cell migration. We suggest that this essential function of Wunen is needed to maintain cell integrity in actively migrating germ cells. PMID:20431117

Role of a new Rho family member in cell migration and axon guidance in C. elegans.

PubMed

Zipkin, I D; Kindt, R M; Kenyon, C J

1997-09-05

Rho family GTPases are thought to regulate actin-dependent processes, but their functions in vivo are still poorly understood. We have investigated the function of a new, widely expressed Rho family member in C. elegans by analyzing mutations in the endogenous gene. Activated and null alleles all inhibit cell migration, demonstrating that this protein is required for cell migration in vivo. Only a small subset of the migrations inhibited by activating mutations are inhibited by null mutations, suggesting that considerable functional redundancy exists within this system. Our findings support this conclusion and show that mig-2 functions redundantly with another pathway to regulate nuclear migration. Surprisingly, activated alleles also cause misguided axon growth, suggesting that Rho family GTPases may couple guidance cues to process outgrowth.

Balinese Y-chromosome perspective on the peopling of Indonesia: genetic contributions from pre-neolithic hunter-gatherers, Austronesian farmers, and Indian traders.

PubMed

Karafet, Tatiana M; Lansing, J S; Redd, Alan J; Reznikova, Svetlana; Watkins, Joseph C; Surata, S P K; Arthawiguna, W A; Mayer, Laura; Bamshad, Michael; Jorde, Lynn B; Hammer, Michael F

2005-02-01

The island of Bali lies near the center of the southern chain of islands in the Indonesian archipelago, which served as a stepping-stone for early migrations of hunter-gatherers to Melanesia and Australia and for more recent migrations of Austronesian farmers from mainland Southeast Asia to the Pacific. Bali is the only Indonesian island with a population that currently practices the Hindu religion and preserves various other Indian cultural, linguistic, and artistic traditions (Lansing 1983). Here, we examine genetic variation on the Y chromosomes of 551 Balinese men to investigate the relative contributions of Austronesian farmers and pre-Neolithic hunter-gatherers to the contemporary Balinese paternal gene pool and to test the hypothesis of recent paternal gene flow from the Indian subcontinent. Seventy-one Y-chromosome binary polymorphisms (single nucleotide polymorphisms, SNPs) and 10 Y-chromosome-linked short tandem repeats (STRs) were genotyped on a sample of 1,989 Y chromosomes from 20 populations representing Indonesia (including Bali), southern China, Southeast Asia, South Asia, the Near East, and Oceania. SNP genotyping revealed 22 Balinese lineages, 3 of which (O-M95, O-M119, and O-M122) account for nearly 83.7% of Balinese Y chromosomes. Phylogeographic analyses suggest that all three major Y-chromosome haplogroups migrated to Bali with the arrival of Austronesian speakers; however, STR diversity patterns associated with these haplogroups are complex and may be explained by multiple waves of Austronesian expansion to Indonesia by different routes. Approximately 2.2% of contemporary Balinese Y chromosomes (i.e., K-M9*, K-M230, and M lineages) may represent the pre-Neolithic component of the Indonesian paternal gene pool. In contrast, eight other haplogroups (e.g., within H, J, L, and R), making up approximately 12% of the Balinese paternal gene pool, appear to have migrated to Bali from India. These results indicate that the Austronesian expansion had a profound effect on the composition of the Balinese paternal gene pool and that cultural transmission from India to Bali was accompanied by substantial levels of gene flow.

CXCL12 Gene Therapy Ameliorates Ischemia-Induced White Matter Injury in Mouse Brain.

PubMed

Li, Yaning; Tang, Guanghui; Liu, Yanqun; He, Xiaosong; Huang, Jun; Lin, Xiaojie; Zhang, Zhijun; Yang, Guo-Yuan; Wang, Yongting

2015-10-01

Remyelination is an important repair process after ischemic stroke-induced white matter injury. It often fails because of the insufficient recruitment of oligodendrocyte progenitor cells (OPCs) to the demyelinated site or the inefficient differentiation of OPCs to oligodendrocytes. We investigated whether CXCL12 gene therapy promoted remyelination after middle cerebral artery occlusion in adult mice. The results showed that CXCL12 gene therapy at 1 week after ischemia could protect myelin sheath integrity in the perifocal region, increase the number of platelet-derived growth factor receptor-α (PDGFRα)-positive and PDGFRα/bromodeoxyuridine-double positive OPCs in the subventricular zone, and further enhance their migration to the ischemic lesion area. Coadministration of AMD3100, the antagonist for CXCL12 receptor CXCR4, eliminated the beneficial effect of CXCL12 on myelin sheath integrity and negatively influenced OPC proliferation and migration. At 5 weeks after ischemia, CXCR4 was found on the PDGFRα- and/or neuron/glia type 2 (NG2)-positive OPCs but not on the myelin basic protein-positive mature myelin sheaths, and CXCR7 was only expressed on the mature myelin sheath in the ischemic mouse brain. Our data indicated that CXCL12 gene therapy effectively protected white matter and promoted its repair after ischemic injury. The treatment at 1 week after ischemia is effective, suggesting that this strategy has a longer therapeutic time window than the treatments currently available. This study has demonstrated for the first time that CXCL12 gene therapy significantly ameliorates brain ischemia-induced white matter injury and promotes oligodendrocyte progenitor cell proliferation in the subventricular zone and migration to the perifocal area in the ischemic mouse brain. Additional data showed that CXCR4 receptor plays an important role during the proliferation and migration of oligodendrocyte progenitor cells, and CXCR7 might play a role during maturation. In contrast to many experimental studies that provide treatment before ischemic insult, CXCL12 gene therapy was performed 1 week after brain ischemia, which significantly prolonged the therapeutic time window of brain ischemia. ©AlphaMed Press.

The Caenorhabditis elegans Q neuroblasts: A powerful system to study cell migration at single-cell resolution in vivo.

PubMed

Rella, Lorenzo; Fernandes Póvoa, Euclides E; Korswagen, Hendrik C

2016-04-01

During development, cell migration plays a central role in the formation of tissues and organs. Understanding the molecular mechanisms that drive and control these migrations is a key challenge in developmental biology that will provide important insights into disease processes, including cancer cell metastasis. In this article, we discuss the Caenorhabditis elegans Q neuroblasts and their descendants as a tool to study cell migration at single-cell resolution in vivo. The highly stereotypical migration of these cells provides a powerful system to study the dynamic cytoskeletal processes that drive migration as well as the evolutionarily conserved signaling pathways (including different Wnt signaling cascades) that guide the cells along their specific trajectories. Here, we provide an overview of what is currently known about Q neuroblast migration and highlight the live-cell imaging, genome editing, and quantitative gene expression techniques that have been developed to study this process. © 2016 Wiley Periodicals, Inc.

A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis

PubMed Central

Subramanian, M; Francis, P; Bilke, S; Li, XL; Hara, T; Lu, X; Jones, MF; Walker, RL; Zhu, Y; Pineda, M; Lee, C; Varanasi, L; Yang, Y; Martinez, LA; Luo, J; Ambs, S; Sharma, S; Wakefield, LM; Meltzer, PS; Lal, A

2015-01-01

Most p53 mutations in human cancers are missense mutations resulting in a full-length mutant p53 protein. Besides losing tumor suppressor activity, some hotspot p53 mutants gain oncogenic functions. This effect is mediated in part, through gene expression changes due to inhibition of p63 and p73 by mutant p53 at their target gene promoters. Here, we report that the tumor suppressor microRNA let-7i is downregulated by mutant p53 in multiple cell lines expressing endogenous mutant p53. In breast cancer patients, significantly decreased let-7i levels were associated with missense mutations in p53. Chromatin immunoprecipitation and promoter luciferase assays established let-7i as a transcriptional target of mutant p53 through p63. Introduction of let-7i to mutant p53 cells significantly inhibited migration, invasion and metastasis by repressing a network of oncogenes including E2F5, LIN28B, MYC and NRAS. Our findings demonstrate that repression of let-7i expression by mutant p53 has a key role in enhancing migration, invasion and metastasis. PMID:24662829

Adaptation, migration or extirpation: climate change outcomes for tree populations

PubMed Central

Aitken, Sally N; Yeaman, Sam; Holliday, Jason A; Wang, Tongli; Curtis-McLane, Sierra

2008-01-01

Abstract Species distribution models predict a wholesale redistribution of trees in the next century, yet migratory responses necessary to spatially track climates far exceed maximum post-glacial rates. The extent to which populations will adapt will depend upon phenotypic variation, strength of selection, fecundity, interspecific competition, and biotic interactions. Populations of temperate and boreal trees show moderate to strong clines in phenology and growth along temperature gradients, indicating substantial local adaptation. Traits involved in local adaptation appear to be the product of small effects of many genes, and the resulting genotypic redundancy combined with high fecundity may facilitate rapid local adaptation despite high gene flow. Gene flow with preadapted alleles from warmer climates may promote adaptation and migration at the leading edge, while populations at the rear will likely face extirpation. Widespread species with large populations and high fecundity are likely to persist and adapt, but will likely suffer adaptational lag for a few generations. As all tree species will be suffering lags, interspecific competition may weaken, facilitating persistence under suboptimal conditions. Species with small populations, fragmented ranges, low fecundity, or suffering declines due to introduced insects or diseases should be candidates for facilitated migration. PMID:25567494

Population Structure and Gene Flow of the Yellow Anaconda (Eunectes notaeus) in Northern Argentina

PubMed Central

McCartney-Melstad, Evan; Waller, Tomás; Micucci, Patricio A.; Barros, Mariano; Draque, Juan; Amato, George; Mendez, Martin

2012-01-01

Yellow anacondas (Eunectes notaeus) are large, semiaquatic boid snakes found in wetland systems in South America. These snakes are commercially harvested under a sustainable management plan in Argentina, so information regarding population structuring can be helpful for determination of management units. We evaluated genetic structure and migration using partial sequences from the mitochondrial control region and mitochondrial genes cyt-b and ND4 for 183 samples collected within northern Argentina. A group of landscape features and environmental variables including several treatments of temperature and precipitation were explored as potential drivers of observed genetic patterns. We found significant population structure between most putative population comparisons and bidirectional but asymmetric migration in several cases. The configuration of rivers and wetlands was found to be significantly associated with yellow anaconda population structure (IBD), and important for gene flow, although genetic distances were not significantly correlated with the environmental variables used here. More in-depth analyses of environmental data may be needed to fully understand the importance of environmental conditions on population structure and migration. These analyses indicate that our putative populations are demographically distinct and should be treated as such in Argentina's management plan for the harvesting of yellow anacondas. PMID:22675425

Multiscale mechanisms of cell migration during development: theory and experiment.

PubMed

McLennan, Rebecca; Dyson, Louise; Prather, Katherine W; Morrison, Jason A; Baker, Ruth E; Maini, Philip K; Kulesa, Paul M

2012-08-01

Long-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration. We find that a simple chemotaxis model is insufficient to explain our experimental data. Instead, model simulations predict that NC cell migration requires leading cells to respond to long-range guidance signals and trailing cells to short-range cues in order to maintain a directed, multicellular stream. Experiments confirm differences in leading versus trailing NC cell subpopulations, manifested in unique cell orientation and gene expression patterns that respond to non-linear tissue growth of the migratory domain. Ablation experiments that delete the trailing NC cell subpopulation reveal that leading NC cells distribute all along the migratory pathway and develop a leading/trailing cellular orientation and gene expression profile that is predicted by model simulations. Transplantation experiments and model predictions that move trailing NC cells to the migratory front, or vice versa, reveal that cells adopt a gene expression profile and cell behaviors corresponding to the new position within the migratory stream. These results offer a mechanistic model in which leading cells create and respond to a cell-induced chemotactic gradient and transmit guidance information to trailing cells that use short-range signals to move in a directional manner.

Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica

PubMed Central

Bazzi, Gaia; Ambrosini, Roberto; Caprioli, Manuela; Costanzo, Alessandra; Liechti, Felix; Gatti, Emanuele; Gianfranceschi, Luca; Podofillini, Stefano; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Saino, Nicola; Rubolini, Diego

2015-01-01

Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving ‘clock’ genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds. PMID:26197782

Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

PubMed

Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

2018-06-01

A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

Mitomycin C retardation of corneal fibroblast migration via sustained dephosphorylation of paxillin at tyrosine 118.

PubMed

Chen, Tsan-Chi; Lai, Chien-Hsueh; Chang, Jie-Ling; Chang, Shu-Wen

2012-03-21

To investigate how mitomycin C (MMC) modulates corneal fibroblast migration and its molecular mechanisms in the wound healing process. After treatment with 0 and 0.2 mg · mL(-1) MMC for 5 minutes, effect of MMC on cell migration of human corneal fibroblasts (HCFs) was examined with a cell migration assay. Both focal adhesion kinase (FAK) and paxillin (PXN) expressions in HCFs were analyzed by semiquantitative real-time PCR, immunoblotting, and immunofluorescence confocal microscopy. Using gene silencing or gene overexpression with lentiviral-based pseudovirion infection, the phosphorylation level of FAK, PXN, and mutated PXNs at tyrosine sites 31 (Y31F-EGFP) and 118 (Y118F-EGFP) were verified in HCFs. MMC retarded HCF migration at 1 and 2 days posttreatment (dpt). MMC reduced levels of FAK transcript and FAK protein, but increased both transcript and protein expression of PXN at 1 and 2 dpt. Furthermore, MMC upregulated FAK-pY397, which subsequently enhanced PXN-pY31 in a dose-dependent manner at 1 dpt. Concurrently, MMC downregulated PXN-pY118 at 1 dpt. However, MMC treatment resulted in dephosphorylation of FAK-pY397, PXN-pY31, and PXN-pY118 at 2 dpt. The FAK/PXN complex in MMC-treated HCFs was detected at focal adhesion sites more than at the leading edge at 1 and 2 dpt, contributing to retardation of HCF migration. Y118F-EGFP-expressing HCFs exhibited lower mobility than that of PXN-EGFP- or Y31F-EGFP-expressing HCFs. The sustained PXN-pY118 dephosphorylation resulted in steadfastness of an incompletely active FAK/PXN complex at focal adhesion sites and played a pivotal role in MMC-retarded HCF migration.

Girdin Is an Intrinsic Regulator of Neuroblast Chain Migration in the Rostral Migratory Stream of the Postnatal Brain

PubMed Central

Wang, Yun; Kaneko, Naoko; Asai, Naoya; Enomoto, Atsushi; Isotani-Sakakibara, Mayu; Kato, Takuya; Asai, Masato; Murakumo, Yoshiki; Ota, Haruko; Hikita, Takao; Namba, Takashi; Kuroda, Keisuke; Kaibuchi, Kozo; Ming, Guo-li; Song, Hongjun; Sawamoto, Kazunobu; Takahashi, Masahide

2017-01-01

In postnatally developing and adult brains, interneurons of the olfactory bulb (OB) are continuously generated at the subventricular zone of the forebrain. The newborn neuroblasts migrate tangentially to the OB through a well defined pathway, the rostral migratory stream (RMS), where the neuroblasts undergo collective migration termed “chain migration.” The cell-intrinsic regulatory mechanism of neuroblast chain migration, however, has not been uncovered. Here we show that mice lacking the actin-binding Akt substrate Girdin (a protein that interacts with Disrupted-In-Schizophrenia 1 to regulate neurogenesis in the dentate gyrus) have profound defects in neuroblast chain migration along the RMS. Analysis of two gene knock-in mice harboring Girdin mutants identified unique amino acid residues in Girdin’s C-terminal domain that are responsible for the regulation of neuroblast chain migration but revealed no apparent requirement of Girdin phosphorylation by Akt. Electron microscopic analyses demonstrated the involvement of Girdin in neuroblast cell–cell interactions. These findings suggest that Girdin is an important intrinsic factor that specifically governs neuroblast chain migration along the RMS. PMID:21632933

Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment

PubMed Central

Zhou, Y; Dong, F; Lanz, T A; Reinhart, V; Li, M; Liu, L; Zou, J; Xi, H S; Mao, Y

2018-01-01

Recent genome-wide association studies identified over 100 genetic loci that significantly associate with schizophrenia (SZ). A top candidate gene, ZNF804A, was robustly replicated in different populations. However, its neural functions are largely unknown. Here we show in mouse that ZFP804A, the homolog of ZNF804A, is required for normal progenitor proliferation and neuronal migration. Using a yeast two-hybrid genome-wide screen, we identified novel interacting proteins of ZNF804A. Rather than transcriptional factors, genes involved in mRNA translation are highly represented in our interactome result. ZNF804A co-fractionates with translational machinery and modulates the translational efficiency as well as the mTOR pathway. The ribosomal protein RPSA interacts with ZNF804A and rescues the migration and translational defects caused by ZNF804A knockdown. RNA immunoprecipitation–RNAseq (RIP-Seq) identified transcripts bound to ZFP804A. Consistently, ZFP804A associates with many short transcripts involved in translational and mitochondrial regulation. Moreover, among the transcripts associated with ZFP804A, a SZ risk gene, neurogranin (NRGN), is one of ZFP804A targets. Interestingly, downregulation of ZFP804A decreases NRGN expression and overexpression of NRGN can ameliorate ZFP804A-mediated migration defect. To verify the downstream targets of ZNF804A, a Duolink in situ interaction assay confirmed genes from our RIP-Seq data as the ZNF804A targets. Thus, our work uncovered a novel mechanistic link of a SZ risk gene to neurodevelopment and translational control. The interactome-driven approach here is an effective way for translating genome-wide association findings into novel biological insights of human diseases. PMID:28924186

The effects of RNA interference mediated VEGF gene silencing on biological behavior of renal cell carcinoma and transplanted renal tumor in nude mice.

PubMed

Wang, Qi; Wang, Shuai; Sun, Si-Qiao; Cheng, Zhi-Hua; Zhang, Yang; Chen, Guang; Gu, Meng; Yao, Hai-Jun; Wang, Zhong; Zhou, Juan; Peng, Yu-Bing; Xu, Ming-Xi; Zhang, Ke; Sun, Xi-Wei

2016-01-01

This study was to explore the effects of RNA interference mediated vascular endothelial growth factor (VEGF) gene silencing on biological behavior of renal cell carcinoma (RCC), transplanted renal tumor and angiogenesis in nude mice. The specific siRNA sequence targeting VEGF were designed and synthesized to construct hVEGF-siRNA plasmid which was transfected into RCC 786-O cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the detection of VEGF gene expression and western blot was adopted for the examination of VEGF protein expression. The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell growth as well as cell migration and invasion. The transplanted renal tumor models in nude mice were established, and the growth condition of nude mice, and VEGF protein expression in transplanted tumor slices and the microvessel density (MVD) were detected. The expression level of VEGF mRNA in VEGF-siRNA group was significant lower than that in the control group and negative group, suggesting that establishment of plasmid specifically inhibited the expression of VEGF gene The expression level of VEGF protein in VEGF-siRNA group was significant lower than that in the control group and negative group. VEGF gene silencing has the significant inhibition effects on proliferation, migration and invasion of RCC 786-O cells. The tumor weight, VEGF protein positive rate and MVD in VEGF-siRNA group were significant lower than those in negative group and blank group. The VEGF gene silencing could inhibit the cell proliferation, migration and invasion of RCC 786-O cells; inhibition of VEGF protein expression could prevent transplanted RCC growth and tumor angiogenesis.

Financial stress, attitudes toward money, and scores on a Dream Inventory.

PubMed

Kroth, Jerry; Mann, Sonia; Cervantes, Carolina; Jaffe, Matthew; Ristic, Vera

2010-08-01

During stock market losses in 2009 and high unemployment, ratings on the KJP Dream Inventory were correlated with factors of the Money Attitude Scale and items on the Contemporary Financial Stress Inventory for 71 graduate students in Counseling Psychology and Education. Correlations were significant for Retention on the Money Attitude Scale with Dissociative Avoidance (-.31), Dreams of falling (.26), Risk-taking in dreams (.24), and Dreaming of being chased (.28). Also, ratings for the Money Attitude Scale of Distrust correlated with Discontentedness in dreams (.33) and Dreams of being chased (.26), Repetitive trauma (.33), Nightmares (.30), and Recurring nightmares (.35). Concern about retention in graduate school due to finances correlated with recalled frequencies of nightmares (.27) and dreams of flying (.25).

76 FR 77593 - Proposed Exemptions From Certain Prohibited Transaction Restrictions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-13

...This document contains notices of pendency before the Department of Labor (the Department) of proposed exemptions from certain of the prohibited transaction restrictions of the Employee Retirement Income Security Act of 1974 (ERISA or the Act) and/or the Internal Revenue Code of 1986 (the Code). This notice includes the following proposed exemptions: D-11517, JPMorgan Chase & Co. and its Current and Future Affiliates and Subsidiaries (JPMorgan Chase); D- 11579, Delaware Charter Guarantee & Trust Co. d\\b\\a\\ Principle Trust Company (Principle Trust); D-11628, Aztec Well Servicing Company and Related Companies Medical Plan Trust Fund (the Plan); D-11669, Genzyme Corporation 401(k) Plan (the Plan or the Applicant); and Retirement Program for Employees of EnPro Industries (the Plan), D-11662 et al.

Wound Healing Is Defective in Mice Lacking Tetraspanin CD151

PubMed Central

Cowin, Allison J.; Adams, Damian; Geary, Sean M.; Wright, Mark D.; Jones, Jonathan C.R.; Ashman, Leonie K.

2010-01-01

The tetraspanin CD151 forms complexes in epithelial cell membranes with laminin-binding integrins α6 β4, α3 β1, and α6 β1, and modifies integrin-mediated cell migration in vitro. We demonstrate in this study that CD151 expression is upregulated in a distinct temporal and spatial pattern during wound healing, particularly in the migrating epidermal tongue at the wound edge, suggesting a role for CD151 in keratinocyte migration. We show that healing is significantly impaired in CD151-null mice, with wounds gaping wider at 7 days post-injury. The rate of re-epithelialization of the CD151-null wounds is adversely affected, with significantly less wound area being covered by migrating epidermal cells. Our studies reveal that although laminin levels are similar in wild-type and CD151-null wounds, the organization of the laminin in the basement membrane is impaired. Furthermore, upregulation of α6 and β4 integrin expression is adversely affected in CD151-null mice wounds. In contrast, we find no significant effect of CD151 gene knockout on α3 and β1 integrin expression in wound repair. We suggest that mice lacking the CD151 gene are defective in wound healing, primarily owing to impairment of the re-epithelialization process. This may be due to defective basement membrane formation and epithelial cell adhesion and migration. PMID:16410781

Dynamical Analysis of Density-dependent Selection in a Discrete one-island Migration Model

Treesearch

James H. Roberds; James F. Selgrade

2000-01-01

A system of non-linear difference equations is used to model the effects of density-dependent selection and migration in a population characterized by two alleles at a single gene locus. Results for the existence and stability of polymorphic equilibria are established. Properties for a genetically important class of equilibria associated with complete dominance in...

[Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

PubMed

Ishigaki, Keiko

2016-02-01

Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via α-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications.

Brazilian Red Propolis Induces Apoptosis-Like Cell Death and Decreases Migration Potential in Bladder Cancer Cells

PubMed Central

Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Moura, Sidnei; Padilha, Francine F.; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

2014-01-01

Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment. PMID:25530785

Brazilian red propolis induces apoptosis-like cell death and decreases migration potential in bladder cancer cells.

PubMed

Begnini, Karine Rech; Moura de Leon, Priscila Marques; Thurow, Helena; Schultze, Eduarda; Campos, Vinicius Farias; Martins Rodrigues, Fernanda; Borsuk, Sibele; Dellagostin, Odir Antônio; Savegnago, Lucielli; Roesch-Ely, Mariana; Moura, Sidnei; Padilha, Francine F; Collares, Tiago; Pêgas Henriques, João Antonio; Seixas, Fabiana Kömmling

2014-01-01

Natural products continue to be an invaluable resource of anticancer drug discovery in recent years. Propolis is known for its biological activities such as antimicrobial and antitumor effects. This study assessed the effects of Brazilian red propolis (BRP) on apoptosis and migration potential in human bladder cancer cells. The effect of BRP ethanolic extract (25, 50, and 100 μg/mL) on 5637 cells was determined by MTT, LIVE/DEAD, and migration (scratch assay) assays. Apoptosis induction was investigated through flow cytometry and gene expression profile was investigated by qRT-PCR. Results showed cytotoxicity on MTT and LIVE/DEAD assays, with IC50 values of 95 μg/mL in 24 h of treatment. Cellular migration of 5637 cells was significantly inhibited through lower doses of BRP ethanolic extract (25 and 50 μg/mL). Flow cytometry analyses showed that BRP induced cytotoxicity through apoptosis-like mechanisms in 5637 cells and qRT-PCR revealed increased levels of Bax/Bcl-2 ratio, p53, AIF, and antioxidant enzymes genes. Data suggest that BRP may be a potential source of drugs to bladder cancer treatment.

Adaptive genetic markers discriminate migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid continued gene flow

PubMed Central

O'Malley, Kathleen G; Jacobson, Dave P; Kurth, Ryon; Dill, Allen J; Banks, Michael A

2013-01-01

Neutral genetic markers are routinely used to define distinct units within species that warrant discrete management. Human-induced changes to gene flow however may reduce the power of such an approach. We tested the efficiency of adaptive versus neutral genetic markers in differentiating temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid high gene flow owing to artificial propagation and habitat alteration. We compared seven putative migration timing genes to ten microsatellite loci in delineating three migratory groups of Chinook in the Feather River, CA: offspring of fall-run hatchery broodstock that returned as adults to freshwater in fall (fall run), spring-run offspring that returned in spring (spring run), and fall-run offspring that returned in spring (FRS). We found evidence for significant differentiation between the fall and federally listed threatened spring groups based on divergence at three circadian clock genes (OtsClock1b, OmyFbxw11, and Omy1009UW), but not neutral markers. We thus demonstrate the importance of genetic marker choice in resolving complex life history types. These findings directly impact conservation management strategies and add to previous evidence from Pacific and Atlantic salmon indicating that circadian clock genes influence migration timing. PMID:24478800

The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration.

PubMed

Cheng, Yating; Jutooru, Indira; Chadalapaka, Gayathri; Corton, J Christopher; Safe, Stephen

2015-05-10

HOTTIP is a long non-coding RNA (lncRNA) transcribed from the 5' tip of the HOXA locus and is associated with the polycomb repressor complex 2 (PRC2) and WD repeat containing protein 5 (WDR5)/mixed lineage leukemia 1 (MLL1) chromatin modifying complexes. HOTTIP is expressed in pancreatic cancer cell lines and knockdown of HOTTIP by RNA interference (siHOTTIP) in Panc1 pancreatic cancer cells decreased proliferation, induced apoptosis and decreased migration. In Panc1 cells transfected with siHOTTIP, there was a decrease in expression of 757 genes and increased expression of 514 genes, and a limited gene analysis indicated that HOTTIP regulation of genes is complex. For example, Aurora kinase A, an important regulator of cell growth, is coregulated by MLL and not WDR5 and, in contrast to previous studies in liver cancer cells, HOTTIP does not regulate HOXA13 but plays a role in regulation of several other HOX genes including HOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. Although HOTTIP and the HOX-associated lncRNA HOTAIR have similar pro-oncogenic functions, they regulate strikingly different sets of genes in Panc1 cells and in pancreatic tumors.

Initial description of primate-specific cystine-knot Prometheus genes and differential gene expansions of D-dopachrome tautomerase genes

PubMed Central

Premzl, Marko

2015-01-01

Using eutherian comparative genomic analysis protocol and public genomic sequence data sets, the present work attempted to update and revise two gene data sets. The most comprehensive third party annotation gene data sets of eutherian adenohypophysis cystine-knot genes (128 complete coding sequences), and d-dopachrome tautomerases and macrophage migration inhibitory factor genes (30 complete coding sequences) were annotated. For example, the present study first described primate-specific cystine-knot Prometheus genes, as well as differential gene expansions of D-dopachrome tautomerase genes. Furthermore, new frameworks of future experiments of two eutherian gene data sets were proposed. PMID:25941635

Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

PubMed Central

Brem, Harold; Stojadinovic, Olivera; Diegelmann, Robert F; Entero, Hyacinth; Lee, Brian; Pastar, Irena; Golinko, Michael; Rosenberg, Harvey; Tomic-Canic, Marjana

2007-01-01

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients’ wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious. PMID:17515955

Ganglioside GM2 mediates migration of tumor cells by interacting with integrin and modulating the downstream signaling pathway.

PubMed

Kundu, Manjari; Mahata, Barun; Banerjee, Avisek; Chakraborty, Sohini; Debnath, Shibjyoti; Ray, Sougata Sinha; Ghosh, Zhumur; Biswas, Kaushik

2016-07-01

The definitive role of ganglioside GM2 in mediating tumor-induced growth and progression is still unknown. Here we report a novel role of ganglioside GM2 in mediating tumor cell migration and uncovered its mechanism. Data shows differential expression levels of GM2-synthase as well as GM2 in different human cancer cells. siRNA mediated knockdown of GM2-synthase in CCF52, A549 and SK-RC-26B cells resulted in significant inhibition of tumor cell migration as well as invasion in vitro without affecting cellular proliferation. Over-expression of GM2-synthase in low-GM2 expressing SK-RC-45 cells resulted in a consequent increase in migration thus confirming the potential role GM2 and its downstream partners play in tumor cell migration and motility. Further, treatment of SK-RC-45 cells with exogenous GM2 resulted in a dramatic increase in migratory and invasive capacity with no change in proliferative capacity, thereby confirming the role of GM2 in tumorigenesis specifically by mediating tumor migration and invasion. Gene expression profiling of GM2-synthase silenced cells revealed altered expression of several genes involved in cell migration primarily those controlling the integrin mediated signaling. GM2-synthase knockdown resulted in decreased phosphorylation of FAK, Src as well as Erk, while over-expression and/or exogenous GM2 treatment caused increased FAK and Erk phosphorylation respectively. Again, GM2 mediated invasion and Erk phosphorylation is blocked in integrin knockdown SK-RC-45 cells, thus confirming that GM2 mediated migration and phosphorylation of Erk is integrin dependent. Finally, confocal microscopy suggested co-localization while co-immunoprecipitation and surface plasmon resonance (SPR) confirmed direct interaction of membrane bound ganglioside, GM2 with the integrin receptor. Copyright © 2016 Elsevier B.V. All rights reserved.

A global evolutionary and metabolic analysis of human obesity gene risk variants.

PubMed

Castillo, Joseph J; Hazlett, Zachary S; Orlando, Robert A; Garver, William S

2017-09-05

It is generally accepted that the selection of gene variants during human evolution optimized energy metabolism that now interacts with our obesogenic environment to increase the prevalence of obesity. The purpose of this study was to perform a global evolutionary and metabolic analysis of human obesity gene risk variants (110 human obesity genes with 127 nearest gene risk variants) identified using genome-wide association studies (GWAS) to enhance our knowledge of early and late genotypes. As a result of determining the mean frequency of these obesity gene risk variants in 13 available populations from around the world our results provide evidence for the early selection of ancestral risk variants (defined as selection before migration from Africa) and late selection of derived risk variants (defined as selection after migration from Africa). Our results also provide novel information for association of these obesity genes or encoded proteins with diverse metabolic pathways and other human diseases. The overall results indicate a significant differential evolutionary pattern for the selection of obesity gene ancestral and derived risk variants proposed to optimize energy metabolism in varying global environments and complex association with metabolic pathways and other human diseases. These results are consistent with obesity genes that encode proteins possessing a fundamental role in maintaining energy metabolism and survival during the course of human evolution. Copyright © 2017. Published by Elsevier B.V.

EDTA conditioning of dentine promotes adhesion, migration and differentiation of dental pulp stem cells.

PubMed

Galler, K M; Widbiller, M; Buchalla, W; Eidt, A; Hiller, K-A; Hoffer, P C; Schmalz, G

2016-06-01

To evaluate the effect of dentine conditioning on migration, adhesion and differentiation of dental pulp stem cells. Dentine discs prepared from extracted human molars were pre-treated with EDTA (10%), NaOCl (5.25%) or H2 O. Migration of dental pulp stem cells towards pre-treated dentine after 24 and 48 h was assessed in a modified Boyden chamber assay. Cell adhesion was evaluated indirectly by measuring cell viability. Expression of mineralization-associated genes (COL1A1, ALP, BSP, DSPP, RUNX2) in cells cultured on pre-treated dentine for 7 days was determined by RT-qPCR. Nonparametric statistical analysis was performed for cell migration and cell viability data to compare different groups and time-points (Mann-Whitney U-test, α = 0.05). Treatment of dentine with H2 O or EDTA allowed for cell attachment, which was prohibited by NaOCl with statistical significance (P = 0.000). Furthermore, EDTA conditioning induced cell migration towards dentine. The expression of mineralization-associated genes was increased in dental pulp cells cultured on dentine after EDTA conditioning compared to H2 O-pre-treated dentine discs. EDTA conditioning of dentine promoted the adhesion, migration and differentiation of dental pulp stem cells towards or onto dentine. A pre-treatment with EDTA as the final step of an irrigation protocol for regenerative endodontic procedures has the potential to act favourably on new tissue formation within the root canal. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Kaposi's Sarcoma-Associated Herpesvirus Interleukin-6 Modulates Endothelial Cell Movement by Upregulating Cellular Genes Involved in Migration.

PubMed

Giffin, Louise; West, John A; Damania, Blossom

2015-12-08

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of human Kaposi's sarcoma, a tumor that arises from endothelial cells, as well as two B cell lymphoproliferative diseases, primary effusion lymphoma and multicentric Castleman's disease. KSHV utilizes a variety of mechanisms to evade host immune responses and promote cellular transformation and growth in order to persist for the life of the host. A viral homolog of human interleukin-6 (hIL-6) named viral interleukin-6 (vIL-6) is encoded by KSHV and expressed in KSHV-associated cancers. Similar to hIL-6, vIL-6 is secreted, but the majority of vIL-6 is retained within the endoplasmic reticulum, where it can initiate functional signaling through part of the interleukin-6 receptor complex. We sought to determine how intracellular vIL-6 modulates the host endothelial cell environment by analyzing vIL-6's impact on the endothelial cell transcriptome. vIL-6 significantly altered the expression of many cellular genes associated with cell migration. In particular, vIL-6 upregulated the host factor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) at the protein and message levels. CEACAM1 has been implicated in tumor invasion and metastasis and promotes migration and vascular remodeling in endothelial cells. We report that vIL-6 upregulates CEACAM1 by a STAT3-dependent mechanism and that CEACAM1 promotes vIL-6-mediated migration. Furthermore, latent and de novo KSHV infections of endothelial cells also induce CEACAM1 expression. Collectively, our data suggest that vIL-6 modulates endothelial cell migration by upregulating the expression of cellular factors, including CEACAM1. Kaposi's sarcoma-associated herpesvirus (KSHV) is linked with the development of three human malignancies, Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. KSHV expresses many factors that enable the virus to manipulate the host environment in order to persist and induce disease. The viral interleukin-6 (vIL-6) produced by KSHV is structurally and functionally homologous to the human cytokine interleukin-6, except that vIL-6 is secreted slowly and functions primarily from inside the host cell. To investigate the unique intracellular role of vIL-6, we analyzed the impact of vIL-6 on endothelial cell gene expression. We report that vIL-6 significantly alters the expression of genes associated with cell movement, including that for CEACAM1. The gene for CEACAM1 was upregulated by vIL-6 and by latent and primary KSHV infection and promotes vIL-6-mediated endothelial cell migration. This work advances the field's understanding of vIL-6 function and its contribution to KSHV pathogenesis. Copyright © 2015 Giffin et al.

Biological effects of RNAi targeted inhibiting Tiam1 gene expression on cholangiocarcinoma cells.

PubMed

Cheng, Wei; Liu, Yaling; Zuo, Zhi; Yin, Xinmin; Jiang, Bo; Chen, Daojin; Peng, Chuang; Yang, Jianhui

2015-01-01

To investigate the characteristics of Tiam1 gene expression in human cholangiocarcinoma tissues and benign bile duct tissues, and to analyze the correlations between Tiam1 gene expression and the degree of tumor differentiation, invasive and metastatic abilities. To explore the effect of targeted inhibiting Tiam1 gene expression on proliferation and migration activity of human cholangiocarcinoma cells. Expression of Tiam1 in 83 cases of cholangiocarcinoma tissues and 25 cases of benign bile tissues was detected using immunohistochemistry. The clinical data of patients with cholangiocarcinoma were collected. The correlations between Tiam1 gene expression and the clinicopathologic features in patients with cholangiocarcinoma were analyzed. The human cholangiocarcinoma RBE cells were divided into 3 groups. Cells in experimental group and control group were respectively transfected with Tiam1 shRNA lentiviral vectors and negative shRNA lentiviral control vectors. Cells in blank group received no treatment. Real-time PCR endogenesis was used to verify Tiam1 gene expression. Cell cycle experiments and MTT assay were used to measure cell proliferation activity. Transwell test was used to detect cell migration activity. The negative rate Tiam1 protein expression in cholangiocarcinoma tissues was significantly higher than that in benign bile tissues (P<0.001). Tiam1 protein expression in cholangiocarcinoma tissues had correlations with cholangiocarcinoma differentiation degree, TNM stage and lymph node metastasis (P<0.05), and had no significant correlations with gender, age and distant metastasis (P>0.05). Real-time PCR detection indicated that Tiam1 expression of experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that Tiam1 shRNA was effective on Tiam1 gene silencing in RBE cells. Cell cycle experiment showed that the percentage of S phase in cell cycle in experimental group was lower than that in control group and blank group (P<0.05), demonstrating that after the down-regulation of Tiam1 gene expression, the speed of cell proliferation was inhibited. MTT assay results showed that the total growth speed in experimental group was significantly lower than that in control group and blank group (P<0.05), indicating that the proliferation activity of cholangiocarcinoma cells was inhibited after targeted inhibition of Tiam1 gene expression. Transwell detection results showed that the metastasis rate in experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that targeted inhibition of Tiam1 gene expression could significantly inhibit migration ability of RBE cells. Tiam1 expression significantly increased in cholangiocarcinoma tissues, and increased along with the degree of malignancy of cholangiocarcinoma. Targeted silencing Tiam1 expression could inhibit proliferation and migration activity of cholangiocarcinoma cells.

Biological effects of RNAi targeted inhibiting Tiam1 gene expression on cholangiocarcinoma cells

PubMed Central

Cheng, Wei; Liu, Yaling; Zuo, Zhi; Yin, Xinmin; Jiang, Bo; Chen, Daojin; Peng, Chuang; Yang, Jianhui

2015-01-01

Objective: To investigate the characteristics of Tiam1 gene expression in human cholangiocarcinoma tissues and benign bile duct tissues, and to analyze the correlations between Tiam1 gene expression and the degree of tumor differentiation, invasive and metastatic abilities. To explore the effect of targeted inhibiting Tiam1 gene expression on proliferation and migration activity of human cholangiocarcinoma cells. Methods: Expression of Tiam1 in 83 cases of cholangiocarcinoma tissues and 25 cases of benign bile tissues was detected using immunohistochemistry. The clinical data of patients with cholangiocarcinoma were collected. The correlations between Tiam1 gene expression and the clinicopathologic features in patients with cholangiocarcinoma were analyzed. The human cholangiocarcinoma RBE cells were divided into 3 groups. Cells in experimental group and control group were respectively transfected with Tiam1 shRNA lentiviral vectors and negative shRNA lentiviral control vectors. Cells in blank group received no treatment. Real-time PCR endogenesis was used to verify Tiam1 gene expression. Cell cycle experiments and MTT assay were used to measure cell proliferation activity. Transwell test was used to detect cell migration activity. Results: The negative rate Tiam1 protein expression in cholangiocarcinoma tissues was significantly higher than that in benign bile tissues (P<0.001). Tiam1 protein expression in cholangiocarcinoma tissues had correlations with cholangiocarcinoma differentiation degree, TNM stage and lymph node metastasis (P<0.05), and had no significant correlations with gender, age and distant metastasis (P>0.05). Real-time PCR detection indicated that Tiam1 expression of experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that Tiam1 shRNA was effective on Tiam1 gene silencing in RBE cells. Cell cycle experiment showed that the percentage of S phase in cell cycle in experimental group was lower than that in control group and blank group (P<0.05), demonstrating that after the down-regulation of Tiam1 gene expression, the speed of cell proliferation was inhibited. MTT assay results showed that the total growth speed in experimental group was significantly lower than that in control group and blank group (P<0.05), indicating that the proliferation activity of cholangiocarcinoma cells was inhibited after targeted inhibition of Tiam1 gene expression. Transwell detection results showed that the metastasis rate in experimental group was significantly lower than that in control group and blank group (P<0.05), demonstrating that targeted inhibition of Tiam1 gene expression could significantly inhibit migration ability of RBE cells. Conclusion: Tiam1 expression significantly increased in cholangiocarcinoma tissues, and increased along with the degree of malignancy of cholangiocarcinoma. Targeted silencing Tiam1 expression could inhibit proliferation and migration activity of cholangiocarcinoma cells. PMID:26884821

Rho GTPase Involvement in Breast Cancer Migration and Invasion

DTIC Science & Technology

2007-03-01

knockdown was established for the kinase and phosphatase genes using branched DNA ( bDNA ) technology (Genospectra) in collaboration with Dharmacon RNA...knockdown value of ង% and of these, 80 genes were previously undetectable by bDNA in baseline detection analysis, reflecting the limited sensitivity of

EBF factors drive expression of multiple classes of target genes governing neuronal development.

PubMed

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Environmental Effects on Compulsive Tail Chasing in Dogs

PubMed Central

Tiira, Katriina; Hakosalo, Osmo; Kareinen, Lauri; Thomas, Anne; Hielm-Björkman, Anna; Escriou, Catherine; Arnold, Paul; Lohi, Hannes

2012-01-01

Obsessive Compulsive Disorder (OCD) is a neuropsychiatric disorder observed both in humans and animals. Examples of Canine Compulsive Disorder (CD) include excessive tail chasing (TC), light/shadow chasing and flank sucking. We performed a questionnaire survey to investigate the characteristics of compulsive (TC) and its possible associations with environmental correlates and personality in a pet population of 368 dogs from four dog breeds. We observed an early onset of TC at 3–6 months of age and a large variation in TC frequency in all breeds, with an overrepresentation of milder cases. Almost half of the TC dogs showed lowered responsiveness during bouts and displayed also other types of compulsions more often than the controls. Interestingly, dogs that received dietary supplements, especially vitamins and minerals, expressed less TC compared to dogs that did not receive any supplements. Neutered females had less TC, suggesting an influence of ovarian hormones on TC. Tail chasers were shyer and had separated earlier from their mothers than the controls. Finally, our genetic study did not find an association between TC and CDH2, a locus previously associated with the canine flank sucking compulsion. In conclusion, the early-onset and the variable nature of the repetitive behaviour, which is affected by environmental factors such as micronutrients, neutering and maternal care, share several similar components between canine and human compulsions and supports canine TC as a model for human OCD. PMID:22844513

Cryptic sexual conflict in gift-giving insects: chasing the chase-away.

PubMed

Sakaluk, Scott K; Avery, Rachel L; Weddle, Carie B

2006-01-01

The chase-away model of sexual selection posits that elaborate male sexual displays arise because they exploit preexisting biases in females' sensory systems and induce females to mate in a suboptimal manner. An essential element of this hypothesis is that such manipulation should quickly lead to female resistance to male displays. Nuptial food gifts may be a frequent conduit by which males attempt to influence the mating behavior of females against females' own reproductive interests. In decorated crickets Gryllodes sigillatus, such inducements come in the form of a spermatophylax, a gelatinous mass forming part of the male's spermatophore and consumed by the female after mating. We conducted experiments in which spermatophylaxes obtained from male G. sigillatus were offered as novel food gifts to females of a non-gift-giving species (Acheta domesticus) having no evolutionary history of spermatophylax consumption. Female A. domesticus that were allowed to consume the spermatophylax took significantly longer to remate than when given no such opportunity. In contrast, when female G. sigillatus were prevented from consuming their partners' nuptial gifts, there was no difference in their propensity to remate relative to females permitted to consume a food gift after mating. These results suggest that the spermatophylax synthesized by male G. sigillatus contains substances designed to inhibit the sexual receptivity of their mates but that female G. sigillatus have evolved reduced responsiveness to these substances.

Development and testing of a prototype tool for integrated assessment of chemical status in marine environments.

PubMed

Andersen, Jesper H; Murray, Ciarán; Larsen, Martin M; Green, Norman; Høgåsen, Tore; Dahlgren, Elin; Garnaga-Budrė, Galina; Gustavson, Kim; Haarich, Michael; Kallenbach, Emilie M F; Mannio, Jaakko; Strand, Jakob; Korpinen, Samuli

2016-02-01

We report the development and application of a prototype tool for integrated assessment of chemical status in aquatic environments based on substance- and matrix-specific environmental assessment criteria (thresholds). The Chemical Status Assessment Tool (CHASE) integrates data on hazardous substances in water, sediments and biota as well as bio-effect indicators and is based on a substance- or bio-effect-specific calculation of a 'contamination ratio' being the ratio between an observed concentration and a threshold value. Values <1.0 indicate areas potentially 'unaffected', while values >1.0 indicate areas potentially 'affected'. These ratios are combined within matrices, i.e. for water, sediment and biota and for biological effects. The overall assessment used a 'one out, all out principle' with regard to each matrix. The CHASE tool was tested in the Baltic Sea and the North Sea in 376 assessment units. In the former, the chemical status was >1.0 in practically all areas indicating that all areas assessed were potentially affected. The North Sea included areas classified as unaffected or affected. The CHASE tool can in combination with temporal trend assessments of individual substances be advantageous for use in remedial action plans and, in particular, for the science-based evaluation of the status and for determining which specific substances are responsible for a status as potentially affected.

A minimal model of predator–swarm interactions

PubMed Central

Chen, Yuxin; Kolokolnikov, Theodore

2014-01-01

We propose a minimal model of predator–swarm interactions which captures many of the essential dynamics observed in nature. Different outcomes are observed depending on the predator strength. For a ‘weak’ predator, the swarm is able to escape the predator completely. As the strength is increased, the predator is able to catch up with the swarm as a whole, but the individual prey is able to escape by ‘confusing’ the predator: the prey forms a ring with the predator at the centre. For higher predator strength, complex chasing dynamics are observed which can become chaotic. For even higher strength, the predator is able to successfully capture the prey. Our model is simple enough to be amenable to a full mathematical analysis, which is used to predict the shape of the swarm as well as the resulting predator–prey dynamics as a function of model parameters. We show that, as the predator strength is increased, there is a transition (owing to a Hopf bifurcation) from confusion state to chasing dynamics, and we compute the threshold analytically. Our analysis indicates that the swarming behaviour is not helpful in avoiding the predator, suggesting that there are other reasons why the species may swarm. The complex shape of the swarm in our model during the chasing dynamics is similar to the shape of a flock of sheep avoiding a shepherd. PMID:24598204

A minimal model of predator-swarm interactions.

PubMed

Chen, Yuxin; Kolokolnikov, Theodore

2014-05-06

We propose a minimal model of predator-swarm interactions which captures many of the essential dynamics observed in nature. Different outcomes are observed depending on the predator strength. For a 'weak' predator, the swarm is able to escape the predator completely. As the strength is increased, the predator is able to catch up with the swarm as a whole, but the individual prey is able to escape by 'confusing' the predator: the prey forms a ring with the predator at the centre. For higher predator strength, complex chasing dynamics are observed which can become chaotic. For even higher strength, the predator is able to successfully capture the prey. Our model is simple enough to be amenable to a full mathematical analysis, which is used to predict the shape of the swarm as well as the resulting predator-prey dynamics as a function of model parameters. We show that, as the predator strength is increased, there is a transition (owing to a Hopf bifurcation) from confusion state to chasing dynamics, and we compute the threshold analytically. Our analysis indicates that the swarming behaviour is not helpful in avoiding the predator, suggesting that there are other reasons why the species may swarm. The complex shape of the swarm in our model during the chasing dynamics is similar to the shape of a flock of sheep avoiding a shepherd.

Aggressive and foraging behavioral interactions among ruffe

USGS Publications Warehouse

Savino, Jacqueline F.; Kostich, Melissa J.

2000-01-01

The ruffe, Gymnocephalus cernuus, is a nonindigenous percid in the Great Lakes. Ruffe are aggressive benthivores and forage over soft substrates. Laboratory studies in pools (100 cm in diameter, 15 cm water depth) were conducted to determine whether fish density (low = 2, medium = 4, high = 6 ruffe per pool) changed foraging and aggressive behaviors with a limited food supply of chironomid larvae. All fish densities demonstrated a hierarchy based on aggressive interactions, but ruffe were most aggressive at low and high fish densities. Time spent in foraging was lowest at the low fish density. The best forager at the low fish density was the most aggressive individual, but the second most aggressive fish at the medium and high fish density was the best forager and also the one chased most frequently. A medium fish density offered the best energetic benefits to ruffe by providing the lowest ratio of time spent in aggression to that spent foraging. Based on our results, ruffe should grow best at an intermediate density. With high ruffe densities, we would also expect disparity in size as the more aggressive fish are able to garner a disproportionate amount of the resources. Alternatively, as the Great Lakes are a fairly open system, ruffe could migrate out of one area to colonize another as populations exceed optimal densities.

Changing pattern of the subcellular distribution of erythroblast macrophage protein (Emp) during macrophage differentiation.

PubMed

Soni, Shivani; Bala, Shashi; Kumar, Ajay; Hanspal, Manjit

2007-01-01

Erythroblast macrophage protein (Emp) mediates the attachment of erythroid cells to macrophages and is required for normal differentiation of both cell lineages. In erythroid cells, Emp is believed to be involved in nuclear extrusion, however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data show that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture shows that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data show that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation and suggest that Emp may be involved in multiple cellular functions.

*CHANGING PATTERN OF THE SUBCELLULAR DISTRIBUTION OF ERYTHROBLAST MACROPHAGE PROTEIN (EMP) DURING MACROPHAGE DIFFERENTIATION

PubMed Central

Soni, Shivani; Bala, Shashi; Kumar, Ajay; Hanspal, Manjit

2007-01-01

Erythroblast macrophage protein (Emp), mediates the attachment of erythroid cells to macrophages, and is required for normal differentiation of both cell lineages. In erythroid cells Emp is believed to be involved in nuclear extrusion however, its role in macrophage differentiation is unknown. Information on the changes in the expression level and subcellular distribution of Emp in differentiating macrophages is essential for understanding the function of Emp. Macrophages of varying maturity were examined by immunofluorescence microscopy and biochemical methods. Our data shows that Emp is expressed in all stages of maturation, but its localization pattern changes dramatically during maturation: in immature macrophages, a substantial fraction of Emp is associated with the nuclear matrix, whereas in more mature cells, Emp is expressed largely at cell surface. Pulse-chase experiments show that nascent Emp migrates intracellularly from the cytoplasm to the plasma membrane more efficiently in mature macrophages than in immature cells. Incubation of erythroid cells with macrophages in culture show that erythroid cells attach to mature macrophages but not to immature macrophage precursors. Together, our data shows that the temporal and spatial expression of Emp correlates with its role in erythroblastic island formation, and suggests that Emp may be involved in multiple cellular functions. PMID:17071116

Ancestral Polymorphisms and Sex-Biased Migration Shaped the Demographic History of Brown Bears and Polar Bears

PubMed Central

Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

2013-01-01

Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA. PMID:24236053

Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears.

PubMed

Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

2013-01-01

Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.

The core planar cell polarity gene, Vangl2, maintains apical-basal organisation of the corneal epithelium.

PubMed

Panzica, D Alessio; Findlay, Amy S; van Ladesteijn, Rianne; Collinson, J Martin

2017-08-17

The role of the core planar cell polarity (PCP) pathway protein, Vangl2, was investigated in the corneal epithelium of the mammalian eye, a paradigm anatomical model of planar cell migration. The gene was conditionally knocked out in vivo and knocked down by siRNA, followed by immunohistochemical, behavioural and morphological analysis of corneal epithelial cells. The primary defects observed in vivo were of apical-basal organisation of the corneal epithelium, with abnormal stratification throughout life, mislocalisation of the cell membrane protein, Scribble, to the basal side of cells, and partial loss of the epithelial basement membrane. Planar defects in migration after wounding and in the presence of an applied electric field were noted. However, knockdown of Vangl2 also retarded cell migration in individual cells that had no contact with their neighbours, which precluded a classic PCP mechanism. It is concluded that some of the planar polarity phenotypes in PCP mutants may arise from disruption of apical-basal polarity. © 2017 Anatomical Society.

Jason Roadman | NREL

Science.gov Websites

using trained raptors, metrology, storm chasing, and wind tunnel testing of atmospheric turbulence. He Wind tunnel testing of atmospheric turbulence Education B.S. in Aerospace Engineering from Virginia

Antimicrobial susceptibility of Escherichia coli isolated from feces of wild cranes migrating to Kagoshima, Japan.

PubMed

Kitadai, Noriyuki; Obi, Takeshi; Yamashita, Shogo; Murase, Toshiyuki; Takase, Kozo

2012-03-01

Susceptibility to 13 antimicrobial agents was examined for 138 Escherichia coli isolates obtained from 192 fecal samples of wild cranes that migrated for wintering to the Izumi plain, Kagoshima prefecture in Japan. The numbers of isolates that were resistant to the antimicrobials used in this study are as follows: oxytetracycline (OTC), 22 isolates; minocycline, 7 isolates; ampicillin (ABPC), 4 isolates; nalidixic acid, 4 isolates; enrofloxacin, 2 isolates; kanamycin, one isolate. Multidrug resistant isolates exhibiting 2-4 drug resistances were obtained. All of the OTC-resistant isolates carried either the tet (A) or tet(B) gene. The bla(TEM) gene was found in all of the ABPC-resistant isolates.

Unified reduction principle for the evolution of mutation, migration, and recombination

PubMed Central

Altenberg, Lee; Liberman, Uri; Feldman, Marcus W.

2017-01-01

Modifier-gene models for the evolution of genetic information transmission between generations of organisms exhibit the reduction principle: Selection favors reduction in the rate of variation production in populations near equilibrium under a balance of constant viability selection and variation production. Whereas this outcome has been proven for a variety of genetic models, it has not been proven in general for multiallelic genetic models of mutation, migration, and recombination modification with arbitrary linkage between the modifier and major genes under viability selection. We show that the reduction principle holds for all of these cases by developing a unifying mathematical framework that characterizes all of these evolutionary models. PMID:28265103

Intercontinental reassortment and genomic variation of low pathogenic avian influenza viruses isolated from northern pintails (Anas acuta) in Alaska: examining the evidence through space and time

USGS Publications Warehouse

Ramey, Andrew M.; Pearce, John M.; Flint, Paul L.; Ip, Hon S.; Derksen, Dirk V.; Franson, J. Christian; Petrula, Michael J.; Scotton, Bradley D.; Sowl, Kristine M.; Wege, Michael L.; Trust, Kimberly A.

2010-01-01

Migration and population genetic data for northern pintails (Anas acuta) and phylogenetic analysis of low pathogenic avian influenza (LPAI) viruses from this host in Alaska suggest that northern pintails are involved in ongoing intercontinental transmission of avian influenza. Here, we further refine this conclusion through phylogenetic analyses which demonstrate that detection of foreign lineage gene segments is spatially dependent and consistent through time. Our results show detection of foreign lineage gene segments to be most likely at sample locations on the Alaska Peninsula and least likely along the Southern Alaska Coast. Asian lineages detected at four gene segments persisted across years, suggesting maintenance in avian hosts that migrate to Alaska each year from Asia or in hosts that remain in Alaska throughout the year. Alternatively, live viruses may persist in the environment and re-infect birds in subsequent seasons.

The pH-sensing receptor OGR1 improves barrier function of epithelial cells and inhibits migration in an acidic environment.

PubMed

de Vallière, Cheryl; Vidal, Solange; Clay, Ieuan; Jurisic, Giorgia; Tcymbarevich, Irina; Lang, Silvia; Ludwig, Marie-Gabrielle; Okoniewski, Michal; Eloranta, Jyrki J; Kullak-Ublick, Gerd A; Wagner, Carsten A; Rogler, Gerhard; Seuwen, Klaus

2015-09-15

The pH-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1; GPR68) is expressed in the gut. Inflammatory bowel disease is typically associated with a decrease in local pH, which may lead to altered epithelial barrier function and subsequent gastrointestinal repair involving epithelial cell adhesion and migration. As the mechanisms underlying the response to pH changes are not well understood, we have investigated OGR1-mediated, pH-dependent signaling pathways in intestinal epithelial cells. Caco-2 cells stably overexpressing OGR1 were created and validated as tools to study OGR1 signaling. Barrier function, migration, and proliferation were measured using electric cell-substrate impedance-sensing technology. Localization of the tight junction proteins zonula occludens protein 1 and occludin and the rearrangement of cytoskeletal actin were examined by confocal microscopy. Paracellular permeability and protein and gene expression analysis using DNA microarrays were performed on filter-grown Caco-2 monolayers. We report that an acidic pH shift from pH 7.8 to 6.6 improved barrier function and stimulated reorganization of filamentous actin with prominent basal stress fiber formation. Cell migration and proliferation during in vitro wound healing were inhibited. Gene expression analysis revealed significant upregulation of genes related to cytoskeleton remodeling, cell adhesion, and growth factor signaling. We conclude that acidic extracellular pH can have a signaling function and impact the physiology of intestinal epithelial cells. The deconstruction of OGR1-dependent signaling may aid our understanding of mucosal inflammation mechanisms. Copyright © 2015 the American Physiological Society.

Isolation-by-distance in landscapes: considerations for landscape genetics

PubMed Central

van Strien, M J; Holderegger, R; Van Heck, H J

2015-01-01

In landscape genetics, isolation-by-distance (IBD) is regarded as a baseline pattern that is obtained without additional effects of landscape elements on gene flow. However, the configuration of suitable habitat patches determines deme topology, which in turn should affect rates of gene flow. IBD patterns can be characterized either by monotonically increasing pairwise genetic differentiation (for example, FST) with increasing interdeme geographic distance (case-I pattern) or by monotonically increasing pairwise genetic differentiation up to a certain geographical distance beyond which no correlation is detectable anymore (case-IV pattern). We investigated if landscape configuration influenced the rate at which a case-IV pattern changed to a case-I pattern. We also determined at what interdeme distance the highest correlation was measured between genetic differentiation and geographic distance and whether this distance corresponded to the maximum migration distance. We set up a population genetic simulation study and assessed the development of IBD patterns for several habitat configurations and maximum migration distances. We show that the rate and likelihood of the transition of case-IV to case-I FST–distance relationships was strongly influenced by habitat configuration and maximum migration distance. We also found that the maximum correlation between genetic differentiation and geographic distance was not related to the maximum migration distance and was measured across all deme pairs in a case-I pattern and, for a case-IV pattern, at the distance where the FST–distance curve flattens out. We argue that in landscape genetics, separate analyses should be performed to either assess IBD or the landscape effects on gene flow. PMID:25052412

Lake-specific variation in growth, migration timing and survival of juvenile sockeye salmon Oncorhynchus nerka: separating environmental from genetic influences.

PubMed

Reed, T E; Martinek, G; Quinn, T P

2010-08-01

Time series on juvenile life-history traits obtained from sockeye salmon Oncorhynchus nerka were analysed to assess lake-specific environmental influences on juvenile migration timing, size and survival of fish from a common gene pool. Every year for the past two decades, O. nerka have been spawned at a hatchery facility, and the progeny released into two lakes that differ in average summer temperatures, limnological attributes and growth opportunities. Juveniles reared in the warmer, more productive Crosswind Lake were larger and heavier as smolts compared to those from the cooler, less productive Summit Lake and had higher in-lake and subsequent marine survival. Crosswind Lake smolts migrated from the lake to sea slightly earlier in the season but the migration timing distributions overlapped considerably across years. Fry stocking density had a negative effect on smolt length for both lakes, and a negative effect on in-lake survival in Summit Lake. Taken together, the results revealed a strong effect of lake-rearing environment on the expression of life-history variation in O. nerka. The stocking of these lakes each year with juveniles from a single mixed-source population provided a large-scale reverse common-garden experiment, where the same gene pool was exposed to different environments, rather than the different gene pools in the same environment approach typical of evolutionary ecology studies. Other researchers are encouraged to seek and exploit similar serendipitous situations, which might allow environmental and genetic influences on ecologically important traits to be distinguished in natural or semi-natural settings.

Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes.

PubMed

Gavalas, Anthony; Ruhrberg, Christiana; Livet, Jean; Henderson, Christopher E; Krumlauf, Robb

2003-12-01

Hox genes are instrumental in assigning segmental identity in the developing hindbrain. Auto-, cross- and para-regulatory interactions help establish and maintain their expression. To understand to what extent such regulatory interactions shape neuronal patterning in the hindbrain, we analysed neurogenesis, neuronal differentiation and motoneuron migration in Hoxa1, Hoxb1 and Hoxb2 mutant mice. This comparison revealed that neurogenesis and differentiation of specific neuronal subpopulations in r4 was impaired in a similar fashion in all three mutants, but with different degrees of severity. In the Hoxb1 mutants, neurons derived from the presumptive r4 territory were re-specified towards an r2-like identity. Motoneurons derived from that territory resembled trigeminal motoneurons in both their migration patterns and the expression of molecular markers. Both migrating motoneurons and the resident territory underwent changes consistent with a switch from an r4 to r2 identity. Abnormally migrating motoneurons initially formed ectopic nuclei that were subsequently cleared. Their survival could be prolonged through the introduction of a block in the apoptotic pathway. The Hoxa1 mutant phenotype is consistent with a partial misspecification of the presumptive r4 territory that results from partial Hoxb1 activation. The Hoxb2 mutant phenotype is a hypomorph of the Hoxb1 mutant phenotype, consistent with the overlapping roles of these genes in facial motoneuron specification. Therefore, we have delineated the functional requirements in hindbrain neuronal patterning that follow the establishment of the genetic regulatory hierarchy between Hoxa1, Hoxb1 and Hoxb2.

Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

PubMed

Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

2017-11-16

Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3K/AKT pathway. Altogether, these results suggest that CaSO 4 scaffolds could have potential applications for bone regeneration.

Oxygen-induced cell migration and on-line monitoring biomarkers modulation of cervical cancers on a microfluidic system

PubMed Central

Lin, Xuexia; Chen, Qiushui; Liu, Wu; Zhang, Jie; Wang, Shiqi; Lin, Zhixiong; Lin, Jin-Ming

2015-01-01

In this work, we report an integrated microfluidic device for cell co-culture under different concentrations of oxygen, in which the secreted protein VEGF165 was on-line qualitatively and semi-quantitatively analyzed by functional nucleic acid, hemin, ABTS and peroxide system. This microfluidic platform allowed investigation of various oxygen and distances effect on cell-to-cell communication. Besides, the microfluidic device was used for real-time analysis of VEGF165 protein by aptamer-functionalized microchannels. Under 5% O2 condition, we found that the migration of CaSki cells was faster than the migration of human umbilical vein endothelial cells. However, the migration of CaSki cells was slower than the migration of HUVECs under 15% O2 condition. Moreover, the shorter intercellular distances, the quicker cells migration. Furthermore, HIF-1α and VEGF165 genes, ROS were analyzed, and the results would provide new perspectives for the diagnosis and medical treatment of cervical cancer. PMID:25905434

N-Cadherin and Fibroblast Growth Factor Receptors crosstalk in the control of developmental and cancer cell migrations.

PubMed

Nguyen, Thao; Mège, René Marc

2016-11-01

Cell migrations are diverse. They constitutemajor morphogenetic driving forces during embryogenesis, but they contribute also to the loss of tissue homeostasis and cancer growth. Capabilities of cells to migrate as single cells or as collectives are controlled by internal and external signalling, leading to the reorganisation of their cytoskeleton as well as by the rebalancing of cell-matrix and cell-cell adhesions. Among the genes altered in numerous cancers, cadherins and growth factor receptors are of particular interest for cell migration regulation. In particular, cadherins such as N-cadherin and a class of growth factor receptors, namely FGFRs cooperate to regulate embryonic and cancer cell behaviours. In this review, we discuss on reciprocal crosstalk between N-cadherin and FGFRs during cell migration. Finally, we aim at clarifying the synergy between N-cadherin and FGFR signalling that ensure cellular reorganization during cell movements, mainly during cancer cell migration and metastasis but also during developmental processes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Association of Regulatory Boards of Optometry

MedlinePlus

... Fraud contact number) or https://www.chase.com/credit-cards/customer-service . In addition, individuals may also consider reviewing their current credit reports at https://www.annualcreditreport.com/index.action . ...

Comparative analysis of gene expression profiles of OPN signaling pathway in four kinds of liver diseases.

PubMed

Wang, Gaiping; Chen, Shasha; Zhao, Congcong; Li, Xiaofang; Zhao, Weiming; Yang, Jing; Chang, Cuifang; Xu, Cunshuan

2016-09-01

To explore the relevance of OPN signalling pathway to the occurrence and development of nonalcoholic fatty liver disease (NAFLD), liver cirrhosis (LC), hepatic cancer (HC) and acute hepatic failure (AHF) at transcriptional level, Rat Genome 230 2.0 Array was used to detect expression profiles of OPN signalling pathway-related genes in four kinds of liver diseases. The results showed that 23, 33, 59 and 74 genes were significantly changed in the above four kinds of liver diseases, respectively. H-clustering analysis showed that the expression profiles of OPN signalling-related genes were notably different in four kinds of liver diseases. Subsequently, a total of above-mentioned 147 genes were categorized into four clusters by k-means according to the similarity of gene expression, and expression analysis systematic explorer (EASE) functional enrichment analysis revealed that OPN signalling pathway-related genes were involved in cell adhesion and migration, cell proliferation, apoptosis, stress and inflammatory reaction, etc. Finally, ingenuity pathway analysis (IPA) software was used to predict the functions of OPN signalling-related genes, and the results indicated that the activities of ROS production, cell adhesion and migration, cell proliferation were remarkably increased, while that of apoptosis, stress and inflammatory reaction were reduced in four kinds of liver diseases. In summary, the above physiological activities changed more obviously in LC, HC and AHF than in NAFLD.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Curcumin may serve an anticancer role in human osteosarcoma cell line U-2 OS by targeting ITPR1.

PubMed

Luo, Zhanpeng; Li, Dawei; Luo, Xiaobo; Li, Litao; Gu, Suxi; Yu, Long; Ma, Yuanzheng

2018-04-01

The present study aimed to determine the mechanisms of action of curcumin in osteosarcoma. Human osteosarcoma U-2 OS cells was purchased from the Cell Bank of the Chinese Academy of Sciences. RNA sequencing analysis was performed for 2 curcumin-treated samples and 2 control samples using Illumina deep sequencing technology. The differentially expressed genes were identified using Cufflink software. Enrichment and protein-protein interaction network analyses were performed separately using cluster Profiler package and Cytoscape software to identify key genes. Then, the mRNA levels of key genes were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in U-2 OS cells. Finally, cell apoptosis, proliferation, migration and invasion arrays were performed. In total, 201 DEGs were identified in the curcumin-treated group. EEF1A1 (degree=88), ATF7IP, HIF1A, SMAD7, CLTC, MCM10, ITPR1, ADAM15, WWP2 and ATP5C1, which were enriched in 'biological process', exhibited higher degrees than other genes in the PPI network. RT-qPCR demonstrated that treatment with curcumin was able to significantly increase the levels of CLTC and ITPR1 mRNA in curcumin-treated cells compared with control. In addition, targeting ITPR1 with curcumin significantly promoted apoptosis and suppressed proliferation, migration and invasion. Targeting ITPR1 via curcumin may serve an anticancer role by mediating apoptosis, proliferation, migration and invasion in U-2 OS cells.

Energetic cost of feeding territories in an Hawaiian honeycreeper.

PubMed

Carpenter, F Lynn; MacMillen, Richard E

1976-09-01

By analysis of time budgets the daily energy expenditure in territorial individuals of a Hawaiian honeycreeper (Vestiaria coccinea, Fam. Drepanididae) were estimated during the nonbreeding season and compared to that of nonterritorial individuals. The mean rise in living costs was 2.3 kcal/24 h or 17% of the nonterritorial energy budget. The most costly territorial behavior was advertisement rather than chasing, and total territorial cost was seen to be little affected by the number of intruders or the size of the territory. These results are compared with data on feeding (nonbreeding) territories of other nectar-feeding birds. The suggestion is made that hummingbirds may be more likely to develop nonbreeding territorial behavior in any set of environmental circumstances than are honeycreepers because of relatively lower total cost of advertisement plus chasing.

NRC, SPI, and chasing arrows: Is there common ground

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabasca, L.

After negotiating for 15 months, issuing three white papers, and conducting consumer research, the National Recycling Coalition (NRC, Washington, DC) and the Society of the Plastics Industry, Inc. (SPI, Washington, DC), have agreed to disagree on the use of the familiar chasing arrows logo in SPI's seven-number resin identification code. The desired end result of the talks and debates was supposed to be a plan to change legislation requiring 39 states to use SPI's current resin identification code and a commitment to remove the old code from durable goods and flexible packaging. Ultimately, these actions could have improved markets formore » polyethylene terephthalate (PET) and high-density polyethylene (HDPE) by reducing contamination caused by confusion over what is actually recycled versus what is merely recyclable.« less

Characterization of Novel Missense Variants of SERPINA1 Gene Causing Alpha-1 Antitrypsin Deficiency.

PubMed

Matamala, Nerea; Lara, Beatriz; Gomez-Mariano, Gema; Martínez, Selene; Retana, Diana; Fernandez, Taiomara; Silvestre, Ramona Angeles; Belmonte, Irene; Rodriguez-Frias, Francisco; Vilar, Marçal; Sáez, Raquel; Iturbe, Igor; Castillo, Silvia; Molina-Molina, María; Texido, Anna; Tirado-Conde, Gema; Lopez-Campos, Jose Luis; Posada, Manuel; Blanco, Ignacio; Janciauskiene, Sabina; Martinez-Delgado, Beatriz

2018-06-01

The SERPINA1 gene is highly polymorphic, with more than 100 variants described in databases. SERPINA1 encodes the alpha-1 antitrypsin (AAT) protein, and severe deficiency of AAT is a major contributor to pulmonary emphysema and liver diseases. In Spanish patients with AAT deficiency, we identified seven new variants of the SERPINA1 gene involving amino acid substitutions in different exons: PiSDonosti (S+Ser14Phe), PiTijarafe (Ile50Asn), PiSevilla (Ala58Asp), PiCadiz (Glu151Lys), PiTarragona (Phe227Cys), PiPuerto Real (Thr249Ala), and PiValencia (Lys328Glu). We examined the characteristics of these variants and the putative association with the disease. Mutant proteins were overexpressed in HEK293T cells, and AAT expression, polymerization, degradation, and secretion, as well as antielastase activity, were analyzed by periodic acid-Schiff staining, Western blotting, pulse-chase, and elastase inhibition assays. When overexpressed, S+S14F, I50N, A58D, F227C, and T249A variants formed intracellular polymers and did not secrete AAT protein. Both the E151K and K328E variants secreted AAT protein and did not form polymers, although K328E showed intracellular retention and reduced antielastase activity. We conclude that deficient variants may be more frequent than previously thought and that their discovery is possible only by the complete sequencing of the gene and subsequent functional characterization. Better knowledge of SERPINA1 variants would improve diagnosis and management of individuals with AAT deficiency.

Migration strategy affects avian influenza dynamics in mallards (Anas platyrhynchos).

USGS Publications Warehouse

Takekawa, John Y.; Hill, Nichola J.; Ackerman, Joshua T.; Herring, Garth; Hobson, Keith; Cardona, Carol J.; Runstadler, Jonathan; Boyce, Walter M.

2012-01-01

Studies of pathogen transmission typically overlook that wildlife hosts can include both migrant and resident populations when attempting to model circulation. Through the application of stable isotopes in flight feathers, we estimated the migration strategy of mallards (Anas platyrhynchos) occurring on California wintering grounds. Our study demonstrates that mallards- a principal host of avian influenza virus (AIV) in nature, contribute differently to virus gene flow depending on migration strategy. No difference in AIV prevalence was detected between resident (9.6%), intermediate-distance (9.6%) and long-distance migrants (7.4%). Viral diversity among the three groups was also comparable, possibly owing to viral pool mixing when birds converge at wetlands during winter. However, migrants and residents contributed differently to the virus gene pool at wintering wetlands. Migrants introduced virus from northern breeding grounds (Alaska and the NW Pacific Rim) into the wintering population, facilitating gene flow at continental scales, but circulation of imported virus appeared to be limited. In contrast, resident mallards acted as AIV reservoirs facilitating year-round circulation of limited subtypes (i.e. H5N2) at lower latitudes. This study supports a model of virus exchange in temperate regions driven by the convergence of wild birds with separate geographic origins and exposure histories.

Reduced endothelin converting enzyme-1 and endothelin-3 mRNA in the developing bowel of male mice may increase expressivity and penetrance of Hirschsprung disease-like distal intestinal aganglionosis.

PubMed

Vohra, Bhupinder P S; Planer, William; Armon, Jennifer; Fu, Ming; Jain, Sanjay; Heuckeroth, Robert O

2007-01-01

Hirschsprung disease (distal intestinal aganglionosis, HSCR) is a multigenic disorder with incomplete penetrance, variable expressivity, and a strong male gender bias. Recent studies demonstrated that these genetic patterns arise because gene interactions determine whether enteric nervous system (ENS) precursors successfully proliferate and migrate into the distal bowel. We now demonstrate that male gender bias in the extent of distal intestinal aganglionosis occurs in mice with Ret dominant-negative mutations (RetDN) that mimic human HSCR. We hypothesized that male gender bias could result from reduced expression of a gene already known to be essential for ENS development. Using quantitative real-time polymerase chain reaction (PCR) we demonstrated reduced levels of endothelin converting enzyme-1 and endothelin-3 mRNA in the male mouse bowel at the time that ENS precursors migrate into the colon. Other HSCR-associated genes are expressed at comparable levels in male and female mice. Testosterone and Mullerian inhibiting substance had no deleterious effect on ENS precursor development, but adding EDN3 peptide to E11.5 male RetDN heterozygous mouse gut explants in organ culture significantly increased the rate of ENS precursor migration through the bowel.

Targeting LC3 and Beclin-1 autophagy genes suppresses proliferation, survival, migration and invasion by inhibition of Cyclin-D1 and uPAR/Integrin β1/ Src signaling in triple negative breast cancer cells.

PubMed

Hamurcu, Zuhal; Delibaşı, Nesrin; Geçene, Seda; Şener, Elif Funda; Dönmez-Altuntaş, Hamiyet; Özkul, Yusuf; Canatan, Halit; Ozpolat, Bulent

2018-03-01

Autophagy is a catabolic process for degrading dysfunctional proteins and organelles, and closely associated with cancer cell survival under therapeutic, metabolic stress, hypoxia, starvation and lack of growth factors, contributing to resistance to therapies. However, the role of autophagy in breast cancer cells is not well understood. In the present study, we investigated the role of autophagy in highly aggressive and metastatic triple negative breast cancer (TNBC) and non-metastatic breast cancer cells and demonstrated that the knockdown of autophagy-related genes (LC3 and Beclin-1) inhibited autophagy and significantly suppressed cell proliferation, colony formation, migration/invasion and induced apoptosis in MDA-MB-231 and BT-549 TNBC cells. Knockdown of LC3 and Beclin-1 led to inhibition of multiple proto-oncogenic signaling pathways, including cyclin D1, uPAR/integrin-β1/Src, and PARP1. In conclusion, our study suggests that LC3 and Beclin-1 are required for cell proliferation, survival, migration and invasion, and may contribute to tumor growth and progression of highly aggressive and metastatic TNBC cells and therapeutic targeting of autophagy genes may be a potential therapeutic strategy for TNBC in breast cancer.

A field reciprocal transplant experiment reveals asymmetric costs of migration between lake and river ecotypes of three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

Kaufmann, J; Lenz, T L; Kalbe, M; Milinski, M; Eizaguirre, C

2017-05-01

Theory of local adaptation predicts that nonadapted migrants will suffer increased costs compared to local residents. Ultimately this process can result in the reduction of gene flow and culminate in speciation. Here, we experimentally investigated the relative fitness of migrants in foreign habitats, focusing on diverging lake and river ecotypes of three-spined sticklebacks. A reciprocal transplant experiment performed in the field revealed asymmetric costs of migration: whereas mortality of river fish was increased under lake conditions, lake migrants suffered from reduced growth relative to river residents. Selection against migrants thus involved different traits in each habitat but generally contributed to bidirectional reduction in gene flow. Focusing particularly on the parasitic environments, migrant fish differed from resident fish in the parasite community they harboured. This pattern correlated with both cellular phenotypes of innate immunity as well as with allelic variation at the genes of the major histocompatibility complex. In addition to showing the costs of migration in three-spined sticklebacks, this study highlights the role of asymmetric selection particularly from parasitism in genotype sorting and in the emergence of local adaptation. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

PubMed

Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

2016-10-23

BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). We found significantly more positively expressed CTGF protein in ESCC tissues was than in normal adjacent esophageal tissues (P<0.01). Dual luciferase reporter gene assay showed that miR-145 can specifically bind with the 3'UTR of CTGF and significantly inhibit the luciferase activity by 55% (P<0.01). Up-regulation of miR-145 or down-regulation of CTGF can suppress the proliferation, migration, invasion, and EMT process of ESCC cells. CONCLUSIONS MiR-145 was significantly down-regulated in ESCC tissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

External beam radiation therapy enhances mesenchymal stem cell-mediated sodium iodide symporter gene delivery.

PubMed

Schug, Christina; Sievert, Wolfgang; Urnauer, Sarah; Müller, Andrea Maria; Schmohl, Kathrin Alexandra; Wechselberger, Alexandra; Schwenk, Nathalie; Lauber, Kirsten; Schwaiger, Markus; Multhoff, Gabriele; Wagner, Ernst; Nelson, Peter J; Spitzweg, Christine

2018-05-04

The tumor-homing properties of mesenchymal stem cells (MSC) have led to their development as delivery vehicles for the targeted delivery of therapeutic genes such as the sodium iodide symporter (NIS) to solid tumors. External beam radiation therapy (EBRT) may represent an ideal setting for the application of engineered MSC-based gene therapy as tumor irradiation may enhance MSC recruitment into irradiated tumors through the increased production of select factors linked to MSC migration. In the present study, the irradiation of human liver cancer cells (HuH7) (1-10 Gy) showed a strong dose-dependent increase in steady state mRNA levels of CXCL8, CXCL12/SDF-1, FGF2, PDGFβ, TGFβ1, TSP-1 and VEGF (0-48 h), which was verified for most factors at the protein level (after 48 h). Radiation effects on directed MSC migration was tested in vitro using a live cell tracking migration assay and supernatants from control and irradiated HuH7 cells. A robust increase in mean forward migration index (yFMI), mean center of mass (yCoM) and mean directionality of MSCs towards supernatants was seen from irradiated as compared to nonirradiated tumor cells. Transferability of this effect to other tumor sources was demonstrated using the human breast adenocarcinoma cell line (MDA-MB-231), which showed a similar behavior to radiation as seen with HuH7 cells in qPCR and migration assay. To evaluate this in a more physiologic in vivo setting, subcutaneously growing HuH7 xenograft tumors were irradiated with 0, 2 or 5 Gy followed by CMV-NIS-MSC application 24 h later. Tumoral iodide uptake was monitored using ¹²³I-scintigraphy. The results showed increased tumor-specific dose-dependent accumulation of radioiodide in irradiated tumors. Our results demonstrate that EBRT enhances the migratory capacity of MSCs and may thus increase the therapeutic efficacy of MSC-mediated NIS radionuclide therapy.

microRNA-150 Regulates Mobilization and Migration of Bone Marrow-Derived Mononuclear Cells by Targeting Cxcr4

PubMed Central

Tano, Nobuko; Kim, Ha Won; Ashraf, Muhammad

2011-01-01

The interaction between chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor (SDF)-1, plays an important role in stem cell mobilization and migration in ischemic tissues. MicroRNAs (miRs) are key regulators of stem cell function and are involved in regulation of stem cell survival and differentiation to adopt different cell lineages. In this study, we show that ischemia inhibits the expression of miR-150 in BM-derived mononuclear cells (MNC) and activates its target Cxcr4 gene. Our results show that miR-150/CXCR4 cascade enhances MNC mobilization and migration. By using mouse acute myocardial infarction (MI) model, we found that MNCs in peripheral blood (PB) were increased significantly at day 5 after AMI as compared to control group and the number of CXCR4 positive MNCs both in bone marrow (BM) and PB was also markedly increased after MI. Analysis by microarray-based miRNA profiling and real-time PCR revealed that the expression of miR-150 which targets Cxcr4 gene as predicted was significantly downregulated in BM-MNCs after MI. Abrogation of miR-150 markedly increased CXCR4 protein expression suggesting its target gene. To show that miR-150 regulates MNC mobilization, knockdown of miR-150 in BM-MNCs by specific antisense inhibitor resulted in their higher migration ability in vitro as compared to scramble-transfected MNCs. Furthermore, in vivo BM transplantation of MNCs lacking miR-150 expression by lentiviral vector into the irradiated wild type mice resulted in the increased number of MNCs in PB after AMI as compared to control. In conclusion, this study demonstrates that ischemia mobilizes BM stem cells via miR-150/CXCR4 dependent mechanism and miR-150 may be a novel therapeutic target for stem cell migration to the ischemic tissue for neovascularization and repair. PMID:22039399

F-18 chase craft with NASA test pilots Schneider and Fulton

NASA Technical Reports Server (NTRS)

1992-01-01

Ed Schneider, (left), is the project pilot for the F-18 High Angle of Attack program at NASA's Dryden Flight Research Center, Edwards, California. He has been a NASA research pilot at Dryden since 1983. In addition to his assignment with the F-18 High Angle of Attack program, Schneider is a project pilot for the F-15B aeronautical research aircraft, the NASA NB-52B launch aircraft, and the SR-71 'Blackbird' aircraft. He is a Fellow and was the 1994 President of the Society of Experimental Test Pilots. In 1996 he was awarded the NASA Exceptional Service Medal. Schneider is seen here with Fitzhugh L. Fulton Jr., (right), who was a civilian research pilot at Dryden. from August 1, 1966, until July 3, 1986, following 23 years of service as a pilot in the U.S. Air Force. Fulton was the project pilot on all early tests of the 747 Shuttle Carrier Aircraft (SCA) used to air launch the Space Shuttle prototype Enterprise in the Approach and Landing Tests (ALT) at Dryden in l977. For his work in the ALT program, Fulton received NASA's Exceptional Service Medal. He also received the Exceptional Service Medal again in 1983 for flying the 747 SCA during the European tour of the Space Shuttle Enterprise. During his career at Dryden, Fulton was project pilot on NASA's NB-52B launch aircraft used to air launch a variety of piloted and unpiloted research aircraft, including the X-15s and lifting bodies. He flew the XB-70 prototype supersonic bomber on both NASA-USAF tests and NASA research flights during the late 1960s, attaining speeds exceeding Mach 3. He was also a project pilot on the YF-12A and YF-12C research program from April 14, 1969, until September 25, 1978. The F/A-18 Hornet seen behind them is used primarily as a safety chase and support aircraft at NASA's Dryden Flight Research Center, Edwards, Calif. As support aircraft, the F-18's are used for safety chase, pilot proficiency and aerial photography. As a safety chase aircraft, F-18's, flown by research pilots, accompany research missions as another 'set of eyes' to visually observe the research event, experiment or test to help make sure the flights are carried out safely. The 'chase' pilots are in constant communication with the research pilots and mission control to report abnormalities that may be seen from the support aircraft. Pilots must also stay proficient by flying a certain number of missions per month. F-18's are used for this. A two-seat support aircraft is also used when research missions require an engineer or photographer on the flights.

JWA gene regulates PANC-1 pancreatic cancer cell behaviors through MEK-ERK1/2 of the MAPK signaling pathway.

PubMed

Wu, Yuan-Yuan; Ma, Tie-Liang; Ge, Zhi-Jun; Lin, Jie; Ding, Wei-Liang; Feng, Jia-Ke; Zhou, Su-Jun; Chen, Guo-Chang; Tan, Yong-Fei; Cui, Guo-Xing

2014-10-01

The present study aimed to investigate the role of JWA gene in the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells and the effect on the MAPK signaling pathway. Human PANC-1 pancreatic cancer cells were cultured in vitro , and small interfering RNA (siRNA) was designed for the JWA gene. The siRNA was transfected into PANC-1 cells. Subsequently, the cell proliferation was measured by MTT assay; cell apoptosis was detected by analyzing BAX and Bcl-2 protein expression; cell migration and invasion were measured using Transwell ® chambers; and the protein expression of JWA and ERK1/2, JNK and p38 and their phosphorylated forms were measured by western blotting. By utilizing the MTT assay, the results showed that when JWA protein expression was inhibited, the proliferation of PANC-1 cells was enhanced. In addition, the expression of apoptosis-associated protein (AAP) BAX was substantially decreased, while the expression of the apoptosis inhibitor gene, Bcl-2 , was significantly enhanced. Using Transwell chambers, it was found that the number of penetrating PANC-1 cells was significantly increased after transfection with JWA siRNA, suggesting that the migration and invasion of the cells was substantially increased. By studying the association between JWA and the MAPK pathway in PANC-1 cells, it was found that the expression of p-ERK1/2 of the MAPK pathway was significantly downregulated following JWA siRNA transfection. However, the expression levels of ERK1/2, JNK, p38, p-JNK and p-p38 showed no significant differences. In conclusion, it was shown that JWA affects the proliferation, apoptosis, invasion and migration of PANC-1 pancreatic cancer cells which could be attributed to effects on the expression of ERK1/2 in the MAPK pathway.

Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6) causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto.

PubMed

Sasado, Takao; Kondoh, Hisato; Furutani-Seiki, Makoto; Naruse, Kiyoshi

2017-01-01

Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC) migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar) is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68). CPSF6 is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3'UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3'UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3'UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo.

Mutation in cpsf6/CFIm68 (Cleavage and Polyadenylation Specificity Factor Subunit 6) causes short 3'UTRs and disturbs gene expression in developing embryos, as revealed by an analysis of primordial germ cell migration using the medaka mutant naruto

PubMed Central

Kondoh, Hisato; Furutani-Seiki, Makoto; Naruse, Kiyoshi

2017-01-01

Our previous studies analyzing medaka mutants defective in primordial germ cell (PGC) migration identified cxcr4b and cxcr7, which are both receptors of the chemokine sdf1/cxcl12, as key regulators of PGC migration. Among PGC migration mutants, naruto (nar) is unique in that the mutant phenotype includes gross morphological abnormalities of embryos, suggesting that the mutation affects a broader range of processes. A fine genetic linkage mapping and genome sequencing showed the nar gene encodes Cleavage and Polyadenylation Specificity Factor subunit 6 (CPSF6/CFIm68). CPSF6 is a component of the Cleavage Factor Im complex (CFIm) which plays a key role in pre-mRNA 3'-cleavage and polyadenylation. 3'RACE of sdf1a/b and cxcr7 transcripts in the mutant embryos indicated shorter 3’UTRs with poly A additions occurring at more upstream positions than wild-type embryos, suggesting CPSF6 functions to prevent premature 3’UTR cleavage. In addition, expression of the coding region sequences of sdf1a/b in nar mutants was more anteriorly extended in somites than wild-type embryos, accounting for the abnormally extended distribution of PGCs in nar mutants. An expected consequence of shortening 3'UTR is the escape from the degradation mechanism mediated by microRNAs interacting with distal 3’UTR sequence. The abnormal expression pattern of sdf1a coding sequence may be at least partially accounted for by this mechanism. Given the pleiotropic effects of nar mutation, further analysis using the nar mutant will reveal processes in which CPSF6 plays essential regulatory roles in poly A site selection and involvement of 3'UTRs in posttranscriptional gene regulation in various genes in vivo. PMID:28253363

HER4 selectively coregulates estrogen stimulated genes associated with breast tumor cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Wen; Jones, Frank E., E-mail: fjones3@tulane.edu

2014-01-10

Highlights: •HER4/4ICD is an obligate coactivator for 37% of estrogen regulated genes. •HER4/4ICD coactivated genes selectively regulate estrogen stimulated proliferation. •Estrogen stimulated tumor cell migration occurs independent of HER4/4ICD. •Disrupting HER4/4ICD and ER coactivated gene expression may suppress breast cancer. -- Abstract: The EGFR-family member HER4 undergoes regulated intramembrane proteolysis (RIP) to generate an intracellular domain (4ICD) that functions as a transcriptional coactivator. Accordingly, 4ICD coactivates the estrogen receptor (ER) and associates with ER at target gene promoters in breast tumor cells. However, the extent of 4ICD coactivation of ER and the functional significance of the 4ICD/ER transcriptional complex ismore » unclear. To identify 4ICD coactivated genes we performed a microarray gene expression analysis of β-estradiol treated cells comparing control MCF-7 breast cancer cells to MCF-7 cells where HER4 expression was stably suppressed using a shRNA. In the MCF-7 cell line, β-estradiol significantly stimulated or repressed by 2-fold or more 726 or 53 genes, respectively. Significantly, HER4/4ICD was an obligate coactivator for 277 or 38% of the β-estradiol stimulated genes. Ingenuity Pathway Analysis of β-estradiol regulated genes identified significant associations with multiple cellular functions regulating cellular growth and proliferation, cell cycle progression, cancer metastasis, decreased hypoplasia, tumor cell migration, apoptotic resistance of tumor cells, and increased transcription. Genes coactivated by 4ICD displayed functional specificity by only significantly contributing to cellular growth and proliferation, cell cycle progression, and decreased hypoplasia. In direct concordance with these in situ results we show that HER4 knockdown in MCF-7 cells results in a loss of estrogen stimulated tumor cell proliferation and cell cycle progression, whereas, estrogen stimulated tumor cell migration was unaffected by loss of HER4 expression. In summary, we demonstrate for the first time that a cell surface receptor functions as an obligate ER coactivator with functional specificity associated with breast tumor cell proliferation and cell cycle progression. Nearly 90% of ER positive tumors coexpress HER4, therefore we predict that the majority of breast cancer patients would benefit from a strategy to therapeutic disengage ER/4ICD coregulated tumor cell proliferation.« less

Effects of zoledronic acid and geranylgeraniol on the cellular behaviour and gene expression of primary human alveolar osteoblasts.

PubMed

Zafar, S; Coates, D E; Cullinan, M P; Drummond, B K; Milne, T; Seymour, G J

2016-11-01

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication of bisphosphonate therapy. The mechanism underlying BRONJ pathogenesis is poorly understood. To determine the effects of zoledronic acid (ZA) and geranylgeraniol (GGOH) on the mevalonate pathway (MVP) in osteoblasts generated from the human mandibular alveolar bone in terms of cell viability/proliferation, migration, apoptosis and gene expression. Primary human osteoblasts (HOBs) isolated from the mandibular alveolar bone were phenotyped. HOBs were cultured with or without ZA and GGOH for up to 72 h. Cellular behaviour was examined using a CellTiter-Blue® viability assay, an Ibidi culture-insert migration assay, an Apo-ONE® Homogeneous Caspase-3/7 apoptosis assay and transmission electron microscopy (TEM). Quantitative real-time reverse transcriptase polymerase chain reaction (qRT 2 -PCR) was used to determine the simultaneous expression of 168 osteogenic and angiogenic genes modulated in the presence of ZA and GGOH. ZA decreased cell viability and migration and induced apoptosis in HOBs. TEM revealed signs of apoptosis in ZA-treated HOBs. However, the co-addition of GGOH ameliorated the effect of ZA and partially restored the cells to the control state. Twenty-eight genes in the osteogenic array and 27 genes in the angiogenic array were significantly regulated in the presence of ZA compared with those in the controls at one or more time points. The cytotoxic effect of ZA on HOBs and its reversal by the addition of GGOH suggests that the effect of ZA on HOBs is mediated via the MVP. The results suggest that GGOH could be used as a possible therapeutic/preventive strategy for BRONJ.

Gene Flow between Sympatric Life History Forms of Oncorhynchus mykiss Located above and below Migratory Barriers

PubMed Central

Van Doornik, Donald M.; Berejikian, Barry A.; Campbell, Lance A.

2013-01-01

Oncorhynchus mykiss have a diverse array of life history types, and understanding the relationship among types is important for management of the species. Patterns of gene flow between sympatric freshwater resident O. mykiss, commonly known as rainbow trout, and anadromous O. mykiss, commonly known as steelhead, populations are complex and poorly understood. In this study, we attempt to determine the occurrence and pathways of gene flow and the degree of genetic similarity between sympatric resident and anadromous O. mykiss in three river systems, and investigate whether resident O. mykiss are producing anadromous offspring in these rivers, two of which have complete barriers to upstream migration. We found that the population structure of the O. mykiss in these rivers appears to be influenced more by the presence of a barrier to upstream migration than by life history type. The sex ratio of resident O. mykiss located above a barrier, and smolts captured in screw traps was significantly skewed in favor of females, whereas the reverse was true below the barriers, suggesting that male resident O. mykiss readily migrate downstream over the barrier, and that precocious male maturation may be occurring in the anadromous populations. Through paternity analyses, we also provide direct confirmation that resident O. mykiss can produce offspring that become anadromous. Most (89%) of the resident O. mykiss that produced anadromous offspring were males. Our results add to the growing body of evidence that shows that gene flow does readily occur between sympatric resident and anadromous O. mykiss life history types, and indicates that resident O. mykiss populations may be a potential repository of genes for the anadromous life history type. PMID:24224023

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration.

PubMed

Sundararajan, Lakshmi; Norris, Megan L; Lundquist, Erik A

2015-05-28

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. Copyright © 2015 Sundararajan et al.

SDN-1/Syndecan Acts in Parallel to the Transmembrane Molecule MIG-13 to Promote Anterior Neuroblast Migration

PubMed Central

Sundararajan, Lakshmi; Norris, Megan L.; Lundquist, Erik A.

2015-01-01

The Q neuroblasts in Caenorhabditis elegans display left-right asymmetry in their migration, with QR and descendants on the right migrating anteriorly, and QL and descendants on the left migrating posteriorly. Initial QR and QL migration is controlled by the transmembrane receptors UNC-40/DCC, PTP-3/LAR, and the Fat-like cadherin CDH-4. After initial migration, QL responds to an EGL-20/Wnt signal that drives continued posterior migration by activating MAB-5/Hox activity in QL but not QR. QR expresses the transmembrane protein MIG-13, which is repressed by MAB-5 in QL and which drives anterior migration of QR descendants. A screen for new Q descendant AQR and PQR migration mutations identified mig-13 as well as hse-5, the gene encoding the glucuronyl C5-epimerase enzyme, which catalyzes epimerization of glucuronic acid to iduronic acid in the heparan sulfate side chains of heparan sulfate proteoglycans (HSPGs). Of five C. elegans HSPGs, we found that only SDN-1/Syndecan affected Q migrations. sdn-1 mutants showed QR descendant AQR anterior migration defects, and weaker QL descendant PQR migration defects. hse-5 affected initial Q migration, whereas sdn-1 did not. sdn-1 and hse-5 acted redundantly in AQR and PQR migration, but not initial Q migration, suggesting the involvement of other HSPGs in Q migration. Cell-specific expression studies indicated that SDN-1 can act in QR to promote anterior migration. Genetic interactions between sdn-1, mig-13, and mab-5 suggest that MIG-13 and SDN-1 act in parallel to promote anterior AQR migration and that SDN-1 also controls posterior migration. Together, our results indicate previously unappreciated complexity in the role of multiple signaling pathways and inherent left-right asymmetry in the control of Q neuroblast descendant migration. PMID:26022293

Connectivity in a pond system influences migration and genetic structure in threespine stickleback.

PubMed

Seymour, Mathew; Räsänen, Katja; Holderegger, Rolf; Kristjánsson, Bjarni K

2013-03-01

Neutral genetic structure of natural populations is primarily influenced by migration (the movement of individuals and, subsequently, their genes) and drift (the statistical chance of losing genetic diversity over time). Migration between populations is influenced by several factors, including individual behavior, physical barriers, and environmental heterogeneity among populations. However, drift is expected to be stronger in populations with low immigration rate and small effective population size. With the technological advancement in geological information systems and spatial analysis tools, landscape genetics now allows the development of realistic migration models and increased insight to important processes influencing diversity of natural populations. In this study, we investigated the relationship between landscape connectivity and genetic distance of threespine stickleback (Gasterosteus aculeatus) inhabiting a pond complex in Belgjarskógur, Northeast Iceland. We used two landscape genetic approaches (i.e., least-cost-path and isolation-by-resistance) and asked whether gene flow, as measured by genetic distance, was more strongly associated with Euclidean distance (isolation-by-distance) or with landscape connectivity provided by areas prone to flooding (as indicated by Carex sp. cover)? We found substantial genetic structure across the study area, with pairwise genetic distances among populations (DPS) ranging from 0.118 to 0.488. Genetic distances among populations were more strongly correlated with least-cost-path and isolation-by-resistance than with Euclidean distance, whereas the relative contribution of isolation-by-resistance and Euclidian distance could not be disentangled. These results indicate that migration among stickleback populations occurs via periodically flooded areas. Overall, this study highlights the importance of transient landscape elements influencing migration and genetic structure of populations at small spatial scales.

Expression of olfactory receptors in different life stages and life histories of wild Atlantic salmon (Salmo salar).

PubMed

Johnstone, K A; Lubieniecki, K P; Koop, B F; Davidson, W S

2011-10-01

It has been hypothesized that salmonids use olfactory cues to return to their natal rivers and streams. However, the key components of the molecular pathway involved in imprinting and homing are still unknown. If odorants are involved in salmon homing migration, then olfactory receptors should play a critical role in the dissipation of information from the environment to the fish. Therefore, we examined the expression profiles of a suite of genes encoding olfactory receptors and other olfactory-related genes in the olfactory rosettes of different life stages in two anadromous and one non-anadromous wild Atlantic salmon populations from Newfoundland, Canada. We identified seven differentially expressed OlfC genes in juvenile anadromous salmon compared to returning adults in both populations of anadromous Atlantic salmon. The salmon from the Campbellton River had an additional 10 genes that were differentially expressed in juveniles compared to returning adults. There was no statistically significant difference in gene expression of any of the genes in the non-anadromous population (P < 0.01). The function of the OlfC gene products is not clear, but they are predicted to be amino acid receptors. Other studies have suggested that salmon use amino acids for imprinting and homing. This study, the first to examine the expression of olfactory-related genes in wild North American Atlantic salmon, has identified seven OlfC genes that may be involved in the imprinting and homeward migration of anadromous Atlantic salmon. © 2011 Blackwell Publishing Ltd.

75 FR 51293 - [Disaster Declaration greek-i12272 and greek-i12273

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

... on 08/10/2010, Private Non- Profit organizations that provide essential services of governmental... Counties: Atchison, Brown, Butler, Chase, Clay, Cloud, Comanche, Doniphan, Ellis, Franklin, Greenwood...

Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis.

PubMed

Yamazaki, Hiroshi; Sekiguchi, Mariko; Takamatsu, Masako; Tanabe, Yasuto; Nakanishi, Shigetada

2004-10-05

Cajal-Retzius (CR) cells are early-generated transient neurons and are important in the regulation of cortical neuronal migration and cortical laminar formation. Molecular entities characterizing the CR cell identity, however, remain largely elusive. We purified mouse cortical CR cells expressing GFP to homogeneity by fluorescence-activated cell sorting and examined a genome-wide expression profile of cortical CR cells at embryonic and postnatal periods. We identified 49 genes that exceeded hybridization signals by >10-fold in CR cells compared with non-CR cells at embryonic day 13.5, postnatal day 2, or both. Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells. These genes, which encode generic properties of CR cell specificity, are eminently characterized as modulatory composites of voltage-dependent calcium channels and sets of functionally related cellular components involved in cell migration, adhesion, and neurite extension. Five genes are highly expressed in CR cells at the early embryonic period and are rapidly down-regulated thereafter. Furthermore, some of these genes have been shown to mark two distinctly different focal regions corresponding to the CR cell origins. At the late prenatal and postnatal periods, 19 genes are selectively up-regulated in CR cells. These genes include functional molecules implicated in synaptic transmission and modulation. CR cells thus strikingly change their cellular phenotypes during cortical development and play a pivotal role in both corticogenesis and cortical circuit maturation.

The long non-coding RNA HOTTIP enhances pancreatic cancer cell proliferation, survival and migration

PubMed Central

Cheng, Yating; Jutooru, Indira; Chadalapaka, Gayathri; Corton, J. Christopher; Safe, Stephen

2015-01-01

HOTTIP is a long non-coding RNA (lncRNA) transcribed from the 5′ tip of the HOXA locus and is associated with the polycomb repressor complex 2 (PRC2) and WD repeat containing protein 5 (WDR5)/mixed lineage leukemia 1 (MLL1) chromatin modifying complexes. HOTTIP is expressed in pancreatic cancer cell lines and knockdown of HOTTIP by RNA interference (siHOTTIP) in Panc1 pancreatic cancer cells decreased proliferation, induced apoptosis and decreased migration. In Panc1 cells transfected with siHOTTIP, there was a decrease in expression of 757 genes and increased expression of 514 genes, and a limited gene analysis indicated that HOTTIP regulation of genes is complex. For example, Aurora kinase A, an important regulator of cell growth, is coregulated by MLL and not WDR5 and, in contrast to previous studies in liver cancer cells, HOTTIP does not regulate HOXA13 but plays a role in regulation of several other HOX genes including HOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. Although HOTTIP and the HOX-associated lncRNA HOTAIR have similar pro-oncogenic functions, they regulate strikingly different sets of genes in Panc1 cells and in pancreatic tumors. PMID:25912306

Alternative life histories shape brain gene expression profiles in males of the same population

USGS Publications Warehouse

Aubin-Horth, N.; Landry, C.R.; Letcher, B.H.; Hofmann, H.A.

2005-01-01

Atlantic salmon (Salmo salar) undergo spectacular marine migrations before homing to spawn in natal rivers. However, males that grow fastest early in life can adopt an alternative 'sneaker' tactic by maturing earlier at greatly reduced size without leaving freshwater. While the ultimate evolutionary causes have been well studied, virtually nothing is known about the molecular bases of this developmental plasticity. We investigate the nature and extent of coordinated molecular changes that accompany such a fundamental transformation by comparing the brain transcription profiles of wild mature sneaker males to age-matched immature males (future large anadromous males) and immature females. Of the ca. 3000 genes surveyed, 15% are differentially expressed in the brains of the two male types. These genes are involved in a wide range of processes, including growth, reproduction and neural plasticity. Interestingly, despite the potential for wide variation in gene expression profiles among individuals sampled in nature, consistent patterns of gene expression were found for individuals of the same reproductive tactic. Notably, gene expression patterns in immature males were different both from immature females and sneakers, indicating that delayed maturation and sea migration by immature males, the 'default' life cycle, may actually result from an active inhibition of development into a sneaker. ?? 2005 The Royal Society.

Alternative life histories shape brain gene expression profiles in males of the same population

PubMed Central

Aubin-Horth, Nadia; Landry, Christian R; Letcher, Benjamin H; Hofmann, Hans A

2005-01-01

Atlantic salmon (Salmo salar) undergo spectacular marine migrations before homing to spawn in natal rivers. However, males that grow fastest early in life can adopt an alternative ‘sneaker’ tactic by maturing earlier at greatly reduced size without leaving freshwater. While the ultimate evolutionary causes have been well studied, virtually nothing is known about the molecular bases of this developmental plasticity. We investigate the nature and extent of coordinated molecular changes that accompany such a fundamental transformation by comparing the brain transcription profiles of wild mature sneaker males to age-matched immature males (future large anadromous males) and immature females. Of the ca. 3000 genes surveyed, 15% are differentially expressed in the brains of the two male types. These genes are involved in a wide range of processes, including growth, reproduction and neural plasticity. Interestingly, despite the potential for wide variation in gene expression profiles among individuals sampled in nature, consistent patterns of gene expression were found for individuals of the same reproductive tactic. Notably, gene expression patterns in immature males were different both from immature females and sneakers, indicating that delayed maturation and sea migration by immature males, the ‘default’ life cycle, may actually result from an active inhibition of development into a sneaker. PMID:16087419

Alternative life histories shape brain gene expression profiles in males of the same population.

PubMed

Aubin-Horth, Nadia; Landry, Christian R; Letcher, Benjamin H; Hofmann, Hans A

2005-08-22

Atlantic salmon (Salmo salar) undergo spectacular marine migrations before homing to spawn in natal rivers. However, males that grow fastest early in life can adopt an alternative 'sneaker' tactic by maturing earlier at greatly reduced size without leaving freshwater. While the ultimate evolutionary causes have been well studied, virtually nothing is known about the molecular bases of this developmental plasticity. We investigate the nature and extent of coordinated molecular changes that accompany such a fundamental transformation by comparing the brain transcription profiles of wild mature sneaker males to age-matched immature males (future large anadromous males) and immature females. Of the ca. 3000 genes surveyed, 15% are differentially expressed in the brains of the two male types. These genes are involved in a wide range of processes, including growth, reproduction and neural plasticity. Interestingly, despite the potential for wide variation in gene expression profiles among individuals sampled in nature, consistent patterns of gene expression were found for individuals of the same reproductive tactic. Notably, gene expression patterns in immature males were different both from immature females and sneakers, indicating that delayed maturation and sea migration by immature males, the 'default' life cycle, may actually result from an active inhibition of development into a sneaker.

Influence of the intensity and loading time of direct current electric field on the directional migration of rat bone marrow mesenchymal stem cells.

PubMed

Wang, Xiaoyu; Gao, Yuxuan; Shi, Haigang; Liu, Na; Zhang, Wei; Li, Hongbo

2016-09-01

Exogenic electric fields can effectively accelerate bone healing and remodeling through the enhanced migration of bone marrow mesenchymal stem cells (BMSCs) toward the injured area. This study aimed to determine the following: (1) the direction of rat BMSC (rBMSC) migration upon exposure to a direct current electric field (DCEF), (2) the optimal DCEF intensity and duration, and (3) the possible regulatory role of SDF-1/CXCR4 axis in rBMSC migration as induced by DCEF. Results showed that rBMSCs migrated to the positive electrode of the DCEF, and that the DCEF of 200 mV/mm for 4 h was found to be optimal in enhancing rBMSC migration. This DCEF strength and duration also upregulated the expression of osteoblastic genes, including ALP and OCN, and upregulated the expression of ALP and Runx2 proteins. Moreover, when CXCR4 was inhibited, rBMSC migration due to DCEF was partially blocked. These findings indicated that DCEF can effectively induce rBMSC migration. A DCEF of 200 mV/mm for 4 h was recommended because of its ability to promote rBMSC migration, proliferation, and osteogenic differentiation. The SDF-1/CXCR4 signaling pathway may play an important role in regulating the DCEF-induced migration of rBMSCs.

Population connectivity and larval dispersal of the exploited mangrove crab Ucides cordatus along the Brazilian coast.

PubMed

Britto, Fábio B; Schmidt, Anders J; Carvalho, Adriana M F; Vasconcelos, Carolina C M P; Farias, Antonia M; Bentzen, Paul; Diniz, Fábio M

2018-01-01

The mangrove crab Ucides cordatus is considered a key species for the ecological balance of mangrove forests and a major source of employment and income for traditional crab collectors in Brazil. Several studies evidenced weak genetic variation among populations due to an efficient larval transport. However, gene flow patterns of the species is poorly understood, with no information about migration rates. The influence of the two main Brazilian currents in larval dispersion is also not clear. In order to provide baseline information for conservation, planning and management of this important fishery resource, the present study aimed to estimate and evaluate spatial distribution of genetic diversity, migration rates and gene flow directivity among populations of U. cordatus in Brazil. Nine microsatellites were used to resolve population structure of 319 crabs collected from six sites located along the Brazilian coast. The degree of geographical differentiation included estimates of genetic diversity, population structure and gene flow models, with spatial analysis of shared alleles (SAShA), isolation by distance tests, AMOVA, discriminant analysis of principal components (DAPC) and Bayesian clustering. We estimated the amount of ongoing gene flow between clusters using the coalescent-based method implemented in Migrate-N. Loci were highly polymorphic (average of 12.4 alleles per locus) evidencing high genetic variability. There was significant differentiation among localities, despite of the low value of F ST (= 0.019; P < 0.001). F ST and Jost's D indexes were also estimated in pairwise comparisons and showed significant differences between most of the surveyed site pairs ( P < 0.05). Structure evidenced a single genetic group among samples, however SAShA pointed to a non-panmictic condition ( P = 0.011). AMOVA detected four statistical significant clusters with low level of differentiation ( F CT = 0.037; P = 0.023). The gene flow model that best described the population connectivity was the island model, with ∼24 crabs being exchanged among localities per generation. The high migration rates found among localities seem to be the main force acting to sustain the distribution of the genetic diversity of U. cordatus . Despite the high gene flow and the weak population structure among samples, the significant genetic differences found suggest that gene flow alone does not bypass the effects of genetic drift, natural selection and/or human exploitation. These findings are vital for the establishment of a database to be used in the development of conservation programs.

Population connectivity and larval dispersal of the exploited mangrove crab Ucides cordatus along the Brazilian coast

PubMed Central

Schmidt, Anders J.; Carvalho, Adriana M.F.; Vasconcelos, Carolina C.M.P.; Farias, Antonia M.; Bentzen, Paul

2018-01-01

Background The mangrove crab Ucides cordatus is considered a key species for the ecological balance of mangrove forests and a major source of employment and income for traditional crab collectors in Brazil. Several studies evidenced weak genetic variation among populations due to an efficient larval transport. However, gene flow patterns of the species is poorly understood, with no information about migration rates. The influence of the two main Brazilian currents in larval dispersion is also not clear. In order to provide baseline information for conservation, planning and management of this important fishery resource, the present study aimed to estimate and evaluate spatial distribution of genetic diversity, migration rates and gene flow directivity among populations of U. cordatus in Brazil. Methods Nine microsatellites were used to resolve population structure of 319 crabs collected from six sites located along the Brazilian coast. The degree of geographical differentiation included estimates of genetic diversity, population structure and gene flow models, with spatial analysis of shared alleles (SAShA), isolation by distance tests, AMOVA, discriminant analysis of principal components (DAPC) and Bayesian clustering. We estimated the amount of ongoing gene flow between clusters using the coalescent-based method implemented in Migrate-N. Results Loci were highly polymorphic (average of 12.4 alleles per locus) evidencing high genetic variability. There was significant differentiation among localities, despite of the low value of FST (= 0.019; P < 0.001). FST and Jost’s D indexes were also estimated in pairwise comparisons and showed significant differences between most of the surveyed site pairs (P < 0.05). Structure evidenced a single genetic group among samples, however SAShA pointed to a non-panmictic condition (P = 0.011). AMOVA detected four statistical significant clusters with low level of differentiation (FCT = 0.037; P = 0.023). The gene flow model that best described the population connectivity was the island model, with ∼24 crabs being exchanged among localities per generation. Discussion The high migration rates found among localities seem to be the main force acting to sustain the distribution of the genetic diversity of U. cordatus. Despite the high gene flow and the weak population structure among samples, the significant genetic differences found suggest that gene flow alone does not bypass the effects of genetic drift, natural selection and/or human exploitation. These findings are vital for the establishment of a database to be used in the development of conservation programs. PMID:29736340

Global analysis of saliva as a source of bacterial genes for insights into human population structure and migration studies.

PubMed

Henne, Karsten; Li, Jing; Stoneking, Mark; Kessler, Olga; Schilling, Hildegard; Sonanini, Anne; Conrads, Georg; Horz, Hans-Peter

2014-08-22

The genetic diversity of the human microbiome holds great potential for shedding light on the history of our ancestors. Helicobacter pylori is the most prominent example as its analysis allowed a fine-scale resolution of past migration patterns including some that could not be distinguished using human genetic markers. However studies of H. pylori require stomach biopsies, which severely limits the number of samples that can be analysed. By focussing on the house-keeping gene gdh (coding for the glucose-6-phosphate dehydrogenase), on the virulence gene gtf (coding for the glucosyltransferase) of mitis-streptococci and on the 16S-23S rRNA internal transcribed spacer (ITS) region of the Fusobacterium nucleatum/periodonticum-group we here tested the hypothesis that bacterial genes from human saliva have the potential for distinguishing human populations. Analysis of 10 individuals from each of seven geographic regions, encompassing Africa, Asia and Europe, revealed that the genes gdh and ITS exhibited the highest number of polymorphic sites (59% and 79%, respectively) and most OTUs (defined at 99% identity) were unique to a given country. In contrast, the gene gtf had the lowest number of polymorphic sites (21%), and most OTUs were shared among countries. Most of the variation in the gdh and ITS genes was explained by the high clonal diversity within individuals (around 80%) followed by inter-individual variation of around 20%, leaving the geographic region as providing virtually no source of sequence variation. Conversely, for gtf the variation within individuals accounted for 32%, between individuals for 57% and among geographic regions for 11%. This geographic signature persisted upon extension of the analysis to four additional locations from the American continent. Pearson correlation analysis, pairwise Fst-cluster analysis as well as UniFrac analyses consistently supported a tree structure in which the European countries clustered tightly together and branched with American countries and South Africa, to the exclusion of Asian countries and the Congo. This study shows that saliva harbours protein-coding bacterial genes that are geographically structured, and which could potentially be used for addressing previously unresolved human migration events.

Casticin impairs cell migration and invasion of mouse melanoma B16F10 cells via PI3K/AKT and NF-κB signaling pathways.

PubMed

Shih, Yung-Luen; Chou, Hsiao-Min; Chou, Hsiu-Chen; Lu, Hsu-Feng; Chu, Yung-Lin; Shang, Hung-Sheng; Chung, Jing-Gung

2017-09-01

Casticin, a polymethoxyflavone, is one of the major active components obtained from Fructus viticis, which have been shown to have anticancer activities including induce cell apoptosis in human cancer cells. The aim of this study was to investigate the molecular mechanisms by which casticin inhibits cell migration and invasion of mouse melanoma B16F10 cells. Cell viability was examined by MTT assay and the results indicated that casticin decreased the total percentages of viable cells in dose-dependent manners. Casticin affected cell migration and invasion in B16F10 cells were examined by wound healing mobility assay and Boyden chamber migration and invasion assay and results indicated that casticin inhibited cell migration and invasion in dose-dependent manners. Western blotting was used to examine the protein expression of B16F10 cells after exposed to casticin and the results showed that casticin decreased the expressions of MMP-9, MMP-2, MMP-1, FAK, 14-3-3, GRB2, Akt, NF-κB p65, SOS-1, p-EGFR, p-JNK 1/2, uPA, and Rho A in B16F10 cells. Furthermore, cDNA microarray assay was used to show that casticin affected associated gene expression of cell migration and invasion and the results indicated that casticin affected some of the gene expression such as increased SCN1B (cell adhesion molecule 1) and TIMP2 (TIMP metallopeptidase inhibitor 2) and decreased NDUFS4 (NADH dehydrogenase (ubiquinone) Fe-S protein4), VEGFA (vascular endothelial growth factor A), and DDIT3 (DNA-damage-inducible transcript 3) which associated cell migration and invasion in B16F10 cells. Based on those observations, we suggest that casticin could be used as a novel anticancer metastasis of melanoma cancer in the future. © 2017 Wiley Periodicals, Inc.

Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells

PubMed Central

2010-01-01

Background Cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. Here, we investigated the genomic events occurring during this process induced by functional blockade of α5β1 integrin in liver progenitor cells. Results Cells treated with a specific antibody against α5β1 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the ERK1/2 and p38 MAPKs signaling cascades, in a similar manner to the process triggered by HGF/SF1 stimulation. Gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. These responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus. Conclusion Collectively, our results demonstrate that α5β1 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape. PMID:20958983

2. Overview of site, looking southeast Naval Air Station ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Overview of site, looking southeast - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

7. Overview of site, looking southwest Naval Air Station ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Overview of site, looking southwest - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

1. Overview of site, looking northwest Naval Air Station ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Overview of site, looking northwest - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

8. Overview of site, looking northeast Naval Air Station ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Overview of site, looking northeast - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

ARC-2007-ACD07-0189-018

NASA Image and Video Library

2007-10-02

International Space Station (ISS) National Laboratory Workshop L-R Lynn Harper, Ames and Baruch Blumberg, Nobel Laureate, Fox Chase Cancer Center during talk on Science on the international Space Station, Past and Future.

An amphioxus winged helix/forkhead gene, AmphiFoxD: insights into vertebrate neural crest evolution

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

2002-01-01

During amphioxus development, the neural plate is bordered by cells expressing many genes with homologs involved in vertebrate neural crest induction. However, these amphioxus cells evidently lack additional genetic programs for the cell delaminations, migrations, and differentiations characterizing definitive vertebrate neural crest. We characterize an amphioxus winged helix/forkhead gene (AmphiFoxD) closely related to vertebrate FoxD genes. Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development. Early in amphioxus development, AmphiFoxD is expressed medially in the anterior neural plate as well as in axial (notochordal) and paraxial mesoderm; later, the gene is expressed in the somites, notochord, cerebral vesicle (diencephalon), and hindgut endoderm. However, there is never any expression in cells bordering the neural plate. We speculate that an AmphiFoxD homolog in the common ancestor of amphioxus and vertebrates was involved in histogenic processes in the mesoderm (evagination and delamination of the somites and notochord); then, in the early vertebrates, descendant paralogs of this gene began functioning in the presumptive neural crest bordering the neural plate to help make possible the delaminations and cell migrations that characterize definitive vertebrate neural crest. Copyright 2002 Wiley-Liss, Inc.

Regulation of tumor cell migration by protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-, and threonine-rich sequence (PEST)

PubMed Central

Zheng, Yanhua; Lu, Zhimin

2013-01-01

Protein tyrosine phosphatase (PTP)–proline-, glutamate-, serine-, and threonine-rich sequence (PEST) is ubiquitously expressed and is a critical regulator of cell adhesion and migration. PTP-PEST activity can be regulated transcriptionally via gene deletion or mutation in several types of human cancers or via post-translational modifications, including phosphorylation, oxidation, and caspase-dependent cleavage. PTP-PEST interacts with and dephosphorylates cytoskeletal and focal adhesion-associated proteins. Dephosphorylation of PTP-PEST substrates regulates their enzymatic activities and/or their interaction with other proteins and plays an essential role in the tumor cell migration process. PMID:23237212

Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models

PubMed Central

Fujihara, Yoshitaka; Miyata, Haruhiko; Ikawa, Masahito

2018-01-01

Mammalian fertilization is comprised of many steps including sperm survival in the uterus, sperm migration in the female reproductive tract, physiological and morphological changes to the spermatozoa, and sperm-egg interaction in the oviduct. In vitro studies have revealed essential factors for these fertilization steps for over half a century. However, the molecular mechanism of fertilization has recently been revised by the emergence of genetically modified animals. Here, we focus on essential factors for sperm fertilizing ability and describe recent advances in our knowledge of the mechanisms of mammalian fertilization, especially of sperm migration from the uterus into the oviduct. PMID:29353867

Temperature sensing in Yersinia pestis: translation of the LcrF activator protein is thermally regulated.

PubMed Central

Hoe, N P; Goguen, J D

1993-01-01

The lcrF gene of Yersinia pestis encodes a transcription activator responsible for inducing expression of several virulence-related proteins in response to temperature. The mechanism of this thermoregulation was investigated. An lcrF clone was found to produce much lower levels of LcrF protein at 26 than at 37 degrees C in Y. pestis, although it was transcribed at similar levels at both temperatures. High-level T7 polymerase-directed transcription of the lcrF gene in Escherichia coli also resulted in temperature-dependent production of the LcrF protein. Pulse-chase experiments showed that the LcrF protein was stable at 26 and 37 degrees C, suggesting that translation rate or message degradation is thermally controlled. The lcrF mRNA appears to be highly unstable and could not be reliably detected in Y. pestis. Insertion of the lcrF gene into plasmid pET4a, which produces high levels of plasmid-length RNA, aided detection of lcrF-specific message in E. coli. Comparison of the amount of LcrF protein produced per unit of message at 26 and 37 degrees C indicated that the efficiency of translation of lcrF message increased with temperature. mRNA secondary structure predictions suggest that the lcrF Shine-Dalgarno sequence is sequestered in a stem-loop. A model in which decreased stability of this stem-loop with increasing temperature leads to increased efficiency of translation initiation of lcrF message is presented. Images PMID:7504666

ABCA Transporter Gene Expression and Poor Outcome in Epithelial Ovarian Cancer

PubMed Central

Hedditch, Ellen L.; Gao, Bo; Russell, Amanda J.; Lu, Yi; Emmanuel, Catherine; Beesley, Jonathan; Johnatty, Sharon E.; Chen, Xiaoqing; Harnett, Paul; George, Joshy; Williams, Rebekka T.; Flemming, Claudia; Lambrechts, Diether; Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace; Karlan, Beth; Lester, Jenny; Orsulic, Sandra; Walsh, Christine; Fasching, Peter; Beckmann, Matthias W.; Ekici, Arif B.; Hein, Alexander; Matsuo, Keitaro; Hosono, Satoyo; Nakanishi, Toru; Yatabe, Yasushi; Pejovic, Tanja; Bean, Yukie; Heitz, Florian; Harter, Philipp; du Bois, Andreas; Schwaab, Ira; Hogdall, Estrid; Kjaer, Susan K.; Jensen, Allan; Hogdall, Claus; Lundvall, Lene; Engelholm, Svend Aage; Brown, Bob; Flanagan, James; Metcalf, Michelle D; Siddiqui, Nadeem; Sellers, Thomas; Fridley, Brooke; Cunningham, Julie; Schildkraut, Joellen; Iversen, Ed; Weber, Rachel P.; Berchuck, Andrew; Goode, Ellen; Bowtell, David D.; Chenevix-Trench, Georgia; deFazio, Anna; Norris, Murray D.; MacGregor, Stuart; Haber, Michelle; Henderson, Michelle J.

2014-01-01

Background ATP-binding cassette (ABC) transporters play various roles in cancer biology and drug resistance, but their association with outcomes in serous epithelial ovarian cancer (EOC) is unknown. Methods The relationship between clinical outcomes and ABC transporter gene expression in two independent cohorts of high-grade serous EOC tumors was assessed with real-time quantitative polymerase chain reaction, analysis of expression microarray data, and immunohistochemistry. Associations between clinical outcomes and ABCA transporter gene single nucleotide polymorphisms were tested in a genome-wide association study. Impact of short interfering RNA–mediated gene suppression was determined by colony forming and migration assays. Association with survival was assessed with Kaplan–Meier analysis and log-rank tests. All statistical tests were two-sided. Results Associations with outcome were observed with ABC transporters of the “A” subfamily, but not with multidrug transporters. High-level expression of ABCA1, ABCA6, ABCA8, and ABCA9 in primary tumors was statistically significantly associated with reduced survival in serous ovarian cancer patients. Low levels of ABCA5 and the C-allele of rs536009 were associated with shorter overall survival (hazard ratio for death = 1.50; 95% confidence interval [CI] =1.26 to 1.79; P = 6.5e−6). The combined expression pattern of ABCA1, ABCA5, and either ABCA8 or ABCA9 was associated with particularly poor outcome (mean overall survival in group with adverse ABCA1, ABCA5 and ABCA9 gene expression = 33.2 months, 95% CI = 26.4 to 40.1; vs 55.3 months in the group with favorable ABCA gene expression, 95% CI = 49.8 to 60.8; P = .001), independently of tumor stage or surgical debulking status. Suppression of cholesterol transporter ABCA1 inhibited ovarian cancer cell growth and migration in vitro, and statin treatment reduced ovarian cancer cell migration. Conclusions Expression of ABCA transporters was associated with poor outcome in serous ovarian cancer, implicating lipid trafficking as a potentially important process in EOC. PMID:24957074

Mesenchymal stem cell-based NK4 gene therapy in nude mice bearing gastric cancer xenografts

PubMed Central

Zhu, Yin; Cheng, Ming; Yang, Zhen; Zeng, Chun-Yan; Chen, Jiang; Xie, Yong; Luo, Shi-Wen; Zhang, Kun-He; Zhou, Shu-Feng; Lu, Nong-Hua

2014-01-01

Mesenchymal stem cells (MSCs) have been recognized as promising delivery vehicles for gene therapy of tumors. Gastric cancer is the third leading cause of worldwide cancer mortality, and novel treatment modalities are urgently needed. NK4 is an antagonist of hepatocyte growth factor receptors (Met) which are often aberrantly activated in gastric cancer and thus represent a useful candidate for targeted therapies. This study investigated MSC-delivered NK4 gene therapy in nude mice bearing gastric cancer xenografts. MSCs were transduced with lentiviral vectors carrying NK4 complementary DNA or enhanced green fluorescent protein (GFP). Such transduction did not change the phenotype of MSCs. Gastric cancer xenografts were established in BALB/C nude mice, and the mice were treated with phosphate-buffered saline (PBS), MSCs-GFP, Lenti-NK4, or MSCs-NK4. The tropism of MSCs toward gastric cancer cells was determined by an in vitro migration assay using MKN45 cells, GES-1 cells and human fibroblasts and their presence in tumor xenografts. Tumor growth, tumor cell apoptosis and intratumoral microvessel density of tumor tissue were measured in nude mice bearing gastric cancer xenografts treated with PBS, MSCs-GFP, Lenti-NK4, or MSCs-NK4 via tail vein injection. The results showed that MSCs migrated preferably to gastric cancer cells in vitro. Systemic MSCs-NK4 injection significantly suppressed the growth of gastric cancer xenografts. MSCs-NK4 migrated and accumulated in tumor tissues after systemic injection. The microvessel density of tumor xenografts was decreased, and tumor cellular apoptosis was significantly induced in the mice treated with MSCs-NK4 compared to control mice. These findings demonstrate that MSC-based NK4 gene therapy can obviously inhibit the growth of gastric cancer xenografts, and MSCs are a better vehicle for NK4 gene therapy than lentiviral vectors. Further studies are warranted to explore the efficacy and safety of the MSC-based NK4 gene therapy in animals and cancer patients. PMID:25525335

Healthy Weight: You Can Do It, Too

MedlinePlus

... diet") and gets regular exercise. Photos: Russell Morgan Russell Morgan changed the way he eats and exercises, ... a recent eight-month period, public health expert Russell Morgan, 66, of Chevy Chase, Md., dropped 60 ...

EC79-11481

NASA Image and Video Library

1979-08-20

A chase plane view of the tufts on the KC-135 winglet. The use of tufts in flight research dates back to the early days of the NACA, and remains an effective means of observing airflow even today. In this procedure, rows of strings are attached to an airplane's surface, with one end of each string taped to the airplane and the other end free to swing about in the airflow. The movements of the tufts are photographed by on-board cameras or a chase plane. If the tufts are arrayed in neat rows, as seen here, then the airflow is smooth over the airplane's surface. If, however, they are moving about violently, it suggests turbulent airflow. Such motions may indicate high drag, flow separation (such as in a stall), or buffeting. In some cases, tufts will actually point forward, indicating the airflow has reversed direction.

Significance chasing in research practice: causes, consequences and possible solutions.

PubMed

Ware, Jennifer J; Munafò, Marcus R

2015-01-01

The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives which, in turn, can misdirect research effort and waste money. We review factors that may contribute to poor study reproducibility and an excess of 'significant' findings within the published literature. Specifically, we consider the influence of current incentive structures and the impact of these on research practices. The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g. unplanned post-hoc tests) to the calculated and serious (e.g. fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasize the research question and study design, rather than the results obtained. This has the potential to minimize significance chasing and non-publication of null findings. Significance chasing, questionable research practices and poor study reproducibility are the unfortunate consequence of a 'publish or perish' culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g. funders and journals) will be required to address problems of poor reproducibility. © 2014 Society for the Study of Addiction.

Evidence for carboxyl-terminal processing and glycolipid-anchoring of human carcinoembryonic antigen.

PubMed

Takami, N; Misumi, Y; Kuroki, M; Matsuoka, Y; Ikehara, Y

1988-09-05

We have investigated the post-translational modification of carcinoembryonic antigen (CEA) for membrane-anchoring in QGP-1 cells derived from a human pancreatic carcinoma. Pulse-chase experiments with [3H]leucine demonstrated that CEA was initially synthesized as a precursor form with Mr 150,000 having N-linked high-mannose-type oligosaccharides, which was then converted to a mature form with Mr 200,000 containing the complex type sugar chains. The mature protein thus labeled was found to be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that CEA is a phosphatidylinositol-linked membrane protein. This was confirmed by metabolic incorporation into CEA of 3H-labeled compounds such as ethanolamine, myo-inositol, palmitic acid, and stearic acid. The 3H-labeled fatty acids incorporated were specifically removed from the protein by nitrous acid deamination as well as by phosphatidylinositol-specific phospholipase C treatment. Since the available cDNA sequence predicts that CEA contains a single methionine residue only in its carboxyl-terminal hydrophobic domain, processing of the carboxyl terminus was examined by pulse-chase experiments with [35S]methionine. It was found that CEA with Mr 150,000 was initially labeled with [35S]methionine but its radioactivity was immediately lost with chase. Taken together, these results suggest that CEA is anchored to the membrane by simultaneously occurring proteolysis of the carboxyl terminus and replacement by the glycophospholipid immediately after the synthesis.

Significance chasing in research practice: Causes, consequences, and possible solutions

PubMed Central

Ware, Jennifer J.; Munafò, Marcus R.

2016-01-01

Background and Aims The low reproducibility of findings within the scientific literature is a growing concern. This may be due to many findings being false positives, which in turn can misdirect research effort and waste money. Methods We review factors that may contribute to poor study reproducibility and an excess of ‘significant’ findings within the published literature. Specifically, we consider the influence of current incentive structures, and the impact of these on research practices. Results The prevalence of false positives within the literature may be attributable to a number of questionable research practices, ranging from the relatively innocent and minor (e.g., unplanned post hoc tests), to the calculated and serious (e.g., fabrication of data). These practices may be driven by current incentive structures (e.g. pressure to publish), alongside the preferential emphasis placed by journals on novelty over veracity. There are a number of potential solutions to poor reproducibility, such as new publishing formats that emphasise the research question and study design, rather than the results obtained. This has the potential to minimise significance chasing and non-publication of null findings. Conclusions Significance chasing, questionable research practices, and poor study reproducibility are the unfortunate consequence of a “publish or perish” culture and a preference among journals for novel findings. It is likely that top-down change implemented by those with the ability to modify current incentive structure (e.g., funders and journals) will be required to address problems of poor reproducibility. PMID:25040652

Neural correlates of effective learning in experienced medical decision-makers.

PubMed

Downar, Jonathan; Bhatt, Meghana; Montague, P Read

2011-01-01

Accurate associative learning is often hindered by confirmation bias and success-chasing, which together can conspire to produce or solidify false beliefs in the decision-maker. We performed functional magnetic resonance imaging in 35 experienced physicians, while they learned to choose between two treatments in a series of virtual patient encounters. We estimated a learning model for each subject based on their observed behavior and this model divided clearly into high performers and low performers. The high performers showed small, but equal learning rates for both successes (positive outcomes) and failures (no response to the drug). In contrast, low performers showed very large and asymmetric learning rates, learning significantly more from successes than failures; a tendency that led to sub-optimal treatment choices. Consistently with these behavioral findings, high performers showed larger, more sustained BOLD responses to failed vs. successful outcomes in the dorsolateral prefrontal cortex and inferior parietal lobule while low performers displayed the opposite response profile. Furthermore, participants' learning asymmetry correlated with anticipatory activation in the nucleus accumbens at trial onset, well before outcome presentation. Subjects with anticipatory activation in the nucleus accumbens showed more success-chasing during learning. These results suggest that high performers' brains achieve better outcomes by attending to informative failures during training, rather than chasing the reward value of successes. The differential brain activations between high and low performers could potentially be developed into biomarkers to identify efficient learners on novel decision tasks, in medical or other contexts.

Characterization of the Photon Counting CHASE Jr., Chip Built in a 40-nm CMOS Process With a Charge Sharing Correction Algorithm Using a Collimated X-Ray Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krzyżanowska, A.; Deptuch, G. W.; Maj, P.

This paper presents the detailed characterization of a single photon counting chip, named CHASE Jr., built in a CMOS 40-nm process, operating with synchrotron radiation. The chip utilizes an on-chip implementation of the C8P1 algorithm. The algorithm eliminates the charge sharing related uncertainties, namely, the dependence of the number of registered photons on the discriminator’s threshold, set for monochromatic irradiation, and errors in the assignment of an event to a certain pixel. The article presents a short description of the algorithm as well as the architecture of the CHASE Jr., chip. The analog and digital functionalities, allowing for proper operationmore » of the C8P1 algorithm are described, namely, an offset correction for two discriminators independently, two-stage gain correction, and different operation modes of the digital blocks. The results of tests of the C8P1 operation are presented for the chip bump bonded to a silicon sensor and exposed to the 3.5- μm -wide pencil beam of 8-keV photons of synchrotron radiation. It was studied how sensitive the algorithm performance is to the chip settings, as well as the uniformity of parameters of the analog front-end blocks. Presented results prove that the C8P1 algorithm enables counting all photons hitting the detector in between readout channels and retrieving the actual photon energy.« less

DNA methylome signature in rheumatoid arthritis.

PubMed

Nakano, Kazuhisa; Whitaker, John W; Boyle, David L; Wang, Wei; Firestein, Gary S

2013-01-01

Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini-Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis.

Enhanced expression of the urokinase-type plasminogen activator gene and reduced colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells.

PubMed Central

Kondoh, N.; Yamada, T.; Kihara-Negishi, F.; Yamamoto, M.; Oikawa, T.

1998-01-01

To investigate the cell biological function of PU.1, a member of the Ets family of transcription factors, a vector capable of expressing the protein was transfected into HT1080 human fibrosarcoma cells. Exogenous expression of PU.1 in HT1080 cells reduced colony-forming efficiency but stimulated cell migration in soft agar, although it did not affect cell growth in adherent culture. Expression of the urokinase-type plasminogen activator (uPA) mRNA, which is known to be correlated with cell migration and invasion, was enhanced in PU.1 transfectants compared with mock transfectants. Run-on analysis demonstrated that uPA transcription was unaffected by PU.1, suggesting that this enhancement mainly occurs at a post-transcriptional level. On the other hand, treatment of HT1080 cells with the synthetic glucocorticoid dexamethasone (DEX; 10(-7) M) significantly reduced uPA gene expression at a transcriptional level. Furthermore, DEX inhibited cell migration in soft agar without affecting cell growth. These negative effects of DEX on uPA expression and cell migration were alleviated by the expression of PU.1 in HT1080 cells, whereas expression of the N-ras oncogene, which is responsible for maintenance of the transformed phenotypes in HT1080 cells, was unaffected by PU.1 expression or DEX treatment in the cells. Our results suggest that expression of PU.1 can stimulate uPA gene expression at the post-transcriptional level, which may subsequently lead to activation of cell motility and/or reduced cell-cell adhesion, but reduces anchorage-independent growth of HT1080 cells. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9743289

Regulation of SMN Protein Stability▿ †

PubMed Central

Burnett, Barrington G.; Muñoz, Eric; Tandon, Animesh; Kwon, Deborah Y.; Sumner, Charlotte J.; Fischbeck, Kenneth H.

2009-01-01

Spinal muscular atrophy (SMA) is caused by mutations of the survival of motor neuron (SMN1) gene and deficiency of full-length SMN protein (FL-SMN). All SMA patients retain one or more copies of the SMN2 gene, but the principal protein product of SMN2 lacks exon 7 (SMNΔ7) and is unable to compensate for a deficiency of FL-SMN. SMN is known to oligomerize and form a multimeric protein complex; however, the mechanisms regulating stability and degradation of FL-SMN and SMNΔ7 proteins have been largely unexplored. Using pulse-chase analysis, we characterized SMN protein turnover and confirmed that SMN was ubiquitinated and degraded by the ubiquitin proteasome system (UPS). The SMNΔ7 protein had a twofold shorter half-life than FL-SMN in cells despite similar intrinsic rates of turnover by the UPS in a cell-free assay. Mutations that inhibited SMN oligomerization and complex formation reduced the FL-SMN half-life. Furthermore, recruitment of SMN into large macromolecular complexes as well as increased association with several Gemin proteins was regulated in part by protein kinase A. Together, our data indicate that SMN protein stability is modulated by complex formation. Promotion of the SMN complex formation may be an important novel therapeutic strategy for SMA. PMID:19103745

Gene-expression profiles of epithelial cells treated with EMD in vitro: analysis using complementary DNA arrays.

PubMed

Kapferer, I; Schmidt, S; Gstir, R; Durstberger, G; Huber, L A; Vietor, I

2011-02-01

During surgical periodontal treatment, EMD is topically applied in order to facilitate regeneration of the periodontal ligament, acellular cementum and alveolar bone. Suppresion of epithelial down-growth is essential for successful periodontal regeneration; however, the underlying mechanisms of how EMD influences epithelial wound healing are poorly understood. In the present study, the effects of EMD on gene-expression profiling in an epithelial cell line (HSC-2) model were investigated. Gene-expression modifications, determined using a comparative genome-wide expression-profiling strategy, were independently validated by quantitative real-time RT-PCR. Additionally, cell cycle, cell growth and in vitro wound-healing assays were conducted. A set of 43 EMD-regulated genes was defined, which may be responsible for the reduced epithelial down-growth upon EMD application. Gene ontology analysis revealed genes that could be attributed to pathways of locomotion, developmental processes and associated processes such as regulation of cell size and cell growth. Additionally, eight regulated genes have previously been reported to take part in the process of epithelial-to-mesenchymal transition. Several independent experimental assays revealed significant inhibition of cell migration, growth and cell cycle by EMD. The set of EMD-regulated genes identified in this study offers the opportunity to clarify mechanisms underlying the effects of EMD on epithelial cells. Reduced epithelial repopulation of the dental root upon periodontal surgery may be the consequence of reduced migration and cell growth, as well as epithelial-to-mesenchymal transition. © 2010 John Wiley & Sons A/S.

The heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5 controls Caenorhabditis elegans Q neuroblast polarization during migration.

PubMed

Wang, Xiangming; Liu, Jianhong; Zhu, Zhiwen; Ou, Guangshuo

2015-03-15

Directional cell migration is fundamental for neural development, and extracellular factors are pivotal for this process. Heparan sulfate proteoglycans (HSPGs) that carry long chains of differentially modified sugar residues contribute to extracellular matrix; however, the functions of HSPG in guiding cell migration remain elusive. Here, we used the Caenorhabditis elegans mutant pool from the Million Mutation Project and isolated a mutant allele of the heparan sulfate-modifying enzyme glucuronyl C5-epimerase HSE-5. Loss-of-function of this enzyme resulted in defective Q neuroblast migration. We showed that hse-5 controlled Q cell migration in a cell non-autonomous manner. By performing live cell imaging in hse-5 mutant animals, we found that hse-5 controlled initial polarization during Q neuroblast migration. Furthermore, our genetic epistasis analysis demonstrated that lon-2 might act downstream of hse-5. Finally, rescue of the hse-5 mutant phenotype by expression of human and mouse hse-5 homologs suggested a conserved function for this gene in neural development. Taken together, our results indicated that proper HSPG modification in the extracellular matrix by HSE-5 is essential for neuroblast polarity during migration. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of ATP Citrate Lyase as a Positive Regulator of Glycolytic Function in Glioblastomas

PubMed Central

Beckner, Marie E.; Fellows-Mayle, Wendy; Zhang, Zhe; Agostino, Naomi R.; Kant, Jeffrey A.; Day, Billy W.; Pollack, Ian F.

2009-01-01

Glioblastomas, the most malignant type of glioma, are more glycolytic than normal brain tissue. Robust migration of glioblastoma cells has been previously demonstrated under glycolytic conditions and their pseudopodia contain increased glycolytic and decreased mitochondrial enzymes. Glycolysis is suppressed by metabolic acids, including citric acid which is excluded from mitochondria during hypoxia. We postulated that glioma cells maintain glycolysis by regulating metabolic acids, especially in their pseudopodia. The enzyme that breaks down cytosolic citric acid is ATP citrate lyase (ACLY). Our identification of increased ACLY in pseudopodia of U87 glioblastoma cells on 1D gels and immunoblots prompted investigation of ACLY gene expression in gliomas for survival data and correlation with expression of ENO1, that encodes enolase 1. Queries of the NIH’s REMBRANDT brain tumor database based on Affymetrix data indicated that decreased survival correlated with increased gene expression of ACLY in gliomas. Queries of gliomas and glioblastomas found an association of upregulated ACLY and ENO1 expression by chi square for all probe sets (reporters) combined and correlation for numbers of probe sets indicating shared upregulation of these genes. Real-time quantitative PCR confirmed correlation between ACLY and ENO1 in 21 glioblastomas (p < 0.001). Inhibition of ACLY with hydroxycitrate suppressed (p < 0.05) in vitro glioblastoma cell migration, clonogenicity and brain invasion under glycolytic conditions and enhanced the suppressive effects of a Met inhibitor on cell migration. In summary, gene expression data, proteomics and functional assays support ACLY as a positive regulator of glycolysis in glioblastomas. PMID:19795461

Migration and differentiation potential of stem cells in the cnidarian Hydractinia analysed in eGFP-transgenic animals and chimeras.

PubMed

Künzel, Timo; Heiermann, Reinhard; Frank, Uri; Müller, Werner; Tilmann, Wido; Bause, Markus; Nonn, Anja; Helling, Matthias; Schwarz, Ryan S; Plickert, Günter

2010-12-01

To analyse cell migration and the differentiation potential of migratory stem cells in Hydractinia, we generated animals with an eGFP reporter gene stably expressed and transmitted via the germline. The transgene was placed under the control of two different actin promoters and the promoter of elongation factor-1α. One actin promoter (Act-II) and the EF-1α promoter enabled expression of the transgene in all cells, the other actin promoter (Act-I) in epithelial and gametogenic cells, but not in the pluripotent migratory stem cells. We produced chimeric animals consisting of histocompatible wild type and transgenic parts. When the transgene was under the control of the epithelial cell specific actin-I promoter, non-fluorescent transgenic stem cells immigrated into wild type tissue, stopped migration and differentiated into epithelial cells which then commenced eGFP-expression. Migratory stem cells are therefore pluripotent and can give rise not only to germ cells, nematocytes and nerve cells, but also to epithelial cells. While in somatic cells expression of the act-I promoter was restricted to epithelial cells it became also active in gametogenesis. The act-I gene is expressed in spermatogonia, oogonia and oocytes. In males the expression pattern showed that migratory stem cells are the precursors of both the spermatogonia and their somatic envelopes. Comparative expression studies using the promoters of the actin-II gene and the elongation factor-1α gene revealed the potential of transgenic techniques to trace the development of the nervous system. Copyright © 2010 Elsevier Inc. All rights reserved.

Shifting Quaternary migration patterns in the Bahamian archipelago: Evidence from the Zamia pumila complex at the northern limits of the Caribbean island biodiversity hotspot.

PubMed

Salas-Leiva, Dayana E; Meerow, Alan W; Calonje, Michael; Francisco-Ortega, Javier; Griffith, M Patrick; Nakamura, Kyoko; Sánchez, Vanessa; Knowles, Lindy; Knowles, David

2017-05-01

The Bahamas archipelago is formed by young, tectonically stable carbonate banks that harbor direct geological evidence of global ice-volume changes. We sought to detect signatures of major changes on gene flow patterns and reconstruct the phylogeographic history of the monophyletic Zamia pumila complex across the Bahamas. Nuclear molecular markers with both high and low mutation rates were used to capture two different time scale signatures and test several gene flow and demographic hypotheses. Single-copy nuclear genes unveiled apparent ancestral admixture on Andros, suggesting a significant role of this island as main hub of diversity of the archipelago. We detected demographic and spatial expansion of the Zamia pumila complex on both paleo-provinces around the Piacenzian (Pliocene)/Gelasian (Pleistocene). Populations evidenced signatures of different migration models that have occurred at two different times. Populations on Long Island ( Z. lucayana ) may either represent a secondary colonization of the Bahamas by Zamia or a rapid and early-divergence event of at least one population on the Bahamas. Despite changes in migration patterns with global climate, expected heterozygosity with both marker systems remains within the range reported for cycads, but with significant levels of increased inbreeding detected by the microsatellites. This finding is likely associated with reduced gene flow between and within paleo-provinces, accompanied by genetic drift, as rising seas enforced isolation. Our study highlights the importance of the maintenance of the predominant direction of genetic exchange and the role of overseas dispersion among the islands during climate oscillations. © 2017 Botanical Society of America.

Genetic susceptibility to Chagas disease cardiomyopathy: involvement of several genes of the innate immunity and chemokine-dependent migration pathways

PubMed Central

2013-01-01

Background Chagas disease, caused by the protozoan Trypanosoma cruzi is endemic in Latin America. Thirty percent of infected individuals develop chronic Chagas cardiomyopathy (CCC), an inflammatory dilated cardiomyopathy that is, by far, the most important clinical consequence of T. cruzi infection. The others remain asymptomatic (ASY). A possible genetic component to disease progression was suggested by familial aggregation of cases and the association of markers of innate and adaptive immunity genes with CCC development. Migration of Th1-type T cells play a major role in myocardial damage. Methods Our genetic analysis focused on CCR5, CCL2 and MAL/TIRAP genes. We used the Tag SNPs based approach, defined to catch all the genetic information from each gene. The study was conducted on a large Brazilian population including 315 CCC cases and 118 ASY subjects. Results The CCL2rs2530797A/A and TIRAPrs8177376A/A were associated to an increase susceptibility whereas the CCR5rs3176763C/C genotype is associated to protection to CCC. These associations were confirmed when we restricted the analysis to severe CCC, characterized by a left ventricular ejection fraction under 40%. Conclusions Our data show that polymorphisms affecting key molecules involved in several immune parameters (innate immunity signal transduction and T cell/monocyte migration) play a role in genetic susceptibility to CCC development. This also points out to the multigenic character of CCC, each polymorphism imparting a small contribution. The identification of genetic markers for CCC will provide information for pathogenesis as well as therapeutic targets. PMID:24330528

Comparative physiology and relative swimming performance of three redhorse (Moxostoma spp.) species: associations with fishway passage success.

PubMed

Hatry, Charles; Thiem, Jason D; Binder, Thomas R; Hatin, Daniel; Dumont, Pierre; Stamplecoskie, Keith M; Molina, Juan M; Smokorowski, Karen E; Cooke, Steven J

2014-01-01

Our understanding of biological criteria to inform fish passage design is limited, partially due to the lack of understanding of biological motivators, cues, and constraints, as well as a lack of biological performance evaluations of structures once they are built. The Vianney-Legendre vertical slot fishway on the Richelieu River, Quebec, Canada, passes large numbers of migrating redhorse (Moxostoma spp.) upriver to spawning grounds each year. We evaluated the physiological capacity and relative swimming ability of three redhorse species (Moxostoma anisurum, Moxostoma carinatum, Moxostoma macrolepidotum; silver, river, and shorthead redhorse, respectively) to determine how these biotic factors relate to variation in fishway passage success and duration. Shorthead redhorse had higher maximum metabolic rates and were faster swimmers than silver and river redhorse at their species-specific peak migration temperatures. Blood lactate and glucose concentrations recovered more quickly for river redhorse than for silver and shorthead redhorse, and river redhorse placed second in terms of metabolic recovery and swim speed. Interestingly, fish sampled from the top of the fishway had nearly identical lactate, glucose, and pH values compared to control fish. Using passive integrated transponders in 2010 and 2012, we observed that passage success and duration were highly variable among redhorse species and were not consistent among years, suggesting that other factors such as water temperature and river flows may modulate passage success. Clearly, additional research is needed to understand how organismal performance, environmental conditions, and other factors (including abundance of conspecifics and other comigrants) interact with fishway features to dictate which fish will be successful and to inform research of future fishways. Our research suggests that there may be an opportunity for a rapid assessment approach where fish chased to exhaustion to determine maximal values of physiological disturbance are compared to fish sampled from the top of the fishway, which could reveal which species (or sizes of fish) are approaching or exceeding their physiological capacity during passage.

The evolution of immunity in relation to colonization and migration.

PubMed

O'Connor, Emily A; Cornwallis, Charlie K; Hasselquist, Dennis; Nilsson, Jan-Åke; Westerdahl, Helena

2018-05-01

Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.

WASP family proteins and formins compete in pseudopod- and bleb-based migration

PubMed Central

2018-01-01

Actin pseudopods induced by SCAR/WAVE drive normal migration and chemotaxis in eukaryotic cells. Cells can also migrate using blebs, in which the edge is driven forward by hydrostatic pressure instead of actin. In Dictyostelium discoideum, loss of SCAR is compensated by WASP moving to the leading edge to generate morphologically normal pseudopods. Here we use an inducible double knockout to show that cells lacking both SCAR and WASP are unable to grow, make pseudopods or, unexpectedly, migrate using blebs. Remarkably, amounts and dynamics of actin polymerization are normal. Pseudopods are replaced in double SCAR/WASP mutants by aberrant filopods, induced by the formin dDia2. Further disruption of the gene for dDia2 restores cells’ ability to initiate blebs and thus migrate, though pseudopods are still lost. Triple knockout cells still contain near-normal F-actin levels. This work shows that SCAR, WASP, and dDia2 compete for actin. Loss of SCAR and WASP causes excessive dDia2 activity, maintaining F-actin levels but blocking pseudopod and bleb formation and migration. PMID:29191847

DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion.

PubMed

McLennan, Rebecca; Bailey, Caleb M; Schumacher, Linus J; Teddy, Jessica M; Morrison, Jason A; Kasemeier-Kulesa, Jennifer C; Wolfe, Lauren A; Gogol, Madeline M; Baker, Ruth E; Maini, Philip K; Kulesa, Paul M

2017-10-02

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling. © 2017 McLennan et al.

DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

PubMed Central

McLennan, Rebecca; Bailey, Caleb M.; Schumacher, Linus J.; Teddy, Jessica M.; Morrison, Jason A.; Kasemeier-Kulesa, Jennifer C.; Wolfe, Lauren A.; Gogol, Madeline M.; Baker, Ruth E.; Maini, Philip K.

2017-01-01

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. In this study, we test the function of differential screening-selected gene aberrant in neuroblastoma (DAN), a bone morphogenetic protein (BMP) antagonist we detected by analysis of the chick cranial mesoderm. Our analysis shows that, before neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, and then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells in vivo and in vitro, respectively. In vivo loss of function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Collectively, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with the inhibition of BMP signaling. PMID:28811280

Induction of type 1 iodothyronine deiodinase expression inhibits proliferation and migration of renal cancer cells.

PubMed

Poplawski, Piotr; Rybicka, Beata; Boguslawska, Joanna; Rodzik, Katarzyna; Visser, Theo J; Nauman, Alicja; Piekielko-Witkowska, Agnieszka

2017-02-15

Type 1 iodothyronine deiodinase (DIO1) regulates peripheral metabolism of thyroid hormones that control cellular proliferation, differentiation and metabolism. The significance of DIO1 in cancer is unknown. In this study we hypothesized that diminished expression of DIO1, observed in renal cancer, contributes to the carcinogenic process in the kidney. Here, we demonstrate that ectopic expression of DIO1 in renal cancer cells changes the expression of genes controlling cell cycle, including cyclin E1 and E2F5, and results in inhibition of proliferation. The expression of genes encoding collagens (COL1A1, COL4A2, COL5A1), integrins (ITGA4, ITGA5, ITGB3) and transforming growth factor-β-induced (TGFBI) is significantly altered in renal cancer cells with induced expression of DIO1. Finally, we show that overexpression of DIO1 inhibits migration of renal cancer cells. In conclusion, we demonstrate for the first time that loss of DIO1 contributes to renal carcinogenesis and that its induced expression protects cells against cancerous proliferation and migration. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Silencing the hsp25 Gene Eliminates Migration Capability of the Highly Metastatic Murine 4T1 Breast Adenocarcinoma Cell

PubMed Central

Bausero, Maria A.; Bharti, Ajit; Page, Diana T.; Perez, Kristen D.; Eng, Jason W.-L.; Ordonez, Susana L.; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

2006-01-01

The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. PMID:16340246

Silencing the hsp25 gene eliminates migration capability of the highly metastatic murine 4T1 breast adenocarcinoma cell.

PubMed

Bausero, Maria A; Bharti, Ajit; Page, Diana T; Perez, Kristen D; Eng, Jason W-L; Ordonez, Susana L; Asea, Edwina E; Jantschitsch, Christian; Kindas-Muegge, Ingela; Ciocca, Daniel; Asea, Alexzander

2006-01-01

The 25-kDa heat shock protein (Hsp25) is associated with various malignancies and is expressed at high levels in biopsies as well as circulating in the serum of breast cancer patients. In this study, we used RNA interference technology to silence the hsp25 gene in 4T1 breast adenocarcinoma cells, known as a poorly immunogenic, highly metastatic cell line. We demonstrate that transfection of 4T1 cells with short interference RNA-Hsp25 dramatically inhibits proliferation as compared with control transfected cells. In addition, we show that 4T1 cells transfected with short interference RNA-Hsp25 abrogates tumor migration potential by a mechanism that is in part due to the repression of matrix metalloproteinase 9 expression and a concomitant upregulation of its antagonist, tissue inhibitor metalloproteinase 1. Taken together, these findings provide a model system for the study of metastatic potential of tumors and are suggestive of an earlier unrecognized role for Hsp25 in tumor migration. Copyright 2006 S. Karger AG, Basel.

ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

2012-01-01

The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

TIF-IC, a factor involved in both transcription initiation and elongation of RNA polymerase I.

PubMed

Schnapp, G; Schnapp, A; Rosenbauer, H; Grummt, I

1994-09-01

We have characterized a transcription factor from Ehrlich ascites cells that is required for ribosomal gene transcription by RNA polymerase I (Pol I). This factor, termed TIF-IC, has a native molecular mass of 65 kDa, associates with Pol I, and is required both for the assembly of Sarkosyl-resistant initiation complexes and for the formation of the first internucleotide bonds. In addition to its function in transcription initiation, TIF-IC also plays a role in elongation of nascent RNA chains. At suboptimal levels of TIF-IC, transcripts with heterogeneous 3' ends are formed which are chased into full-length transcripts by the addition of more TIF-IC. Moreover, on a tailed template, which allows initiation in the absence of auxiliary factors, TIF-IC was found to stimulate the overall rate of transcription elongation and suppress pausing of Pol I. Thus TIF-IC appears to serve a function similar to the Pol II-specific factor TFIIF which is required for Pol II transcription initiation and elongation.

Tropine Forming Tropinone Reductase Gene from Withania somnifera (Ashwagandha): Biochemical Characteristics of the Recombinant Enzyme and Novel Physiological Overtones of Tissue-Wide Gene Expression Patterns

PubMed Central

Kushwaha, Amit Kumar; Sangwan, Neelam Singh; Trivedi, Prabodh Kumar; Negi, Arvind Singh; Misra, Laxminarain; Sangwan, Rajender Singh

2013-01-01

Withania somnifera is one of the most reputed medicinal plants of Indian systems of medicine synthesizing diverse types of secondary metabolites such as withanolides, alkaloids, withanamides etc. Present study comprises cloning and E. coli over-expression of a tropinone reductase gene (WsTR-I) from W. somnifera, and elucidation of biochemical characteristics and physiological role of tropinone reductase enzyme in tropane alkaloid biosynthesis in aerial tissues of the plant. The recombinant enzyme was demonstrated to catalyze NADPH-dependent tropinone to tropine conversion step in tropane metabolism, through TLC, GC and GC-MS-MS analyses of the reaction product. The functionally active homodimeric ∼60 kDa enzyme catalyzed the reaction in reversible manner at optimum pH 6.7. Catalytic kinetics of the enzyme favoured its forward reaction (tropine formation). Comparative 3-D models of landscape of the enzyme active site contours and tropinone binding site were also developed. Tissue-wide and ontogenic stage-wise assessment of WsTR-I transcript levels revealed constitutive expression of the gene with relatively lower abundance in berries and young leaves. The tissue profiles of WsTR-I expression matched those of tropine levels. The data suggest that, in W. somnifera, aerial tissues as well possess tropane alkaloid biosynthetic competence. In vivo feeding of U-[14C]-sucrose to orphan shoot (twigs) and [14C]-chasing revealed substantial radiolabel incorporation in tropinone and tropine, confirming the de novo synthesizing ability of the aerial tissues. This inherent independent ability heralds a conceptual novelty in the backdrop of classical view that these tissues acquire the alkaloids through transportation from roots rather than synthesis. The TR-I gene expression was found to be up-regulated on exposure to signal molecules (methyl jasmonate and salicylic acid) and on mechanical injury. The enzyme's catalytic and structural properties as well as gene expression profiles are discussed with respect to their physiological overtones. PMID:24086372

Tropine forming tropinone reductase gene from Withania somnifera (Ashwagandha): biochemical characteristics of the recombinant enzyme and novel physiological overtones of tissue-wide gene expression patterns.

PubMed

Kushwaha, Amit Kumar; Sangwan, Neelam Singh; Trivedi, Prabodh Kumar; Negi, Arvind Singh; Misra, Laxminarain; Sangwan, Rajender Singh

2013-01-01

Withania somnifera is one of the most reputed medicinal plants of Indian systems of medicine synthesizing diverse types of secondary metabolites such as withanolides, alkaloids, withanamides etc. Present study comprises cloning and E. coli over-expression of a tropinone reductase gene (WsTR-I) from W. somnifera, and elucidation of biochemical characteristics and physiological role of tropinone reductase enzyme in tropane alkaloid biosynthesis in aerial tissues of the plant. The recombinant enzyme was demonstrated to catalyze NADPH-dependent tropinone to tropine conversion step in tropane metabolism, through TLC, GC and GC-MS-MS analyses of the reaction product. The functionally active homodimeric ~60 kDa enzyme catalyzed the reaction in reversible manner at optimum pH 6.7. Catalytic kinetics of the enzyme favoured its forward reaction (tropine formation). Comparative 3-D models of landscape of the enzyme active site contours and tropinone binding site were also developed. Tissue-wide and ontogenic stage-wise assessment of WsTR-I transcript levels revealed constitutive expression of the gene with relatively lower abundance in berries and young leaves. The tissue profiles of WsTR-I expression matched those of tropine levels. The data suggest that, in W. somnifera, aerial tissues as well possess tropane alkaloid biosynthetic competence. In vivo feeding of U-[(14)C]-sucrose to orphan shoot (twigs) and [(14)C]-chasing revealed substantial radiolabel incorporation in tropinone and tropine, confirming the de novo synthesizing ability of the aerial tissues. This inherent independent ability heralds a conceptual novelty in the backdrop of classical view that these tissues acquire the alkaloids through transportation from roots rather than synthesis. The TR-I gene expression was found to be up-regulated on exposure to signal molecules (methyl jasmonate and salicylic acid) and on mechanical injury. The enzyme's catalytic and structural properties as well as gene expression profiles are discussed with respect to their physiological overtones.

[Knock-down of ZEB1 inhibits the proliferation, invasion and migration of gastric cancer cells].

PubMed

Chen, Dengyu; Chu, Yifan; Zheng, Qingwei; Xu, Zhiben; Zhou, Ping; Li, Sheng

2017-08-01

Objective To down-regulate the expression of zinc-finger E-box binding homeobox 1 (ZEB1) gene by shRNA, and investigate its effect on invasion, migration and proliferation, as well as the related gene expressions of lncRNA HOTAIR and E-cadherin in human gastric cancer BGC823 cells. Methods RNA interfering (RNAi) was used to knock down ZEB1 in gastric cancer BGC823 cells. The recombinant plasmid shZEB1 was constructed and transfected into the gastric cancer BGC823 cells by Lipofectamine TM 2000, and the stably transfected cells were isolated by G418 selection and limited dilution. The expression of ZEB1 mRNA and protein was detected by real-time quantitative PCR and Western blot analysis. Cell proliferation was determined by MTT assay, and the invasion and migration abilities of BGC823 cells were monitored by Transwell TM invasion assay and wound healing assay, respectively. The expressions of lncRNA HOTAIR and E-cadherin mRNA were detected by real-time quantitative PCR. Results After ZEB1 expression was successfully down-regulated in BGC823 cells by siRNA, the proliferation, invasion and migration rates in shZEB1 transfection group were significantly lower than those in control group; meanwhile, the expression of lncRNA HOTAIR was reduced and E-cadherin expression was enhanced. Conclusion Knock-down of ZEB1 expression by RNA interference can decease lncRNA HOTAIR expression and restrain cell proliferation, invasion and migration in gastric cancer BGC823 cells.

Combined Genetic and Telemetry Data Reveal High Rates of Gene Flow, Migration, and Long-Distance Dispersal Potential in Arctic Ringed Seals (Pusa hispida)

PubMed Central

Martinez-Bakker, Micaela E.; Sell, Stephanie K.; Swanson, Bradley J.; Kelly, Brendan P.; Tallmon, David A.

2013-01-01

Ringed seals (Pusa hispida) are broadly distributed in seasonally ice covered seas, and their survival and reproductive success is intricately linked to sea ice and snow. Climatic warming is diminishing Arctic snow and sea ice and threatens to endanger ringed seals in the foreseeable future. We investigated the population structure and connectedness within and among three subspecies: Arctic (P. hispida hispida), Baltic (P. hispida botnica), and Lake Saimaa (P. hispida saimensis) ringed seals to assess their capacity to respond to rapid environmental changes. We consider (a) the geographical scale of migration, (b) use of sea ice, and (c) the amount of gene flow between subspecies. Seasonal movements and use of sea ice were determined for 27 seals tracked via satellite telemetry. Additionally, population genetic analyses were conducted using 354 seals representative of each subspecies and 11 breeding sites. Genetic analyses included sequences from two mitochondrial regions and genotypes of 9 microsatellite loci. We found that ringed seals disperse on a pan-Arctic scale and both males and females may migrate long distances during the summer months when sea ice extent is minimal. Gene flow among Arctic breeding sites and between the Arctic and the Baltic Sea subspecies was high; these two subspecies are interconnected as are breeding sites within the Arctic subspecies. PMID:24130843

Distribution and movement of Caenorhabditis elegans on a thermal gradient.

PubMed

Yamada, Yohko; Ohshima, Yasumi

2003-08-01

To analyze thermal responses of Caenorhabditis elegans in detail, distribution of a worm population and movement of individual worms were examined on a linear, reproducible and broad temperature gradient. Assay methods were improved compared with those reported previously to ensure good motility and dispersion of worms. Well-fed, wild-type worms distributed over a wide temperature range of up to 10 degrees C, and, within this range, worms migrated in both directions of the gradient at similar frequencies without any specific response to the growth temperature in most cases. By contrast, worms migrated down the gradient if put in a region warmer than the warm boundary of distribution. The distribution range changed depending on the growth temperature and starvation, but active avoidance of a starvation temperature was not detected. These findings contradict previous hypotheses of taxis or migration to the growth temperature in association with food and instead indicate avoidance of a warm temperature. Our results favor a model for thermal response of C. elegans that postulates a single drive based on warm sensation rather than downward and upward drives in the physiological temperature range. Mutants in ttx-3, tax-2, tax-4 or egl-4 genes showed abnormal thermal responses, suggesting that these genes are involved in warm avoidance. Laser ablation and gene expression studies suggest that AFD neurons are not important, and tax-4 expression in neurons other than AFD is required, for warm avoidance.

DefenseLink Special: Doolittle Raid, April 18, 1942

Science.gov Websites

enhanced viewing {Flash 8} Macromedia Flash Player 8 required Download free Macromedia Flash Player Download free Internet Explorer DOOLITTLE RAIDERS – Retired Lt. Col. Chase Nelson, a Doolittle Raider

9. Interior of Building 1040 (gym), looking west Naval ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

9. Interior of Building 1040 (gym), looking west - Naval Air Station Chase Field, Building 1040, Enterprise Street, .37 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

10. Interior of Building 1040 (chapel), looking north Naval ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

10. Interior of Building 1040 (chapel), looking north - Naval Air Station Chase Field, Building 1040, Enterprise Street, .37 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

8. Overview of Building 1009, looking south Naval Air ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Overview of Building 1009, looking south - Naval Air Station Chase Field, Building 1009, Essex Street, .68 mile South-southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration.

PubMed

Walsh, Gregory S; Grant, Paul K; Morgan, John A; Moens, Cecilia B

2011-07-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons.

Planar polarity pathway and Nance-Horan syndrome-like 1b have essential cell-autonomous functions in neuronal migration

PubMed Central

Walsh, Gregory S.; Grant, Paul K.; Morgan, John A.; Moens, Cecilia B.

2011-01-01

Components of the planar cell polarity (PCP) pathway are required for the caudal tangential migration of facial branchiomotor (FBM) neurons, but how PCP signaling regulates this migration is not understood. In a forward genetic screen, we identified a new gene, nhsl1b, required for FBM neuron migration. nhsl1b encodes a WAVE-homology domain-containing protein related to human Nance-Horan syndrome (NHS) protein and Drosophila GUK-holder (Gukh), which have been shown to interact with components of the WAVE regulatory complex that controls cytoskeletal dynamics and with the polarity protein Scribble, respectively. Nhsl1b localizes to FBM neuron membrane protrusions and interacts physically and genetically with Scrib to control FBM neuron migration. Using chimeric analysis, we show that FBM neurons have two modes of migration: one involving interactions between the neurons and their planar-polarized environment, and an alternative, collective mode involving interactions between the neurons themselves. We demonstrate that the first mode of migration requires the cell-autonomous functions of Nhsl1b and the PCP components Scrib and Vangl2 in addition to the non-autonomous functions of Scrib and Vangl2, which serve to polarize the epithelial cells in the environment of the migrating neurons. These results define a role for Nhsl1b as a neuronal effector of PCP signaling and indicate that proper FBM neuron migration is directly controlled by PCP signaling between the epithelium and the migrating neurons. PMID:21693519

Conserved pattern of tangential neuronal migration during forebrain development.

PubMed

Métin, Christine; Alvarez, Chantal; Moudoux, David; Vitalis, Tania; Pieau, Claude; Molnár, Zoltán

2007-08-01

Origin, timing and direction of neuronal migration during brain development determine the distinct organization of adult structures. Changes in these processes might have driven the evolution of the forebrain in vertebrates. GABAergic neurons originate from the ganglionic eminence in mammals and migrate tangentially to the cortex. We are interested in differences and similarities in tangential migration patterns across corresponding telencephalic territories in mammals and reptiles. Using morphological criteria and expression patterns of Darpp-32, Tbr1, Nkx2.1 and Pax6 genes, we show in slice cultures of turtle embryos that early cohorts of tangentially migrating cells are released from the medial ganglionic eminence between stages 14 and 18. Additional populations migrate tangentially from the dorsal subpallium. Large cohorts of tangentially migrating neurons originate ventral to the dorsal ventricular ridge at stage 14 and from the lateral ganglionic eminence from stage 15. Release of GABAergic cells from these regions was investigated further in explant cultures. Tangential migration in turtle proceeds in a fashion similar to mammals. In chimeric slice culture and in ovo graft experiments, the tangentially migrating cells behaved according to the host environment - turtle cells responded to the available cues in mouse slices and mouse cells assumed characteristic migratory routes in turtle brains, indicating highly conserved embryonic signals between these distant species. Our study contributes to the evaluation of theories on the origin of the dorsal cortex and indicates that tangential migration is universal in mammals and sauropsids.

Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae.

PubMed

Hover, Tal; Maya, Tal; Ron, Sapir; Sandovsky, Hani; Shadkchan, Yana; Kijner, Nitzan; Mitiagin, Yulia; Fichtman, Boris; Harel, Amnon; Shanks, Robert M Q; Bruna, Roberto E; García-Véscovi, Eleonora; Osherov, Nir

2016-05-01

We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well.S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Mechanisms of Bacterial (Serratia marcescens) Attachment to, Migration along, and Killing of Fungal Hyphae

PubMed Central

Hover, Tal; Maya, Tal; Ron, Sapir; Sandovsky, Hani; Shadkchan, Yana; Kijner, Nitzan; Mitiagin, Yulia; Fichtman, Boris; Harel, Amnon; Shanks, Robert M. Q.; Bruna, Roberto E.; García-Véscovi, Eleonora

2016-01-01

We have found a remarkable capacity for the ubiquitous Gram-negative rod bacterium Serratia marcescens to migrate along and kill the mycelia of zygomycete molds. This migration was restricted to zygomycete molds and several basidiomycete species. No migration was seen on any molds of the phylum Ascomycota. S. marcescens migration did not require fungal viability or surrounding growth medium, as bacteria migrated along aerial hyphae as well. S. marcescens did not exhibit growth tropism toward zygomycete mycelium. Bacterial migration along hyphae proceeded only when the hyphae grew into the bacterial colony. S. marcescens cells initially migrated along the hyphae, forming attached microcolonies that grew and coalesced to generate a biofilm that covered and killed the mycelium. Flagellum-defective strains of S. marcescens were able to migrate along zygomycete hyphae, although they were significantly slower than the wild-type strain and were delayed in fungal killing. Bacterial attachment to the mycelium does not necessitate type 1 fimbrial adhesion, since mutants defective in this adhesin migrated equally well as or faster than the wild-type strain. Killing does not depend on the secretion of S. marcescens chitinases, as mutants in which all three chitinase genes were deleted retained wild-type killing abilities. A better understanding of the mechanisms by which S. marcescens binds to, spreads on, and kills fungal hyphae might serve as an excellent model system for such interactions in general; fungal killing could be employed in agricultural fungal biocontrol. PMID:26896140

Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow

PubMed Central

Saino, Nicola; Ambrosini, Roberto; Albetti, Benedetta; Caprioli, Manuela; De Giorgio, Barbara; Gatti, Emanuele; Liechti, Felix; Parolini, Marco; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Gianfranceschi, Luca; Bollati, Valentina; Rubolini, Diego

2017-01-01

Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change. PMID:28361883

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow.

PubMed

Saino, Nicola; Ambrosini, Roberto; Albetti, Benedetta; Caprioli, Manuela; De Giorgio, Barbara; Gatti, Emanuele; Liechti, Felix; Parolini, Marco; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Gianfranceschi, Luca; Bollati, Valentina; Rubolini, Diego

2017-03-31

Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5'-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation at Clock poly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation at Clock may be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.

Transcriptional Profiling of Ileocecal Valve of Holstein Dairy Cows Infected with Mycobacterium avium subsp. Paratuberculosis

PubMed Central

Hempel, Randy J.; Bannantine, John P.

2016-01-01

Johne’s disease is a chronic infection of the small intestine caused by Mycobacterium avium subspecies paratuberculosis (MAP), an intracellular bacterium. The events of pathogen survival within the host cell(s), chronic inflammation and the progression from asymptomatic subclinical stage to an advanced clinical stage of infection, are poorly understood. This study examines gene expression in the ileocecal valve (ICV) of Holstein dairy cows at different stages of MAP infection. The ICV is known to be a primary site of MAP colonization and provides an ideal location to identify genes that are relevant to the progression of this disease. RNA was prepared from ICV tissues and RNA-Seq was used to compare gene transcription between clinical, subclinical, and uninfected control animals. Interpretation of the gene expression data was performed using pathway analysis and gene ontology categories containing multiple differentially expressed genes. Results demonstrated that many of the pathways that had strong differential gene expression between uninfected control and clinical cows were related to the immune system, such as the T- and B-cell receptor signaling, apoptosis, NOD-like receptor signaling, and leukocyte transendothelial migration pathways. In contrast, the comparison of gene transcription between control and subclinical cows identified pathways that were primarily involved in metabolism. The results from the comparison between clinical and subclinical animals indicate recruitment of neutrophils, up regulation of lysosomal peptidases, increase in immune cell transendothelial migration, and modifications of the extracelluar matrix. This study provides important insight into how cattle respond to a natural MAP infection at the gene transcription level within a key target tissue for infection. PMID:27093613

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

PubMed Central

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-01-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

PubMed

Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

2014-11-01

Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Avian influenza H5N1 viral and bird migration networks in Asia

USGS Publications Warehouse

Tian, Huaivu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia.

Avian influenza H5N1 viral and bird migration networks in Asia

PubMed Central

Tian, Huaiyu; Zhou, Sen; Dong, Lu; Van Boeckel, Thomas P.; Cui, Yujun; Newman, Scott H.; Takekawa, John Y.; Prosser, Diann J.; Xiao, Xiangming; Wu, Yarong; Cazelles, Bernard; Huang, Shanqian; Yang, Ruifu; Grenfell, Bryan T.; Xu, Bing

2015-01-01

The spatial spread of the highly pathogenic avian influenza virus H5N1 and its long-term persistence in Asia have resulted in avian influenza panzootics and enormous economic losses in the poultry sector. However, an understanding of the regional long-distance transmission and seasonal patterns of the virus is still lacking. In this study, we present a phylogeographic approach to reconstruct the viral migration network. We show that within each wild fowl migratory flyway, the timing of H5N1 outbreaks and viral migrations are closely associated, but little viral transmission was observed between the flyways. The bird migration network is shown to better reflect the observed viral gene sequence data than other networks and contributes to seasonal H5N1 epidemics in local regions and its large-scale transmission along flyways. These findings have potentially far-reaching consequences, improving our understanding of how bird migration drives the periodic reemergence of H5N1 in Asia. PMID:25535385

Notch1-Dll4 signaling and mechanical force regulate leader cell formation during collective cell migration

PubMed Central

Riahi, Reza; Sun, Jian; Wang, Shue; Long, Min; Zhang, Donna D.; Wong, Pak Kin

2015-01-01

At the onset of collective cell migration, a subset of cells within an initially homogenous population acquires a distinct “leader” phenotype with characteristic morphology and motility. However, the factors driving leader cell formation as well as the mechanisms regulating leader cell density during the migration process remain to be determined. Here, we use single cell gene expression analysis and computational modeling to show that leader cell identity is dynamically regulated by Dll4 signaling through both Notch1 and cellular stress in a migrating epithelium. Time-lapse microscopy reveals that Dll4 is induced in leader cells after the creation of the cell-free region and leader cells are regulated via Notch1-Dll4 lateral inhibition. Furthermore, mechanical stress inhibits Dll4 expression and leader cell formation in the monolayer. Collectively, our findings suggest that a reduction of mechanical force near the boundary promotes Notch1-Dll4 signaling to dynamically regulate the density of leader cells during collective cell migration. PMID:25766473

A methodology to migrate the gene ontology to a description logic environment using DAML+OIL.

PubMed

Wroe, C J; Stevens, R; Goble, C A; Ashburner, M

2003-01-01

The Gene Ontology Next Generation Project (GONG) is developing a staged methodology to evolve the current representation of the Gene Ontology into DAML+OIL in order to take advantage of the richer formal expressiveness and the reasoning capabilities of the underlying description logic. Each stage provides a step level increase in formal explicit semantic content with a view to supporting validation, extension and multiple classification of the Gene Ontology. The paper introduces DAML+OIL and demonstrates the activity within each stage of the methodology and the functionality gained.

The D153del Mutation in GNB3 Gene Causes Tissue Specific Signalling Patterns and an Abnormal Renal Morphology in Rge Chickens

PubMed Central

Tummala, Hemanth; Fleming, Stewart; Hocking, Paul M.; Wehner, Daniel; Naseem, Zahid; Ali, Manir; Inglehearn, Christopher F.; Zhelev, Nikolai; Lester, Douglas H.

2011-01-01

Background The GNB3 gene is expressed in cone but not rod photoreceptors of vertebrates, where it acts as the β transducin subunit in the colour visual transduction process. A naturally occurring mutation ‘D153del’ in the GNB3 gene causes the recessively inherited blinding phenotype retinopathy globe enlarged (rge) disease in chickens. GNB3 is however also expressed in most other vertebrate tissues suggesting that the D153del mutation may exert pathological effects that outlie from eye. Principal Findings Recombinant studies in COS-7 cells that were transfected with normal and mutant recombinant GNB3 constructs and subjected to cycloheximide chase showed that the mutant GNB3d protein had a much shorter half life compared to normal GNB3. GNB3 codes for the Gβ3 protein subunit that, together with different Gγ and Gα subunits, activates and regulates phosphorylation cascades in different tissues. As expected, the relative levels of cGMP and cAMP secondary messengers and their activated kinases such as MAPK, AKT and GRK2 were also found to be altered significantly in a tissue specific manner in rge chickens. Histochemical analysis on kidney tissue sections, from rge homozygous affected chickens, showed the chickens had enlargement of the glomerular capsule, causing glomerulomegaly and tubulointerstitial inflammation whereas other tissues (brain, heart, liver, pancreas) were unaffected. Significance These findings confirm that the D153del mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3 signalling causes reduced phosphorylation activity of ERK2 and AKT leading to severe pathological phenotypes such as blindness and renal abnormalities in rge chickens. PMID:21887213

Drosophila gene tao-1 encodes proteins with and without a Ste20 kinase domain that affect cytoskeletal architecture and cell migration differently

PubMed Central

Pflanz, Ralf; Voigt, Aaron; Yakulov, Toma; Jäckle, Herbert

2015-01-01

Tao-1, the single representative of the Sterile 20 kinase subfamily in Drosophila, is best known for destabilizing microtubules at the actin-rich cortex, regulating the cytoskeletal architecture of cells. More recently, Tao-1 was shown to act in the Salvador–Warts–Hippo pathway by phosphorylating Hippo, regulating cell growth as well as cell polarity. Here, we show that tao-1 encodes two proteins, one with the Sterile 20 kinase domain (Tao-L) and one without it (Tao-S), and that they act in an antagonistic manner. Tao-L expression causes lamellipodia-like cell protrusions, whereas Tao-S expression results in filopodia-like structures that make cells stick to the surface they attach to. Ectopic Tao-1 expression in the anterior region of Drosophila embryos results in pole cell formation as normally observed at the posterior end. Tao-S expression causes primordial germ cells (PGCs) to adhere to the inner wall of the gut primordia and prevents proper transepithelial migration to the gonads. Conversely, RNAi knockdowns of Tao-1 cause disordered migration of PGCs out of the gut epithelium, their dispersal within the embryo and cell death. The results reveal a novel function of Tao-1 in cell migration, which is based on antagonistic activities of two proteins encoded by a single gene. PMID:25589578

Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

PubMed

Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2018-01-01

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

The Zebrafish G12 Gene is required for Nuclear Positioning and Cell Migrations during Early Development

NASA Technical Reports Server (NTRS)

Reinsch, S. S.; Conway, G. C.

2003-01-01

After fertilization Zebrafish embryos undergo synchronous cleavage to form a blastula of cells sitting upon a single multinucleate yolk cell. At the beginning of gastrulation these cells undergo extensive cell migrations to form the major body axes. We have discovered a gene, G12, which is required for cell migrations and positioning of nuclei in the large syncytial yolk cell. Overexpression of a G12-GFP fusion protein is not toxic and shows that the protein localizes inside the yolk cell to the yolk nuclei, microtubules, and to the margin between the blastomeres and the large yolk cell. Morpholino (MO) injection into the 1-cell embryo or into just the yolk syncytium conipletely inhibits cell migrations, doming of the yolk cell, and positioning of nuclei around the margin. This effect can be partially rescued by injection of G12-GFP encoding RNA. Given the known role of microtubules in nuclear positioning of yolk nuclei in Zebrafish, we investigated the microtubules in morpholiiio injected and rescued embryos. We find that microtubules are sparse and disorganized in MO-injected embryos and are restored to normal organization upon G12-GFP rescue. G12 plays a pivotal role in organization of inicrotubules during early development. G12 is highly conserved in vertebrates and two homologues exist in the human genome. One of the human hoinologues is amplified in aggressive breast tumors.

Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

PubMed

Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

2013-01-01

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

Placing Ion Channels into a Signaling Network of T Cells: From Maturing Thymocytes to Healthy T Lymphocytes or Leukemic T Lymphoblasts

PubMed Central

Delgado-Enciso, Iván; Best-Aguilera, Carlos; Rojas-Sotelo, Rocío Monserrat; Pottosin, Igor

2015-01-01

T leukemogenesis is a multistep process, where the genetic errors during T cell maturation cause the healthy progenitor to convert into the leukemic precursor that lost its ability to differentiate but possesses high potential for proliferation, self-renewal, and migration. A new misdirecting “leukemogenic” signaling network appears, composed by three types of participants which are encoded by (1) genes implicated in determined stages of T cell development but deregulated by translocations or mutations, (2) genes which normally do not participate in T cell development but are upregulated, and (3) nondifferentially expressed genes which become highly interconnected with genes expressed differentially. It appears that each of three groups may contain genes coding ion channels. In T cells, ion channels are implicated in regulation of cell cycle progression, differentiation, activation, migration, and cell death. In the present review we are going to reveal a relationship between different genetic defects, which drive the T cell neoplasias, with calcium signaling and ion channels. We suggest that changes in regulation of various ion channels in different types of the T leukemias may provide the intracellular ion microenvironment favorable to maintain self-renewal capacity, arrest differentiation, induce proliferation, and enhance motility. PMID:25866806

Primordial Germ Cell Specification and Migration

PubMed Central

Marlow, Florence

2015-01-01

Primordial germ cells are the progenitor cells that give rise to the gametes. In some animals, the germline is induced by zygotic transcription factors, whereas in others, primordial germ cell specification occurs via inheritance of maternally provided gene products known as germ plasm. Once specified, the primordial germ cells of some animals must acquire motility and migrate to the gonad in order to survive. In all animals examined, perinuclear structures called germ granules form within germ cells. This review focuses on some of the recent studies, conducted by several groups using diverse systems, from invertebrates to vertebrates, which have provided mechanistic insight into the molecular regulation of germ cell specification and migration. PMID:26918157

6. West side of Building 1001 (administration building), looking southeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. West side of Building 1001 (administration building), looking southeast - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

5. Interior of Building 1042 (brig), cell, looking northeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Interior of Building 1042 (brig), cell, looking northeast - Naval Air Station Chase Field, Building 1042, Ofstie Road, .6 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

4. South side of Building 1001 (administration building), looking north ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. South side of Building 1001 (administration building), looking north - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

3. East side of Building 1001 (administration building), looking west ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. East side of Building 1001 (administration building), looking west - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

3. Southwest side of Building 1042 (brig), looking northeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Southwest side of Building 1042 (brig), looking northeast - Naval Air Station Chase Field, Building 1042, Ofstie Road, .6 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

8. Southwest side of Building 1040 (chapel), looking northeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Southwest side of Building 1040 (chapel), looking northeast - Naval Air Station Chase Field, Building 1040, Enterprise Street, .37 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

4. Southwest side of Building 1042 (brig), looking northeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Southwest side of Building 1042 (brig), looking northeast - Naval Air Station Chase Field, Building 1042, Ofstie Road, .6 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

2. Southeast side of Building 1042 (brig), looking northwest ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

2. Southeast side of Building 1042 (brig), looking northwest - Naval Air Station Chase Field, Building 1042, Ofstie Road, .6 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

5. North side of Building 1001 (administration building), looking southeast ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. North side of Building 1001 (administration building), looking southeast - Naval Air Station Chase Field, Building 1001, Independence Street, .45 mile south of intersection of Texas State Highway & Independence Street, Beeville, Bee County, TX

1. Northeast side of Building 1042 (brig), looking southwest ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Northeast side of Building 1042 (brig), looking southwest - Naval Air Station Chase Field, Building 1042, Ofstie Road, .6 mile South-Southeast of intersection of Texas State Highway 202 & Independence Street, Beeville, Bee County, TX

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication

PubMed Central

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro, overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated (P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway. PMID:28194372

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication.

PubMed

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 ( MDA5 ) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro , overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated ( P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway.

Autonomous docking ground demonstration

NASA Technical Reports Server (NTRS)

Lamkin, Steve L.; Le, Thomas Quan; Othon, L. T.; Prather, Joseph L.; Eick, Richard E.; Baxter, Jim M.; Boyd, M. G.; Clark, Fred D.; Spehar, Peter T.; Teters, Rebecca T.

1991-01-01

The Autonomous Docking Ground Demonstration is an evaluation of the laser sensor system to support the docking phase (12 ft to contact) when operated in conjunction with the guidance, navigation, and control (GN&C) software. The docking mechanism being used was developed for the Apollo/Soyuz Test Program. This demonstration will be conducted using the 6-DOF Dynamic Test System (DTS). The DTS simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration, the laser sensor will be mounted on the target vehicle and the retroflectors will be on the chase vehicle. This arrangement was chosen to prevent potential damage to the laser. The laser sensor system, GN&C, and 6-DOF DTS will be operated closed-loop. Initial conditions to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved.

Mate-finding behaviour in Calanus marshallae Frost

PubMed Central

Tsuda, A.

1998-01-01

Mate-finding behaviour by Calanus marshallae Frost, 1974, was observed and video recorded in a 1 m diameter kreisel. Newly moulted females signal to males by depositing vertical pheromone trails many tens of centimetres long. Males search for trails along primarily horizontal trajectories. The orthogonality of signal trace and search trail trajectory maximizes the chance of intersection. Males often initiate a dance of rapid, tight turns upon encountering a pheromone trail, then waggle down it (chase swimming) to the signalling female. She jumps away after initial contact, and the male follows. Many successive approach, bump and jump sequences follow, with mating eventually ensuing. The actual copulatory clasp and spermatophore transfer were not observed, although a few instances of brief attachment and tandem swimming were seen. Male dances occur at times when chase swimming does not follow, and the function of dances is not yet known.

Toxic leucoencephalopathy after 'chasing the dragon'.

PubMed

Singh, Rajinder; Saini, Monica

2015-06-01

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

Resin bleed improvement on surface mount semiconductor device

NASA Astrophysics Data System (ADS)

Rajoo, Indra Kumar; Tahir, Suraya Mohd; Aziz, Faieza Abdul; Shamsul Anuar, Mohd

2018-04-01

Resin bleed is a transparent layer of epoxy compound which occurs during molding process but is difficult to be detected after the molding process. Resin bleed on the lead on the unit from the focused package, SOD123, can cause solderability failure at end customer. This failed unit from the customer will be considered as a customer complaint. Generally, the semiconductor company has to perform visual inspection after the plating process to detect resin bleed. Mold chase with excess hole, split cavity & stepped design ejector pin hole have been found to be the major root cause of resin bleed in this company. The modifications of the mold chase, changing of split cavity to solid cavity and re-design of the ejector pin proposed were derived after a detailed study & analysis conducted to arrive at these solutions. The solutions proposed have yield good results during the pilot run with zero (0) occurrence of resin bleed for 3 consecutive months.

An Unsupervised Approach for Extraction of Blood Vessels from Fundus Images.

PubMed

Dash, Jyotiprava; Bhoi, Nilamani

2018-04-26

Pathological disorders may happen due to small changes in retinal blood vessels which may later turn into blindness. Hence, the accurate segmentation of blood vessels is becoming a challenging task for pathological analysis. This paper offers an unsupervised recursive method for extraction of blood vessels from ophthalmoscope images. First, a vessel-enhanced image is generated with the help of gamma correction and contrast-limited adaptive histogram equalization (CLAHE). Next, the vessels are extracted iteratively by applying an adaptive thresholding technique. At last, a final vessel segmented image is produced by applying a morphological cleaning operation. Evaluations are accompanied on the publicly available digital retinal images for vessel extraction (DRIVE) and Child Heart And Health Study in England (CHASE_DB1) databases using nine different measurements. The proposed method achieves average accuracies of 0.957 and 0.952 on DRIVE and CHASE_DB1 databases respectively.

Fringe chasing by three-point spatial phase shifting for discrimination of the motion direction in the long-range homodyne laser Doppler vibrometry

NASA Astrophysics Data System (ADS)

Daemi, Mohammad Hossein; Rasouli, Saifollah

2018-07-01

In this work, a three-point spatial phase shifting (SPS) method is implemented for chasing of the moving interference fringes in the homodyne laser Doppler vibrometry (HoLDV). By the use of SPS method, we remove disability of the HoLDV in the discrimination of the motion direction for long-range displacements. From the phase increments histogram, phase unwrapping tolerance value is selected, and adequacy of the data acquisition rate and required bandwidth limit are determined. Also in this paper, a detailed investigation on the effect of detectors positioning errors and influence of the Gaussian profile of the interfering beams on the measurements are presented. Performance of the method is verified by measuring a given harmonic vibration produced by a loudspeaker. Also, by the proposed method, vibration of mounting system of a disk laser gain medium is characterized.

Constraining chameleon field theories using the GammeV afterglow experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Upadhye, A.; /Chicago U., EFI /KICP, Chicago; Steffen, J.H.

2009-11-01

The GammeV experiment has constrained the couplings of chameleon scalar fields to matter and photons. Here we present a detailed calculation of the chameleon afterglow rate underlying these constraints. The dependence of GammeV constraints on various assumptions in the calculation is studied. We discuss GammeV-CHASE, a second-generation GammeV experiment, which will improve upon GammeV in several major ways. Using our calculation of the chameleon afterglow rate, we forecast model-independent constraints achievable by GammeV-CHASE. We then apply these constraints to a variety of chameleon models, including quartic chameleons and chameleon dark energy models. The new experiment will be able to probemore » a large region of parameter space that is beyond the reach of current tests, such as fifth force searches, constraints on the dimming of distant astrophysical objects, and bounds on the variation of the fine structure constant.« less

KC-135A in flight - closeup of winglet with attached tufts

NASA Technical Reports Server (NTRS)

1979-01-01

A chase plane view of the tufts on the KC-135 winglet. The use of tufts in flight research dates back to the early days of the NACA, and remains an effective means of observing airflow even today. In this procedure, rows of strings are attached to an airplane's surface, with one end of each string taped to the airplane and the other end free to swing about in the airflow. The movements of the tufts are photographed by on-board cameras or a chase plane. If the tufts are arrayed in neat rows, as seen here, then the airflow is smooth over the airplane's surface. If, however, they are moving about violently, it suggests turbulent airflow. Such motions may indicate high drag, flow separation (such as in a stall), or buffeting. In some cases, tufts will actually point forward, indicating the airflow has reversed direction.

Coplanar tail-chase aerial combat as a differential game

NASA Technical Reports Server (NTRS)

Merz, A. W.; Hague, D. S.

1977-01-01

A reduced-order version of the one-on-one aerial combat problem is studied as a pursuit-evasion differential game. The coplanar motion takes place at given speeds and given maximum available turn rates, and is described by three state equations which are equivalent to the range, bearing, and heading of one aircraft relative to the other. The purpose of the study is to determine those relative geometries from which either aircraft can be guaranteed a win, regardless of the maneuver strategies of the other. Termination is specified by the tail-chase geometry, at which time the roles of pursuer and evader are known. The roles are found in general, together with the associated optimal turn maneuvers, by solution of the differential game of kind. For the numerical parameters chosen, neither aircraft can win from the majority of possible initial conditions if the other turns optimally in certain critical geometries.

Chasing The 'Like': Adolescent Use Of Social Networking Sites In Australia.

PubMed

la Sala, Louise; Skues, Jason; Wise, Lisa; Theiler, Stephen

2015-01-01

The current study investigated how adolescents behave on Social Networking Sites (SNSs) and how they interpret the feedback they receive online from others. Thirty-four Australian adolescents (26 girls, 8 boys) aged 13 to 17 years participated in the study. Five semi-structured focus groups (3 mixed groups, 2 all-girl groups) were conducted to explore how adolescents perceive their own and others' SNS behaviours, the motivation underlying these behaviours, and the expected outcomes related to particular behaviours. Teenagers reported that they spend a good deal of time planning their SNS posts, felt that the information they posted was a true reflection of them as a person, and thus interpreted feedback ("likes") as measuring their self-worth. In contrast, some teenagers were perceived as "chasing the like" for status and popularity while not caring about how accurately their posts represented them as a person. A potential gender bias in these findings is discussed.

NO2 DOAS Measurements of Traffic Emissions by Chasing Cars

NASA Astrophysics Data System (ADS)

Zhu, Ying; Lipkowitsch, Ivo; Chan, Ka Lok; Bräu, Melanie; Wenig, Mark

2016-04-01

On this poster we present NO2 measurements using a Cavity-Enhanced DOAS on a measurement bus which we used to chase other vehicles to measure their NO2 emissions. Emissions of nitrogen oxides from on-road vehicles have received highly attention recently due to the increasing trend of ambient NOx level. It is particularly important to identify and quantify the direct emission and secondary formation of NO2 contributed by traffic emissions, in order to study the impact to the local air quality. We sampled on-road emissions in different environments and different driving conditions (e.g. urban, highway, different speeds). We analyse the data set in terms of spatial and temporal variability to search for temporal and spatial patterns. We present mean values sorted for different vehicle types, distance to the target car and travelling speeds to provide an emission data base from this measurement study.

In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis.

PubMed

Lim, Daniel A; Suárez-Fariñas, Mayte; Naef, Felix; Hacker, Coleen R; Menn, Benedicte; Takebayashi, Hirohide; Magnasco, Marcelo; Patil, Nila; Alvarez-Buylla, Arturo

2006-01-01

Neural stem cells and neurogenesis persist in the adult mammalian brain subventricular zone (SVZ). Cells born in the rodent SVZ migrate to the olfactory bulb (Ob) where they differentiate into interneurons. To determine the gene expression and functional profile of SVZ neurogenesis, we performed three complementary sets of transcriptional analysis experiments using Affymetrix GeneChips: (1) comparison of adult mouse SVZ and Ob gene expression profiles with those of the striatum, cerebral cortex, and hippocampus; (2) profiling of SVZ stem cells and ependyma isolated by fluorescent-activated cell sorting (FACS); and (3) analysis of gene expression changes during in vivo SVZ regeneration after anti-mitotic treatment. Gene Ontology (GO) analysis of data from these three separate approaches showed that in adult SVZ neurogenesis, RNA splicing and chromatin remodeling are biological processes as statistically significant as cell proliferation, transcription, and neurogenesis. In non-neurogenic brain regions, RNA splicing and chromatin remodeling were not prominent processes. Fourteen mRNA splicing factors including Sf3b1, Sfrs2, Lsm4, and Khdrbs1/Sam68 were detected along with 9 chromatin remodeling genes including Mll, Bmi1, Smarcad1, Baf53a, and Hat1. We validated the transcriptional profile data with Northern blot analysis and in situ hybridization. The data greatly expand the catalogue of cell cycle components, transcription factors, and migration genes for adult SVZ neurogenesis and reveal RNA splicing and chromatin remodeling as prominent biological processes for these germinal cells.

Gene expression of human lung cancer cell line CL1-5 in response to a direct current electric field.

PubMed

Huang, Ching-Wen; Chen, Huai-Yi; Yen, Meng-Hua; Chen, Jeremy J W; Young, Tai-Horng; Cheng, Ji-Yen

2011-01-01

Electrotaxis is the movement of adherent living cells in response to a direct current (dc) electric field (EF) of physiological strength. Highly metastatic human lung cancer cells, CL1-5, exhibit directional migration and orientation under dcEFs. To understand the transcriptional response of CL1-5 cells to a dcEF, microarray analysis was performed in this study. A large electric-field chip (LEFC) was designed, fabricated, and used in this study. CL1-5 cells were treated with the EF strength of 0 mV/mm (the control group) and 300 mV/mm (the EF-treated group) for two hours. Signaling pathways involving the genes that expressed differently between the two groups were revealed. It was shown that the EF-regulated genes highly correlated to adherens junction, telomerase RNA component gene regulation, and tight junction. Some up-regulated genes such as ACVR1B and CTTN, and some down-regulated genes such as PTEN, are known to be positively and negatively correlated to cell migration, respectively. The protein-protein interactions of adherens junction-associated EF-regulated genes suggested that platelet-derived growth factor (PDGF) receptors and ephrin receptors may participate in sensing extracellular electrical stimuli. We further observed a high percentage of significantly regulated genes which encode cell membrane proteins, suggesting that dcEF may directly influence the activity of cell membrane proteins in signal transduction. In this study, some of the EF-regulated genes have been reported to be essential whereas others are novel for electrotaxis. Our result confirms that the regulation of gene expression is involved in the mechanism of electrotactic response.

MicroRNA-9 promotes the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

PubMed

Liu, D-Z; Chang, B; Li, X-D; Zhang, Q-H; Zou, Y-H

2017-09-01

The objective of the study was to investigate the role of microRNA-9 (miR-9) targeting forkhead box O1 (FOXO1) in the proliferation, migration, and invasion of breast cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expressions of miR-9 and FOXO1 mRNA in breast cancer tissues, normal breast tissues, breast cancer cell lines, and normal breast epithelial cells. After the up-regulation of miR-9 expression, qRT-PCR and Western blotting were used to determine the expression of FOXO1. The luciferase reporter gene assay was used to validate the target gene. The CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay were used to investigate the changes in the proliferation, migration, and invasion of breast cancer cells, respectively. MicroRNA-9 expression was significantly up-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). FOXO1 mRNA and protein expressions were substantially down-regulated in breast cancer tissues and breast cancer cell lines when compared with normal breast tissues and normal breast epithelial cells (both P < 0.05). There can be a negative correlation between miR-9 and FOXO1 mRNA in breast cancer. Luciferase reporter gene assay indicated that miR-9 can down-regulate FOXO1 expression at a post-transcriptional level through binding specifically to FOXO1 3'UTR. The results of CCK-8 assay, scratch-wound healing assay, and Transwell invasion assay revealed that the inhibition of miR-9 can suppress MCF7 cell proliferation, migration, and invasion. Additionally, the expression of miR-9 increased significantly whilst that of FOXO1 decreased substantially as the disease progressed (P < 0.05). Our study provides evidence that miR-9 can promote the proliferation, migration, and invasion of breast cancer cells via down-regulating FOXO1.

Hypoxia-regulated human periodontal ligament cells via Wnt/β-catenin signaling pathway

PubMed Central

Xiao, Zhili; Han, Yineng; Zhang, Yan; Zhang, Xiaonan

2017-01-01

Abstract Background: The aim of this study is to investigate the effects of hypoxia on the proliferation, morphology, migration ability, hypoxia inducible factor (HIF) 1 (HIF-1) expression, and the relationship with Wnt/β-catenin signaling of human periodontal ligament cells (hPDLCs) in vitro. Methods: hPDLCs (4th passage) cultured by the tissue culture method were randomly assigned to slight (5% O2), severe hypoxia (1% O2) groups, and the control (21% O2) group, respectively. From 1st to 7th day, the optical density values were detected, and the growth curve was described. Wound healing assay was done to observe the migration ability of hPDLCs under various O2 conditions. Then reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of cementum-related genes and Wnt signaling pathway-related genes. Further, RT-qPCR, Western blot, and immunofluorescence staining method were constructed to show HIF expressions under different O2 concentrations in hPDLCs. Results: The growth rate of hPDLCs decreased with the reduction of O2 content by degree, and the morphology of hPDLCs changed in different O2 contents. Besides, hPDLCs migrate faster in 21% and 5% O2 than in 1% O2, and both the expressions of cementum-related genes and Wnt signaling pathway-related genes were raised under hypoxic conditions. In addition, with the reduction of O2 concentration, the messenger RNA and protein level expression of HIF were all increased, and HIF was gradually transported from cytoplasm into the nucleus and in 1% O2 concentration, it was mainly expressed in the nucleus. Conclusion: This finding demonstrated that hypoxia was capable of suppressing the proliferation and migration ability, changing the morphology of hPDLCs, and stabilizing HIF-1α against degradation and promoting its translocation to the nucleus. Meanwhile, hypoxia may regulate hPDLCs proliferation and cementogenic differentiation via Wnt/β-catenin signaling pathway, which may potentially provide a novel insight into the etiology and treatment of periodontal diseases. PMID:28422843

Cellular and molecular mechanisms of pomegranate juice-induced anti-metastatic effect on prostate cancer cells.

PubMed

Wang, Lei; Alcon, Andre; Yuan, Hongwei; Ho, Jeffrey; Li, Qi-Jing; Martins-Green, M

2011-07-01

Prostate cancer is the second leading cause of cancer-related deaths among US males. Pomegranate juice (PJ), a natural product, was shown in a clinical trial to inhibit progression of this disease. However, the underlying mechanisms involved in the anti-progression effects of PJ on prostate cancer remain unclear. Here we show that, in addition to causing cell death of hormone-refractory prostate cancer cells, PJ also increases cell adhesion and decreases cell migration of the cells that do not die. We hypothesized that PJ does so by stimulating the expression and/or activation of molecules that alter the cytoskeleton and the adhesion machinery of prostate cancer cells, resulting in enhanced cell adhesion and reduced cell migration. We took an integrative approach to these studies by using Affimetrix gene arrays to study gene expression, microRNA arrays to study the non-coding RNAs, molecules known to be disregulated in cancer cells, and Luminex Multiplex array assays to study the level of secreted pro-inflammatory cytokines/chemokines. PJ up-regulates genes involved in cell adhesion such as E-cadherin, intercellular adhesion molecule 1 (ICAM-1) and down-regulates genes involved in cell migration such as hyaluranan-mediated motility receptor (HMMR) and type I collagen. In addition, anti-invasive microRNAs such as miR-335, miR-205, miR-200, and miR-126, were up-regulated, whereas pro-invasive microRNA such as miR-21 and miR-373, were down-regulated. Moreover, PJ significantly reduced the level of secreted pro-inflammatory cytokines/chemokines such as IL-6, IL-12p40, IL-1β and RANTES, thereby having the potential to decrease inflammation and its impact on cancer progression. PJ also inhibits the ability of the chemokine SDF1α to chemoattract these cancer cells. SDF1α and its receptor CXCR4 are important in metastasis of cancer cells to the bone. Discovery of the mechanisms by which this enhanced adhesion and reduced migration are accomplished can lead to sophisticated and effective prevention of metastasis in prostate and potentially other cancers. This journal is © The Royal Society of Chemistry 2011

Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bozza, M.; Gerard, C.; Kolakowski, L.F. Jr.

1995-06-10

Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to integrate peripheral and central inflammatory responses. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside of the immune system. Here we report the structure and chromosomal location of the mouse Mif gene and the partial characterization of five Mif pseudogenes. The mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of three exons. A comparison between the mouse and the human genes shows a similar gene structure and common regulatory elements inmore » both promoter regions. The mouse Mif gene maps to the middle region of chromosome 10, between Bcr and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respectively. The entire sequence of two pseudogenes demonstrates the absence of introns, the presence of the 5{prime} untranslated region of the cDNA, a 3{prime} poly(A) tail, and the lack of sequence similarity with untranscribed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produce mutated or truncated MIF-like proteins. Phylogenetic analyses of MIF genes and pseudogenes indicate several independent genetic events that can account for multiple genomic integrations. Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition. 46 refs., 5 figs., 1 tab.« less

Processing of human cytomegalovirus glycoprotein B in recombinant adenovirus-infected cells.

PubMed

Marshall, G S; Fenger, D P; Stout, G G; Knights, M E; Hunt, L A

1996-07-01

Intracellular processing of human cytomegalovirus (HCMV) glycoprotein B (gB; gpUL55) expressed by a recombinant adenovirus (Ad-gB) was studied in human A549 cells as processing events could affect immunogenicity when such viruses are used as live-recombinant vaccines. Cleavage of [35S]methionine-labelled gp13O into gp93 and gp55 reached a maximum after a 3 h chase. Cleavage was completely inhibited by brefeldin A, suggesting that processing normally occurs as a late Golgi or post-Golgi event. Uncleaved gp 130 remained completely sensitive to endo-beta-N-acetylglucosaminidase H (Endo-H) in untreated cells following long chase periods, indicating high-mannose oligosaccharides at all of the 18 N-linked glycosylation sites (Asn-X-Ser/Thr) and retention in the endoplasmic reticulum. Endo-H analysis of gp55 from swainsonine-treated and untreated cells was consistent with glycosylation at all three potential sites, with two oligosaccharides remaining sensitive to Endo-H and one being processed to Endo-H resistance. The heavily glycosylated N-terminal gp93 subunit was not detected by [35S]methionine-labelling but was easily detected along with gp55 after labelling with [3H]mannose. No cleavage of gp 130 was observed in analogous pulse-chase radiolabelling of Ad-gB-infected human fibroblasts, even though these cells are permissive for HCMV replication and can process the native gB molecule. Processing of gB in recombinant adenovirus-infected A549 cells was generally similar to that previously reported for native gB in HCMV-infected fibroblasts.

Phosphatidylserine translocation to the mitochondrion is an ATP-dependent process in permeabilized animal cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Voelker, D.R.

1989-12-01

Chinese hamster ovary (CHO-K1) cells were pulse labeled with ({sup 3}H)serine, and the synthesis of phosphatidyl({sup 3}H)ethanolamine from phosphatidyl({sup 3}H)serine during the subsequent chase was used as a measure of lipid translocation to the mitochondria. When the CHO-K1 cells were pulse labeled and subsequently permeabilized with 50 {mu}g of saponin per ml, there was no significant turnover of nascent phosphatidyl({sup 3}H)serine to form phosphatidyl({sup 3}H)ethanolamine during an ensuring chase. Supplementation of the permeabilized cells with 2 mM ATP resulted in significant phosphatidyl({sup 3}H)ethanolamine synthesis (83% of that found in intact cells) from phosphatidyl({sup 3}H)serine during a subsequent 2-hr chase. Phosphatidyl({supmore » 3}H)ethanolamine synthesis essentially ceased after 2 hr in the permeabilized cells. The translocation-dependent synthesis of phosphatidyl({sup 3}H)ethanolamine was a saturable process with respect to ATP concentration in permeabilized cells. The conversion of phosphatidyl({sup 3}H)serine to phosphatidyl({sup 3}H)ethanolamine did not occur in saponin-treated cultures supplemented with 2 mM AMP, 2 mM 5{prime}-adenylyl imidodiphosphate, or apyrase plus 2 mM ATP. ATP was the most effective nucleotide, but the addition of GTP, CTP, UTP, and ADP also supported the translocation-dependent synthesis of phosphatidyl({sup 3}H)ethanolamine albeit to a lesser extent. These data provide evidence that the interorganelle translocation of phosphatidylserine requires ATP and is largely independent of soluble cytosolic proteins.« less

Smoking tobacco along with marijuana increases symptoms of cannabis dependence

PubMed Central

Ream, Geoffrey L.; Benoit, Ellen; Johnson, Bruce D.; Dunlap, Eloise

2008-01-01

Aim User practices/rituals that involve concurrent use of tobacco and marijuana – smoking blunts and “chasing” marijuana with tobacco – are hypothesized to increase cannabis dependence symptoms. Design Ethnographers administered group surveys to a diverse, purposive sample of marijuana users who appeared to be 17–35 years old. Setting New York City, including non-impoverished areas of Manhattan, the transitional area of East Village/Lower East Side, low-income areas of northern Manhattan and South Bronx, and diverse areas of Brooklyn and Queens. Participants 481 marijuana users ages 14–35, 57% male, 43% female; 27% White, 30% Black, 19% Latino, 5% Asian, 20% of other/multiple race. Measurements Among many other topics, group surveys measured cannabis dependence symptoms; frequencies of chasing, blunt smoking, joint/pipe smoking, using marijuana while alone, and general tobacco use; and demographic factors. Findings Blunt smoking and chasing marijuana with tobacco were each uniquely associated with five of the seven cannabis dependence symptoms. Across symptoms, predicted odds were 2.4–4.1 times greater for participants who smoked blunts on all 30 of the past 30 days than for participants who did not smoke blunts in the past 30 days. Significant increases in odds over the whole range of the five-point chasing frequency measure (from never to always) ranged from 3.4 times to 5.1 times. Conclusions Using tobacco with marijuana – smoking blunts and “chasing” marijuana with tobacco – contributes to cannabis dependence symptoms. Treatment for cannabis dependence may be more effective it addresses the issue of concurrent tobacco use. PMID:18339491