Sample records for dually control migration

  1. Access to Care for Medicare-Medicaid Dually Eligible Beneficiaries: The Role of State Medicaid Payment Policies.

    PubMed

    Zheng, Nan Tracy; Haber, Susan; Hoover, Sonja; Feng, Zhanlian

    2017-12-01

    Medicaid programs are not required to pay the full Medicare coinsurance and deductibles for Medicare-Medicaid dually eligible beneficiaries. We examined the association between the percentage of Medicare cost sharing paid by Medicaid and the likelihood that a dually eligible beneficiary used evaluation and management (E&M) services and safety net provider services. Medicare and Medicaid Analytic eXtract enrollment and claims data for 2009. Multivariate analyses used fee-for-service dually eligible and Medicare-only beneficiaries in 20 states. A comparison group of Medicare-only beneficiaries controlled for state factors that might influence utilization. Paying 100 percent of the Medicare cost sharing compared to 20 percent increased the likelihood (relative to Medicare-only) that a dually eligible beneficiary had any E&M visit by 6.4 percent. This difference in the percentage of cost sharing paid decreased the likelihood of using safety net providers, by 37.7 percent for federally qualified health centers and rural health centers, and by 19.8 percent for hospital outpatient departments. Reimbursing the full Medicare cost-sharing amount would improve access for dually eligible beneficiaries, although the magnitude of the effect will vary by state and type of service. © Health Research and Educational Trust.

  2. Teaching self-control to small groups of dually diagnosed adults.

    PubMed

    Dixon, M R; Holcomb, S

    2000-01-01

    The present study examined the use of a progressive delay procedure to teach self-control to two groups of dually diagnosed adults. When given a choice between an immediate smaller reinforcer and a larger delayed reinforcer, both groups chose the smaller reinforcer during baseline. During treatment, progressive increases in work requirements for gaining access to a larger reinforcer resulted in both groups selecting larger delayed reinforcers. The results are discussed with respect to increasing cooperative work behavior and self-control.

  3. Comparative effects of vaccination against porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) in a PCV2-PRRSV challenge model.

    PubMed

    Park, Changhoon; Oh, Yeonsu; Seo, Hwi Won; Han, Kiwon; Chae, Chanhee

    2013-03-01

    The objective of the present study was to determine the effects of porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) vaccinations in an experimental PCV2-PRRSV challenge model, based on virological (viremia), immunological (neutralizing antibodies [NAs], gamma interferon-secreting cells [IFN-γ-SCs], and CD4(+) CD8(+) double-positive cells), and pathological (lesions and antigens in lymph nodes and lungs) evaluations. A total of 72 pigs were randomly divided into 9 groups (8 pigs per group): 5 vaccinated and challenged groups, 3 nonvaccinated and challenged groups, and a negative-control group. Vaccination against PCV2 induced immunological responses (NAs and PCV2-specific IFN-γ-SCs) and reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PCV2 did not affect the PRRSV immunological responses (NAs and PRRSV-specific IFN-γ-SCs), PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. Vaccination against PRRSV did not induce immunological responses (PRRSV-specific IFN-γ-SCs) or reduce PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. In addition, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. In summary, vaccination against PCV2 reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. Therefore, the PCV2 vaccine decreased the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs. In contrast, the PRRSV vaccine alone did not decrease the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs.

  4. Comparative Effects of Vaccination against Porcine Circovirus Type 2 (PCV2) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in a PCV2-PRRSV Challenge Model

    PubMed Central

    Park, Changhoon; Oh, Yeonsu; Seo, Hwi Won; Han, Kiwon

    2013-01-01

    The objective of the present study was to determine the effects of porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) vaccinations in an experimental PCV2-PRRSV challenge model, based on virological (viremia), immunological (neutralizing antibodies [NAs], gamma interferon-secreting cells [IFN-γ-SCs], and CD4+ CD8+ double-positive cells), and pathological (lesions and antigens in lymph nodes and lungs) evaluations. A total of 72 pigs were randomly divided into 9 groups (8 pigs per group): 5 vaccinated and challenged groups, 3 nonvaccinated and challenged groups, and a negative-control group. Vaccination against PCV2 induced immunological responses (NAs and PCV2-specific IFN-γ-SCs) and reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PCV2 did not affect the PRRSV immunological responses (NAs and PRRSV-specific IFN-γ-SCs), PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. Vaccination against PRRSV did not induce immunological responses (PRRSV-specific IFN-γ-SCs) or reduce PRRSV viremia, PRRSV-induced lesions, or PRRSV antigens in the dually infected pigs. In addition, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. In summary, vaccination against PCV2 reduced PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. However, vaccination against PRRSV increased PCV2 viremia, PCV2-induced lesions, and PCV2 antigens in the dually infected pigs. Therefore, the PCV2 vaccine decreased the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs. In contrast, the PRRSV vaccine alone did not decrease the potentiation of PCV2-induced lesions by PRRSV in dually infected pigs. PMID:23302743

  5. Medicaid Highlights: Dually Eligible Enrollees: 2002

    PubMed Central

    Lied, Terry R.

    2006-01-01

    Individuals eligible in both Medicaid and Medicare, the dually eligible enrollees, account for a disproportionate share of Medicaid utilization and payments. While comprising 14.7 percent of the Medicaid population, they accounted for 40.5 percent of Medicaid payments in 2002. Mean reimbursement for the dually eligible enrollees was nearly four times that of non-dually eligible Medicaid enrollees. This highlight examines utilization and payment data for the dually eligible enrollees in 2002. PMID:17290663

  6. Equivalent model of a dually-fed machine for electric drive control systems

    NASA Astrophysics Data System (ADS)

    Ostrovlyanchik, I. Yu; Popolzin, I. Yu

    2018-05-01

    The article shows that the mathematical model of a dually-fed machine is complicated because of the presence of a controlled voltage source in the rotor circuit. As a method of obtaining a mathematical model, the method of a generalized two-phase electric machine is applied and a rotating orthogonal coordinate system is chosen that is associated with the representing vector of a stator current. In the chosen coordinate system in the operator form the differential equations of electric equilibrium for the windings of the generalized machine (the Kirchhoff equation) are written together with the expression for the moment, which determines the electromechanical energy transformation in the machine. Equations are transformed so that they connect the currents of the windings, that determine the moment of the machine, and the voltages on these windings. The structural diagram of the machine is assigned to the written equations. Based on the written equations and accepted assumptions, expressions were obtained for the balancing the EMF of windings, and on the basis of these expressions an equivalent mathematical model of a dually-fed machine is proposed, convenient for use in electric drive control systems.

  7. Estimating the effects of the Balanced Budget act of 1997 on the home health care use of the dually eligible: a natural experiments approach.

    PubMed

    Williamson, James M

    2013-01-01

    This research examines the use of home health agency services used by older adults after the implementation of changes to Medicare's payment scheme mandated by the Balanced Budget Act (BBA) of 1997. The objective of this study is to identify differential effects the BBA may have had on home health service use between dually eligible and Medicare-only beneficiaries. The results of this study suggest that although dually eligible and Medicare-only beneficiaries experienced a substantial decline in home health service use, the dually eligible had a relatively larger decline. Following the BBA, the dually eligible had more office-based physician visits but fewer inpatient hospital days, relative to the Medicare-only population. Finally, the author estimates cost savings to Medicare due to the BBA to be $1 billion in the 2 years following the legislation, whereas Medicaid programs shouldered a larger percentage of the home health service bill.

  8. Exploring how residential mobility and migration influences teenage pregnancy in five rural communities in California: youth and adult perceptions.

    PubMed

    Lara, Diana; Decker, Martha J; Brindis, Claire D

    2016-09-01

    Teenage birth rates among young people aged 15-19 years in California, USA, have declined from 47 births per 1000 in 2000 to 24 per 1000 in 2013. Nevertheless, the US counties with the highest teenage birth rates are predominantly rural and have a high proportion of Latinos/as. We conducted 42 interviews with key stakeholders and 12 focus groups with 107 young people in five rural communities to better understand local migration patterns and their influence on intermediate and proximate variables of pregnancy, such as interaction with role models and barriers to access contraception. The migration patterns identified were: residential mobility due to seasonal jobs, residential mobility due to economic and housing changes and migration from other countries to California. These patterns affect young people and families' interactions with school and health systems and other community members, creating both opportunities and barriers to prevent risky sexual behaviours. In rural areas, residential mobility and migration to the USA interconnect. As a result, young people dually navigate the challenges of residential mobility, while also adapting to the dominant US culture. It is important to promote programmes that support the integration of immigrant youth to reduce their sense of isolation, as well as to assure access to sexual health education and reproductive health services.

  9. Teaching Self-Control to Small Groups of Dually Diagnosed Adults.

    ERIC Educational Resources Information Center

    Dixon, Mark R.; Holcomb, Sharon

    2000-01-01

    A study used a progressive delay procedure to teach self-control to six adults with mental retardation. At baseline, participants chose an immediate smaller reinforcer rather than a larger delayed reinforcer. Progressive increases in work requirements for gaining access to a larger reinforcer resulted in participants selecting larger delayed…

  10. Teaching Self-Control to Dually Diagnosed Deaf Students: Promising Procedures.

    ERIC Educational Resources Information Center

    Morrow, Lonny W.

    1985-01-01

    Three pilot studies suggested that deaf multiply disabled students (ages 15-18) can learn and implement self-control strategies while becoming more independent and engaging in more age-appropriate prosocial behavior. Use of the skills was maintained and appeared to generalize to other school and nonschool environments. (CL)

  11. Dually diagnosed patients' benefits of mutual-help groups and the role of social anxiety.

    PubMed

    Timko, Christine; Cronkite, Ruth C; McKellar, John; Zemore, Sarah; Moos, Rudolf H

    2013-02-01

    There is debate about whether dually diagnosed patients benefit from mutual-help groups (MHGs), partly because social anxiety may make participation problematic. We examined dually diagnosed patients' participation in MHGs and outcomes at 6, 12, and 24 months post-treatment, and the extent to which social anxiety was associated with participation. We also examined whether MHG participation and social anxiety were related to outcomes, and whether social anxiety moderated associations between participation and outcomes. We found high rates of MHG participation. Among patients who attended at least one meeting, outcomes were positive. Social anxiety was not associated with levels of MHG participation, but more participation was associated with better outcomes. When social anxiety moderated associations between MHG participation and outcomes, patients with more social anxiety benefited more from participation. Treated dually diagnosed patients participate in, and benefit from, MHGs, and participation and benefits are comparable, or even strengthened, among more socially-anxious patients. Published by Elsevier Inc.

  12. Childhood Risk Factors in Dually Diagnosed Homeless Adults.

    ERIC Educational Resources Information Center

    Blankertz, Laura E.; And Others

    1993-01-01

    Examined prevalence of five childhood risk factors (sexual abuse, physical abuse, parental mental illness, substance abuse, out-of-home placement) among dually diagnosed (mentally ill and substance abusing) homeless adults (n=156) in rehabilitation programs. Findings suggest that childhood risk factors, whether single or multiple, are very…

  13. The impact of substance abuse on osteoporosis screening and risk of osteoporosis in women with psychotic disorders.

    PubMed

    Kelly, D L; Myers, C S; Abrams, M T; Feldman, S; Park, J; McMahon, R P; Shim, J-C

    2011-04-01

    Review of the 1-year prevalence of screening for osteoporosis and of osteoporosis or idiopathic fracture in Maryland Medicaid administrative records found that screening rates did not differ among women in the control population, women with psychosis, and women with major mood disorders, but were reduced compared to controls in women with substance use disorder, with or without psychosis. Prevalence of osteoporosis was increased compared to controls in women with major mood disorders or women over 55 dually diagnosed with psychosis and substance use disorder. Osteoporosis is a major public health concern. Substance abuse and psychosis may be risk factors, however, frequency of screening and disease risk in women with psychotic disorders and substance use disorder (SUD) remains unknown. This study examined rates (FY 2005) of osteoporosis screening and disease risk in Medicaid enrolled women aged 50 to 64 (N = 18,953). Four diagnostic groups were characterized: (1) psychosis, (2) SUD, (3) major mood disorder, and (4) controls. The interaction of psychosis and SUD on screening and disease prevalence of osteoporosis was tested. The prevalence of osteoporosis across the entire population was 6.7%. Four percent of those without an osteoporosis diagnosis received osteoporosis screening with no notable differences between psychosis and controls. Those with SUD, however, had a significant reduction in screening compared to controls (OR = 0.61, 95% CI = 0.40-0.91, p = 0.016). Women with a major mood disorder were more likely to have osteoporosis in their administrative record (OR = 1.32, 95% CI = 1.03-1.70, p = 0.028) compared to controls. Those who were dually diagnosed (SUD and psychosis) in the oldest ages (55-64 years) had a markedly higher prevalence of osteoporosis compared to controls (OR = 6.4 CI = 1.51-27.6, p = 0.012), whereas this interaction (SUD and psychosis) was not significant in the entire population over age 49. Osteoporosis screening in the Medicaid population is significantly lower for women with SUD, after adjusting for age, race, and Medicaid enrollment category. The prevalence of osteoporosis appears markedly elevated in those with major mood disorders and those over age 55 dually diagnosed with schizophrenia and SUD.

  14. The Quality of Care under a Managed-Care Program for Dual Eligibles

    ERIC Educational Resources Information Center

    Kane, Robert L.; Homyak, Patricia; Bershadsky, Boris; Lum, Terry; Flood, Shannon; Zhang, Hui

    2005-01-01

    Purpose: Our objective in this study was to compare the quality of care provided under the Minnesota Senior Health Options (MSHO), a special program designed to serve dually eligible older persons, to care provided to controls who received fee-for-service Medicare and Medicaid managed care. Design and Methods: Two control groups were used; one was…

  15. A Follow-Up Study of Dually Diagnosed (Chemically Dependent) Adolescents.

    ERIC Educational Resources Information Center

    Griffin-Shelley, Eric; And Others

    1991-01-01

    Conducted follow-up study of 13 dually diagnosed adolescents (original sample N=100), 22% of whom were estimated to be chemical free. Sample reported improvement on 21 of 29 program goals. Improvement was reported in chemical dependency, coping skills, relations with parents, dealing with reality, avoiding addictive people, problem solving,…

  16. Emotional Disturbance and Substance Abuse/Addiction Special Education Programming for the Dually-Diagnosed Adolescent.

    ERIC Educational Resources Information Center

    Bogdaniak, Roman C.

    Dually diagnosed adolescents suffering from both severe emotional disturbance and substance abuse/addiction constitute a special population which poses a challenge to health professionals in special education as well as clinical settings. The prevalence of substance use, abuse, and addiction has been shown to be significantly above the national…

  17. The Impact of Enhanced Incentives on Vocational Rehabilitation Outcomes for Dually Diagnosed Veterans

    ERIC Educational Resources Information Center

    Drebing, Charles E.; Van Ormer, E. Alice; Krebs, Christopher; Rosenheck, Robert; Rounsaville, Bruce; Herz, Lawrence; Penk, Walter

    2005-01-01

    This study evaluated the efficacy of adding contingency management techniques to vocational rehabilitation (VR) to improve treatment outcome as measured by entry into competitive employment. Nineteen dually diagnosed veterans who entered VR in the Veterans' Administration's compensated work therapy (CWT) program were randomly assigned to CWT (n =…

  18. Identification of dually acylated proteins from complementary DNA resources by cell-free and cellular metabolic labeling.

    PubMed

    Moriya, Koko; Kimoto, Mayumi; Matsuzaki, Kanako; Kiwado, Aya; Takamitsu, Emi; Utsumi, Toshihiko

    2016-10-15

    To establish a strategy to identify dually fatty acylated proteins from cDNA resources, seven N-myristoylated proteins with cysteine (Cys) residues within the 10 N-terminal residues were selected as potential candidates among 27 N-myristoylated proteins identified from a model human cDNA resource. Seven proteins C-terminally tagged with FLAG tag or EGFP were generated and their susceptibility to protein N-myristoylation and S-palmitoylation were evaluated by metabolic labeling with [(3)H]myristic acid or [(3)H]palmitic acid either in an insect cell-free protein synthesis system or in transfected mammalian cells. As a result, EEPD1, one of five proteins (RFTN1, EEPD1, GNAI1, PDE2A, RNF11) found to be dually acylated, was shown to be a novel dually fatty acylated protein. Metabolic labeling experiments using G2A and C7S mutants of EEPD1-EGFP revealed that the palmitoylation site of EEPD1 is Cys at position 7. Analysis of the intracellular localization of EEPD1 C-terminally tagged with FLAG tag or EGFP and its G2A and C7S mutants revealed that the dual acylation directs EEPD1 to localize to the plasma membrane. Thus, dually fatty acylated proteins can be identified from cDNA resources by cell-free and cellular metabolic labeling of N-myristoylated proteins with Cys residue(s) close to the N-myristoylated N-terminus. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of The West African Database to evaluate AIDS collaboration

    PubMed Central

    Tchounga, Boris K; Inwoley, Andre; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Bado, Guillaume; Minga, Albert; Hawerlander, Denise; Kane, Coumba; Eholie, Serge P; Dabis, François; Ekouevi, Didier K

    2014-01-01

    Introduction West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. Method A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d’Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d’Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot – Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). Results A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm3 and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). Conclusions Patients with HIV-2 mono-infection are correctly discriminated by the national algorithms used in West African countries. HIV-1&2 dually reactive patients should be systematically investigated, with a standardized algorithm using more accurate tests, before initiating ART as at least 4 out of 10 of them could initiate an effective first-line ART for HIV-1 and optimize their second-line treatment options. PMID:25128907

  20. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  1. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  2. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  3. 42 CFR 488.431 - Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Civil money penalties imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF-only facilities. 488... imposed by CMS and independent informal dispute resolution: for SNFS, dually-participating SNF/NFs, and NF...

  4. Functional Analysis and Treatment of the Bizarre Speech of Dually Diagnosed Adults

    ERIC Educational Resources Information Center

    Lancaster, Blake M.; LeBlanc, Linda A.; Carr, James E.; Brenske, Shasta; Peet, Mary M.; Culver, Steven J.

    2004-01-01

    Nine behavior-analytic studies, each reporting data for a single participant, have shown that bizarre speech can be maintained by social reinforcement. In the current study, we controlled for a possible referral bias in this literature by including nonreferred participants with dual diagnoses. Functional analyses identified attention functions for…

  5. A Language Programme to Increase the Verbal Production of a Child Dually Diagnosed with Down Syndrome and Autism

    ERIC Educational Resources Information Center

    Kroeger, K. A.; Nelson, W. M., III

    2006-01-01

    Background: The incidence of children dually diagnosed with Down syndrome and autism is estimated to be as high as 11%. There is a paucity of research investigating linguistic treatment interventions for such children. This single-subject experiment examined a programme designed to increase the language production and verbal behaviour of a…

  6. 42 CFR 488.452 - State and Federal disagreements involving findings not in agreement in non-State operated NFs and...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually participating facilities when there is no... State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually...

  7. 42 CFR 488.452 - State and Federal disagreements involving findings not in agreement in non-State operated NFs and...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually participating facilities when there is no... State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually...

  8. 42 CFR 488.452 - State and Federal disagreements involving findings not in agreement in non-State operated NFs and...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually participating facilities when there is no... State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually...

  9. 42 CFR 488.452 - State and Federal disagreements involving findings not in agreement in non-State operated NFs and...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually participating facilities when there is no... State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually...

  10. 42 CFR 488.452 - State and Federal disagreements involving findings not in agreement in non-State operated NFs and...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually participating facilities when there is no... State and Federal disagreements involving findings not in agreement in non-State operated NFs and dually...

  11. Medicare and Medicaid Home Health and Medicaid Waiver Services for Dually Eligible Older Adults: Risk Factors for Use and Correlates of Expenditures

    ERIC Educational Resources Information Center

    Fortinsky, Richard H.; Fenster, Juliane R.; Judge, James O.

    2004-01-01

    Purpose: The purpose of this work was to, among frail dually eligible older adults, determine risk factors for the likelihood of using Medicare home health and Medicaid home health services and to, among service users, determine correlates of Medicare home health, Medicaid home health, and Medicaid waiver service expenditures. Design and Methods:…

  12. Correlates of improvement in substance abuse among dually diagnosed veterans with post-traumatic stress disorder in specialized intensive VA treatment.

    PubMed

    Coker, Kendell L; Stefanovics, Elina; Rosenheck, Robert

    2016-01-01

    Substantial rates of substance use comorbidity have been observed among veterans with Post-Traumatic Stress Disorder (PTSD), highlighting the need to identify patient and program characteristics associated with improved outcomes for substance abuse. Data were drawn from 12,270 dually diagnosed veterans who sought treatment from specialized intensive Veterans Health Administration PTSD programs between 1993 and 2011. The magnitude of the improvement in Addiction Severity Index (ASI) alcohol and drug use composite scores from baseline was moderate, with effect sizes (ES) of -.269 and -.287, respectively. Multivariate analyses revealed that treatment in longer-term programs, being prescribed psychiatric medication, and planned participation in reunions were all associated with slightly improved outcomes. Reductions in substance use measures were associated with robust improvements in PTSD symptoms and violent behavior. These findings suggest not only synergistic treatment effects linking improvement in PTSD symptoms with substance use disorders among dually diagnosed veterans with PTSD, but also to reductions in violent behavior. Furthermore, the findings indicate that proper discharge planning in addition to intensity and duration of treatment for dually diagnosed veterans with severe PTSD may result in better outcomes. Further dissemination of evidence-based substance abuse treatment may benefit this population. (c) 2016 APA, all rights reserved).

  13. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study

    PubMed Central

    Ekouevi, Didier K.; Balestre, Eric; Coffie, Patrick A.; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P.; Gottlieb, Geoffrey S.; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d’Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N’Gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Østergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'Diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S.; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; PAC-CI; Abidjan

    2013-01-01

    Background HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). Methods We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d’Ivoire, Mali, and Senegal, in the West Africa region. Results Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3–51.7) and 42.4 years, IQR (37.0–47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm3, IQR (83–247) among HIV-2 infected patients and 146 cells/mm3, IQR (55–249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm3 after 24 months on ART for HIV-2 patients and 169 cells/mm3 for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7–4.3). Conclusions This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population. PMID:23824279

  14. Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

    PubMed

    Ekouevi, Didier K; Balestre, Eric; Coffie, Patrick A; Minta, Daouda; Messou, Eugene; Sawadogo, Adrien; Minga, Albert; Sow, Papa Salif; Bissagnene, Emmanuel; Eholie, Serge P; Gottlieb, Geoffrey S; Dabis, François; Zannou, Djimon Marcel; Ahouada, Carin; Akakpo, Jocelyn; Ahomadegbé, Christelle; Bashi, Jules; Gougounon-Houéto, Alice; Azon-Kouanou, Angèle; Houngbé, Fabien; Koumakpaï, Sikiratou; Alihonou, Florence; d'Almeida, Marcelline; Hodonou, Irvine; Hounhoui, Ghislaine; Sagbo, Gracien; Tossa-Bagnan, Leïla; Adjide, Herman; Drabo, Joseph; Bognounou, René; Dienderé, Arnaud; Traore, Eliezer; Zoungrana, Lassane; Zerbo, Béatrice; Sawadogo, Adrien Bruno; Zoungrana, Jacques; Héma, Arsène; Soré, Ibrahim; Bado, Guillaume; Tapsoba, Achille; Yé, Diarra; Kouéta, Fla; Ouedraogo, Sylvie; Ouédraogo, Rasmata; Hiembo, William; Gansonré, Mady; Messou, Eugène; Gnokoro, Joachim Charles; Koné, Mamadou; Kouakou, Guillaume Martial; Bosse, Clarisse Amani; Brou, Kouakou; Assi, Achi Isidore; Chenal, Henri; Hawerlander, Denise; Soppi, Franck; Minga, Albert; Abo, Yao; Bomisso, Germain; Eholié, Serge Paul; Amego, Mensah Deborah Noelly; Andavi, Viviane; Diallo, Zelica; Ello, Frédéric; Tanon, Aristophane Koffi; Koule, Serge Olivier; Anzan, Koffi Charles; Guehi, Calixte; Aka, Edmond Addi; Issouf, Koffi Ladji; Kouakou, Jean-Claude; N'gbeche, Marie-Sylvie; Touré, Pety; Avit-Edi, Divine; Kouakou, Kouadio; Moh, Magloire; Yao, Valérie Andoblé; Folquet, Madeleine Amorissani; Dainguy, Marie-Evelyne; Kouakou, Cyrille; Méa-Assande, Véronique Tanoh; Oka-Berete, Gladys; Zobo, Nathalie; Acquah, Patrick; Kokora, Marie-Berthe; Eboua, Tanoh François; Timité-Konan, Marguerite; Ahoussou, Lucrèce Diecket; Assouan, Julie Kebé; Sami, Mabéa Flora; Kouadio, Clémence; Renner, Lorna; Goka, Bamenla; Welbeck, Jennifer; Sackey, Adziri; Owiafe, Seth Ntiri; Wejse, Christian; Silva, Zacarias José Da; Paulo, Joao; Rodrigues, Amabelia; da Silva, David; Medina, Candida; Oliviera-Souto, Ines; Ostergaard, Lars; Laursen, Alex; Sodemann, Morten; Aaby, Peter; Fomsgaard, Anders; Erikstrup, Christian; Eugen-Olsen, Jesper; Maïga, Moussa Y; Diakité, Fatoumata Fofana; Kalle, Abdoulaye; Katile, Drissa; Traore, Hamar Alassane; Minta, Daouda; Cissé, Tidiani; Dembelé, Mamadou; Doumbia, Mohammed; Fomba, Mahamadou; Kaya, Assétou Soukho; Traoré, Abdoulaye M; Traoré, Hamady; Toure, Amadou Abathina; Dicko, Fatoumata; Sylla, Mariam; Berthé, Alima; Traoré, Hadizatou Coulibaly; Koïta, Anta; Koné, Niaboula; N'diaye, Clémentine; Coulibaly, Safiatou Touré; Traoré, Mamadou; Traoré, Naïchata; Charurat, Man; Ajayi, Samuel; Dapiap, Stephen; Otu; Igbinoba, Festus; Benson, Okwara; Adebamowo, Clément; James, Jesse; Obaseki; Osakede, Philip; Olasode, John; Sow, Papa Salif; Diop, Bernard; Manga, Noël Magloire; Tine, Judicael Malick; Signate Sy, Haby; Ba, Abou; Diagne, Aida; Dior, Hélène; Faye, Malick; Gueye, Ramatoulaye Diagne; Mbaye, Aminata Diack; Patassi, Akessiwe; Kotosso, Awèrou; Kariyare, Benjamin Goilibe; Gbadamassi, Gafarou; Komi, Agbo; Mensah-Zukong, Kankoé Edem; Pakpame, Pinuwe; Lawson-Evi, Annette Koko; Atakouma, Yawo; Takassi, Elom; Djeha, Améyo; Ephoévi-Gah, Ayoko; Djibril, Sherifa El-Hadj; Dabis, François; Bissagnene, Emmanuel; Arrivé, Elise; Coffie, Patrick; Ekouevi, Didier; Jaquet, Antoine; Leroy, Valériane; Lewden, Charlotte; Sasco, Annie; Azani, Jean-Claude; Allou, Gérard; Balestre, Eric; Bohossou, Franck; Karcher, Sophie; Gonsan, Jules Mahan; Carrou, Jérôme Le; Lenaud, Séverin; Nchot, Célestin; Malateste, Karen; Yao, Amon Roseamonde; Siloué, Bertine; Clouet, Gwenaelle; Djetouan, Hugues; Doring, Alexandra; Kouakou, Adrienne; Rabourdin, Elodie; Rivenc, Jean; Anglaret, Xavier; Ba, Boubacar; Essanin, Jean Bosco; Ciaranello, Andrea; Datté, Sébastien; Desmonde, Sophie; Diby, Jean-Serge Elvis; Gottlieb, Geoffrey S; Horo, Apollinaire Gninlgninrin; Kangah, Serge N'zoré; Malvy, Denis; Meless, David; Mounkaila-Harouna, Aida; Ndondoki, Camille; Shiboski, Caroline; Thiébaut, Rodolphe; Pac-Ci; Abidjan

    2013-01-01

    HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

  15. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among Veterans dually enrolled in VA and Medicare Part D

    PubMed Central

    Gellad, Walid F.; Zhao, Xinhua; Thorpe, Carolyn T.; Thorpe, Joshua M.; Sileanu, Florentina E.; Cashy, John P.; Mor, Maria; Hale, Jennifer A.; Radomski, Thomas; Hausmann, Leslie R. M.; Fine, Michael J.; Good, Chester B.

    2016-01-01

    Background Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among Veterans dually enrolled in VA and Medicare Part D. Methods We constructed a cohort of all Veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a non-buprenorphine opioid or benzodiazepine, focusing on Veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). Results We identified 1,790 dually enrolled Veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1,091 (61%) from Part D (61 Veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Conclusions Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their buprenorphine was filled. These findings highlight a previously undocumented safety risk for Veterans dually enrolled in VA and Medicare. PMID:27925868

  16. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among veterans dually enrolled in Department of Veterans Affairs and Medicare Part D.

    PubMed

    Gellad, Walid F; Zhao, Xinhua; Thorpe, Carolyn T; Thorpe, Joshua M; Sileanu, Florentina E; Cashy, John P; Mor, Maria; Hale, Jennifer A; Radomski, Thomas; Hausmann, Leslie R M; Fine, Michael J; Good, Chester B

    2017-01-01

    Buprenorphine is a key tool in the management of opioid use disorder, but there are growing concerns about abuse, diversion, and safety. These concerns are amplified for the Department of Veterans Affairs (VA), whose patients may receive care concurrently from multiple prescribers within and outside VA. To illustrate the extent of this challenge, we examined overlapping prescriptions for buprenorphine, opioids, and benzodiazepines among veterans dually enrolled in VA and Medicare Part D. We constructed a cohort of all veterans dually enrolled in VA and Part D who filled an opioid prescription in 2012. We identified patients who received tablet or film buprenorphine products from either source. We calculated the proportion of buprenorphine recipients with any overlapping prescription (based on days supply) for a nonbuprenorphine opioid or benzodiazepine, focusing on veterans who received overlapping prescriptions from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). There were 1790 dually enrolled veterans with buprenorphine prescriptions, including 760 (43%) from VA and 1091 (61%) from Part D (61 veterans with buprenorphine from both systems were included in each group). Among VA buprenorphine recipients, 199 (26%) received an overlapping opioid prescription and 11 (1%) received an overlapping benzodiazepine prescription from Part D. Among Part D buprenorphine recipients, 208 (19%) received an overlapping opioid prescription and 178 (16%) received an overlapping benzodiazepine prescription from VA. Among VA and Part D buprenorphine recipients with cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap. Many buprenorphine recipients receive overlapping prescriptions for opioids and benzodiazepines from a different health care system than the one in which their buprenorphine was filled. These findings highlight a previously undocumented safety risk for veterans dually enrolled in VA and Medicare.

  17. The influence of abuse victimization on attendance and involvement in mutual-help groups among dually diagnosed male veterans.

    PubMed

    Makin-Byrd, Kerry; Cronkite, Ruth C; Timko, Christine

    2011-07-01

    Although abuse victimization and dual diagnosis are associated with poor functioning across numerous domains, their impact on attendance and involvement in mutual-help groups (MHGs) is not well understood. This study examined the impact of physical or sexual abuse victimization on MHG attendance and involvement and the influence of abuse on the association between MHG involvement and outcomes of abstinence and psychiatric health. Participants were 217 dually diagnosed men assessed at intake into mental health treatment and 6 months later. Compared with nonabused patients, sexually abused patients exhibited more substance use, psychiatric, and social problems at baseline and attended and were involved with MHGs more than nonabused patients at follow-up. Moreover, MHG involvement was most predictive of abstinence for sexually abused patients, as compared with nonabused and physically abused patients. Although dually diagnosed patients with abuse histories demonstrate more severe initial problems, they are likely to utilize MHGs, which may benefit efforts to achieve abstinence. Published by Elsevier Inc.

  18. Extending the data rate of non-line-of-sight UV communication with polarization modulation

    NASA Astrophysics Data System (ADS)

    Yin, Hongwei; Jia, Honghui; Zhang, Hailiang; Wang, Xiaofeng; Chang, Shengli; Yang, Juncai

    2012-10-01

    With low radiation background of solar-blind UV and strong scattering of UV photons by atmospheric particles, UV communication can be made use of to set up a non-line-of-sight (NLOS) free-space optical communication link. Polarization modulation, besides the traditional intensity modulation, is presented to enhance the data rate of the UV communication system. The configuration and the working process of the dually modulated UV communication system with intensity modulation and polarization, the theoretical evaluation of polarization modulation, and a numerical of the scattering matrix are presented, with the conclusion that polarization modulation is achievable. By adding the polarizing devices and changing the coding procedures, the existing singly-modulated UV communication systems with intensity modulation are easily modified to be dually-modulated ones with polarization modulation and intensity modulation. Ideally speaking, the data rate of the dually-modulated UV communication system is the product of the data rate of the singly modulated system and the number of polarization modulation.

  19. Ziprasidone versus clozapine in the treatment of dually diagnosed (DD) patients with schizophrenia and cannabis use disorders: a randomized study.

    PubMed

    Schnell, Thomas; Koethe, Dagmar; Krasnianski, Anna; Gairing, Stefanie; Schnell, Knut; Daumann, Jörg; Gouzoulis-Mayfrank, Euphrosyne

    2014-01-01

    Clozapine is considered to be particularly effective in the treatment of dually diagnosed (DD) patients with psychosis and substance use disorders. However, its use is restricted by potentially severe side effects. The aim of the present pilot study was to compare the effects of clozapine with the newer second generation antipsychotic (SGA) ziprasidone in DD-patients. Thirty (n = 30) patients with schizophrenia and cannabis abuse/dependence were randomized to ziprasidone or clozapine and were followed up for up to 12 months. Cannabis use was reduced in both groups during follow-up. Clozapine treatment was associated with less positive symptoms of schizophrenia, more side effects and poorer compliance with treatment. Results from this small pilot RCT suggest beneficial effects of both clozapine and ziprasidone in the treatment of cannabis use disorders in psychotic patients. Larger-scale RCTs are needed in order to assess advantages and disadvantages of the different SGAs in dually diagnosed populations. © American Academy of Addiction Psychiatry.

  20. Serving the dually diagnosed homeless: program development and interventions.

    PubMed

    Blankertz, L E; Cnaan, R A

    1993-01-01

    In this paper the authors present the specific characteristics of the dually diagnosed (severely mentally ill and substance abusers) population and describe a hybridized program and interventions which have been empirically shown to be effective in working with these multiply impaired individuals. The article is based upon a three-year federally funded demonstration project. The following interventions were found to be effective: engagement, care and nurturing, structure, limit setting and the development of responsibility, positive reinforcement, and self esteem. The authors describe these interventions and highlight their impact in both staff management and working with funding sources.

  1. Dually diagnosed: a retrospective study of the process of diagnosing autism spectrum disorders in children who are deaf and hard of hearing.

    PubMed

    Szarkowski, Amy; Flynn, Suzanne; Clark, Terrell

    2014-11-01

    Utilizing a retrospective chart review of 30 children who have been dually diagnosed with hearing loss and autism spectrum disorders (ASDs), this study explores the process of arriving at the diagnosis of ASD in this population. Factors of interest include the age of ASD diagnosis in children who are deaf and hard of hearing, the types of professionals involved in making the diagnosis, and the measures used for assessment. Complications in the diagnostic process are highlighted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  2. Impact of surface grafting density of PEG macromolecules on dually fluorescent silica nanoparticles used for the in vivo imaging of subcutaneous tumors.

    PubMed

    Adumeau, Laurent; Genevois, Coralie; Roudier, Lydia; Schatz, Christophe; Couillaud, Franck; Mornet, Stéphane

    2017-06-01

    In the context of systematically administered nanomedicines, the physicochemistry of NP surfaces must be controlled as a prerequisite to improve blood circulation time, and passive and active targeting. In particular, there is a real need to develop NP stealth and labelling for both in vivo and microscopic fluorescence imaging in a mice model. We have synthesized NIR/red dually fluorescent silica nanoparticles of 19nm covalently covered by a PEG layer of different grafting density in the brush conformational regime by using a reductive amination reaction. These particles were characterized by TEM, DRIFT, DLS, TGA, ζ potential measurements, UV-vis and fluorescence spectroscopy. Prostate tumors were generated in mice by subcutaneous injection of RM1-CMV-Fluc cells. Tumor growth was monitored by BLI after a D-luciferin injection. Four samples of PEGylated fluorescent NPs were individually intravenously injected into 6 mice (N=6, total 24 mice). Nanoparticle distribution was investigated using in vivo fluorescence reflectance imaging (FRI) over 48h and microscopy imaging was employed to localize the NPs within tumors in vitro. Fluorescent NP accumulation, due to the enhanced permeability and retention (EPR) effect, increases gradually as a function of increased PEG surface grafting density with a huge difference observed for the highest density grafting. For the highest grafting density, a blood circulation time of up to 24h was observed with a strong reduction in uptake by the liver. In vivo experimental results suggest that the biodistribution of NPs is very sensitive to slight variations in surface grafting density when the NPs present a high curvature radius. This study underlines the need to compensate a high curvature radius with a PEG-saturated NP surface to improve blood circulation and accumulation within tumors through the EPR effect. Dually fluorescent NPs PEGylated to saturation display physical properties useful for assessing the susceptibility of tumors to the EPR effect. Control of the physicochemical features of nanoparticle surfaces to improve blood circulation times and monitoring of the EPR effect. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Engineering cholesterol-based fibers for antibody immobilization and cell capture

    NASA Astrophysics Data System (ADS)

    Cohn, Celine

    In 2015, the United States is expected to have nearly 600,000 deaths attributed to cancer. Of these 600,000 deaths, 90% will be a direct result of cancer metastasis, the spread of cancer throughout the body. During cancer metastasis, circulating tumor cells (CTCs) are shed from primary tumors and migrate through bodily fluids, establishing secondary cancer sites. As cancer metastasis is incredibly lethal, there is a growing emphasis on developing "liquid biopsies" that can screen peripheral blood, search for and identify CTCs. One popular method for capturing CTCs is the use of a detection platform with antibodies specifically suited to recognize and capture cancer cells. These antibodies are immobilized onto the platform and can then bind and capture cells of interest. However, current means to immobilize antibodies often leave them with drastically reduced function. The antibodies are left poorly suited for cell capture, resulting in low cell capture efficiencies. This body of work investigates the use of lipid-based fibers to immobilize proteins in a way that retains protein function, ultimately leading to increased cell capture efficiencies. The resulting increased efficiencies are thought to arise from the retained three-dimensional structure of the protein as well as having a complete coating of the material surface with antibodies that are capable of interacting with their antigens. It is possible to electrospin cholesterol-based fibers that are similar in design to the natural cell membrane, providing proteins a more natural setting during immobilization. Such fibers have been produced from cholesterol-based cholesteryl succinyl silane (CSS). These fibers have previously illustrated a keen aptitude for retaining protein function and increasing cell capture. Herein the work focuses on three key concepts. First, a model is developed to understand the immobilization mechanism used by electrospun CSS fibers. The antibody immobilization and cell capturing abilities of the CSS fibers were compared to that of hydrophobic polycaprolactone (PCL) fibers and hydrophilic plasma-treated PCL fibers. Electrospun CSS fibers were found to immobilize equivalent amounts of protein as hydrophobically immobilized proteins. However, these proteins captured 6 times more cells, indicative of retained protein function. The second key concept was the design and fabrication of a hybridized lipid fiber. Lipid fibers provide improved protein function but fabrication difficulties have limited their adoption. Thus, we sought to fabricate a lipid-polymer hybrid that is easily fabricated while maintaining protein function. The hybrid fiber consists of a PCL backbone with conjugated CSS. The hybrid lipid fibers showed improved protein function. In addition, higher lipid concentrations were directly correlated to higher cell capture efficiencies. The third key concept was on the development of dually functionalized lipid fibers and understanding the resulting cell capture efficiencies. Many platforms are unable to simultaneously search for heterogeneous populations of CTCs -- the ability to dually functionalize cell-capturing platforms would address this technological weakness. Studies indicated that dually functionalizing the lipid fibers did not compromise the platforms' abilities to capture the cells of interest. Such dually functionalized fibers allow for a single cell-capture platform to successfully detect heterogeneous populations of CTCs. The body of work encompassed herein describes the use of lipid fibers for antibody immobilization and cell capture. Data from various projects indicate that the use of cholesterol-based fibers produced from electrospun CSS are well suited for protein immobilization. The CSS fibers are able to immobilize equivalent amounts of protein as compared to other immobilization techniques. However, the benefit of these fibers is illustrated by the strong cell-capturing efficiencies, indicating that the immobilized proteins are able to retain their function and selectively target cells of interest. The successful immobilization of proteins and their retained function allows for the development of increasingly sensitive cancer diagnostic tools that are able to screen for CTCs early on in the cancer disease cycle.

  4. Medicare and Medicaid: Conflicting Incentives for Long-Term Care

    PubMed Central

    Grabowski, David C

    2007-01-01

    The structure of Medicare and Medicaid creates conflicting incentives regarding dually eligible beneficiaries without coordinating their care. Both Medicare and Medicaid have an interest in limiting their costs, and neither has an incentive to take responsibility for the management or quality of care. Examples of misaligned incentives are Medicare's cost-sharing rules, cost shifting within home health care and nursing homes, and cost shifting across chronic and acute care settings. Several policy initiatives—capitation, pay-for-performance, and the shift of the dually eligible population's Medicaid costs to the federal government—may address these conflicting incentives, but all have strengths and weaknesses. With the aging baby boom generation and projected federal and state budget shortfalls, this issue will be a continuing focus of policymakers in the coming decades. PMID:18070331

  5. Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

    PubMed Central

    Smith, Leann E.; Barker, Erin T.; Seltzer, Marsha Mailick; Abbeduto, Leonard; Greenberg, Jan S.

    2012-01-01

    The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n = 30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n = 106) and (b) individuals diagnosed with autism (but not fragile X syndrome; n = 135) on measures of autism symptoms, adaptive functioning, behavior problems, and psychological symptoms. Results indicated that individuals dually diagnosed with fragile X syndrome and autism displayed greater communication and social reciprocity impairments than individuals with fragile X syndrome only. Individuals in the dually diagnosed group also exhibited higher levels of repetitive and challenging behaviors than either comparison group, suggesting a unique profile of vulnerability for those diagnosed with both fragile X syndrome and autism. PMID:22264109

  6. Use of VA and Medicare Services By Dually Eligible Veterans with Psychiatric Problems

    PubMed Central

    Carey, Kathleen; Montez-Rath, Maria E; Rosen, Amy K; Christiansen, Cindy L; Loveland, Susan; Ettner, Susan L

    2008-01-01

    Objective To examine how service accessibility measured by geographic distance affects service sector choices for veterans who are dually eligible for veterans affairs (VA) and Medicare services and who are diagnosed with mental health and/or substance abuse (MH/SA) disorders. Data Sources Primary VA data sources were the Patient Treatment (acute care), Extended Care (long-term care), and Outpatient Clinic files. VA cost data were obtained from (1) inpatient and outpatient cost files developed by the VA Health Economics and Resource Center and (2) outpatient VA Decision Support System files. Medicare data sources were the denominator, Medicare Provider Analysis Review (MEDPAR), Provider-of-Service, Outpatient Standard Analytic and Physician/Supplier Standard Analytic files. Additional sources included the Area Resource File and Census Bureau data. Study Design We identified dually eligible veterans who had either an inpatient or outpatient MH/SA diagnosis in the VA system during fiscal year (FY)'99. We then estimated one- and two-part regression models to explain the effects of geographic distance on both VA and Medicare total and MH/SA costs. Principal Findings Results provide evidence for substitution between the VA and Medicare, demonstrating that poorer geographic access to VA inpatient and outpatient clinics decreased VA expenditures but increased Medicare expenditures, while poorer access to Medicare-certified general and psychiatric hospitals decreased Medicare expenditures but increased VA expenditures. Conclusions As geographic distance to VA medical facility increases, Medicare plays an increasingly important role in providing mental health services to veterans. PMID:18355256

  7. Does Mind Wandering Reflect Executive Function or Executive Failure? Comment on Smallwood and Schooler (2006) and Watkins (2008)

    PubMed Central

    McVay, Jennifer C.; Kane, Michael J.

    2010-01-01

    In this Comment, we contrast different conceptions of mind wandering that were presented in two recent theoretical reviews: Smallwood and Schooler (2006) and Watkins (2008). We also introduce a new perspective on the role of executive control in mind wandering by integrating empirical evidence presented in Smallwood and Schooler (2006) with two theoretical frameworks: Watkins’s (2008) elaborated control theory and Klinger’s (1971; 2009) current concerns theory. In contrast to the Smallwood-Schooler claim that mind-wandering recruits executive resources, we argue that mind wandering represents a failure of executive control and that it is dually determined by the presence of automatically generated thoughts in response to environmental and mental cues and the ability of the executive-control system to deal with this interference. We present empirical support for this view from experimental, neuroimaging, and individual-differences research. PMID:20192557

  8. Transplacental transfer of vancomycin and telavancin

    PubMed Central

    NANOVSKAYA, Tatiana; PATRIKEEVA, Svetlana; ZHAN, Ying; FOKINA, Valentina; HANKINS, Gary DV; AHMED, Mahmoud S.

    2014-01-01

    Objectives Determine the bidirectional transfer and distribution of vancomycin and telavancin across the dually perfused term human placental lobule. Study design The technique of dually perfused placental lobule was used in its recirculating mode to determine the Maternal-to-Fetal (n=20) and Fetal-to-Maternal (n=18) transfer of each antibiotic which were co-perfused with their radioactive isotopes. The concentrations of drugs were determined by liquid scintillation spectrometry. Results In the Maternal-to-Fetal direction, the transfer of vancomycin (9.6 ± 4%) and telavancin (6.5 ± 2%) were low; however, telavancin retention by the perfused lobule was greater than that of vancomycin (p < 0.01). The normalized transplacental transfer of telavancin across the placental lobule in the F→M direction was higher than in the M→F direction (p < 0.01), suggesting the involvement of placental efflux transporters. Conclusions The ex vivo perfusion experiments revealed low transfer of vancomycin and telavancin to the fetal circuit. PMID:22867688

  9. The effect of dual accreditation on family medicine residency programs.

    PubMed

    Mims, Lisa D; Bressler, Lindsey C; Wannamaker, Louise R; Carek, Peter J

    2015-04-01

    In 1985, the American Osteopathic Association (AOA) Board of Trustees agreed to allow residency programs to become dually accredited by the AOA and Accreditation Council for Graduate Medical Education (ACGME). Despite the increase in such programs, there has been minimal research comparing these programs to exclusively ACGME-accredited residencies. This study examines the association between dual accreditation and suggested markers of quality. Standard characteristics such as regional location, program structure (community or university based), postgraduate year one (PGY-1) positions offered, and salary (PGY-1) were obtained for each residency program. In addition, the faculty to resident ratio in the family medicine clinic and the number of half days residents spent in the clinic each week were recorded. Initial Match rates and pass rates of new graduates on the ABFM examination from 2009 to 2013 were also obtained. Variables were analyzed using chi-square and Student's t test. Logistic regression models were then created to predict a program's 5-year aggregate initial Match rate and Board pass rate in the top tertile as compared to the lowest tertile. Dual accreditation was obtained by 117 (27.0%) of programs. Initial analyses revealed associations between dually accredited programs and mean year of initial ACGME program accreditation, regional location, program structure, tracks, and alternative medicine curriculum. When evaluated in logistic regression, dual accreditation status was not associated with Match rates or ABFM pass rates. By examining suggested markers of program quality for dually accredited programs in comparison to ACGME-only accredited programs, this study successfully established both differences and similarities among the two types.

  10. Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

    PubMed

    Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

    2018-05-23

    Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

  11. INTEREST IN AND OBSTACLES TO PURSUING WORK AMONG UNEMPLOYED DUALLY DIAGNOSED INDIVIDUALS

    PubMed Central

    Laudet, Alexandre B.; Magura, Stephen; Vogel, Howard S.; Knight, Edward L.

    2007-01-01

    Employment status is commonly used as a sign of stability in recovery and an outcome variable for substance abuse treatment and research. However, there has been little attention in the literature on the topic of work for the dually diagnosed (i.e., persons diagnosed with both substance use and mental health disorders). Data collected in 1999 are presented on expressed interest in and perceived barriers to pursuing work and on the utilization of vocational rehabilitation (voc-rehab) services among unemployed members of a dual recovery self-help fellowship (N = 130). While members generally expressed high interest in working, they also cited multiple obstacles to attaining and maintaining employment. A path model was specified and tested. Significant contributors to interest in working were substance use status and physical health rating. Consistent with our hypotheses, mental health symptoms and greater perceived obstacles (e.g., stigma, fear of failure, and insufficient skills) were significant contributors to perceived difficulty in pursuing work, whereas substance use, physical health, and recency of employment were not. Finally, those who perceived less difficulty in pursuing work were more likely to utilize voc-rehab services, and men were more likely than women to use these facilities; interest in work was not significantly associated with utilizing voc-rehab services. The roles of mental health disorders and substance use in relation to pursuit of employment are discussed, as well as that of perceived obstacles such as stigma. The paper addresses the setting of realistic vocational goals and possible strategies to mitigate barriers to increased employment of dually diagnosed individuals. PMID:11863273

  12. Interest in and obstacles to pursuing work among unemployed dually diagnosed individuals.

    PubMed

    Laudet, Alexandre B; Magura, Stephen; Vogel, Howard S; Knight, Edward L

    2002-01-01

    Employment status is commonly used as a sign of stability in recovery and an outcome variable for substance abuse treatment and research. However, there has been little attention in the literature on the topic of work for the dually diagnosed (i.e., persons diagnosed with both substance use and mental health disorders). Data collected in 1999 are presented on expressed interest in and perceived barriers to pursuing work and on the utilization of vocational rehabilitation (voc-rehab) services among unemployed members of a dual recovery self-help fellowship (N= 130). While members generally expressed high interest in working, they also cited multiple obstacles to attaining and maintaining employment. A path model was specified and tested. Significant contributors to interest in working were substance use status and physical health rating. Consistent with our hypotheses, mental health symptoms and greater perceived obstacles (e.g., stigma, fear of failure, and insufficient skills) were significant contributors to perceived difficulty in pursuing work, whereas substance use, physical health, and recency of employment were not. Finally, those who perceived less difficulty in pursuing work were more likely to utilize voc-rehab services, and men were more likely than women to use these facilities; interest in work was not significantly associated with utilizing voc-rehab services. The roles of mental health disorders and substance use in relation to pursuit of employment are discussed, as well as that of perceived obstacles such as stigma. The paper addresses the setting of realistic vocational goals and possible strategies to mitigate barriers to increased employment of dually diagnosed individuals.

  13. Correlation between muscle structure and filter characteristics of the muscle-joint system in three orthopteran insect species

    PubMed

    BÄSsler; BÜSchges; Meditz; BÄSsler

    1996-01-01

    In orthopteran insects, neural networks for joint control exhibit different characteristics due to behavioural specializations. We investigated whether these differences are generated purely by the neuronal networks, or whether characteristics of the muscles or joint architecture (muscle­joint system) are also involved in these behavioural specializations. We compared the properties of the muscle system moving the femur­tibia joint of the middle and hindleg of three species, Carausius morosus, Cuniculina impigra and Locusta migratoria. Four aspects were analysed for the tibial extensor muscle: (i) the frequency-dependence of motoneuronal activity in response to sinusoidal stimulation of the femoral chordotonal organ (fCO), (ii) the muscle structure, (iii) the innervation pattern of the muscle and (iv) the histochemical properties of the muscle fibres. These aspects were compared with the filter characteristics of the open-loop femur­tibia control system and of the muscle­joint system involved. Whereas in both phasmid species (Carausius morosus and Cuniculina impigra) the motoneuronal activity steadily increases with sinusoidal stimulation of the fCO in the frequency range 0.01­5 Hz, in Locusta migratoria there is a decrease in motoneuronal activity between 0.01 and 0.3 Hz. The muscle structure is basically similar in all three species, as the number of singly innervated muscle fibres (supplied by the fast extensor tibiae motor neurone, FETi) decreases from proximal to distal. The number of triply innervated fibres supplied by the FETi, the slow extensor tibiae (SETi) and the common inhibitor 1 (CI1) is maximal in the middle of the muscle, and the number of dually innervated fibres (supplied by SETi, CI1) increases from proximal to distal. Differences between the locust and the two phasmid species exist in the distal portion of the muscle. The phasmid extensor tibiae muscle contains a morphologically distinct bundle of muscle fibres, not present in the locust, which is mostly dually innervated and which is larger in Cuniculina impigra. Similar results were obtained for the histochemical characterisation of the muscle fibres as revealed from their staining for myofibrillar ATPase activity. The number of histochemically identified fast fibres decreased from proximal to distal, while the number of slow fibres increased. In Carausius morosus and Locusta migratoria, the percentage of slow fibres increased by up to 60­70 % at the distal end, while this increase was to almost 100 % in Cuniculina impigra. Apparently, the larger this distal region and the higher the percentage of slow, dually innervated fibres in it, the lower is the upper corner frequency (the stimulus frequency at which the joint control system produces a movement with 70 % of its maximal response amplitude) of the muscle­joint system. In summary, it appears that the upper corner frequency of the open-loop system in Locusta migratoria (<0.05 Hz) results at least in part from properties of the neuronal joint control network, but in Carausius morosus (0.5­1.0 Hz) and Cuniculina impigra (0.1­0.2 Hz) it results from the upper corner frequency of the muscle­joint system.

  14. Operationalizing the Impossible: The Responsibility to Protect Movement

    DTIC Science & Technology

    2015-05-23

    colonies. However one question remained; what acts constitute the authority to wage a just punitive war? According to Grotius, natural law dually...of this formerly communist nation immediately resulted in the creation of the nations of Slovenia and Croatia who

  15. From "DSM" to "DM-ID"

    ERIC Educational Resources Information Center

    Fletcher, Robert J.; Barnhill, Jarrett; McCarthy, Jane; Strydom, André

    2016-01-01

    Recognizing the diagnostic challenges that clinicians face when attempting to arrive at an accurate psychiatric diagnosis for individuals with intellectual and developmental disabilities (IDD) co-occurring with mental illness (MI), in 2007 the National Association for the Dually Diagnosed (NADD), in association with the American Psychiatric…

  16. Differential effects of sex in a West African cohort of HIV-1, HIV-2 and HIV-1/2 dually infected patients: men are worse off.

    PubMed

    Jespersen, Sanne; Hønge, Bo Langhoff; Esbjörnsson, Joakim; Medina, Candida; da Silva Té, David; Correira, Faustino Gomes; Laursen, Alex Lund; Østergaard, Lars; Andersen, Andreas; Aaby, Peter; Erikstrup, Christian; Wejse, Christian

    2016-02-01

    Several studies have reported conflicting effects of sex on HIV-1 infection. We describe differences in baseline characteristics and assess the impact of sex on HIV progression among patients at a clinic with many HIV-2 and HIV-1/2 dually infected patients. This study utilised a retrospective cohort of treatment-naïve adults at the largest HIV clinic in Guinea-Bissau from 6 June 2005 to 1 December 2013. Baseline characteristics were assessed and the patients followed until death, transfer, loss to follow-up, or 1 June 2014. We estimated the time from the first clinic visit until initiation of ART, death or loss to follow-up using Cox proportional hazard models. A total of 5694 patients were included in the study, 3702 women (65%) and 1992 men (35%). Women were more likely than men to be infected with HIV-2 (19% vs. 15%, P < 0.01) or dually infected with HIV-1/2 (11% vs. 9%, P = 0.02). For all HIV types, women were younger (median 35 vs. 40 years), less likely to have schooling (55% vs. 77%) or to be married (46% vs. 67%), and had higher baseline CD4 cell counts (median 214 vs. 178 cells/μl). Men had a higher age-adjusted mortality rate (hazard rate ratio (HRR) 1.29, 95% confidence interval (CI) 1.09-1.52) and were more often lost to follow-up (HRR 1.27, 95% CI 1.17-1.39). Significant differences exist between HIV-infected men and women regardless of HIV type. Men seek treatment at a later stage and, despite better socio-economic status, have higher mortality and loss to follow-up than women. © 2015 John Wiley & Sons Ltd.

  17. Who Treats Patients with Diabetes and Compensated Cirrhosis

    PubMed Central

    Barritt IV, A. Sidney; Weinberger, Morris; Paul, John E.; Fried, Bruce; Trogdon, Justin G.

    2016-01-01

    Background Increasingly, patients with multiple chronic conditions are being managed in patient-centered medical homes (PCMH) that coordinate primary and specialty care. However, little is known about the types of providers treating complex patients with diabetes and compensated cirrhosis. Objective We examined the mix of physician specialties who see patients dually-diagnosed with diabetes and compensated cirrhosis. Design Retrospective cross-sectional study using 2000–2013 MarketScan® Commercial Claims and Encounters and Medicare Supplemental Databases. Patients We identified 22,516 adults (≥ 18 years) dually-diagnosed with diabetes and compensated cirrhosis. Patients with decompensated cirrhosis, HIV/AIDS, or liver transplantation prior to dual diagnosis were excluded. Main Measures Physician mix categories: patients were assigned to one of four physician mix categories: primary care physicians (PCP) with no gastroenterologists (GI) or endocrinologists (ENDO); GI/ENDO with no PCP; PCP and GI/ENDO; and neither PCP nor GI/ENDO. Health care utilization: annual physician visits and health care expenditures were assessed by four physician mix categories. Key Results Throughout the 14 years of study, 92% of patients visited PCPs (54% with GI/ENDO and 39% with no GI/ENDO). The percentage who visited PCPs without GI/ENDO decreased 22% (from 63% to 49%), while patients who also visited GI/ENDO increased 71% (from 25% to 42%). Conclusions This is the first large nationally representative study to document the types of physicians seen by patients dually-diagnosed with diabetes and cirrhosis. A large proportion of these complex patients only visited PCPs, but there was a trend toward greater specialty care. The trend toward co-management by both PCPs and GI/ENDOs suggests that PCMH initiatives will be important for these complex patients. Documenting patterns of primary and specialty care is the first step toward improved care coordination. PMID:27783702

  18. On Probability Domains IV

    NASA Astrophysics Data System (ADS)

    Frič, Roman; Papčo, Martin

    2017-12-01

    Stressing a categorical approach, we continue our study of fuzzified domains of probability, in which classical random events are replaced by measurable fuzzy random events. In operational probability theory (S. Bugajski) classical random variables are replaced by statistical maps (generalized distribution maps induced by random variables) and in fuzzy probability theory (S. Gudder) the central role is played by observables (maps between probability domains). We show that to each of the two generalized probability theories there corresponds a suitable category and the two resulting categories are dually equivalent. Statistical maps and observables become morphisms. A statistical map can send a degenerated (pure) state to a non-degenerated one —a quantum phenomenon and, dually, an observable can map a crisp random event to a genuine fuzzy random event —a fuzzy phenomenon. The dual equivalence means that the operational probability theory and the fuzzy probability theory coincide and the resulting generalized probability theory has two dual aspects: quantum and fuzzy. We close with some notes on products and coproducts in the dual categories.

  19. Psychological and behavioral implications of connectedness to communities with opposing values and beliefs

    PubMed Central

    Mashek, Debra; Stuewig, Jeffrey; Furukawa, Emi; Tangney, June

    2011-01-01

    Without a doubt, people can feel simultaneously connected to multiple communities (e.g., Deaux, 1993; Roccas & Brewer, 2002). But, to what degree can people feel simultaneously connected to communities with opposing beliefs and values? And, more importantly, what are the psychological implications of being dually connected to these communities? Capitalizing on a sample of individuals positioned to potentially feel connected to two very distinct communities, we examined jail inmates’ (N = 256) sense of connectedness to the criminal community and to the community at large. Results indicated that (a) connectedness to the community at large is orthogonal to connectedness to the criminal community, supporting the supposition that it is possible to be dually connected to opposing communities; and (b) connectedness to the community at large moderated the relationship between criminal connectedness and indicators of psychological distress, suggesting that connectedness to the criminal community is especially problematic when it occurs in tandem with connectedness to the community at large. These findings are consistent with predictions from the self-expansion model. PMID:21532983

  20. Teachers for Inclusive, Diverse Urban Settings

    ERIC Educational Resources Information Center

    Reese, Leslie; Richards-Tutor, Cara; Hansuvadha, Nat; Pavri, Shireen; Xu, Shelley

    2018-01-01

    In this article, the authors discuss the creation of an Urban Dual Credential Program (UDCP) at a large, comprehensive state university in California, a program meant to prepare dually-certified teachers in general education (California Multiple Subject Credential) and special education (California Education Specialist Credential in mild/moderate…

  1. The ABC Approach to Teaching Letter Writing (Instructional Note).

    ERIC Educational Resources Information Center

    Chin, Susan Ho

    1994-01-01

    Describes how one English teacher used a method of teaching letter writing to foster students' communication and thinking skills. Outlines a method which involves students dually as both consumer complainant and company representative responding to the complaints. Claims that such a process enhances student learning. (HB)

  2. The Amusement Park Technique in the Treatment of Dually Diagnosed, Psychiatric Inpatients.

    ERIC Educational Resources Information Center

    Hrenko, Kathy D.; Willis, Robert

    1996-01-01

    Identifies common imagery created by psychiatric inpatients through the amusement park technique; demonstrates how the artwork serves to identify the psychodynamic concerns of the mentally ill substance abuser. Connections are examined relating patients choice of image, psychiatric diagnosis, and drug of choice. This technique offers promise for…

  3. Teacher Counternarratives: Transgressing and "Restorying" Disability in Education

    ERIC Educational Resources Information Center

    Broderick, Alicia A.; Hawkins, Greta; Henze, Stefanie; Mirasol-Spath, Corinthia; Pollack-Berkovits, Rachel; Clune, Holly Prozzo; Skovera, Elizabeth; Steel, Christina

    2012-01-01

    This inquiry aims to explore the disconnect between the disability studies in education (DSE) perspectives on inclusive schooling held by a group of dually certified inclusive educators and the everyday, lived experiences of these same teachers who find themselves teaching students with labelled disabilities within the confines of the special…

  4. Multiple Addictions among Dually Diagnosed Adolescents.

    ERIC Educational Resources Information Center

    Griffin-Shelley, Eric; And Others

    1992-01-01

    Studied 76 adolescents admitted to dual diagnosis unit of private psychiatric hospital, 72 of whom identified themselves as chemically dependent. Results support idea that chemically dependent adolescents may have compulsive/addictive behaviors in more areas than drug and alcohol abuse. More than 50% of subjects saw themselves as having symptoms…

  5. 78 FR 21046 - Amendment to Rule Filing Requirements for Dually-Registered Clearing Agencies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-09

    ... relating to foreign currency, or, in general, any instrument commonly known as a `security'; or any..., potentially, energy and foreign exchange swaps.\\35\\ CME raised concerns that, by omitting swaps and certain... substantial potential delays'' when implementing rule changes that deal with products over which the...

  6. Validation of the Inventory of Depressive Symptomatology (IDS) in Cocaine Dependent Inmates.

    ERIC Educational Resources Information Center

    Suris, Alina; Kashner, T. Michael; Gillaspy, James A., Jr.; Biggs, Melanie; Rush, A. John

    2001-01-01

    While the reliability and validity of Inventory of Depressive Symptomatology (IDS) scores have been established with outpatient adults being treated in community psychiatric clinics, it has not been used in special or dually diagnosed populations. Establishes internal consistency, concurrent validity, and construct validity for both the clinical…

  7. 76 FR 41056 - Amendment to Rule Filing Requirements for Dually-Registered Clearing Agencies

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-13

    ... we receive and intend to respond as necessary or appropriate. I. Introduction A. Background on... successor entity of ICE Trust (``ICE Trust'') will become Registered Clearing Agencies solely for the... rule amendments that, among other things, present novel or complex issues that require additional time...

  8. Clozapine in Three Individuals with Mild Mental Retardation and Treatment-Refractory Psychiatric Disorders.

    ERIC Educational Resources Information Center

    Pary, Robert J.

    1994-01-01

    Although clozapine is a drug specifically approved for people with schizophrenia, it has not been systematically evaluated with dually diagnosed individuals having mental retardation. This article reviews the drug's use in the general population, discusses potential difficulties in prescribing it for individuals with mental retardation, and…

  9. Effect of PTSD diagnosis and contingency management procedures on cocaine use in dually cocaine and opioid-dependent individuals maintained on LAAM: A retrospective analysis

    PubMed Central

    Mancino, M.; McGaugh, J.; Feldman, Z.; Poling, J.; Oliveto, A.

    2012-01-01

    This randomized clinical trial retrospectively examined the effect of Post Traumatic Stress Disorder (PTSD) and contingency management (CM) on cocaine use in opioid and cocaine dependent individuals maintained on high or low-dose LAAM randomly assigned to CM or a yoked-control condition. Cocaine-positive urines decreased more rapidly over time in those without PTSD versus those with PTSD in the non-contingency condition. In participants with PTSD, CM resulted in fewer cocaine positive urines compared to the non-contingent condition. This suggests that CM may help improve the potentially worse outcomes in opioid-and cocaine dependent individuals with PTSD compared to those without PTSD. PMID:20163389

  10. Outcome Data for MICA Clients after Participation in an Institutional Therapeutic Community

    ERIC Educational Resources Information Center

    Van Stelle, Kit R.; Moberg, D. Paul

    2004-01-01

    The current study assessed the effectiveness of a prison-based substance abuse treatment therapeutic community (TC) providing treatment to male inmates dually diagnosed with both substance abuse and mental health disorders. The findings show a short-term impact of the program on arrest after release, with program participants significantly less…

  11. Constructing the Academic Category of Teacher Educator in Universities' Recruitment Processes in Aotearoa, New Zealand

    ERIC Educational Resources Information Center

    Gunn, Alexandra C.; Berg, David; Hill, Mary F.; Haigh, Mavis

    2015-01-01

    An examination of recruitment materials and interviews with personnel involved in the employment of teacher educators to positions in university-based New Zealand initial teacher education (ITE) courses reveals three constructions of teacher educator as academic worker: the professional expert, the dually qualified, and the traditional academic.…

  12. State Approaches to Funding Dual Enrollment. ECS Education Policy Analysis

    ERIC Educational Resources Information Center

    Zinth, Jennifer

    2015-01-01

    Research shows that students who dually enroll are more likely to finish high school and succeed in postsecondary education than their peers with a similar grade point average (GPA), test scores, demographics, etc. Yet in many states, students and parents are largely--if not entirely--responsible for covering dual enrollment course costs, placing…

  13. The National Association of School Psychologists and the Division of School Psychology--APA: Now and Beyond.

    ERIC Educational Resources Information Center

    Fagan, Thomas K.; Gorin, Susan; Tharinger, Deborah

    2000-01-01

    Since 1969, the National Association of School Psychologists (NASP) and the Division of School Psychology within the American Psychological Association have dually influenced many psychological and educational issues in school psychology. Following a summary of the organizational topography of school psychology, the status and future directions…

  14. Assessing Student Scientific Expression Using Media: The Media-Enhanced Science Presentation Rubric (MESPR)

    ERIC Educational Resources Information Center

    Mott, Michael S.; Chessin, Debby A.; Sumrall, William J.; Rutherford, Angela S.; Moore, Virginia J.

    2011-01-01

    The current study evaluated an assessment designed to dually promote student understanding of the experimental method and student ability to include digital and visual qualities in their presentations of scientific experiment results. The rubric, the Media-Enhanced Science Presentation Rubric (MESPR) focuses teacher-student dialogue along the…

  15. Vanishing Hopes and Dreams: Which Comes First? Addictions or Problems.

    ERIC Educational Resources Information Center

    Tomblin, Mary; Haring, Kathryn A.

    This paper discusses the increasing number of teenagers who are dually diagnosed with both learning disabilities and substance abuse and are not receiving appropriate treatment to deal with their special needs. It reports the outcomes of a phenomenological analysis of six young adults who discussed their problems with drug and alcohol abuse,…

  16. The impact of enhanced incentives on vocational rehabilitation outcomes for dually diagnosed veterans.

    PubMed

    Drebing, Charles E; Van Ormer, E Alice; Krebs, Christopher; Rosenheck, Robert; Rounsaville, Bruce; Herz, Lawrence; Penk, Walter

    2005-01-01

    This study evaluated the efficacy of adding contingency management techniques to vocational rehabilitation (VR) to improve treatment outcome as measured by entry into competitive employment. Nineteen dually diagnosed veterans who entered VR in the Veterans' Administration's compensated work therapy (CWT) program were randomly assigned to CWT (n = 8) or to CWT with enhanced incentives (n = 11). Over the first 16 weeks of rehabilitation, those in the incentives condition could earn up to dollar 1,006 in cash for meeting two sets of clinical goals: (a) remaining abstinent from drugs and alcohol and (b) taking steps to obtain and maintain a competitive job. Results indicate that relative to participants in the CWT-only group, those in the incentives condition engaged in more job-search activities, were more likely to remain abstinent from drugs and alcohol, were more likely to obtain competitive employment, and earned an average of 68% more in wages. These results suggest that rehabilitation outcomes may be enhanced by restructuring traditional work-for-pay contingencies to include direct financial rewards for meeting clinical goals.

  17. High-throughput alternative splicing detection using dually constrained correspondence analysis (DCCA).

    PubMed

    Baty, Florent; Klingbiel, Dirk; Zappa, Francesco; Brutsche, Martin

    2015-12-01

    Alternative splicing is an important component of tumorigenesis. Recent advent of exon array technology enables the detection of alternative splicing at a genome-wide scale. The analysis of high-throughput alternative splicing is not yet standard and methodological developments are still needed. We propose a novel statistical approach-Dually Constrained Correspondence Analysis-for the detection of splicing changes in exon array data. Using this methodology, we investigated the genome-wide alteration of alternative splicing in patients with non-small cell lung cancer treated by bevacizumab/erlotinib. Splicing candidates reveal a series of genes related to carcinogenesis (SFTPB), cell adhesion (STAB2, PCDH15, HABP2), tumor aggressiveness (ARNTL2), apoptosis, proliferation and differentiation (PDE4D, FLT3, IL1R2), cell invasion (ETV1), as well as tumor growth (OLFM4, FGF14), tumor necrosis (AFF3) or tumor suppression (TUSC3, CSMD1, RHOBTB2, SERPINB5), with indication of known alternative splicing in a majority of genes. DCCA facilitates the identification of putative biologically relevant alternative splicing events in high-throughput exon array data. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Emotion regulation and coping motives serially affect cannabis cessation problems among dually diagnosed outpatients.

    PubMed

    Buckner, Julia D; Walukevich, Katherine A; Zvolensky, Michael J; Gallagher, Matthew W

    2017-11-01

    Little empirical work has evaluated why anxious cannabis users are especially vulnerable to poorer cannabis cessation outcomes. Presumably, these individuals rely on cannabis because they have difficulties with emotion regulation and they therefore use cannabis to manage their negative emotions. The current study examined the direct and indirect effects of anxiety severity on a range of cannabis cessation variables among 79 (63.3% non-Hispanic White; 43.0% female) adults with anxiety disorders seeking outpatient treatment for cannabis use disorder. The independent and serial indirect effects of difficulties with emotion regulation and coping motives were examined in relation to the anxiety-cannabis variables. Anxiety severity was directly and robustly related to greater cannabis withdrawal symptom severity, less self-efficacy to refrain from using cannabis in emotionally distressing situations, and more reasons for quitting. Anxiety was indirectly related to cannabis outcomes via the serial effects of emotion regulation and coping motives. These findings document the important role of emotion regulation and coping motives in the relations of anxiety with cannabis cessation variables among dually diagnosed outpatients. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. The Impact of Enhanced Incentives on Vocational Rehabilitation Outcomes for Dually Diagnosed Veterans

    PubMed Central

    2005-01-01

    This study evaluated the efficacy of adding contingency management techniques to vocational rehabilitation (VR) to improve treatment outcome as measured by entry into competitive employment. Nineteen dually diagnosed veterans who entered VR in the Veterans' Administration's compensated work therapy (CWT) program were randomly assigned to CWT (n  =  8) or to CWT with enhanced incentives (n  =  11). Over the first 16 weeks of rehabilitation, those in the incentives condition could earn up to $1,006 in cash for meeting two sets of clinical goals: (a) remaining abstinent from drugs and alcohol and (b) taking steps to obtain and maintain a competitive job. Results indicate that relative to participants in the CWT-only group, those in the incentives condition engaged in more job-search activities, were more likely to remain abstinent from drugs and alcohol, were more likely to obtain competitive employment, and earned an average of 68% more in wages. These results suggest that rehabilitation outcomes may be enhanced by restructuring traditional work-for-pay contingencies to include direct financial rewards for meeting clinical goals. PMID:16270845

  20. Synergy, Salary, and Satisfaction: Benefits of Training in Critical Care Medicine and Infectious Diseases Gleaned From a National Pilot Survey of Dually Trained Physicians.

    PubMed

    Kadri, Sameer S; Rhee, Chanu; Magda, Gabriela; Strich, Jeffrey R; Cai, Rongman; Sun, Junfeng; Decker, Brooke K; O'Grady, Naomi P

    2016-10-01

    An increasing number of physicians are seeking dual training in critical care medicine (CCM) and infectious diseases (ID). Understanding experiences and perceptions of CCM-ID physicians could inform career choices and programmatic innovation. All physicians trained and/or certified in both CCM and ID to date in the United States were sent a Web-based questionnaire in 2015. Responses enabled a cross-sectional analysis of physician demographics and training and practice characteristics and satisfaction. Of 202 CCM-ID physicians, 196 were alive and reachable. The response rate was 79%. Forty-six percent trained and 34% practice in the northeastern United States. Only 40% received dual training at the same institution. Eighty-three percent identified as either an intensivist with ID expertise (44%) or as equally an intensivist and ID physician (38%). Median salary was $265 000 (interquartile range [IQR], $215 000-$350 000). Practice settings were split between academic (45%) and community settings (42%). Two-thirds are clinicians but 62% conduct some research and 26% practice outpatient ID. Top reasons to dually specialize included clinical synergy (70%), procedural activity (50%), and less interest in pulmonology (49%). Although 38% cited less proficiency with bronchoscopy as a disadvantage, 87% seldom need pulmonary consultation in the intensive care unit. Median career satisfaction was 4 (IQR, 4-5) out of 5, and 76% would dually train again. CCM-ID graduates prefer the acute care setting, predominantly CCM or a combination of CCM and ID. They find combination training and practice to be synergistic and satisfying, but most have had to seek CCM and ID training independently at separate institutions. Given these findings, avenues for combined training in CCM-ID should be considered. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Effectiveness of case management for homeless persons: a systematic review.

    PubMed

    de Vet, Renée; van Luijtelaar, Maurice J A; Brilleslijper-Kater, Sonja N; Vanderplasschen, Wouter; Beijersbergen, Mariëlle D; Wolf, Judith R L M

    2013-10-01

    We reviewed the literature on standard case management (SCM), intensive case management (ICM), assertive community treatment (ACT), and critical time intervention (CTI) for homeless adults. We searched databases for peer-reviewed English articles published from 1985 to 2011 and found 21 randomized controlled trials or quasi-experimental studies comparing case management to other services. We found little evidence for the effectiveness of ICM. SCM improved housing stability, reduced substance use, and removed employment barriers for substance users. ACT improved housing stability and was cost-effective for mentally ill and dually diagnosed persons. CTI showed promise for housing, psychopathology, and substance use and was cost-effective for mentally ill persons. More research is needed on how case management can most effectively support rapid-rehousing approaches to homelessness.

  2. Effectiveness of Case Management for Homeless Persons: A Systematic Review

    PubMed Central

    de Vet, Renée; van Luijtelaar, Maurice J. A.; Brilleslijper-Kater, Sonja N.; Vanderplasschen, Wouter; Beijersbergen, Mariëlle D.

    2013-01-01

    We reviewed the literature on standard case management (SCM), intensive case management (ICM), assertive community treatment (ACT), and critical time intervention (CTI) for homeless adults. We searched databases for peer-reviewed English articles published from 1985 to 2011 and found 21 randomized controlled trials or quasi-experimental studies comparing case management to other services. We found little evidence for the effectiveness of ICM. SCM improved housing stability, reduced substance use, and removed employment barriers for substance users. ACT improved housing stability and was cost-effective for mentally ill and dually diagnosed persons. CTI showed promise for housing, psychopathology, and substance use and was cost-effective for mentally ill persons. More research is needed on how case management can most effectively support rapid-rehousing approaches to homelessness. PMID:23947309

  3. Predicting Sobriety from the Employment Status of Dually Diagnosed Clients Who Are Opiate Dependent

    ERIC Educational Resources Information Center

    Scorzelli, James F.

    2007-01-01

    The purpose of this study was to determine the relationship between Minnesota Multiphasic Personality Inventory-2 (E. S. Neukrug & R. C. Fawcett, 2006) profiles and employment status for clients who are opiate dependent. A discriminant function analysis indicated that employment was a predictor in maintaining sobriety after 6 months. (Contains…

  4. A Systematic Review of the Autism Research with Children Who Are Deaf or Hard of Hearing

    ERIC Educational Resources Information Center

    Hansen, Sarah; Scott, Jessica

    2018-01-01

    The current study is a systematic review on the available evidence on language development, assessment, challenging behavior, and instruction for children dually diagnosed with autism spectrum disorder and deafness. Results indicate a strong need for additional research in these areas, especially in the areas of evidence-based practices.

  5. Co-Occurring Severe Mental Illnesses and Substance Abuse Disorders as Predictors of State Prison Inmate Assaults

    ERIC Educational Resources Information Center

    Wood, Steven R.; Buttaro, Anthony, Jr.

    2013-01-01

    Using hierarchical logistic regression with a nationally representative sample of state prisoners ("n" = 12,504), we found inmates with dual severe psychiatric and substance abuse disorders to be at higher risk of being assaulted and to assault others in prison than nonmentally ill inmates. Dually disordered inmates may be "importing"…

  6. Families of Individuals with Intellectual Disability and Comorbid Mental Health Problems

    ERIC Educational Resources Information Center

    Esbensen, Anna J.

    2011-01-01

    This review focuses on the families of individuals dually diagnosed with intellectual disability (ID) and comorbid mental health problems. The review examines the impact of caring for individuals with ID and comorbid mental health problems on family well-being, the impact of the family on these individuals, and intervention and support needs of…

  7. The Effects of Two Language-Focused Preschool Curricula on Children's Achievement through First Grade

    ERIC Educational Resources Information Center

    Kaiser, Ann; Dickinson, David; Roberts, Megan; Darrow, Catherine; Freiberg, Jill; Hofer, Kerry

    2011-01-01

    Effective early language and literacy instruction to remediate language deficits and to prevent problems in learning to read is an important area for intervention research. Children with early language deficits who are growing up in poverty are dually at risk. Early deficits in language development predict both continued delays in language…

  8. Characteristics of the Population of Deaf and Hard of Hearing Students with Emotional Disturbance in Illinois

    ERIC Educational Resources Information Center

    Sinnott, C. L.; Jones, T. W.

    2005-01-01

    The study summarizes a database for the years 1994-1999 on deaf and hard of hearing students in Illinois with a diagnosis of emotional disturbance (N = 115). Data are reported on the group's demographic, domestic, etiologic, communication-related, and intervention-related characteristics. These dually diagnosed students differed from Illinois's…

  9. An Integrated, Multidimensional Treatment Model for Individuals Living with HIV, Mental Illness, and Substance Abuse

    ERIC Educational Resources Information Center

    Bouis, Stephanie; Reif, Susan; Whetten, Kathryn; Scovil, Janet; Murray, Andrea; Swartz, Marvin

    2007-01-01

    The challenge of providing effective treatment services for the growing population of HIV-positive individuals who are also dually diagnosed with substance use and mental disorders has only recently been recognized as an important public health concern affecting both HIV treatment and prevention. This article describes a treatment model that was…

  10. Origin of the Species: An Epistemological Tale of Classroom Management Theory and the Evolution of a Teacher Preparation Course Syllabus

    ERIC Educational Resources Information Center

    Hertel, Nichole L.

    2012-01-01

    This dissertation dually explores the topics of classroom management theory as it occurs in teacher preparation programs in American colleges of education and of curriculum syllabus design of undergraduate education classes teaching such. It begins with the classroom management and teaching pedagogical knowledges gained through my experience as a…

  11. Exploring Perspectives of Individuals with Intellectual Disabilities and Histories of Challenging Behaviors about Family Relationships: An Emergent Topic in a Grounded Theory Focus Group Study

    ERIC Educational Resources Information Center

    Brown, Julie F.; Hamilton-Mason, Johnnie; Maramaldi, Peter; Barnhill, L. Jarrett

    2016-01-01

    The perspectives of individuals with intellectual disabilities (ID) about family relationships are underrepresented in the literature. The topic of family relationships emerged in a grounded theory exploratory focus group study that involved thirty dually diagnosed participants with moderate or mild intellectual disabilities and histories of…

  12. Longitudinal Study on the Effects of Child Abuse and Children's Exposure to Domestic Violence, Parent-Child Attachments, and Antisocial Behavior in Adolescence

    ERIC Educational Resources Information Center

    Sousa, Cindy; Herrenkohl, Todd I.; Moylan, Carrie A.; Tajima, Emiko A.; Klika, J. Bart; Herrenkohl, Roy C.; Russo, M. Jean

    2011-01-01

    This study examined the unique and combined effects of child abuse and children's exposure to domestic violence on later attachment to parents and antisocial behavior during adolescence. Analyses also investigated whether the interaction of exposure and low attachment predicted youth outcomes. Findings suggest that, although youth dually exposed…

  13. [Pilot study on the prevalence of dual pathology in community mental health and substance misuse services in Madrid].

    PubMed

    Szerman Bolotner, Néstor; Arias Horcajadas, Francisco; Vega Astudillo, Pablo; Babín Vich, Francisco; Mesías Perez, Beatriz; Basurte Villamor, Ignacio; Morant, Consuelo; Ochoa Mangado, Enriqueta; Poyo Calvo, Félix

    2011-01-01

    To evaluate retrospectively the comorbidity of mental and addictive disorders in community mental health and substance misuse services in Madrid. The medical records of 400 patients from mental health and substance misuse services in Madrid were evaluated. Records were examined for the last 20 patients from each service unit. Dual pathology was constituted when a current diagnosis of mental and addictive disorders, excluding nicotine addiction, appeared on the patient's records. Prevalence of dual pathology was 34%. There were differences in the prevalence figures for the two kinds of service: 36.78% in substance misuse services, and 28.78% in mental health services. There was an association of dual diagnosis with alcohol or cocaine dependence, but not with opioid dependence. The mental disorders more prevalent in dually diagnosed than in non-dually diagnosed patients were mood disorders, personality disorders, and schizophrenia. There is a high prevalence of dual pathology in those seeking treatment, being higher in substance misuse services than in mental health services, and higher in patients with alcohol or cocaine dependence. These findings could be of help in the planning of care resource policies for these patients.

  14. Qualitative analysis of high-risk drug and alcohol use situations among severely mentally ill substance abusers.

    PubMed

    Bradizza, Clara M; Stasiewicz, Paul R

    2003-01-01

    Situational factors have been found to influence relapse to alcohol and drug use in general samples of substance abusers. However, little research exists examining the influence of interpersonal and intrapersonal determinants in samples of individuals dually diagnosed with a severe mental illness (SMI) and a substance use disorder (SUD). This study assessed high-risk alcohol and drug use situations in dually diagnosed individuals using focus group methodology. Qualitative data analysis yielded 10 themes that encompassed 33 high-risk situations: Psychological symptoms, positive and negative affect, reminders of substance use, being around people who use drugs and alcohol, interpersonal conflict, offers of drugs or alcohol, experiencing loss, receiving money, loss of appetite, and being abstinent. These results suggest that individuals with an SMI and SUD experience a number of unique high-risk situations that differ from those reported by non-SMI substance abusers. This study provides the basis for future quantitative studies assessing the prevalence of these situations in representative samples of SMI alcohol and drug abusers. This information allows for the development of relapse assessment instruments and treatment strategies appropriate for this population. Copyright 2002 Elsevier Science Ltd.

  15. Smart Fluid System Dually Responsive to Light and Electric Fields: An Electrophotorheological Fluid.

    PubMed

    Yoon, Chang-Min; Jang, Yoonsun; Noh, Jungchul; Kim, Jungwon; Jang, Jyongsik

    2017-10-24

    Electrophotorheological (EPR) fluids, whose rheological activity is dually responsive to light and electric fields (E fields), is formulated by mixing photosensitive spiropyran-decorated silica (SP-sSiO 2 ) nanoparticles with zwitterionic lecithin and mineral oil. A reversible photorheological (PR) activity of the EPR fluid is developed via the binding and releasing mechanism of lecithin and merocyanine (MC, a photoisomerized form of SP) under ultraviolet (UV) and visible (VIS) light applications. Moreover, the EPR fluid exhibits an 8-fold higher electrorheological (ER) performance compared to the SP-sSiO 2 nanoparticle-based ER fluid (without lecithin) under an E field, which is attributed to the enhanced dielectric properties facilitated by the binding of the lecithin and SP molecules. Upon dual application of UV light and an E field, the EPR fluid exhibits high EPR performance (ca. 115.3 Pa) that far exceeds its separate PR (ca. 0.8 Pa) and ER (ca. 57.5 Pa) activities, because of the synergistic contributions of the PR and ER effects through rigid and fully connected fibril-like structures. Consequently, this study offers a strategy on formulation of dual-stimuli responsive smart fluid systems.

  16. Rapid ILs-polishing Processes Toward Flexible Nanostructured Paper with Dually High Transparency and Haze.

    PubMed

    Ou, Yanghao; Chen, Jinbo; Lu, Pengbo; Cheng, Fan; Lin, Meiyan; Su, Lingfeng; Li, Jun; Liu, Detao

    2017-07-31

    Biodegradable highly nanostructured paper has received great interest in past years due to its excellent optical properties which facilitate its wide applications in green flexible electronics and devices. However, energy and/or time-consuming procedure during the process of fabricating most nanostructured transparent paper are presently the main obstacle to their scalable production. In this work, we demonstrated a novel nanostructured paper with dually high transparency (∼91%) and high haze (∼89%) that was directly fabricated from original paper with rapid ILs-polishing processes. The whole fabricating time only requires 10 min. Compared to the previously reported nanopaper made of the isolated cellulose nanofibers by pure mechanical and/or chemical approaches, this work presented herein is devoted to use green ILs to polish directly the micrometer-sized fibrous paper into the nanostructured paper. This new method brings a rapid fabrication of transparent nanostructured paper while also retaining dual intriguing properties both in optical transmittance and haze. This work is capable of fabricating next-generation flexible and highly transparent and haze paper by a high-speed roll-to-roll manufacturing process with a much lower cost.

  17. Dual Diagnosis Motivational Interviewing: a modification of Motivational Interviewing for substance-abusing patients with psychotic disorders

    PubMed Central

    Martino, Steve; Carroll, Kathleen; Kostas, Demetrios; Perkins, Jennifer; Rounsaville, Bruce

    2013-01-01

    Motivational Interviewing (MI) is a brief treatment approach for helping patients develop intrinsic motivation to change addictive behaviors. While initially developed to target primary substance using populations, professionals are increasingly recognizing the promise this approach has for addressing the motivational dilemmas faced by patients who have co-occurring psychiatric and psychoactive substance use disorders. Unfortunately, this recognition has not lead to a clear explication of how MI might be adopted for specific diagnostic populations of dually diagnosed patients. In this article we describe how we have applied the principles and practices of MI to patients who have psychotic disorders and co-occurring drug or alcohol use problems. Specifically, we provide two supplemental guidelines to augment basic MI principles (adopting an integrated dual diagnosis approach, accommodating cognitive impairments and disordered thinking). We present recommended modifications to primary MI skill sets (simplifying open-ended questions, refining reflective listening skills, heightening emphasis on affirmations, integrating psychiatric issues into personalized feedback and decisional balance matrices). Finally, we highlight other clinical considerations (handling psychotic exacerbation and crisis events, recommended professional qualifications) when using MI with psychotic disordered dually diagnosed patients. PMID:12495791

  18. From Bifunctional to Trifunctional (Tricomponent Nucleophile-Transition Metal-Lewis Acid) Catalysis: The Catalytic, Enantioselective α-Fluorination of Acid Chlorides

    PubMed Central

    Erb, Jeremy; Paull, Daniel H.; Dudding, Travis; Belding, Lee

    2012-01-01

    We report in full detail our studies on the catalytic, asymmetric α-fluorination of acid chlorides, a practical method that produces an array of α-fluorocarboxylic acid derivatives in which improved yield and virtually complete enantioselectivity are controlled through electrophilic fluorination of a ketene enolate intermediate. We discovered, for the first time, that a third catalyst, a Lewis acidic lithium salt, could be introduced into a dually-activated system to amplify yields of aliphatic products, primarily through activation of the fluorinating agent. Through our mechanistic studies (based on kinetic data, isotopic labeling, spectroscopic measurements, and theoretical calculations) we were able to utilize our understanding of this “trifunctional” reaction to optimize the conditions and obtain new products in good yield and excellent enantioselectivity. PMID:21513338

  19. The Mental Health Recovery Movement and Family Therapy, Part I: Consumer-Led Reform of Services to Persons Diagnosed with Severe Mental Illness

    ERIC Educational Resources Information Center

    Gehart, Diane R.

    2012-01-01

    In 2004, the U.S. Department of Health and Human Services issued a consensus statement on mental health recovery based on the New Freedom Commission's recommendation that public mental health organizations adopt a "recovery" approach to severe and persistent mental illness, including services to those dually diagnosed with mental health…

  20. If You Want to Know, Consider Asking: How Likely Is It that Patients Will Hurt Themselves in the Future?

    ERIC Educational Resources Information Center

    Peterson, Jillian; Skeem, Jennifer; Manchak, Sarah

    2011-01-01

    Although self-harming behavior is a common and costly problem for psychiatric inpatients released from the hospital, standardized tools that assess patients' risk for self-harm are rarely used in clinical settings. In this study of dually diagnosed psychiatric inpatients (N = 147), we assessed the utility of patients' self-perceptions of risk in…

  1. Motivation and Dual Enrollment: An Analysis of the Motivation of High School Students to Participate in Dual Enrollment in Association of Christian Schools International Schools

    ERIC Educational Resources Information Center

    Salerno, Mitchell Acri

    2011-01-01

    A phenomenological study utilizing the Consensual Qualitative Research method was conducted to understand the motivation of high school students dually enrolled in high school and college, commonly referred to as dual enrollment, in relation to the Self-Determination Theory and to connect this motivation to research on personal calling. This…

  2. Prolonged exposure therapy for the treatment of patients diagnosed with psychogenic non-epileptic seizures (PNES) and post-traumatic stress disorder (PTSD).

    PubMed

    Myers, Lorna; Vaidya-Mathur, Urmi; Lancman, Marcelo

    2017-01-01

    Although there is general consensus that psychogenic non-epileptic seizures (PNES) are treated with psychotherapy, the effectiveness of most psychotherapeutic modalities remains understudied. In this treatment series of 16 patients dually diagnosed with PNES and post-traumatic stress disorder (PTSD), we evaluated the effect of prolonged exposure therapy (PE) on reduction of PNES. Secondary measures included Beck Depression Inventory (BDI-II) and Post-Traumatic Disorder Diagnostic Scale (PDS). Subjects diagnosed with video EEG-confirmed PNES and PTSD confirmed through neuropsychological testing and clinical interview were treated with traditional PE psychotherapy with certain modifications for the PNES. Treatment was conducted over the course of 12-15 weekly sessions. Seizure frequency was noted in each session by examining the patients' seizure logs, and mood and PTSD symptomatology was assessed at baseline and on the final session. Eighteen subjects enrolled, and 16 (88.8%) completed the course of treatment. Thirteen of the 16 (81.25%) therapy completers reported no seizures by their final PE session, and the other three reported a decline in seizure frequency (Z=-3.233, p=0.001). Mean scores on scales of depression (M=-13.56, SD=12.27; t (15)=-4.420, p<0,001) and PTSD symptoms (M=-17.1875, SD=13.01; t (15)=-5.281, p<0.001) showed significant improvement from baseline to final session. Longitudinal seizure follow up in 14 patients revealed that gains made on the final session were maintained at follow-up (Z=-1.069 p=0.285). Prolonged exposure therapy for patients dually diagnosed with PNES and PTSD reduced the number of PNES and improved mood and post traumatic symptomatology. Follow-up revealed that gains made in seizure control on the last day of treatment were maintained over time. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Dual acylation and lipid raft association of Src-family protein tyrosine kinases are required for SDF-1/CXCL12-mediated chemotaxis in the Jurkat human T cell lymphoma cell line.

    PubMed

    Zaman, Sabiha N; Resek, Mary E; Robbins, Stephen M

    2008-10-01

    Chemokines play pivotal roles in regulating a wide variety of biological processes by modulating cell migration and recruitment. Deregulation of chemokine signaling can alter cell recruitment, contributing to the pathogenic states associated with autoimmune disease, inflammatory disorders, and sepsis. During chemotaxis, lipid rafts and their resident signaling molecules have been demonstrated to partition to different parts of the cell. Herein, we investigated the role of lipid raft resident Src-family kinases (SFK) in stromal cell-derived factor 1/CXCL12-mediated chemotaxis. We have shown that Lck-deficient J.CaM 1.6 cells are defective in CXCL12-mediated chemotaxis in contrast to their parental counterpart, Jurkat cells. Ectopic expression of the SFK hematopoietic cell kinase (Hck) in J.CaM 1.6 cells reconstituted CXCL12 responsiveness. The requirement of lipid raft association of SFK was assessed using both isoforms of Hck: the dually acylated p59(Hck) isoform that is targeted to lipid rafts and the monoacylated p61(Hck) isoform that is nonraft-associated. We have shown using several gain and loss of acylation alleles that dual acylation of Hck was required for CXCL12-mediated chemotaxis in J.CaM 1.6 cells. These results highlight the importance of the unique microenvironment provided by lipid rafts and their specific contribution in providing specificity to CXCL12 signaling.

  4. Control of cortical neuronal migration by glutamate and GABA

    PubMed Central

    Luhmann, Heiko J.; Fukuda, A.; Kilb, W.

    2015-01-01

    Neuronal migration in the cortex is controlled by the paracrine action of the classical neurotransmitters glutamate and GABA. Glutamate controls radial migration of pyramidal neurons by acting primarily on NMDA receptors and regulates tangential migration of inhibitory interneurons by activating non-NMDA and NMDA receptors. GABA, acting on ionotropic GABAA-rho and GABAA receptors, has a dichotomic action on radially migrating neurons by acting as a GO signal in lower layers and as a STOP signal in upper cortical plate (CP), respectively. Metabotropic GABAB receptors promote radial migration into the CP and tangential migration of interneurons. Besides GABA, the endogenous GABAergic agonist taurine is a relevant agonist controlling radial migration. To a smaller extent glycine receptor activation can also influence radial and tangential migration. Activation of glutamate and GABA receptors causes increases in intracellular Ca2+ transients, which promote neuronal migration by acting on the cytoskeleton. Pharmacological or genetic manipulation of glutamate or GABA receptors during early corticogenesis induce heterotopic cell clusters in upper layers and loss of cortical lamination, i.e., neuronal migration disorders which can be associated with neurological or neuropsychiatric diseases. The pivotal role of NMDA and ionotropic GABA receptors in cortical neuronal migration is of major clinical relevance, since a number of drugs acting on these receptors (e.g., anti-epileptics, anesthetics, alcohol) may disturb the normal migration pattern when present during early corticogenesis. PMID:25688185

  5. Chemical Dependency and Violence: Working with Dually Affected Families. A Cross-Training Program Manual for Counselors and Advocates.

    ERIC Educational Resources Information Center

    Wright, Janet M.

    This manual is designed as a cross-training program guide for counselors working in the fields of woman abuse and chemical dependency. (A cross-training program is a system for one (or more) agency personnel to train each other in their respective areas of expertise.) Chapter 1 discusses the rationale and goals of a cross-training program; issues…

  6. Generalized Entropies and Legendre Duality

    DTIC Science & Technology

    2012-04-22

    region because of their one-to-one functional relationship. The standard algorithm using projection of a polyhedron [29, 6] commonly works well to...coordinate system is chosen to realize the corresponding Voronoi diagrams. In this coordinate system with one extra complementary coordinate the polyhedron is...dually flat. Using this property, α-Voronoi diagrams on Rn+1+ is discussed in [31]. While both of the above methods require computation of the polyhedrons

  7. A Study in Child Care (Case Study from Volume II-A): "Children as 'Kids'." Day Care Programs Reprint Series.

    ERIC Educational Resources Information Center

    O'Farrell, Brigid

    The Georgetown Day Care Center, in Washington, D.C., is dually sponsored by a large hospital and a private non-profit organization and offers day care services to a small number of the children of parents who work at the hospital. The center also functions as a halfway house for children in a diagnostic center which identifies preschool children…

  8. Enzymatically hydrolysed, acetylated and dually modified corn starch: physico-chemical, rheological and nutritional properties and effects on cake quality.

    PubMed

    Sahnoun, Mouna; Ismail, Nouha; Kammoun, Radhouane

    2016-01-01

    Corn starch was treated by enzymatic hydrolysis with Aspergillus oryzae S2 α-amylase, acetylation with vinyl acetate, and dual modification. The dual modified starch displayed a higher substitution degree than the acetylated starch and lower reducing sugar content than the hydrolysed starch. The results revealed that the cooling viscosity and amylose content of those products decrease (P < 0.05). An increase in moisture, water, and oil absorption capacity was observed for the acetylated starch and, which was less pronounced for the enzymatically hydrolysed starch but more pronounced for the enzymatically hydrolysed acetylated product. The latter product underwent an increase in resistant starch content, which is induced by a rise in hydrolysis time to attain about 67 % after 1 h of reaction. The modified starch samples were added to cake formulations at 5 and 10 % concentrations on a wheat flour basis and compared to native starch. The results revealed that when applied at 5 % concentrations, the modified starches reduced the hardness, cohesion, adhesion and chewiness of baked cakes and enhanced their elasticity, volume, height, crust color, and appearance as compared to native starch. These effects were more pronounced for the cake incorporating the dually modified starch.

  9. Modeling Finite-Time Failure Probabilities in Risk Analysis Applications.

    PubMed

    Dimitrova, Dimitrina S; Kaishev, Vladimir K; Zhao, Shouqi

    2015-10-01

    In this article, we introduce a framework for analyzing the risk of systems failure based on estimating the failure probability. The latter is defined as the probability that a certain risk process, characterizing the operations of a system, reaches a possibly time-dependent critical risk level within a finite-time interval. Under general assumptions, we define two dually connected models for the risk process and derive explicit expressions for the failure probability and also the joint probability of the time of the occurrence of failure and the excess of the risk process over the risk level. We illustrate how these probabilistic models and results can be successfully applied in several important areas of risk analysis, among which are systems reliability, inventory management, flood control via dam management, infectious disease spread, and financial insolvency. Numerical illustrations are also presented. © 2015 Society for Risk Analysis.

  10. Macrophage migration inhibitory factor as an incriminating agent in vitiligo.

    PubMed

    Farag, Azza Gaber Antar; Hammam, Mostafa Ahmed; Habib, Mona SalahEldeen; Elnaidany, Nada Farag; Kamh, Mona Eaid

    2018-03-01

    Vitiligo is an autoimmune skin disorder in which the loss of melanocytes is mainly attributed to defective autoimmune mechanisms and, lately, there has been more emphasis on autoinflammatory mediators. Among these is the macrophage migration inhibitory factor, which is involved in many autoimmune skin diseases. However, little is known about the contribution of this factor to vitiligo vulgaris. To determine the hypothesized role of migration inhibitory factor in vitiligo via estimation of serum migration inhibitory factor levels and migration inhibitory factor mRNA concentrations in patients with vitiligo compared with healthy controls. We also aimed to assess whether there is a relationship between the values of serum migration inhibitory factor and/or migration inhibitory factor mRNA with disease duration, clinical type and severity in vitiligo patients. Evaluation of migration inhibitory factor serum level and migration inhibitory factor mRNA expression by ELISA and real-time PCR, respectively, were performed for 50 patients with different degrees of vitiligo severity and compared to 15 age- and gender-matched healthy volunteers as controls. There was a highly significant increase in serum migration inhibitory factor and migration inhibitory factor mRNA levels in vitiligo cases when compared to controls (p<0.001). There was a significant positive correlation between both serum migration inhibitory factor and migration inhibitory factor mRNA concentrations in vitiligo patients, and each of them with duration and severity of vitiligo. In addition, patients with generalized vitiligo have significantly elevated serum migration inhibitory factor and mRNA levels than control subjects. Small number of investigated subjects. Migration inhibitory factor may have an active role in the development of vitiligo, and it may also be a useful index of disease severity. Consequently, migration inhibitory factor may be a new treatment target for vitiligo patients.

  11. Spatial-temporal migration laws of Cd in Jiaozhou Bay

    NASA Astrophysics Data System (ADS)

    Yang, Dongfang; Li, Haixia; Zhang, Xiaolong; Wang, Qi; Miao, Zhenqing

    2018-02-01

    Many marine bays have been polluted by various pollutants, and understanding the migration laws is essential to scientific research and pollution control. This paper analyzed the spatial and temporal migration laws of Cd in waters in Jiaozhou Bay during 1979—1983. Results showed that there were twenty spatial-temporal migration law for the migration processes of Cd. These laws were helpful for better understanding the migration of Cd in marine bay, providing basis for scientific research and pollution control.

  12. Novel, dually radiolabeled peptides for simultaneous monitoring of enzymatic activity and protein targets

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

    Efrem Mebrahtu, Suzanne Lapi

    2012-12-13

    This application investigated a novel imaging approach to develop methods to incorporate multiple radionuclides into a single peptide at chemoselective sites for simultaneous monitoring of cell-bound protein targets as well as specific enzymatic activity, both of which are associated with enhanced tumor growth and metastasis. This imaging construct was synthesized in such a manner so that the PET radionuclide will remain associated with the tumor cells and the SPECT radionuclide was cleaved from the imaging agent. Measurement of the PET agent only will yield information about the tumor marker density while measurement of the amount of co-localization and mismatch ofmore » the two radionuclides will yield information about the enzymatic activity. This coincident measuring technique using both PET and SPECT agents allows us to draw correlations involving the interactions of enzymes (cathepsin, serine-protease urokinase (uPA) and matrix metalloproteases) and other cellular proteins which play a role in cancer growth and metastasis. This technique will allow for studies in xenograft or genetic models of cancer in the same animal at the same time, thus eliminating problems that may occur when trying to invoke comparisons across animals or timepoints. By using radionuclide imaging as opposed to other imaging modalities, this technique has the potential to be translatable and can exploit the high specific activity probes which can be generated with radiotracers. The proof of principle test of this system investigated simultaneous monitoring of matrix metalloprotease (MMP) activity in the extracellular matrix (ECM) as well as density of integrins on the cell surface, both of which can serve as tumor markers. The outcomes/deliverables of this project were as follows: 1. Peptides were synthesized dually labeled at chemospecific sites with PET and SPECT agents. 2. Stability (intrinsic and to radiolysis) and specific activity of these labeled compounds were determined. 3. The feasibility of using these agents for simultaneous monitoring of MMP-2 enzymatic activity and ²3 integrin density was demonstrated in several in vitro assays Radiotracers can be detected at concentrations up to 1000 fold lower than those labeled with non-radioactive markers (e.g. MRI contrast agents), thus using this technique has the advantage of very high sensitivity to measure these processes in vivo. Hence, the development of an efficient approach to the dual labeling of these molecular probes is embodied within this project, with the end result yielding a molecular imaging probe with the highest specific activity possible. An advantage to this dual labeling approach is the ability to measure two different biochemical processes at the same time, a benefit which is not possible in scans involving protocols utilizing two different radiolabeled agents injected sequentially. Another advantage to this technique is the ability to measure enzymatic activity in the form of substrate cleavage. This can only be achieved with a dually labeled compound as has been demonstrated in the case of FRET1. To our knowledge this is the first instance of a measurement of enzymatic substrate cleavage by a dually labeled PET/SPECT radionuclide imaging agent.« less

  13. Epithelial-mesenchymal transition transcription factors control pluripotent adult stem cell migration in vivo in planarians

    PubMed Central

    Abnave, Prasad; Aboukhatwa, Ellen; Kosaka, Nobuyoshi; Thompson, James; Hill, Mark A.

    2017-01-01

    Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infection. Inappropriate migration also underpins metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in planarians. We demonstrate the use of this system to study the molecular control of stem cell migration and show that snail-1, snail-2 and zeb-1 EMT transcription factor homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. We also observed that stem cells undergo homeostatic migration to anterior regions that lack local stem cells, in the absence of injury, maintaining tissue homeostasis. This requires the polarity determinant notum. Our work establishes planarians as a suitable model for further in-depth study of the processes controlling stem cell migration in vivo. PMID:28893948

  14. Outcomes and Costs of Community Health Worker Interventions: A Systematic Review

    DTIC Science & Technology

    2010-09-01

    E7(/(3+21(180%(5 ,QFOXGHDUHDFRGH Sep 2010 Journal article 1980 - Nov 2008 Outcomes and costs of community health worker interventions: a...the Cumulative Index to Nursing and Allied Health Literature for studies conducted in the United States and published in English from 1980 through...to Nursing and Allied Health Literature for studies conducted in the United States and published in English from 1980 through November 2008. We dually

  15. Sources of international migration statistics in Africa.

    PubMed

    1984-01-01

    The sources of international migration data for Africa may be classified into 2 main categories: administrative records and 2) censuses and survey data. Both categories are sources for the direct measurement of migration, but the 2nd category can be used for the indirect estimation of net international migration. The administrative records from which data on international migration may be derived include 1) entry/departure cards or forms completed at international borders, 2) residence/work permits issued to aliens, and 3) general population registers and registers of aliens. The statistics derived from the entry/departure cards may be described as 1) land frontier control statistics and 2) port control statistics. The former refer to data derived from movements across land borders and the latter refer to information collected at international airports and seaports. Other administrative records which are potential sources of statistics on international migration in some African countries include some limited population registers, records of the registration of aliens, and particulars of residence/work permits issued to aliens. Although frontier control data are considered the most important source of international migration statistics, in many African countries these data are too deficient to provide a satisfactory indication of the level of international migration. Thus decennial population censuses and/or sample surveys are the major sources of the available statistics on the stock and characteristics of international migration. Indirect methods can be used to supplement census data with intercensal estimates of net migration using census data on the total population. This indirect method of obtaining information on migration can be used to evaluate estimates derived from frontier control records, and it also offers the means of obtaining alternative information on international migration in African countries which have not directly investigated migration topics in their censuses or surveys.

  16. 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

  17. Epithelial-mesenchymal transition transcription factors control pluripotent adult stem cell migration in vivo in planarians.

    PubMed

    Abnave, Prasad; Aboukhatwa, Ellen; Kosaka, Nobuyoshi; Thompson, James; Hill, Mark A; Aboobaker, A Aziz

    2017-10-01

    Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infection. Inappropriate migration also underpins metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in planarians. We demonstrate the use of this system to study the molecular control of stem cell migration and show that snail-1 , snail-2 and zeb-1 EMT transcription factor homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. We also observed that stem cells undergo homeostatic migration to anterior regions that lack local stem cells, in the absence of injury, maintaining tissue homeostasis. This requires the polarity determinant notum Our work establishes planarians as a suitable model for further in-depth study of the processes controlling stem cell migration in vivo . © 2017. Published by The Company of Biologists Ltd.

  18. A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

    PubMed

    Amodeo, Valeria; A, Deli; Betts, Joanne; Bartesaghi, Stefano; Zhang, Ying; Richard-Londt, Angela; Ellis, Matthew; Roshani, Rozita; Vouri, Mikaella; Galavotti, Sara; Oberndorfer, Sarah; Leite, Ana Paula; Mackay, Alan; Lampada, Aikaterini; Stratford, Eva Wessel; Li, Ningning; Dinsdale, David; Grimwade, David; Jones, Chris; Nicotera, Pierluigi; Michod, David; Brandner, Sebastian; Salomoni, Paolo

    2017-07-11

    Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Treatment of comorbid adolescent cannabis use and major depressive disorder.

    PubMed

    Kaminer, Yifrah; Connor, Daniel F; Curry, John F

    2008-09-01

    The comorbidity of unipolar depression with substance use disorders (SUD) in adolescents is well established and accounts for 24 to 50 percent in clinical samples. Very little empirical data exist on the treatment of dually diagnosed youth. The objective of this paper is twofold: 1) We will review the literature on SUD and unipolar depression; and 2) we will provide guidelines for a combined pharmacological and psychosocial intervention based on a clinical case example.

  20. Evolving a model for integrated treatment in a residential setting for people with psychiatric and substance use disorders.

    PubMed

    Mayes, John; Handley, Samantha

    2005-01-01

    This paper discusses the implementation of a residential, integrated treatment program serving dually diagnosed people with histories of homelessness. Attention is focused on the program structure and how the program developed over time. Program modifications tended to relax program rules and embrace a motivational, stage-wise model using harm-reduction principles. Despite initial skepticism regarding these modifications, outcomes such as program retention, abstinence from substances, employment, and hospitalization improved.

  1. Thermo- and light-regulated formation and disintegration of double hydrophilic block copolymer assemblies with tunable fluorescence emissions.

    PubMed

    Wu, Yonghao; Hu, Huamin; Hu, Jinming; Liu, Tao; Zhang, Guoying; Liu, Shiyong

    2013-03-19

    We report on thermo- and light-regulated formation and disintegration of double hydrophilic block copolymer (DHBC) micelles associated with tunable fluorescence emissions by employing two types of DHBCs covalently labeled with fluorescence resonance energy transfer (FRET) donor and acceptor moieties, respectively, within the light and temperature dually responsive block. Both DHBCs are molecularly soluble at room temperature in their aqueous mixture, whereas, upon heating to above the critical micellization temperature (CMT, ~31 °C), they coassemble into mixed micelles possessing hydrophilic coronas and mixed cores containing FRET donors and acceptors. Accordingly, the closer spatial proximity between the FRET pair (NBDAE and RhBEA moieties) within micellar cores leads to substantially enhanced FRET efficiency, compared to that in the non-aggregated unimer state. Moreover, upon UV irradiation, the light-reactive moieties undergo light-cleavage reaction and transform into negatively charged carboxylate residues, leading to elevated CMT (∼46 °C). Thus, thermo-induced mixed micelles in the intermediate temperature range (31 °C < T < 46 °C) undergo light-triggered disintegration into unimers, accompanied with the decrease of FRET efficiency. Overall, the coassembly and disassembly occurring in the mixed DHBC solution can be dually regulated by temperature and UV irradiation, and most importantly, these processes can be facilely monitored via changes in FRET efficiency and distinct emission colors.

  2. Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum.

    PubMed

    Winnicki, Konrad; Żabka, Aneta; Bernasińska, Joanna; Matczak, Karolina; Maszewski, Janusz

    2015-06-01

    In plants, phosphorylated MAPKs display constitutive nuclear localization; however, not all studied plant species show co-localization of activated MAPKs to mitotic microtubules. The mitogen-activated protein kinase (MAPK) signaling pathway is involved not only in the cellular response to biotic and abiotic stress but also in the regulation of cell cycle and plant development. The role of MAPKs in the formation of a mitotic spindle has been widely studied and the MAPK signaling pathway was found to be indispensable for the unperturbed course of cell division. Here we show cellular localization of activated MAPKs (dually phosphorylated at their TXY motifs) in both interphase and mitotic root meristem cells of Lupinus luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization of activated MAPKs has been found in all species. Co-localization of these kinases to mitotic microtubules was most evident in L. esculentum, while only about 50% of mitotic cells in the root meristems of P. sativum and V. faba displayed activated MAPKs localized to microtubules during mitosis. Unexpectedly, no evident immunofluorescence signals at spindle microtubules and phragmoplast were noted in L. luteus. Considering immunocytochemical analyses and studies on the impact of FR180204 (an inhibitor of animal ERK1/2) on mitotic cells, we hypothesize that MAPKs may not play prominent role in the regulation of microtubule dynamics in all plant species.

  3. Bipolar disorder and substance use disorders. Madrid study on the prevalence of dual disorders/pathology.

    PubMed

    Arias, Francisco; Szerman, Nestor; Vega, Pablo; Mesías, Beatriz; Basurte, Ignacio; Rentero, David

    2017-06-28

    Given its prevalence and impact on public health, the comorbidity of bipolar and substance use disorders is one of the most relevant of dual diagnoses. The objective was to evaluate the characteristics of patients from community mental health and substance abuse centres in Madrid. The sample consisted of 837 outpatients from mental health and substance abuse centres. We used the Mini International Neuropsychiatric Interview (MINI) and Personality Disorder Questionnaire (PDQ4+) to evaluate axis I and II disorders. Of these patients, 174 had a lifetime bipolar disorder, 83 had bipolar disorder type I and 91 had type II. Most patients had dual pathology. Of the 208 participants from the mental health centres, 21 had bipolar disorder and 13 (61.9%) were considered dually-diagnosed patients, while 33.2% of non-bipolar patients had a dual diagnoses (p = 0.03). Of the 629 participants from the substance abuse centres, 153 patients (24.3%) had a bipolar diagnosis. Bipolar dual patients had higher rates of alcohol and cocaine dependence than non-bipolar patients. Moreover, age at onset of alcohol use was earlier in bipolar duallydiagnosed patients than in other alcoholics. Bipolar dually-diagnosed patients had higher personality and anxiety disorder comorbidities and greater suicide risk. Thus, alcohol and cocaine are the drugs most associated with bipolar disorder. Given the nature of the study, the type of relationship between these disorders cannot be determined.

  4. 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.

  5. 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

  6. Fierce Competition between Toxoplasma and Chlamydia for Host Cell Structures in Dually Infected Cells

    PubMed Central

    Romano, Julia D.; de Beaumont, Catherine; Carrasco, Jose A.; Ehrenman, Karen; Bavoil, Patrik M.

    2013-01-01

    The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma outcompetes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion, while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients. PMID:23243063

  7. Fierce competition between Toxoplasma and Chlamydia for host cell structures in dually infected cells.

    PubMed

    Romano, Julia D; de Beaumont, Catherine; Carrasco, Jose A; Ehrenman, Karen; Bavoil, Patrik M; Coppens, Isabelle

    2013-02-01

    The prokaryote Chlamydia trachomatis and the protozoan Toxoplasma gondii, two obligate intracellular pathogens of humans, have evolved a similar modus operandi to colonize their host cell and salvage nutrients from organelles. In order to gain fundamental knowledge on the pathogenicity of these microorganisms, we have established a cell culture model whereby single fibroblasts are coinfected by C. trachomatis and T. gondii. We previously reported that the two pathogens compete for the same nutrient pools in coinfected cells and that Toxoplasma holds a significant competitive advantage over Chlamydia. Here we have expanded our coinfection studies by examining the respective abilities of Chlamydia and Toxoplasma to co-opt the host cytoskeleton and recruit organelles. We demonstrate that the two pathogen-containing vacuoles migrate independently to the host perinuclear region and rearrange the host microtubular network around each vacuole. However, Toxoplasma outcompetes Chlamydia to the host microtubule-organizing center to the detriment of the bacterium, which then shifts to a stress-induced persistent state. Solely in cells preinfected with Chlamydia, the centrosomes become associated with the chlamydial inclusion, while the Toxoplasma parasitophorous vacuole displays growth defects. Both pathogens fragment the host Golgi apparatus and recruit Golgi elements to retrieve sphingolipids. This study demonstrates that the productive infection by both Chlamydia and Toxoplasma depends on the capability of each pathogen to successfully adhere to a finely tuned developmental program that aims to remodel the host cell for the pathogen's benefit. In particular, this investigation emphasizes the essentiality of host organelle interception by intravacuolar pathogens to facilitate access to nutrients.

  8. Magnetic Control of Lateral Migration of Ellipsoidal Microparticles in Microscale Flows

    NASA Astrophysics Data System (ADS)

    Zhou, Ran; Sobecki, Christopher A.; Zhang, Jie; Zhang, Yanzhi; Wang, Cheng

    2017-08-01

    Precise manipulations of nonspherical microparticles by shape have diverse applications in biology and biomedical engineering. Here, we study lateral migration of ellipsoidal paramagnetic microparticles in low-Reynolds-number flows under uniform magnetic fields. We show that magnetically induced torque alters the rotation dynamics of the particle and results in shape-dependent lateral migration. By adjusting the direction of the magnetic field, we demonstrate versatile control of the symmetric and asymmetric rotation of the particles, thereby controlling the direction of the particle's lateral migration. The particle rotations are experimentally measured, and their symmetry or asymmetry characteristics agree well with the prediction from a simple theory. The lateral migration mechanism is found to be valid for nonmagnetic particles suspended in a ferrofluid. Finally, we demonstrate shape-based sorting of microparticles by exploiting the proposed migration mechanism.

  9. Lamellipodin and the Scar/WAVE complex cooperate to promote cell migration in vivo

    PubMed Central

    Law, Ah-Lai; Vehlow, Anne; Kotini, Maria; Dodgson, Lauren; Soong, Daniel; Theveneau, Eric; Bodo, Cristian; Taylor, Eleanor; Navarro, Christel; Perera, Upamali; Michael, Magdalene; Dunn, Graham A.; Bennett, Daimark; Mayor, Roberto

    2013-01-01

    Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds active Rac, which regulates a direct interaction between Lpd and the Scar/WAVE complex via Abi. Consequently, Lpd controls lamellipodium size, cell migration speed, and persistence via Scar/WAVE in vitro. Moreover, Lpd knockout mice display defective pigmentation because fewer migrating neural crest-derived melanoblasts reach their target during development. Consistently, Lpd regulates mesenchymal neural crest cell migration cell autonomously in Xenopus laevis via the Scar/WAVE complex. Further, Lpd’s Drosophila melanogaster orthologue Pico binds Scar, and both regulate collective epithelial border cell migration. Pico also controls directed cell protrusions of border cell clusters in a Scar-dependent manner. Taken together, Lpd is an essential, evolutionary conserved regulator of the Scar/WAVE complex during cell migration in vivo. PMID:24247431

  10. Patterns of Migration and Risks Associated with Leprosy among Migrants in Maranhão, Brazil

    PubMed Central

    Murto, Christine; Chammartin, Frédérique; Schwarz, Karolin; da Costa, Lea Marcia Melo; Kaplan, Charles; Heukelbach, Jorg

    2013-01-01

    Leprosy remains a public health problem in Brazil with new case incidence exceeding World Health Organization (WHO) goals in endemic clusters throughout the country. Migration can facilitate movement of disease between endemic and non-endemic areas, and has been considered a possible factor in continued leprosy incidence in Brazil. A study was conducted to investigate migration as a risk factor for leprosy. The study had three aims: (1) examine past five year migration as a risk factor for leprosy, (2) describe and compare geographic and temporal patterns of migration among past 5-year migrants with leprosy and a control group, and (3) examine social determinants of health associated with leprosy among past 5-year migrants. The study implemented a matched case-control design and analysis comparing individuals newly diagnosed with leprosy (n = 340) and a clinically unapparent control group (n = 340) without clinical signs of leprosy, matched for age, sex and location in four endemic municipalities in the state of Maranhão, northeastern Brazil. Fishers exact test was used to conduct bivariate analyses. A multivariate logistic regression analysis was employed to control for possible confounding variables. Eighty cases (23.5%) migrated 5-years prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the corresponding case diagnosis. Past 5 year migration was found to be associated with leprosy (OR: 1.59; 95% CI 1.07–2.38; p = 0.02), and remained significantly associated with leprosy after controlling for leprosy contact in the family, household, and family/household contact. Poverty, as well as leprosy contact in the family, household and other leprosy contact, was associated with leprosy among past 5-year migrants in the bivariate analysis. Alcohol consumption was also associated with leprosy, a relevant risk factor in susceptibility to infection that should be explored in future research. Our findings provide insight into patterns of migration to localize focused control efforts in endemic areas with high population mobility. PMID:24040433

  11. Coral physiology and microbiome dynamics under combined warming and ocean acidification

    PubMed Central

    Dalcin Martins, Paula; Wilkins, Michael J.; Johnston, Michael D.; Warner, Mark E.; Cai, Wei-Jun; Melman, Todd F.; Hoadley, Kenneth D.; Pettay, D. Tye; Levas, Stephen; Schoepf, Verena

    2018-01-01

    Rising seawater temperature and ocean acidification threaten the survival of coral reefs. The relationship between coral physiology and its microbiome may reveal why some corals are more resilient to these global change conditions. Here, we conducted the first experiment to simultaneously investigate changes in the coral microbiome and coral physiology in response to the dual stress of elevated seawater temperature and ocean acidification expected by the end of this century. Two species of corals, Acropora millepora containing the thermally sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5°C and pCO2 of 364 μatm) and treatment (29.0°C and pCO2 of 750 μatm) conditions for 24 days, after which we measured the microbial community composition. These microbial findings were interpreted within the context of previously published physiological measurements from the exact same corals in this study (calcification, organic carbon flux, ratio of photosynthesis to respiration, photosystem II maximal efficiency, total lipids, soluble animal protein, soluble animal carbohydrates, soluble algal protein, soluble algal carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall, dually stressed A. millepora had reduced microbial diversity, experienced large changes in microbial community composition, and experienced dramatic physiological declines in calcification, photosystem II maximal efficiency, and algal carbohydrates. In contrast, the dually stressed coral T. reniformis experienced a stable and more diverse microbiome community with minimal physiological decline, coupled with very high total energy reserves and particulate organic carbon release rates. Thus, the microbiome changed and microbial diversity decreased in the physiologically sensitive coral with the thermally sensitive endosymbiotic algae but not in the physiologically tolerant coral with the thermally tolerant endosymbiont. Our results confirm recent findings that temperature-stress tolerant corals have a more stable microbiome, and demonstrate for the first time that this is also the case under the dual stresses of ocean warming and acidification. We propose that coral with a stable microbiome are also more physiologically resilient and thus more likely to persist in the future, and shape the coral species diversity of future reef ecosystems. PMID:29338021

  12. Coral physiology and microbiome dynamics under combined warming and ocean acidification.

    PubMed

    Grottoli, Andréa G; Dalcin Martins, Paula; Wilkins, Michael J; Johnston, Michael D; Warner, Mark E; Cai, Wei-Jun; Melman, Todd F; Hoadley, Kenneth D; Pettay, D Tye; Levas, Stephen; Schoepf, Verena

    2018-01-01

    Rising seawater temperature and ocean acidification threaten the survival of coral reefs. The relationship between coral physiology and its microbiome may reveal why some corals are more resilient to these global change conditions. Here, we conducted the first experiment to simultaneously investigate changes in the coral microbiome and coral physiology in response to the dual stress of elevated seawater temperature and ocean acidification expected by the end of this century. Two species of corals, Acropora millepora containing the thermally sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5°C and pCO2 of 364 μatm) and treatment (29.0°C and pCO2 of 750 μatm) conditions for 24 days, after which we measured the microbial community composition. These microbial findings were interpreted within the context of previously published physiological measurements from the exact same corals in this study (calcification, organic carbon flux, ratio of photosynthesis to respiration, photosystem II maximal efficiency, total lipids, soluble animal protein, soluble animal carbohydrates, soluble algal protein, soluble algal carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall, dually stressed A. millepora had reduced microbial diversity, experienced large changes in microbial community composition, and experienced dramatic physiological declines in calcification, photosystem II maximal efficiency, and algal carbohydrates. In contrast, the dually stressed coral T. reniformis experienced a stable and more diverse microbiome community with minimal physiological decline, coupled with very high total energy reserves and particulate organic carbon release rates. Thus, the microbiome changed and microbial diversity decreased in the physiologically sensitive coral with the thermally sensitive endosymbiotic algae but not in the physiologically tolerant coral with the thermally tolerant endosymbiont. Our results confirm recent findings that temperature-stress tolerant corals have a more stable microbiome, and demonstrate for the first time that this is also the case under the dual stresses of ocean warming and acidification. We propose that coral with a stable microbiome are also more physiologically resilient and thus more likely to persist in the future, and shape the coral species diversity of future reef ecosystems.

  13. 17 CFR 240.3a68-4 - Regulation of mixed swaps.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....S.C. 78c(a)(68)(D)). (b) Regulation of bilateral uncleared mixed swaps entered into by dually...(f) and 12; (B) Enforcement: 7 U.S.C. 2(a)(1)(B), 6(b), 6b, 6c, 6s(h)(1)(A), 6s(h)(4)(A), 9, 13b, 13a-1, 13a-2, 13, 13c(a), 13c(b), 15 and 26; (C) Reporting to a swap data repository: 7 U.S.C. 6r; (D...

  14. Excitatory motor neurons are local oscillators for backward locomotion

    PubMed Central

    Guan, Sihui Asuka; Fouad, Anthony D; Meng, Jun; Kawano, Taizo; Huang, Yung-Chi; Li, Yi; Alcaire, Salvador; Hung, Wesley; Lu, Yangning; Qi, Yingchuan Billy; Jin, Yishi; Alkema, Mark; Fang-Yen, Christopher

    2018-01-01

    Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron’s oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron’s intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network. PMID:29360035

  15. Character expansion methods for matrix models of dually weighted graphs

    NASA Astrophysics Data System (ADS)

    Kazakov, Vladimir A.; Staudacher, Matthias; Wynter, Thomas

    1996-04-01

    We consider generalized one-matrix models in which external fields allow control over the coordination numbers on both the original and dual lattices. We rederive in a simple fashion a character expansion formula for these models originally due to Itzykson and Di Francesco, and then demonstrate how to take the large N limit of this expansion. The relationship to the usual matrix model resolvent is elucidated. Our methods give as a by-product an extremely simple derivation of the Migdal integral equation describing the large N limit of the Itzykson-Zuber formula. We illustrate and check our methods by analysing a number of models solvable by traditional means. We then proceed to solve a new model: a sum over planar graphys possessing even coordination numbers on both the original and the dual lattice. We conclude by formulating the equations for the case of arbitrary sets of even, self-dual coupling constants. This opens the way for studying the deep problems of phase transitions from random to flat lattices. January 1995

  16. Excitatory motor neurons are local oscillators for backward locomotion.

    PubMed

    Gao, Shangbang; Guan, Sihui Asuka; Fouad, Anthony D; Meng, Jun; Kawano, Taizo; Huang, Yung-Chi; Li, Yi; Alcaire, Salvador; Hung, Wesley; Lu, Yangning; Qi, Yingchuan Billy; Jin, Yishi; Alkema, Mark; Fang-Yen, Christopher; Zhen, Mei

    2018-01-23

    Cell- or network-driven oscillators underlie motor rhythmicity. The identity of C. elegans oscillators remains unknown. Through cell ablation, electrophysiology, and calcium imaging, we show: (1) forward and backward locomotion is driven by different oscillators; (2) the cholinergic and excitatory A-class motor neurons exhibit intrinsic and oscillatory activity that is sufficient to drive backward locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high-voltage-activated calcium current underlies A motor neuron's oscillation; (4) descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap junction and chemical synapse configuration, exert state-dependent inhibition and potentiation of A motor neuron's intrinsic activity to regulate backward locomotion. Thus, motor neurons themselves derive rhythms, which are dually regulated by the descending interneurons to control the reversal motor state. These and previous findings exemplify compression: essential circuit properties are conserved but executed by fewer numbers and layers of neurons in a small locomotor network. © 2017, Gao et al.

  17. Malaise, Motivation and Motherhood: Predictors of Engagement in Behavioral Interventions from a Randomized Controlled Trial for HIV+ Women in Drug Abuse Recovery

    PubMed Central

    Feaster, Daniel J.; Weiss-Laxer, Nomi S.; McCabe, Brian E.

    2011-01-01

    Drug abuse has serious consequences for the wellbeing of persons with HIV/AIDS but suboptimal rates of client engagement limit the efficacy of interventions. The present study examines and compares client characteristics that predicted engagement (defined as attendance at two or more sessions) in a family intervention (SET) and a group intervention within a randomized trial aimed at preventing relapse and improving medication adherence for 126 predominantly African American HIV+ women in drug abuse recovery. Intervention engagement (60% overall) was not significantly different across the two interventions. Fewer physical and mental symptoms (malaise) (P < 0.05), living independently (P < 0.05), living with children (P < 0.05), and readiness to change (P < 0.05) were associated with engagement across the two interventions. Results from this study can be used to inform outreach and engagement approaches for women dually affected by drug abuse and HIV/AIDS. PMID:20512409

  18. Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma

    PubMed Central

    Gilmore, Sarah A.; Voorhies, Mark; Gebhart, Dana; Sil, Anita

    2015-01-01

    Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5’ leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature. PMID:26177267

  19. Genome-Wide Reprogramming of Transcript Architecture by Temperature Specifies the Developmental States of the Human Pathogen Histoplasma.

    PubMed

    Gilmore, Sarah A; Voorhies, Mark; Gebhart, Dana; Sil, Anita

    2015-07-01

    Eukaryotic cells integrate layers of gene regulation to coordinate complex cellular processes; however, mechanisms of post-transcriptional gene regulation remain poorly studied. The human fungal pathogen Histoplasma capsulatum (Hc) responds to environmental or host temperature by initiating unique transcriptional programs to specify multicellular (hyphae) or unicellular (yeast) developmental states that function in infectivity or pathogenesis, respectively. Here we used recent advances in next-generation sequencing to uncover a novel re-programming of transcript length between Hc developmental cell types. We found that ~2% percent of Hc transcripts exhibit 5' leader sequences that differ markedly in length between morphogenetic states. Ribosome density and mRNA abundance measurements of differential leader transcripts revealed nuanced transcriptional and translational regulation. One such class of regulated longer leader transcripts exhibited tight transcriptional and translational repression. Further examination of these dually repressed genes revealed that some control Hc morphology and that their strict regulation is necessary for the pathogen to make appropriate developmental decisions in response to temperature.

  20. Trajectory Analysis Unveils Reelin's Role in the Directed Migration of Granule Cells in the Dentate Gyrus.

    PubMed

    Wang, Shaobo; Brunne, Bianka; Zhao, Shanting; Chai, Xuejun; Li, Jiawei; Lau, Jeremie; Failla, Antonio Virgilio; Zobiak, Bernd; Sibbe, Mirjam; Westbrook, Gary L; Lutz, David; Frotscher, Michael

    2018-01-03

    Reelin controls neuronal migration and layer formation. Previous studies in reeler mice deficient in Reelin focused on the result of the developmental process in fixed tissue sections. It has remained unclear whether Reelin affects the migratory process, migration directionality, or migrating neurons guided by the radial glial scaffold. Moreover, Reelin has been regarded as an attractive signal because newly generated neurons migrate toward the Reelin-containing marginal zone. Conversely, Reelin might be a stop signal because migrating neurons in reeler , but not in wild-type mice, invade the marginal zone. Here, we monitored the migration of newly generated proopiomelanocortin-EGFP -expressing dentate granule cells in slice cultures from reeler , reeler -like mutants and wild-type mice of either sex using real-time microscopy. We discovered that not the actual migratory process and migratory speed, but migration directionality of the granule cells is controlled by Reelin. While wild-type granule cells migrated toward the marginal zone of the dentate gyrus, neurons in cultures from reeler and reeler -like mutants migrated randomly in all directions as revealed by vector analyses of migratory trajectories. Moreover, live imaging of granule cells in reeler slices cocultured to wild-type dentate gyrus showed that the reeler neurons changed their directions and migrated toward the Reelin-containing marginal zone of the wild-type culture, thus forming a compact granule cell layer. In contrast, directed migration was not observed when Reelin was ubiquitously present in the medium of reeler slices. These results indicate that topographically administered Reelin controls the formation of a granule cell layer. SIGNIFICANCE STATEMENT Neuronal migration and the various factors controlling its onset, speed, directionality, and arrest are poorly understood. Slice cultures offer a unique model to study the migration of individual neurons in an almost natural environment. In the present study, we took advantage of the expression of proopiomelanocortin-EGFP by newly generated, migrating granule cells to analyze their migratory trajectories in hippocampal slice cultures from wild-type mice and mutants deficient in Reelin signaling. We show that the compartmentalized presence of Reelin is essential for the directionality, but not the actual migratory process or speed, of migrating granule cells leading to their characteristic lamination in the dentate gyrus. Copyright © 2018 the authors 0270-6474/18/380137-12$15.00/0.

  1. Chemoattraction and chemorepulsion of Strongyloides stercoralis infective larvae on a sodium chloride gradient is mediated by amphidial neuron pairs ASE and ASH, respectively.

    PubMed

    Forbes, W M; Ashton, F T; Boston, R; Zhu, X; Schad, G A

    2004-03-25

    Depending on its concentration, sodium chloride acts as either an attractant or a repellant to the infective larvae (L3i) of Strongyloides stercoralis. On a concentration gradient, L3i are attracted to 0.05 M NaCl, but repelled by 2.8M. To test the hypothesis that amphidial neurons ASE and ASH might mediate attraction and repulsion, respectively, these neurons, and control neurons as well, were ablated in hatchling larvae with a laser microbeam. After the larvae attained infectivity (L3i), they were tested on a NaCl gradient. When placed at low salinity, 73.5% of normal controls migrated "up" the gradient, while 26.4% crawled randomly. In contrast, only 20.6% of ASE-ablated L3i migrated "up" the gradient, while 79.4% migrated randomly. Ablation-control ASK-ablated L3i (58.8%) migrated "up" the gradient while 41.1% crawled randomly. When placed at a region of high salinity, 100% of normal control L3i migrated "down" the gradient, whereas 62.5% of ASH-ablated L3i migrated randomly, the remaining 37.5% migrating "down" the gradient. In sharp contrast with ASH-ablated L3i, 94.1% of ablation-control larvae, i.e. ASK-ablated L3i, migrated "down" the gradient. Migration behavior of ASE- and ASH-ablated L3i was significantly different (P < 0.001) from that of ASK-ablated L3i and normal controls. It is noteworthy that 87.5% of ASE-ablated L3i that failed to exhibit chemoattractive behavior were actively chemorepelled from high salinity. Also, 70.0% of ASH-ablated L3i that failed to be chemorepelled from high salinity were capable of chemoattractive behavior, indicating that the worms had retained their behavioral responses except for those associated with the targeted neurons.

  2. Phosphorylation of Lbx1 controls lateral myoblast migration into the limb.

    PubMed

    Masselink, Wouter; Masaki, Megumi; Sieiro, Daniel; Marcelle, Christophe; Currie, Peter D

    2017-10-15

    The migration of limb myogenic precursors from limb level somites to their ultimate site of differentiation in the limb is a paradigmatic example of a set of dynamic and orchestrated migratory cell behaviours. The homeobox containing transcription factor ladybird homeobox 1 (Lbx1) is a central regulator of limb myoblast migration, null mutations of Lbx1 result in severe disruptions to limb muscle formation, particularly in the distal region of the limb in mice (Gross et al., 2000). As such Lbx1 has been hypothesized to control lateral migration of myoblasts into the distal limb anlage. It acts as a core regulator of the limb myoblast migration machinery, controlled by Pax3. A secondary role for Lbx1 in the differentiation and commitment of limb musculature has also been proposed (Brohmann et al., 2000; Uchiyama et al., 2000). Here we show that lateral migration, but not differentiation or commitment of limb myoblasts, is controlled by the phosphorylation of three adjacent serine residues of LBX1. Electroporation of limb level somites in the chick embryo with a dephosphomimetic form of Lbx1 results in a specific defect in the lateral migration of limb myoblasts. Although the initial delamination and migration of myoblasts is unaffected, migration into the distal limb bud is severely disrupted. Interestingly, myoblasts undergo normal differentiation independent of their migratory status, suggesting that the differentiation potential of hypaxial muscle is not regulated by the phosphorylation state of LBX1. Furthermore, we show that FGF8 and ERK mediated signal transduction, both critical regulators of the developing limb bud, have the capacity to induce the phosphorylation of LBX1 at these residues. Overall, this suggests a mechanism whereby the phosphorylation of LBX1, potentially through FGF8 and ERK signalling, controls the lateral migration of myoblasts into the distal limb bud. Copyright © 2017. Published by Elsevier Inc.

  3. A pilgrim's progress: Seeking meaning in primordial germ cell migration.

    PubMed

    Cantú, Andrea V; Laird, Diana J

    2017-10-01

    Comparative studies of primordial germ cell (PGC) development across organisms in many phyla reveal surprising diversity in the route of migration, timing and underlying molecular mechanisms, suggesting that the process of migration itself is conserved. However, beyond the perfunctory transport of cellular precursors to their later arising home of the gonads, does PGC migration serve a function? Here we propose that the process of migration plays an additional role in quality control, by eliminating PGCs incapable of completing migration as well as through mechanisms that favor PGCs capable of responding appropriately to migration cues. Focusing on PGCs in mice, we explore evidence for a selective capacity of migration, considering the tandem regulation of proliferation and migration, cell-intrinsic and extrinsic control, the potential for tumors derived from failed PGC migrants, the potential mechanisms by which migratory PGCs vary in their cellular behaviors, and corresponding effects on development. We discuss the implications of a selective role of PGC migration for in vitro gametogenesis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. 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.

  5. 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

  6. Scanning MWCNT-Nanopipette and Probe Microscopy: Li Patterning and Transport Studies.

    PubMed

    Larson, Jonathan M; Bharath, Satyaveda C; Cullen, William G; Reutt-Robey, Janice E

    2015-10-07

    A carbon-nanotube-enabling scanning probe technique/nanotechnology for manipulating and measuring lithium at the nano/mesoscale is introduced. Scanning Li-nanopipette and probe microscopy (SLi-NPM) is based on a conductive atomic force microscope (AFM) cantilever with an open-ended multi-walled carbon nanotube (MWCNT) affixed to its apex. SLi-NPM operation is demonstrated with a model system consisting of a Li thin film on a Si(111) substrate. By control of bias, separation distance, and contact time, attograms of Li can be controllably pipetted to or from the MWCNT tip. Patterned surface Li features are then directly probed via noncontact AFM measurements with the MWCNT tip. The subsequent decay of Li features is simulated with a mesoscale continuum model, developed here. The Li surface diffusion coefficient for a four (two) Li layer thick film is measured as D=8(±1.2)×10(-15) cm(2) s(-1) (D=1.75(±0.15)×10(-15) cm(2) s(-1)). Dual-Li pipetting/measuring with SLi-NPM enables a broad range of time-dependent Li and nanoelectrode characterization studies of fundamental importance to energy-storage research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Particle shape inhomogeneity and plasmon-band broadening of solar-control LaB6 nanoparticles

    NASA Astrophysics Data System (ADS)

    Machida, Keisuke; Adachi, Kenji

    2015-07-01

    An ensemble inhomogeneity of non-spherical LaB6 nanoparticles dispersion has been analyzed with Mie theory to account for the observed broad plasmon band. LaB6 particle shape has been characterized using small-angle X-ray scattering (SAXS) and electron tomography (ET). SAXS scattering intensity is found to vary exponentially with exponent -3.10, indicating the particle shape of disk toward sphere. ET analysis disclosed dually grouped distribution of nanoparticle dispersion; one is large-sized at small aspect ratio and the other is small-sized with scattered high aspect ratio, reflecting the dual fragmentation modes during the milling process. Mie extinction calculations have been integrated for 100 000 particles of varying aspect ratio, which were produced randomly by using the Box-Muller method. The Mie integration method has produced a broad and smooth absorption band expanded towards low energy, in remarkable agreement with experimental profiles by assuming a SAXS- and ET-derived shape distribution, i.e., a majority of disks with a little incorporation of rods and spheres for the ensemble. The analysis envisages a high potential of LaB6 with further-increased visible transparency and plasmon peak upon controlled particle-shape and its distribution.

  8. Transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 control anterior-posterior neuroblast migration with left-right functional asymmetry in Caenorhabditis elegans.

    PubMed

    Sundararajan, Lakshmi; Lundquist, Erik A

    2012-12-01

    Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left-right axis. Initial migration is independent of a Wnt signal that controls later anterior-posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other's role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration.

  9. [Ecological risk assessment of typical karst basin based on land use change: A case study of Lijiang River basin, Southern China].

    PubMed

    Hu, Jin Long; Zhou, Zhi Xiang; Teng, Ming Jun; Luo, Nan

    2017-06-18

    Taking Lijiang River basin as study area, and based on the remote sensing images of 1973, 1986, 2000 and 2013, the land-use data were extracted, the ecological risk index was constructed, and the characteristics of spatiotemporal variation of ecological risk were analyzed by "3S" technique. The results showed that land use structure of Lijiang River basin was under relatively reasonable state and it was constantly optimizing during 1973-2013. Overall, the ecological risk of Lijiang River basin was maintained at a low level. Lowest and lower ecological risk region was dominant in Lijiang River basin, but the area of highest ecological risk expanded quickly. The spatial distribution of ecological risk was basically stable and showed an obvious ring structure, which gra-dually decreased from the axis of Xingan County Town-Lingchuan County Town-Guilin City-Yangshuo County Town to other regions. Region with lowest ecological risk mainly distributed in natural mountain forest area of the north and mid-eastern parts of Lijiang River basin, and region with highe-st ecological risk concentrated in Guilin City. The ecological risk distribution of Lijiang River basin presented significant slope and altitude differences, and it decreased with increasing slope and altitude. During the study period, the area of low ecological risk converted to high ecological risk gra-dually decreased and vice versa. On the whole, the ecological risk tended to decline rapidly in the Lijiang River basin.

  10. ApoER2 Controls Not Only Neuronal Migration in the Intermediate Zone But Also Termination of Migration in the Developing Cerebral Cortex.

    PubMed

    Hirota, Yuki; Kubo, Ken-Ichiro; Fujino, Takahiro; Yamamoto, Tokuo T; Nakajima, Kazunori

    2018-01-01

    Neuronal migration contributes to the establishment of mammalian brain. The extracellular protein Reelin sends signals to various downstream molecules by binding to its receptors, the apolipoprotein E receptor 2 (ApoER2) and very low-density lipoprotein receptor and exerts essential roles in the neuronal migration and formation of the layered neocortex. However, the cellular and molecular functions of Reelin signaling in the cortical development are not yet fully understood. Here, to gain insight into the role of Reelin signaling during cortical development, we examined the migratory behavior of Apoer2-deficient neurons in the developing brain. Stage-specific labeling of newborn neurons revealed that the neurons ectopically invaded the marginal zone (MZ) and that neuronal migration of both early- and late-born neurons was disrupted in the intermediate zone (IZ) in the Apoer2 KO mice. Rescue experiments showed that ApoER2 functions both in cell-autonomous and noncell-autonomous manners, that Rap1, integrin, and Akt are involved in the termination of migration beneath the MZ, and that Akt also controls neuronal migration in the IZ downstream of ApoER2. These data indicate that ApoER2 controls multiple processes in neuronal migration, including the early stage of radial migration and termination of migration beneath the MZ in the developing neocortex. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. 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.

  12. 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

  13. Steering cell migration by alternating blebs and actin-rich protrusions.

    PubMed

    Diz-Muñoz, Alba; Romanczuk, Pawel; Yu, Weimiao; Bergert, Martin; Ivanovitch, Kenzo; Salbreux, Guillaume; Heisenberg, Carl-Philipp; Paluch, Ewa K

    2016-09-02

    High directional persistence is often assumed to enhance the efficiency of chemotactic migration. Yet, cells in vivo usually display meandering trajectories with relatively low directional persistence, and the control and function of directional persistence during cell migration in three-dimensional environments are poorly understood. Here, we use mesendoderm progenitors migrating during zebrafish gastrulation as a model system to investigate the control of directional persistence during migration in vivo. We show that progenitor cells alternate persistent run phases with tumble phases that result in cell reorientation. Runs are characterized by the formation of directed actin-rich protrusions and tumbles by enhanced blebbing. Increasing the proportion of actin-rich protrusions or blebs leads to longer or shorter run phases, respectively. Importantly, both reducing and increasing run phases result in larger spatial dispersion of the cells, indicative of reduced migration precision. A physical model quantitatively recapitulating the migratory behavior of mesendoderm progenitors indicates that the ratio of tumbling to run times, and thus the specific degree of directional persistence of migration, are critical for optimizing migration precision. Together, our experiments and model provide mechanistic insight into the control of migration directionality for cells moving in three-dimensional environments that combine different protrusion types, whereby the proportion of blebs to actin-rich protrusions determines the directional persistence and precision of movement by regulating the ratio of tumbling to run times.

  14. Theories on migration processes of Cd in Jiaozhou Bay

    NASA Astrophysics Data System (ADS)

    Yang, Dongfang; Li, Haixia; Wang, Qi; Ding, Jun; Zhang, Longlei

    2018-03-01

    Understanding the migration progress is essential to pollution control, while developing theories for the migration progress is the scientific basis. This paper further developed five key theories on migration processes of Cd including homogeneous theory, environmental dynamic theory, horizontal loss theory, migration trend theory and vertical migration theory, respectively. The performance and practical values of these theories were demonstrated in the application of these on analyzing the migration process of Cd in Jiaozhou Bay. Results these theory helpful to better understand the migration progress of pollutants in marine bay.

  15. S-Fms signalobody enhances myeloid cell growth and migration.

    PubMed

    Kawahara, Masahiro; Hitomi, Azusa; Nagamune, Teruyuki

    2014-07-01

    Since receptor tyrosine kinases (RTKs) control various cell fates in many types of cells, mimicry of RTK functions is promising for artificial control of cell fates. We have previously developed single-chain Fv (scFv)/receptor chimeras named signalobodies that can mimic receptor signaling in response to a specific antigen. While the RTK-based signalobodies enabled us to control cell growth and migration, further extension of applicability in another cell type would underlie the impact of the RTK-based signalobodies. In this study, we applied the scFv-c-Fms (S-Fms) signalobody in a murine myeloid progenitor cell line, FDC-P1. S-Fms transduced a fluorescein-conjugated BSA (BSA-FL)-dependent growth signal and activated downstream signaling molecules including MEK, ERK, Akt, and STAT3, which are major constituents of Ras/MAPK, PI3K/Akt, and JAK/STAT signaling pathways. In addition, S-Fms transduced a migration signal as demonstrated by the transwell-based migration assay. Direct real-time observation of the cells further confirmed that FDC/S-Fms cells underwent directional cell migration toward a positive gradient of BSA-FL. These results demonstrated the utility of the S-Fms signalobody for controlling growth and migration of myeloid cells. Further extension of our approach includes economical large-scale production of practically relevant blood cells as well as artificial control of cell migration for tissue regeneration and immune response. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Controls on drainage divide migration in the northern Sierras Pampeanas assessed through morphometric indicators

    NASA Astrophysics Data System (ADS)

    Seagren, E. G.; Schoenbohm, L. M.

    2017-12-01

    Drainage reorganization, primarily through progressive divide migration leading to discrete stream captures, is increasingly recognized as a common phenomenon during mountain-building events. This drainage rearrangement reflects complex interactions between tectonics, climate, and lithology, and can fundamentally change erosion and sedimentation patterns; therefore, determining the spatial extent and potential controls of divide migration is vital to understanding the topographic evolution of orogenic landscapes. Both geomorphic and morphometric evidence can be used to identify such drainage reorganization. The northern Sierras Pampeanas is an ideal location in which to study divide migration as limited glaciation and low out-of-channel erosion rates preserve evidence of reorganization. Additionally, several ranges in the region, such as Sierra de las Planchadas, exhibit geomorphic evidence of drainage rearrangement, including wind gaps and hairpin turns. Using ArcGIS, LSDTopoTools, and TopoToolbox, we conducted a systematic analysis of the spatial distribution of three morphometric indicators of divide migration: χ, Mx, and local headwater relief. Local `hotspots' undergoing drainage divide migration were identified using spatial autocorrelation and clustering methods - Gi* and Moran's I. Using spatial regression analysis, we assessed the potential controls of lithology, modern TRMM precipitation rates, and tectonics over divide migration. Preliminary results suggest broad westward migration of main drainage divides, following both the orographic precipitation gradient and regional slope.

  17. Gender, Power, and Emigration From Mexico.

    PubMed

    Nobles, Jenna; McKelvey, Christopher

    2015-10-01

    The prevailing model of migration in developing countries conceives of a risk-diversifying household in which members act as a single entity when making migration decisions. Ethnographic studies challenge this model by documenting gender hierarchy in family decisions and arguing that, in many contexts, men and women have differing views on the value of migration. We assess these perspectives using longitudinal survey data from Mexico. We show that Mexican households are heterogeneous in terms of women's decision-making authority and control over resources, and this variation predicts the subsequent emigration of their male partners to the United States. We then use data from a policy experiment to demonstrate that an exogenous increase in a woman's control over household resources decreases the probability that her spouse migrates. Our findings support the presence of important gender differences in how migration is valued. They also suggest that women's role in these decisions is inadvertently underrepresented in studies of migrant families. Staying is also a migration decision, and it is more likely in homes in which women have greater authority. From a policy perspective, the results suggest that Mexican migration is influenced not only by increases in household resources but also by which members of the household control them.

  18. Gender, Power, and Emigration From Mexico

    PubMed Central

    Nobles, Jenna; McKelvey, Christopher

    2015-01-01

    The prevailing model of migration in developing countries conceives of a risk-diversifying household in which members act as a single entity when making migration decisions. Ethnographic studies challenge this model by documenting gender hierarchy in family decisions and arguing that, in many contexts, men and women have differing views on the value of migration. We assess these perspectives using longitudinal survey data from Mexico. We show that Mexican households are heterogeneous in terms of women's decision-making authority and control over resources, and this variation predicts the subsequent emigration of their male partners to the United States. We then use data from a policy experiment to demonstrate that an exogenous increase in a woman's control over household resources decreases the probability that her spouse migrates. Our findings support the presence of important gender differences in how migration is valued. They also suggest that women's role in these decisions is inadvertently underrepresented in studies of migrant families. Staying is also a migration decision, and it is more likely in homes in which women have greater authority. From a policy perspective, the results suggest that Mexican migration is influenced not only by increases in household resources but also by which members of the household control them. PMID:26100982

  19. 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.

  20. Bovine Respiratory Syncytial Virus and Histophilus somni Interaction at the Alveolar Barrier

    PubMed Central

    Agnes, J. T.; Zekarias, B.; Shao, M.; Anderson, M. L.; Gershwin, L. J.

    2013-01-01

    Our previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSV-plus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection. PMID:23649093

  1. Bovine respiratory syncytial virus and Histophilus somni interaction at the alveolar barrier.

    PubMed

    Agnes, J T; Zekarias, B; Shao, M; Anderson, M L; Gershwin, L J; Corbeil, L B

    2013-07-01

    Our previous studies showed that Histophilus somni and bovine respiratory syncytial virus (BRSV) act synergistically in vivo to cause more severe bovine respiratory disease than either agent alone causes. Since H. somni surface and secreted immunoglobulin binding protein A (IbpA) causes retraction of bovine alveolar type 2 (BAT2) cells and invasion between BAT2 cells in vitro, we investigated mechanisms of BRSV-plus-H. somni infection at the alveolar barrier. BRSV treatment of BAT2 cells prior to treatment with IbpA-rich H. somni concentrated culture supernatant (CCS) resulted in increased BAT2 cell rounding and retraction compared to those with either treatment alone. This mimicked the increased alveolar cell thickening in calves experimentally infected with BRSV followed by H. somni compared to that in calves infected with BRSV or H. somni alone. BRSV-plus-H. somni CCS treatment of BAT2 cells also enhanced paracellular migration. The effect of matrix metalloproteinases (MMPs) was investigated as well because microarray analysis revealed that treatment with BRSV plus H. somni synergistically upregulated BAT2 cell expression of mmp1 and mmp3 compared to that in cells treated with either agent alone. Enzyme-linked immunosorbent assay (ELISA) confirmed that MMP1 and MMP3 protein levels were similarly upregulated. In collagen I and collagen IV (targets for MMP1 and MMP3, respectively) substrate zymography, digestion was increased with supernatants from dually treated BAT2 cells compared with those from singly treated cells. Enhanced breakdown of collagen IV in the basal lamina and of fibrillar collagen I in the adjacent interstitium in the dual infection may facilitate dissemination of H. somni infection.

  2. PDGF controls contact inhibition of locomotion by regulating N-cadherin during neural crest migration.

    PubMed

    Bahm, Isabel; Barriga, Elias H; Frolov, Antonina; Theveneau, Eric; Frankel, Paul; Mayor, Roberto

    2017-07-01

    A fundamental property of neural crest (NC) migration is contact inhibition of locomotion (CIL), a process by which cells change their direction of migration upon cell contact. CIL has been proven to be essential for NC migration in amphibians and zebrafish by controlling cell polarity in a cell contact-dependent manner. Cell contact during CIL requires the participation of the cell adhesion molecule N-cadherin, which starts to be expressed by NC cells as a consequence of the switch between E- and N-cadherins during epithelial-to-mesenchymal transition (EMT). However, the mechanism that controls the upregulation of N-cadherin remains unknown. Here, we show that platelet-derived growth factor receptor alpha (PDGFRα) and its ligand platelet-derived growth factor A (PDGF-A) are co-expressed in migrating cranial NC. Inhibition of PDGF-A/PDGFRα blocks NC migration by inhibiting N-cadherin and, consequently, impairing CIL. Moreover, we identify phosphatidylinositol-3-kinase (PI3K)/AKT as a downstream effector of the PDGFRα cellular response during CIL. Our results lead us to propose PDGF-A/PDGFRα signalling as a tissue-autonomous regulator of CIL by controlling N-cadherin upregulation during EMT. Finally, we show that once NC cells have undergone EMT, the same PDGF-A/PDGFRα works as an NC chemoattractant, guiding their directional migration. © 2017. Published by The Company of Biologists Ltd.

  3. Modular control of endothelial sheet migration

    PubMed Central

    Vitorino, Philip; Meyer, Tobias

    2008-01-01

    Growth factor-induced migration of endothelial cell monolayers enables embryonic development, wound healing, and angiogenesis. Although collective migration is widespread and therapeutically relevant, the underlying mechanism by which cell monolayers respond to growth factor, sense directional signals, induce motility, and coordinate individual cell movements is only partially understood. Here we used RNAi to identify 100 regulatory proteins that enhance or suppress endothelial sheet migration into cell-free space. We measured multiple live-cell migration parameters for all siRNA perturbations and found that each targeted protein primarily regulates one of four functional outputs: cell motility, directed migration, cell–cell coordination, or cell density. We demonstrate that cell motility regulators drive random, growth factor-independent motility in the presence or absence of open space. In contrast, directed migration regulators selectively transduce growth factor signals to direct cells along the monolayer boundary toward open space. Lastly, we found that regulators of cell–cell coordination are growth factor-independent and reorient randomly migrating cells inside the sheet when boundary cells begin to migrate. Thus, cells transition from random to collective migration through a modular control system, whereby growth factor signals convert boundary cells into pioneers, while cells inside the monolayer reorient and follow pioneers through growth factor-independent migration and cell–cell coordination. PMID:19056882

  4. Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior–Posterior Neuroblast Migration with Left–Right Functional Asymmetry in Caenorhabditis elegans

    PubMed Central

    Sundararajan, Lakshmi; Lundquist, Erik A.

    2012-01-01

    Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left–right axis. Initial migration is independent of a Wnt signal that controls later anterior–posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other’s role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left–right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration. PMID:23051647

  5. Regulation of Phagocyte Migration by Signal Regulatory Protein-Alpha Signaling.

    PubMed

    Alvarez-Zarate, Julian; Matlung, Hanke L; Matozaki, Takashi; Kuijpers, Taco W; Maridonneau-Parini, Isabelle; van den Berg, Timo K

    2015-01-01

    Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes. However, there are also indications that interactions between SIRPα and its ligand CD47 are involved in phagocyte transendothelial migration. We have investigated the involvement of SIRPα signaling in phagocyte migration in vitro and in vivo using mice that lack the SIRPα cytoplasmic tail. During thioglycolate-induced peritonitis in SIRPα mutant mice, both neutrophil and macrophage influx were found to occur, but to be significantly delayed. SIRPα signaling appeared to be essential for an optimal transendothelial migration and chemotaxis, and for the amoeboid type of phagocyte migration in 3-dimensional environments. These findings demonstrate, for the first time, that SIRPα signaling can directly control phagocyte migration, and this may contribute to the impaired inflammatory phenotype that has been observed in the absence of SIRPα signaling.

  6. Migration of guinea pig airway epithelial cells in response to bombesin analogues.

    PubMed

    Kim, J S; McKinnis, V S; White, S R

    1997-03-01

    Bombesin-like peptides within neuroepithelial cells elicit proliferation of normal and malignant airway epithelial cells. It is not clear that these peptides also elicit epithelial cell migration, a necessary component of airway repair after injury. We studied the effects of the bombesin analogues, gastrin releasing peptide (GRP) and neuromedin B (NMB), on guinea pig tracheal epithelial cell (GPTEC) migration. Primary GPTEC were allowed to migrate through 8-microm-pore gelatin-coated filters for 6 h in a chemotaxis chamber, after which the number of migrated cells per 10 high power fields (10 hpf) were counted. Both neuropeptides elicited migration of GPTEC: 24.8 +/- 4.5 cells for 10(-11) M NMB (P < 0.001 versus control, n = 4) and 16.8 +/- 1.2 cells for 10(-12) M GRP (P < 0.001 versus control, n = 8). Migration was attenuated substantially by a bombesin receptor antagonist. To investigate further the relationship of migration through a filter to the repair of a damaged epithelium, we studied the repair of epithelial cells by video microscopy. A 0.3- to 0.5-microm2 wound was created in a confluent monolayer of GPTEC, and wound closure was followed over 24 h. There was no significant acceleration in the rate of repair of GRP- or NMB-stimulated monolayers compared to control. These data demonstrate that GRP and NMB elicit migration of airway epithelial cells but may not play a significant role in the early repair of the airway epithelium in culture.

  7. Migration from Rural Areas: Employment and Education. IIEP Seminar Paper: 26.

    ERIC Educational Resources Information Center

    Hallak, Jacques

    Discussing migration and migration patterns in the third world, this paper asserts that the failure of plans for controlling rural to urban migration is due to: lack of knowledge about the phenomenon; the favor given to one-dimensional interpretations stressing certain aspects of urban economies; and the implicit assumptions underlying most…

  8. Activation of Rho GTPase Cdc42 promotes adhesion and invasion in colorectal cancer cells.

    PubMed

    Gao, Lei; Bai, Lan; Nan, Qing zhen

    2013-07-25

    The purpose of this study was to investigate the role of activated Rho GTPase cell division control protein 42 homolog (Cdc42) in colorectal cancer cell adhesion, migration, and invasion. The constitutively active form of Cdc42 (GFP-Cdc42L61) or control vector was overexpressed in the colorectal cancer cell line SW480. The localization of active Cdc42 was monitored by immunofluorescence staining, and the effects of active Cdc42 on cell migration and invasion were examined using an attachment assay, a wound healing assay, and a Matrigel migration assay in vitro. Immunofluorescence staining revealed that constitutively active Cdc42 predominately localized to the plasma membrane. Compared to SW480 cells transfected with the control vector, overexpression of constitutively active Cdc42 in SW480 cells promoted filopodia formation and cell stretch and dramatically enhanced cell adhesion to the coated plates. The wound healing assay revealed a significant increase of migration capability in SW480 cells expressing active Cdc42 compared to the control cells. Additionally, the Matrigel invasion assay demonstrated that active Cdc42 significantly promoted SW480 cell migration through the chamber. Our results suggest that active Rho GTPase Cdc42 can greatly enhance colorectal cancer cell SW480 to spread, migrate, and invade, which may contribute to colorectal cancer metastasis.

  9. Phosphoinositide Signaling Regulates the Exocyst Complex and Polarized Integrin Trafficking in Directionally Migrating Cells

    PubMed Central

    Thapa, Narendra; Sun, Yue; Schramp, Mark; Choi, Suyoung; Ling, Kun; Anderson, Richard A

    2011-01-01

    Summary Polarized delivery of signaling and adhesion molecules to the leading edge is required for directional migration of cells. Here, we describe a role for the PIP2 synthesizing enzyme, PIPKIγi2, in regulation of exocyst complex control of cell polarity and polarized integrin trafficking during migration. Loss of PIPKIγi2 impaired directional migration, formation of cell polarity, and integrin trafficking to the leading edge. Upon initiation of directional migration PIPKIγi2 via PIP2 generation controls the integration of the exocyst complex into an integrin-containing trafficking compartment(s) that requires the talin-binding ability of PIPKIγi2, and talin for integrin recruitment to the leading edge. A PIP2 requirement is further emphasized by inhibition of PIPKIγi2-regulated directional migration by an Exo70 mutant deficient in PIP2 binding. These results reveal how phosphoinositide generation orchestrates polarized trafficking of integrin in coordination with talin that links integrins to the actin cytoskeleton, processes that are required for directional migration. PMID:22264730

  10. Human migration, protected areas, and conservation outreach in Tanzania.

    PubMed

    Salerno, Jonathan D; Borgerhoff Mulder, Monique; Kefauver, Shawn C

    2014-06-01

    A recent discussion debates the extent of human in-migration around protected areas (PAs) in the tropics. One proposed argument is that rural migrants move to bordering areas to access conservation outreach benefits. A counter proposal maintains that PAs have largely negative effects on local populations and that outreach initiatives even if successful present insufficient benefits to drive in-migration. Using data from Tanzania, we examined merits of statistical tests and spatial methods used previously to evaluate migration near PAs and applied hierarchical modeling with appropriate controls for demographic and geographic factors to advance the debate. Areas bordering national parks in Tanzania did not have elevated rates of in-migration. Low baseline population density and high vegetation productivity with low interannual variation rather than conservation outreach explained observed migration patterns. More generally we argue that to produce results of conservation policy significance, analyses must be conducted at appropriate scales, and we caution against use of demographic data without appropriate controls when drawing conclusions about migration dynamics. © 2014 Society for Conservation Biology.

  11. Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.

    PubMed

    Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

    2014-10-27

    Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

  12. Rear-polarized Wnt5a-receptor-actin-myosin-polarity (WRAMP) structures promote the speed and persistence of directional cell migration

    PubMed Central

    Connacher, Mary Katherine; Tay, Jian Wei; Ahn, Natalie G.

    2017-01-01

    In contrast to events at the cell leading edge, rear-polarized mechanisms that control directional cell migration are poorly defined. Previous work described a new intracellular complex, the Wnt5a-receptor-actomyosin polarity (WRAMP) structure, which coordinates the polarized localization of MCAM, actin, and myosin IIB in a Wnt5a-induced manner. However, the polarity and function for the WRAMP structure during cell movement were not determined. Here we characterize WRAMP structures during extended cell migration using live-cell imaging. The results demonstrate that cells undergoing prolonged migration show WRAMP structures stably polarized at the rear, where they are strongly associated with enhanced speed and persistence of directional movement. Strikingly, WRAMP structures form transiently, with cells displaying directional persistence during periods when they are present and cells changing directions randomly when they are absent. Cells appear to pause locomotion when WRAMP structures disassemble and then migrate in new directions after reassembly at a different location, which forms the new rear. We conclude that WRAMP structures represent a rear-directed cellular mechanism to control directional migration and that their ability to form dynamically within cells may control changes in direction during extended migration. PMID:28592632

  13. MACF1 Controls Migration and Positioning of Cortical GABAergic Interneurons in Mice.

    PubMed

    Ka, Minhan; Moffat, Jeffrey J; Kim, Woo-Yang

    2017-12-01

    GABAergic interneurons develop in the ganglionic eminence in the ventral telencephalon and tangentially migrate into the cortical plate during development. However, key molecules controlling interneuron migration remain poorly identified. Here, we show that microtubule-actin cross-linking factor 1 (MACF1) regulates GABAergic interneuron migration and positioning in the developing mouse brain. To investigate the role of MACF1 in developing interneurons, we conditionally deleted the MACF1 gene in mouse interneuron progenitors and their progeny using Dlx5/6-Cre-IRES-EGFP and Nkx2.1-Cre drivers. We found that MACF1 deletion results in a marked reduction and defective positioning of interneurons in the mouse cerebral cortex and hippocampus, suggesting abnormal interneuron migration. Indeed, the speed and mode of interneuron migration were abnormal in the MACF1-mutant brain, compared with controls. Additionally, MACF1-deleted interneurons showed a significant reduction in the length of their leading processes and dendrites in the mouse brain. Finally, loss of MACF1 decreased microtubule stability in cortical interneurons. Our findings suggest that MACF1 plays a critical role in cortical interneuron migration and positioning in the developing mouse brain. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Regulation of Phagocyte Migration by Signal Regulatory Protein-Alpha Signaling

    PubMed Central

    Alvarez-Zarate, Julian; Matlung, Hanke L.; Matozaki, Takashi; Kuijpers, Taco W.; Maridonneau-Parini, Isabelle; van den Berg, Timo K.

    2015-01-01

    Signaling through the inhibitory receptor signal regulatory protein-alpha (SIRPα) controls effector functions in phagocytes. However, there are also indications that interactions between SIRPα and its ligand CD47 are involved in phagocyte transendothelial migration. We have investigated the involvement of SIRPα signaling in phagocyte migration in vitro and in vivo using mice that lack the SIRPα cytoplasmic tail. During thioglycolate-induced peritonitis in SIRPα mutant mice, both neutrophil and macrophage influx were found to occur, but to be significantly delayed. SIRPα signaling appeared to be essential for an optimal transendothelial migration and chemotaxis, and for the amoeboid type of phagocyte migration in 3-dimensional environments. These findings demonstrate, for the first time, that SIRPα signaling can directly control phagocyte migration, and this may contribute to the impaired inflammatory phenotype that has been observed in the absence of SIRPα signaling. PMID:26057870

  15. Using population-based data to examine preventive services by disability type among dually eligible (Medicare/Medicaid) adults.

    PubMed

    Reichard, Amanda; Fox, Michael H

    2013-04-01

    Individuals dually eligible for Medicaid and Medicare constitute a small percentage of these program's populations but account for a disproportionately large percent of their total costs. While much work has examined high expenditures, little is known about their health and details of their health care utilization. Utilize an important public health surveillance tool to better understand preventive service use among the dual eligible population. This study involved descriptive and regression analyses of dual eligibles in the Medical Expenditure Panel Survey data from pooled alternate years 2000-2008. We classified the sample into 4 mutually exclusive groups: cognitive limitations, physical disabilities, double diagnosis (cognitive limitations and physical disability), or neither cognitive limitations nor physical disability. For most groups, age was significantly associated with preventive services, though direction varies. Older age was linked to greater receipt of flu shots while younger age was associated with greater receipt of Pap tests, mammograms and dental services. Black women in all groups (except cognitive limitations) had an increased likelihood of receiving a Pap test and a mammogram. A subset of dual eligibles drives the majority of expenditures. People with physical disabilities, regardless of whether they also have a cognitive limitation, are among the highest costing and sickest of our non-institutionalized dual eligible population. Efforts to understand and address the challenges faced by women with physical disabilities in accessing Pap tests or mammograms may be helpful in improving the overall health status for this disability group, but also for all dual eligibles. Published by Elsevier Inc.

  16. Hospital Distance and Readmissions Among VA-Medicare Dual-Enrolled Veterans.

    PubMed

    Wong, Edwin S; Rinne, Seppo T; Hebert, Paul L; Cook, Meredith A; Liu, Chuan-Fen

    2016-09-01

    Geographic access to inpatient care at the Veterans Affairs (VA) Health Care System is challenging for many veterans with chronic obstructive pulmonary disease (COPD) given relatively few VA hospitals nationwide. Veterans with lengthy travel distances may obtain non-VA care, particularly those dually enrolled in Medicare. Our primary objective was to assess whether distance from VA patients' residence to the nearest VA and non-VA hospitals was associated with 30-day all-cause readmission and the system where patients were readmitted (VA or Medicare). Using VA and Medicare administrative data, we identified 21,273 patients hospitalized for COPD between October 2008 and September 2011 and dually enrolled in VA and fee-for-service Medicare. Outcome variables were dichotomous measures denoting readmission for any cause within 30 days following discharge and whether the readmission occurred in a non-VA hospital through Medicare. Distance to the nearest hospital was defined as the number of miles between patients' residence ZIP code and the ZIP code of the nearest VA and non-VA hospital accepting Medicare, respectively. Probit models with sample selection were applied to examine the relationship between hospital distance and outcome measures. Respective distances to the nearest VA and non-VA hospital were not associated with 30-day all-cause readmission. Greater distance to the nearest VA hospital was associated with a greater conditional probability of choosing non-VA hospitals for readmission. COPD patients with poor geographic access to VA hospitals did not forgo subsequent inpatient care following their index hospitalization, but they were more likely to seek non-VA substitutes. © 2016 National Rural Health Association.

  17. Terpenoid biosynthesis in Arabidopsis attacked by caterpillars and aphids: effects of aphid density on the attraction of a caterpillar parasitoid.

    PubMed

    Kroes, Anneke; Weldegergis, Berhane T; Cappai, Francesco; Dicke, Marcel; van Loon, Joop J A

    2017-12-01

    One of the responses of plants to insect attack is the production of volatile organic compounds that mediate indirect defence of plants by attracting natural enemies of the attacking herbivores. Herbivore-induced plant volatiles (HIPVs) include terpenoids that play key roles in the attraction of natural enemies. Crosstalk between phytohormonal signalling pathways is well known to affect the regulation of plant defences, including the emission of HIPVs. Thus, simultaneous feeding on the same plant by caterpillars and aphids, can affect the attraction of parasitoids by the plant compared to single insect attack. The role of aphid density in the regulation of HIPV emission by plants under dual attack has not been studied previously. Here, we investigated the attraction of Diadegma semiclausum, a parasitoid of the Diamondback moth Plutella xylostella, to volatiles emitted by Arabidopsis thaliana plants, simultaneously attacked by host caterpillars, and by the non-host aphid Brevicoryne brassicae. Our study shows that the effect of aphid infestation on parasitoid attraction is influenced by the density of the aphids. Biosynthesis and emission of (E,E)-α-farnesene could be linked to the observed preference of D. semiclausum parasitoids for the HIPV blend emitted by plants dually infested by caterpillars and aphids at a high density compared to dually infested plants with a low aphid density. Parasitoids such as D. semiclausum are important enemies of herbivorous insects and a better understanding of how plants express indirect defence mechanisms in response to multiple insect attack will provide important knowledge on plant-herbivore-parasitoid interactions under multiple stress conditions.

  18. Outcomes of managed care of dually eligible older persons.

    PubMed

    Kane, Robert L; Homyak, Patricia; Bershadsky, Boris; Lum, Yat-Sang; Siadaty, Mir Said

    2003-04-01

    To assess changes in various functional and satisfaction measures between older persons enrolled in Minnesota Senior Health Options (MSHO), a managed care program for older persons eligible for both Medicare and Medicaid. We used two sets of matched controls for MSHO enrollees and their families and matched controls living in the community and in nursing homes: Persons in the same county who were eligible to enroll but did not enroll in MSHO and persons in other metropolitan areas where MSHO is not available. For the community sample, we used questionnaires to measure functional status (activities of daily living), pain, unmet care needs, satisfaction, and caregiver burden. Approximately 2 years after the first survey, we resurveyed respondents who lived in the community at the time of the first survey. For the nursing home residents, we used annual assessments to calculate case mix to compare changes in functional levels over time. There were few significant differences in change over time between the MSHO sample and the two control groups. Out-of-area controls showed greater increases in pain but in-area controls showed less interference from pain. Compared with out-of-area controls, MSHO clients showed greater increase in homemaker use, meals on wheels, and outpatient rehabilitation. Compared with in-area controls, they showed more use of meals on wheels and less help from family with household tasks. There were few differences in satisfaction, but the MSHO families showed significantly lower burden than controls on five items. The analyses show only modest evidence of benefit from MSHO compared with the two control groups. The model represented by MSHO does not appear to generate substantial differences in outcomes across function, satisfaction, and caregiver burden.

  19. Xenon decreases cell migration and secretion of a pro-angiogenesis factor in breast adenocarcinoma cells: comparison with sevoflurane.

    PubMed

    Ash, S A; Valchev, G I; Looney, M; Ni Mhathuna, A; Crowley, P D; Gallagher, H C; Buggy, D J

    2014-07-01

    While volatile agents have been implicated in metastasis-enhancing effects on cancer cells, the effects of xenon are unknown. We investigated xenon- and sevoflurane-mediated effects on migration and expression of angiogenesis biomarkers in human breast adenocarcinoma cells. MDA-MB-231 and MCF-7 cells were exposed to xenon 70% with O2 25%, CO2 5%; control gas containing O2 25%, CO2 5%, N2 70%; or sevoflurane 2.5 vol% administered in O2 60%, N2 37%, or control gas. Cell viability was determined by the MTT assay. Migration at 24 h was determined using the Oris™ Cell Migration Assay. Secretion of angiogenesis factors was measured using a membrane-based immunoassay array. Xenon reduced MDA-MB-231 migration to 59 (13%) after 1-h exposure (P=0.02), 64 (10%) after 3 h (P=0.01), and 71 (9%) after 5 h (P=0.04) compared with control gas, without affecting viability. Similarly, MCF-7 migration was significantly reduced at all timepoints [to 58 (12%) at 1 h, 65 (12%) at 3 h, and 65% (12%) at 5 h]. Sevoflurane did not affect migration when delivered in control gas. Glycine, an N-methyl-d-aspartate receptor co-agonist, antagonized the effects of xenon on migration. Expression of the pro-angiogenesis factor regulated on activation, normal T cell expressed and secreted (RANTES) was reduced in conditioned medium from xenon-exposed MDA-MB-231 cells compared with cells exposed to either control gas or sevoflurane [mean dot density 2.0 (0.2) compared with 3.0 (0.1) and 3.1 (0.3), respectively (P=0.02)]. Xenon, but not sevoflurane, inhibited migration in both oestrogen receptor positive and negative breast adenocarcinoma cells. Furthermore, xenon decreased release of the pro-angiogenic factor RANTES from MDA-MB-231 cells. © The Author [2014]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Increased Migration of Monocytes in Essential Hypertension Is Associated with Increased Transient Receptor Potential Channel Canonical Type 3 Channels

    PubMed Central

    Chen, Jing; Zhong, Jian; Yu, Hao; Xu, Xingsen; He, Hongbo; Yan, Zhencheng; Scholze, Alexandra; Liu, Daoyan; Zhu, Zhiming; Tepel, Martin

    2012-01-01

    Increased transient receptor potential canonical type 3 (TRPC3) channels have been observed in patients with essential hypertension. In the present study we tested the hypothesis that increased monocyte migration is associated with increased TRPC3 expression. Monocyte migration assay was performed in a microchemotaxis chamber using chemoattractants formylated peptide Met-Leu-Phe (fMLP) and tumor necrosis factor-α (TNF-α). Proteins were identified by immunoblotting and quantitative in-cell Western assay. The effects of TRP channel-inhibitor 2–aminoethoxydiphenylborane (2-APB) and small interfering RNA knockdown of TRPC3 were investigated. We observed an increased fMLP-induced migration of monocytes from hypertensive patients compared with normotensive control subjects (246±14% vs 151±10%). The TNF-α-induced migration of monocytes in patients with essential hypertension was also significantly increased compared to normotensive control subjects (221±20% vs 138±18%). In the presence of 2-APB or after siRNA knockdown of TRPC3 the fMLP-induced monocyte migration was significantly blocked. The fMLP-induced changes of cytosolic calcium were significantly increased in monocytes from hypertensive patients compared to normotensive control subjects. The fMLP-induced monocyte migration was significantly reduced in the presence of inhibitors of tyrosine kinase and phosphoinositide 3-kinase. We conclude that increased monocyte migration in patients with essential hypertension is associated with increased TRPC3 channels. PMID:22438881

  1. List memory in young adults with language learning disability.

    PubMed

    Sheng, Li; Byrd, Courtney T; McGregor, Karla K; Zimmerman, Hannah; Bludau, Kadee

    2015-04-01

    The purpose of this study was to characterize the verbal memory limitations of young adults with language learning disability (LLD). Sixteen young adults with LLD and 34 age- and education-matched controls with typical language participated in a Deese-Roediger-McDermott (DRM; Deese, 1959; Roediger & McDermott, 1995) list recall experiment. Participants listened to 12-item word lists that converged on a nonpresented critical item (e.g., rain) semantically (umbrella, drench, weather, hail), phonologically (train, main, ran, wren), or dually in a hybrid list (umbrella, train, drench, main) and recalled words in no particular order. Group comparisons were made on veridical recall (i.e., words that were presented) and false recall of nonpresented critical items. Recall performance was analyzed by list type and list position to examine potential differences in the quality of memorial processes. The LLD group produced fewer veridical recalls than the controls. Both groups demonstrated list type and list position effects in veridical recall. False recall of the critical items was comparable in the 2 groups and varied by list type in predictable ways. Young adults with LLD have verbal memory limitations characterized by quantitatively low levels of accurate recall. Qualitative patterns of recall are similar to those of unaffected peers. Therefore, the memory problem is characterized by limited capacity; memorial processes appear to be intact.

  2. Threats from emerging and re-emerging neglected tropical diseases (NTDs).

    PubMed

    Mackey, Tim K; Liang, Bryan A

    2012-01-01

    Neglected tropical diseases impact over 1 billion of the world's poorest populations and require special attention. However, within the NTDs recognized by the World Health Organization, some are also dually categorized as emerging and re-emerging infectious diseases requiring more detailed examination on potential global health risks. We reviewed the 17 NTDs classified by the WHO to determine if those NTDs were also categorized by the US Centers for Disease Control and Prevention as emerging and re-emerging infectious diseases (''EReNTDs''). We then identified common characteristics and risks associated with EReNTDs. Identified EReNTDs of dengue, rabies, Chagas Disease, and cysticercosis disproportionately impact resource-poor settings with poor social determinants of health, spread through globalization, are impacted by vector control, lack available treatments, and threaten global health security. This traditionally neglected subset of diseases requires urgent attention and unique incentive structures to encourage investment in innovation and coordination. Multi-sectorial efforts and targeted public-private partnerships would spur needed R&D for effective and accessible EReNTD treatments, improvement of social determinants of health, crucial low-income country development, and health system strengthening efforts. Utilization of One Health principles is essential for enhancing knowledge to efficaciously address public health aspects of these EReNTDs globally.

  3. A brief neurocognitive assessment of patients with psychosis following traumatic brain injury (PFTBI): Use of the Repeatable battery for the Assessment of Neuropsychological Status (RBANS).

    PubMed

    Batty, Rachel A; Francis, Andrew; Thomas, Neil; Hopwood, Malcolm; Ponsford, Jennie; Rossell, Susan L

    2016-03-30

    Patients who develop psychosis following a traumatic brain injury (PFTBI) show impaired neurocognition; however, the degree of impairment has not been empirically investigated using a standardised battery. We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to patients with PFTBI (n=10), and to three groups of controls: traumatic brain injury (TBI) (n=10), schizophrenia (n=23), and nonclinical controls (n=23). The results confirmed that the cognitive neuropsychological profile of dually-diagnosed patients with PFTBI is significantly and substantially impaired. Seventy per cent of patients with PFTBI received a neuropsychological classification between the "extremely low" and "low average" ranges. Group-wise analyses on the RBANS indices indicated that patients with PFTBI had the lowest (Immediate Memory, Attention, Delayed Memory, Total Score), or equal lowest (visuospatial, equivalent with schizophrenia patients) scores, with the exception of the Language Index where no group differences were shown (however, the mean PFTBI score on the Language Index was two standard deviations below the RBANS normative score). These findings provide novel evidence of impaired cognitive neuropsychological processing in patients with PFTBI using a standardised and replicable battery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Maternal Malaria and Perinatal HIV Transmission, Western Kenya1,2

    PubMed Central

    Ayisi, John G.; van Eijk, Anna M.; ter Kuile, Feiko O.; Shi, Ya Ping; Yang, Chunfu; Kolczak, Margarette S.; Otieno, Juliana A.; Misore, Ambrose O.; Kager, Piet A.; Lal, Renu B.; Steketee, Richard W.; Nahlen, Bernard L.

    2004-01-01

    To determine whether maternal placental malaria is associated with an increased risk for perinatal mother-to-child HIV transmission (MTCT), we studied HIV-positive women in western Kenya. We enrolled 512 mother-infant pairs; 128 (25.0%) women had malaria, and 102 (19.9%) infants acquired HIV perinatally. Log10 HIV viral load and episiotomy or perineal tear were associated with increased perinatal HIV transmission, whereas low-density malaria (<10,000 parasites/μL) was associated with reduced risk (adjusted relative risk [ARR] 0.4). Among women dually infected with malaria and HIV, high-density malaria (>10,000 parasites/μL) was associated with increased risk for perinatal MTCT (ARR 2.0), compared to low-density malaria. The interaction between placental malaria and MTCT appears to be variable and complex: placental malaria that is controlled at low density may cause an increase in broad-based immune responses that protect against MTCT; uncontrolled, high-density malaria may simultaneously disrupt placental architecture and generate substantial antigen stimulus to HIV replication and increase risk for MTCT. PMID:15200854

  5. Hard-hard coupling assisted anomalous magnetoresistance effect in amine-ended single-molecule magnetic junction

    NASA Astrophysics Data System (ADS)

    Tang, Y.-H.; Lin, C.-J.; Chiang, K.-R.

    2017-06-01

    We proposed a single-molecule magnetic junction (SMMJ), composed of a dissociated amine-ended benzene sandwiched between two Co tip-like nanowires. To better simulate the break junction technique for real SMMJs, the first-principles calculation associated with the hard-hard coupling between a amine-linker and Co tip-atom is carried out for SMMJs with mechanical strain and under an external bias. We predict an anomalous magnetoresistance (MR) effect, including strain-induced sign reversal and bias-induced enhancement of the MR value, which is in sharp contrast to the normal MR effect in conventional magnetic tunnel junctions. The underlying mechanism is the interplay between four spin-polarized currents in parallel and anti-parallel magnetic configurations, originated from the pronounced spin-up transmission feature in the parallel case and spiky transmission peaks in other three spin-polarized channels. These intriguing findings may open a new arena in which magnetotransport and hard-hard coupling are closely coupled in SMMJs and can be dually controlled either via mechanical strain or by an external bias.

  6. Influence of psychotherapy attendance on buprenorphine treatment outcome

    PubMed Central

    Montoya, Iván D.; Schroeder, Jennifer R.; Preston, Kenzie L.; Covi, Lino; Umbricht, Annie; Contoreggi, Carlo; Fudala, Paul J.; Johnson, Rolley E.; Gorelick, David A.

    2008-01-01

    We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p = 0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p = 0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence. PMID:15857725

  7. Focal adhesion kinase is involved in mechanosensing during fibroblast migration

    NASA Technical Reports Server (NTRS)

    Wang, H. B.; Dembo, M.; Hanks, S. K.; Wang, Y.

    2001-01-01

    Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. We have transfected FAK-null fibroblasts with FAK gene under the control of the tetracycline repression system. Cells were cultured on flexible polyacrylamide substrates for the detection of traction forces and the application of mechanical stimulation. Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. Our results suggest that FAK plays an important role in the response of migrating cells to mechanical input. In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration.

  8. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain.

    PubMed

    Nakamuta, Shinichi; Yang, Yu-Ting; Wang, Chia-Lin; Gallo, Nicholas B; Yu, Jia-Ray; Tai, Yilin; Van Aelst, Linda

    2017-12-04

    Throughout life, stem cells in the ventricular-subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts' morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase-RhoA-interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. © 2017 Nakamuta et al.

  9. Dual role for DOCK7 in tangential migration of interneuron precursors in the postnatal forebrain

    PubMed Central

    Yang, Yu-Ting; Yu, Jia-Ray; Tai, Yilin

    2017-01-01

    Throughout life, stem cells in the ventricular–subventricular zone generate neuroblasts that migrate via the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into local interneurons. Although progress has been made toward identifying extracellular factors that guide the migration of these cells, little is known about the intracellular mechanisms that govern the dynamic reshaping of the neuroblasts’ morphology required for their migration along the RMS. In this study, we identify DOCK7, a member of the DOCK180-family, as a molecule essential for tangential neuroblast migration in the postnatal mouse forebrain. DOCK7 regulates the migration of these cells by controlling both leading process (LP) extension and somal translocation via distinct pathways. It controls LP stability/growth via a Rac-dependent pathway, likely by modulating microtubule networks while also regulating F-actin remodeling at the cell rear to promote somal translocation via a previously unrecognized myosin phosphatase–RhoA–interacting protein-dependent pathway. The coordinated action of both pathways is required to ensure efficient neuroblast migration along the RMS. PMID:29089377

  10. Dual and parallel postdoctoral training programs: implications for the osteopathic medical profession.

    PubMed

    Burkhart, Diane N; Lischka, Terri A

    2011-04-01

    Students in colleges of osteopathic medicine have several options when considering postdoctoral training programs. In addition to training programs approved solely by the American Osteopathic Association or accredited solely by the Accreditation Council for Graduate Medical Education (ACGME), students can pursue programs accredited by both organizations (ie, dually accredited programs) or osteopathic programs that occur side-by-side with ACGME programs (ie, parallel programs). In the present article, we report on the availability and growth of these 2 training options and describe their benefits and drawbacks for trainees and the osteopathic medical profession as a whole.

  11. Prevalence of hepatitis B and delta according to HIV-type: a multi-country cross-sectional survey in West Africa.

    PubMed

    Coffie, Patrick A; Tchounga, Boris K; Bado, Guillaume; Kabran, Mathieu; Minta, Daouda K; Wandeler, Gilles; Gottlieb, Geoffrey S; Dabis, François; Eholie, Serge P; Ekouevi, Didier K

    2017-07-04

    In West Africa where HIV-1 and HIV-2 co-circulate, the co-infection with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is not well described. This study aimed at estimating the prevalence of HBV and HBV/HDV co-infection according to HIV types and risk factors for HBV infection among West African HIV-infected patients. A cross-sectional survey was conducted within the IeDEA West Africa cohort from March to December 2012 in Côte d'Ivoire (three sites), Burkina Faso and Mali (one site each). All HIV-infected adult patients on antiretroviral therapy (ART) or not who attended one of the participating HIV clinics during the study period and agreed to participate were included. Blood samples were collected and re-tested for HIV type discrimination, HBV and HDV serology as well as HBV viral load. Logistic regression was used to identify risk factors for HBV infection. A total of 791 patients were included: 192 HIV-1, 447 HIV-2 and 152 HIV-1&2 dually reactive. At time of sampling, 555 (70.2%) were on ART and median CD4+ cell count was 472/mm 3 (inter-quartile range [IQR]: IQR: 294-644). Sixty-seven (8.5%, 95% CI 6.6-10.6) patients were HBsAg positive without any difference according to HIV type (7.9% in HIV-1, 7.2% in HIV-1&2 dually reactive and 9.4% in HIV-2; p = 0.61). In multivariate logistic analysis, age ≤ 30 years old (adjusted odds ratio [aOR] 5.00, 95% CI 1.96-12.76), age between 31 and 49 years old (aOR 1.78, 95% CI 1.00-2.21) and male gender (aOR 2.15, 95% CI 1.25-3.69) were associated with HBsAg positivity. HBV DNA testing was performed in 36 patients with blood sample available (25 on ART) and 8 (22.2%) had detectable HBV DNA. Among the HBsAg-positive individuals, 14.9% (95% CI 7.4-25.7) were also positive for anti-HDV antibody without any difference according to HIV type (28.6% in HIV-1, 14.3% in HIV-2 and 0.0% in HIV-1&2 dually reactive; p = 0.15). HBV and HBV/HDV co-infection are common in West Africa, irrespective of HIV type. Therefore, screening for both viruses should be systematically performed to allow a better management of HIV-infected patients. Follow-up studies are necessary to determine the impact of these two viruses on HIV infection.

  12. Is feeding behaviour related to glass eel propensity to migrate?

    NASA Astrophysics Data System (ADS)

    Bureau du Colombier, Sarah; Lambert, Patrick; Bardonnet, Agnès

    2008-11-01

    Several studies have shown that eel diadromy is facultative and that migratory divergences may appear during glass eel estuarine migration. The origin of the differences in migratory behaviour among glass eels remains unclear but initial evidence supports the role of individual energetic and thyroidal status. Even if starvation is usually associated with glass eel migration, feeding does seem to occur in some glass eels. The aim of the present study was to investigate feeding behaviour and glass eel growth in relation to the propensity to migrate. Feeding rate and weight gain were higher in fish having a high propensity to migrate (M + fish) than in fish having a low propensity to migrate (M - fish) in fed glass eels, whereas no clear difference in the variation in body weight was observed among unfed fish (controls). M - fish initially had lower percent dry weight than M + fish, which suggests a link between appetite, propensity to migrate, and energy content. We discuss the role played by endocrine signals on these processes. In fish, thyroid hormones contribute to the control of growth and development. In addition, they play a role in flatfish and leptocephalus metamorphosis and appear to be involved in smolt and glass eel migratory behaviour. As such, they represent a good candidate which would promote the propensity to migrate as well as digestive system development. Their role in the hormonal control of food intake however remains vague. The large and sharp decline in glass eel abundances observed since the 1980s could partly be explained by changes in ocean productivity. If so, it could be accompanied by a decrease in glass eel energy stores. The ability to resume feeding in the course of the estuarine crossing would then represent a serious advantage to maintain energy levels compatible with migration.

  13. The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

    PubMed Central

    Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

    2016-01-01

    Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

  14. Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration

    PubMed Central

    Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L.; Vanacker, Jean-Marc

    2014-01-01

    Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration. PMID:25288732

  15. Estrogen-related receptor α decreases RHOA stability to induce orientated cell migration.

    PubMed

    Sailland, Juliette; Tribollet, Violaine; Forcet, Christelle; Billon, Cyrielle; Barenton, Bruno; Carnesecchi, Julie; Bachmann, Alice; Gauthier, Karine Cécile; Yu, Shan; Giguère, Vincent; Chan, Franky L; Vanacker, Jean-Marc

    2014-10-21

    Several physiopathological processes require orientated cellular migration. This phenomenon highly depends on members of the RHO family of GTPases. Both excessive and deficient RHO activity impair directional migration. A tight control is thus exerted on these proteins through the regulation of their activation and of their stability. Here we show that the estrogen-related receptor α (ERRα) directly activates the expression of TNFAIP1, the product of which [BTB/POZ domain-containing adapter for Cullin3-mediated RhoA degradation 2 (BACURD2)] regulates RHOA protein turnover. Inactivation of the receptor leads to enhanced RHOA stability and activation. This results in cell disorientation, increased actin network, and inability to form a lamellipodium at the migration edge. As a consequence, directional migration, but not cell motility per se, is impaired in the absence of the receptor, under pathological as well as physiological conditions. Altogether, our results show that the control exerted by ERRα on RHOA stability is required for directional migration.

  16. 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.

  17. Sox2 in the dermal papilla niche controls hair growth by fine-tuning Bmp signaling in differentiating hair shaft progenitors

    PubMed Central

    Clavel, Carlos; Grisanti, Laura; Zemla, Roland; Rezza, Amelie; Barros, Rita; Sennett, Rachel; Mazloom, Amin; Chung, Chi-Yeh; Cai, Xiaoqiang; Cai, Chen-Leng; Pevny, Larysa; Nicolis, Silvia; Ma’ayan, Avi; Rendl, Michael

    2012-01-01

    SUMMARY How dermal papilla (DP) niche cells regulate hair follicle progenitors to control hair growth remains unclear. Using Tbx18Cre to target embryonic DP precursors, we ablate the transcription factor Sox2 early and efficiently, resulting in diminished hair shaft outgrowth. We find that DP niche expression of Sox2 controls the migration rate of differentiating hair shaft progenitors. Transcriptional profiling of Sox2 null DPs reveals increased Bmp6 and decreased Bmp inhibitor Sostdc1, a direct Sox2 transcriptional target. Subsequently, we identify upregulated Bmp signaling in knockout hair shaft progenitors and demonstrate that Bmps inhibit cell migration, an effect that can be attenuated by Sostdc1. A shorter and Sox2-negative hair type lacks Sostdc1 in the DP and shows reduced migration and increased Bmp activity of hair shaft progenitors. Collectively, our data identify Sox2 as a key regulator of hair growth that controls progenitor migration by fine-tuning Bmp-mediated mesenchymal-epithelial crosstalk. PMID:23153495

  18. Controlling Oxygen Mobility in Ruddlesden–Popper Oxides

    PubMed Central

    Lee, Dongkyu; Lee, Ho Nyung

    2017-01-01

    Discovering new energy materials is a key step toward satisfying the needs for next-generation energy conversion and storage devices. Among the various types of oxides, Ruddlesden–Popper (RP) oxides (A2BO4) are promising candidates for electrochemical energy devices, such as solid oxide fuel cells, owing to their attractive physicochemical properties, including the anisotropic nature of oxygen migration and controllable stoichiometry from oxygen excess to oxygen deficiency. Thus, understanding and controlling the kinetics of oxygen transport are essential for designing optimized materials to use in electrochemical energy devices. In this review, we first discuss the basic mechanisms of oxygen migration in RP oxides depending on oxygen nonstoichiometry. We then focus on the effect of changes in the defect concentration, crystallographic orientation, and strain on the oxygen migration in RP oxides. We also briefly review their thermal and chemical stability. Finally, we conclude with a perspective on potential research directions for future investigation to facilitate controlling oxygen ion migration in RP oxides. PMID:28772732

  19. 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.

  20. 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

  1. Quantitative impedimetric monitoring of cell migration under the stimulation of cytokine or anti-cancer drug in a microfluidic chip

    PubMed Central

    Xiao, Xia; Lei, Kin Fong; Huang, Chia-Hao

    2015-01-01

    Cell migration is a cellular response and results in various biological processes such as cancer metastasis, that is, the primary cause of death for cancer patients. Quantitative investigation of the correlation between cell migration and extracellular stimulation is essential for developing effective therapeutic strategies for controlling invasive cancer cells. The conventional method to determine cell migration rate based on comparison of successive images may not be an objective approach. In this work, a microfluidic chip embedded with measurement electrodes has been developed to quantitatively monitor the cell migration activity based on the impedimetric measurement technique. A no-damage wound was constructed by microfluidic phenomenon and cell migration activity under the stimulation of cytokine and an anti-cancer drug, i.e., interleukin-6 and doxorubicin, were, respectively, investigated. Impedance measurement was concurrently performed during the cell migration process. The impedance change was directly correlated to the cell migration activity; therefore, the migration rate could be calculated. In addition, a good match was found between impedance measurement and conventional imaging analysis. But the impedimetric measurement technique provides an objective and quantitative measurement. Based on our technique, cell migration rates were calculated to be 8.5, 19.1, and 34.9 μm/h under the stimulation of cytokine at concentrations of 0 (control), 5, and 10 ng/ml. This technique has high potential to be developed into a powerful analytical platform for cancer research. PMID:26180566

  2. The multiple faces of leukocyte interstitial migration

    PubMed Central

    Lämmermann, Tim; Germain, Ronald N.

    2014-01-01

    Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments. PMID:24573488

  3. Constrained Adherable Area of Nanotopographic Surfaces Promotes Cell Migration through the Regulation of Focal Adhesion via Focal Adhesion Kinase/Rac1 Activation.

    PubMed

    Lim, Jiwon; Choi, Andrew; Kim, Hyung Woo; Yoon, Hyungjun; Park, Sang Min; Tsai, Chia-Hung Dylan; Kaneko, Makoto; Kim, Dong Sung

    2018-05-02

    Cell migration is crucial in physiological and pathological processes such as embryonic development and wound healing; such migration is strongly guided by the surrounding nanostructured extracellular matrix. Previous studies have extensively studied the cell migration on anisotropic nanotopographic surfaces; however, only a few studies have reported cell migration on isotropic nanotopographic surfaces. We herein, for the first time, propose a novel concept of adherable area on cell migration using isotropic nanopore surfaces with sufficient nanopore depth by adopting a high aspect ratio. As the pore size of the nanopore surface was controlled to 200, 300, and 400 nm in a fixed center-to-center distance of 480 nm, it produced 86, 68, and 36% of adherable area, respectively, on the fabricated surface. A meticulous investigation of the cell migration in response to changes in the constrained adherable area of the nanotopographic surface showed 1.4-, 1.5-, and 1.6-fold increase in migration speeds and a 1.4-, 2-, and 2.5-fold decrease in the number of focal adhesions as the adherable area was decreased to 86, 68, and 36%, respectively. Furthermore, a strong activation of FAK/Rac1 signaling was observed to be involved in the promoted cell migration. These results suggest that the reduced adherable area promotes cell migration through decreasing the FA formation, which in turn upregulates FAK/Rac1 activation. The findings in this study can be utilized to control the cell migration behaviors, which is a powerful tool in the research fields involving cell migration such as promoting wound healing and tissue repair.

  4. Flexibility of Continental Navigation and Migration in European Mallards

    PubMed Central

    van Toor, Mariëlle L.; Hedenström, Anders; Waldenström, Jonas; Fiedler, Wolfgang; Holland, Richard A.; Thorup, Kasper; Wikelski, Martin

    2013-01-01

    The ontogeny of continent-wide navigation mechanisms of the individual organism, despite being crucial for the understanding of animal movement and migration, is still poorly understood. Several previous studies, mainly conducted on passerines, indicate that inexperienced, juvenile birds may not generally correct for displacement during fall migration. Waterbirds such as the mallard (Anas platyrhynchos, Linnaeus 1758) are more flexible in their migration behavior than most migratory songbirds, but previous experiments with waterbirds have not yet allowed clear conclusions about their navigation abilities. Here we tested whether immature mallard ducks correct for latitudinal displacement during fall migration within Europe. During two consecutive fall migration periods, we caught immature females on a stopover site in southeast Sweden, and translocated a group of them ca. 1,000 km to southern Germany. We followed the movements of the ducks via satellite GPS-tracking and observed their migration decisions during the fall and consecutive spring migration. The control animals released in Ottenby behaved as expected from banding recoveries: they continued migration during the winter and in spring returned to the population’s breeding grounds in the Baltics and Northwest Russia. Contrary to the control animals, the translocated mallards did not continue migration and stayed at Lake Constance. In spring, three types of movement tactics could be observed: 61.5% of the ducks (16 of 26) stayed around Lake Constance, 27% (7 of 26) migrated in a northerly direction towards Sweden and 11.5% of the individuals (3 of 26) headed east for ca. 1,000 km and then north. We suggest that young female mallards flexibly adjust their migration tactics and develop a navigational map that allows them to return to their natal breeding area. PMID:24023629

  5. 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

  6. The effect of growth hormone on fibroblast proliferation and keratinocyte migration.

    PubMed

    Lee, Sang Woo; Kim, Suk Hwa; Kim, Ji Youn; Lee, Yoonho

    2010-04-01

    The beneficial effects of growth hormones (GHs) on wound healing have been reported. Although the mechanism of how GH promotes wound healing is unclear, there are reports showing that the principal factor lies in the GH-stimulated production of IGF-1 in topical wounds. In this study, a human primary cell model was devised to examine how the topical application of GHs affects fibroblast proliferation and keratinocyte migration, which play fundamental roles in wound healing. The fibroblasts were cultured in media with different concentrations of GH. The amount of fibroblast proliferation was assessed using a tetrazolium-based colourimetric assay (MTT assay). The amount of newly formed IGF-I mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR). Keratinocyte migration was compared using a migration assay. Fibroblast proliferation was significantly higher in the experimental group than in the control group (the absorbance of 2.5IU L(-1) GH applied group: 0.3954+/-0.056, control group: 0.2943+/-0.0554, P<0.05), and the promotion of IGF-I formation by fibroblasts was observed. There was more keratinocyte migration in the experimental group than in the control group (the remaining gap in the 2.5IU L(-1) GH applied group after keratinocyte migration: 46.57+/-2.22% of the primary gap, control group: 75.14+/-3.44%, P<0.05). GH enhances the local formation of IGF-1, which activates fibroblast proliferation and keratinocyte migration. These results highlight the potential of the topical application of GHs in the treatment of wounds. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

  7. Regulation of migration in Mythimna separata (Walker) in China: A review integrating environmental, physiological, hormonal, genetic, and molecular factors

    USDA-ARS?s Scientific Manuscript database

    Each year the oriental armyworm, Mythimna separata, undertakes a seasonal, long-distance, multigeneration roundtrip migration between Southern and Northern China. The developmental decision to migrate is facultative and controlled by environmental, physiological, hormonal, genetic, and molecular fac...

  8. 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

  9. Least squares reverse time migration of controlled order multiples

    NASA Astrophysics Data System (ADS)

    Liu, Y.

    2016-12-01

    Imaging using the reverse time migration of multiples generates inherent crosstalk artifacts due to the interference among different order multiples. Traditionally, least-square fitting has been used to address this issue by seeking the best objective function to measure the amplitude differences between the predicted and observed data. We have developed an alternative objective function by decomposing multiples into different orders to minimize the difference between Born modeling predicted multiples and specific-order multiples from observational data in order to attenuate the crosstalk. This method is denoted as the least-squares reverse time migration of controlled order multiples (LSRTM-CM). Our numerical examples demonstrated that the LSRTM-CM can significantly improve image quality compared with reverse time migration of multiples and least-square reverse time migration of multiples. Acknowledgments This research was funded by the National Nature Science Foundation of China (Grant Nos. 41430321 and 41374138).

  10. "It Might Actually Work This Time": Benefits and Barriers to Adapted 12-Step Facilitation Therapy and Mutual-Help Group Attendance From the Perspective of Dually Diagnosed Individuals.

    PubMed

    Hagler, Kylee J; Rice, Samara L; Muñoz, Rosa E; Salvador, Julie G; Forcehimes, Alyssa A; Bogenschutz, Michael P

    2015-01-01

    Most U.S. healthcare professionals encourage mutual-help group involvement as an adjunct to treatment or aftercare for individuals with substance use disorders, yet there are multiple challenges in engaging in these community groups. Dually diagnosed individuals (DDIs) may face additional challenges in affiliating with mutual-help groups. Twelve-step facilitation for DDIs (TSF-DD), a manualized treatment to facilitate mutual-help group involvement, was developed to help patients engage in Double Trouble in Recovery (DTR), a mutual-help group tailored to DDIs. Given the promising role that TSF-DD and DTR may have for increasing abstinence while managing psychiatric symptoms, the aim of the current study was to systematically examine reasons for TSF-DD and DTR attendance from the perspective of DDIs using focus group data. Participants were a subset (n = 15) of individuals diagnosed with an alcohol use disorder as well as a major depressive, bipolar, or psychotic disorder who participated in a parent study testing the efficacy of TSF-DD for increasing mutual-help group involvement and reducing alcohol use. Analyses of focus group data revealed that participants construed DTR and TSF-DD as helpful tools in the understanding and management of their disorders. Relative to other mutual-help groups in which participants reported feeling ostracized because of their dual diagnoses, participants reported that it was beneficial to learn about dual disorders in a safe and accepting environment. Participants also expressed aspects that they disliked. Results from this study yield helpful empirical recommendations to healthcare professionals seeking to increase DDIs' participation in DTR or other mutual-help groups.

  11. Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa.

    PubMed

    Fox, James M; Mutalima, Nora; Molyneux, Elizabeth; Carpenter, Lucy M; Taylor, Graham P; Bland, Martin; Newton, Robert; Martin, Fabiola

    2016-03-01

    Human T-lymphotropic virus (HTLV)-1 causes T-cell leukaemia and myelopathy. Together with HTLV-2, it is endemic in some African nations. Seroprevalence data from Malawi are scarce, with no reports on associated disease incidence. HTLV seroprevalence and type were tested in 418 healthy mothers from Malawi. In addition, we tested the sera of 534 children to investigate mother-to-child transmission. To provide context, we conducted a systematic review and meta-analysis of HTLV seroprevalence in African women and children. Stored samples from a previous childhood cancer and BBV study were analysed. ELISA was used for HTLV screening followed by immunoblot for confirmation and typing. Standard methods were used for the systematic review. HTLV seroprevalence was 2.6% (11/418) in mothers and 2.2% (12/534) in children. Three mothers carried HTLV-1 alone, seven had HTLV-2 and one was dually infected. Three children carried HTLV-1 alone, seven had HTLV-2 and two were dually infected. Only two corresponding mothers of the 12 HTLV-positive children were HTLV positive. The systematic review included 66 studies of women and 13 of children conducted in 25 African countries. Seroprevalence of HTLV-1 varied from 0 to 17% and of HTLV-2 from 0 to 4%. In contrast to findings from other studies in Africa, the seroprevalence of HTLV-2 was higher than that of HTLV-1 in Malawi and one of the highest for the African region. The lack of mother-child concordance suggests alternative sources of infection among children. Our data and analyses contribute to HTLV prevalence mapping in Africa. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  12. Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

    PubMed

    Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

    2008-11-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

  13. Functional interactions of HIV-infection and methamphetamine dependence during motor programming.

    PubMed

    Archibald, Sarah L; Jacobson, Mark W; Fennema-Notestine, Christine; Ogasawara, Miki; Woods, Steven P; Letendre, Scott; Grant, Igor; Jernigan, Terry L

    2012-04-30

    Methamphetamine (METH) dependence is frequently comorbid with HIV infection and both have been linked to alterations of brain structure and function. In a previous study, we showed that the brain volume loss characteristic of HIV infection contrasts with METH-related volume increases in striatum and parietal cortex, suggesting distinct neurobiological responses to HIV and METH (Jernigan et al., 2005). Functional magnetic resonance imaging (fMRI) has the potential to reveal functional interactions between the effects of HIV and METH. In the present study, 50 participants were studied in four groups: an HIV+ group, a recently METH-dependent group, a dually affected group, and a group of unaffected community comparison subjects. An fMRI paradigm consisting of motor sequencing tasks of varying levels of complexity was administered to examine blood oxygenation level dependent (BOLD) changes. Within all groups, activity increased significantly with increasing task complexity in large clusters within sensorimotor and parietal cortex, basal ganglia, cerebellum, and cingulate. The task complexity effect was regressed on HIV status, METH status, and the HIV×METH interaction term in a simultaneous multiple regression. HIV was associated with less complexity-related activation in striatum, whereas METH was associated with less complexity-related activation in parietal regions. Significant interaction effects were observed in both cortical and subcortical regions; and, contrary to expectations, the complexity-related activation was less aberrant in dually affected than in single risk participants, in spite of comparable levels of neurocognitive impairment among the clinical groups. Thus, HIV and METH dependence, perhaps through their effects on dopaminergic systems, may have opposing functional effects on neural circuits involved in motor programming. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Food and drink consumption among 1-5-year-old Los Angeles County children from households receiving dual SNAP and WIC v. only WIC benefits.

    PubMed

    Liu, Jane; Kuo, Tony; Jiang, Lu; Robles, Brenda; Whaley, Shannon E

    2017-10-01

    The Supplemental Nutrition Assistance Program (SNAP) and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) are two of the more well-known food assistance programmes in the USA. The current study describes food consumption patterns of children aged 1-5 years living in households dually enrolled in these two programmes v. households enrolled only in WIC. Food consumption and SNAP participation were assessed using data from the 2014 Survey of Los Angeles County (LAC) WIC Participants and the Follow-Up Survey of the same households that were also SNAP beneficiaries. Telephone interviews were conducted with WIC parents regarding each child's (i.e. beneficiary's) food consumption patterns. Follow-up interviews were conducted with those who reported receiving SNAP. Multivariable regression analyses were performed to assess the relationships between food and beverage consumption and dual v. single food assistance programme participation. LAC, California. Children of WIC-enrolled households in LAC during 2014 (n 3248). This included a sub-sample of dual WIC- and SNAP-enrolled households (n 1295). Survey participants were the beneficiaries' parents. Children from dually enrolled households consumed 1·03 (P<0·05) and 1·04 (P<0·01) more servings of fruits and vegetables daily respectively, 1·07 more sugar-sweetened beverages daily (P<0·001) and ate sweets/sweetened foods 1·04 more times daily (P<0·001) than children from households participating only in WIC. Results suggest that SNAP+WIC enrolment is associated with increased consumption of both healthy foods and foods containing minimal nutritional value. Complementary nutrition education efforts across the two programmes may help beneficiaries maximize healthful food purchases with SNAP dollars.

  15. Acyl-protein thioesterase 2 catalyzes the deacylation of peripheral membrane-associated GAP-43.

    PubMed

    Tomatis, Vanesa M; Trenchi, Alejandra; Gomez, Guillermo A; Daniotti, Jose L

    2010-11-30

    An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution.

  16. Gravitational Instabilities in a Young Protoplanetary Disk with Embedded Objects

    NASA Astrophysics Data System (ADS)

    Desai, Karna M.; Steiman-Cameron, Thomas Y.; Durisen, Richard H.

    2018-01-01

    Gravitational Instabilities (GIs), a mechanism for angular momentum transport, are more prominent during the early phases of protoplanetary disk evolution when the disk is relatively massive. In my dissertation work, I performed radiative 3D hydrodynamics simulations (by employing the code, CHYMERA) and extensively studied GIs by inserting different objects in the ‘control disk’ (a 0.14 M⊙ protoplanetary disk around a 1 M⊙ star).Studying planetary migration helps us better constrain planet formation models. To study the migration of Jovian planets, in 9 separate simulations, each of the 0.3 MJ, 1 MJ, and 3 MJ planets was inserted near the Inner and Outer Lindblad Resonances and the Corotation Radius (CR) of the dominant GI-induced two-armed spiral density wave in the disk. I found the migration timescales to be longer in a GI-active disk when compared to laminar disks. The 3 MJ planet controls its own orbital evolution, while the migration of a 0.3 MJ planet is stochastic in nature. I defined a ‘critical mass’ as the mass of an arm of the dominant two-armed spiral density wave within the planet’s Hill diameter. Planets above this mass control their own destiny, and planets below this mass are scattered by the disk. This critical mass could provide a recipe for predicting the migration behavior of planets in GI-active disks.To understand the stochastic migration of low-mass planets, I performed a simulation of 240 zero-mass planet-tracers (hereafter, planets) by inserting these at a range of locations in the control disk (an equivalent of 240 simulations of Saturn-mass or lower-mass objects). I calculated a Diffusion Coefficient (3.6 AU2/ 1000 yr) to characterize the stochastic migration of planets. I analyzed the increase in the eccentricity dispersion and compared it with the observed exoplanet eccentricities. The diffusion of planets can be a slow process, resulting in the survival of small planetary cores. Stochastic migration of planets is dynamically similar to the radial migration of stars in the Milky Way (MW). In MW, the CR of transient spiral arms can cause radial migration of stars.Also, to determine the effects of a companion, I studied GIs in a circumbinary disk with a 0.2 M⊙ brown dwarf companion.

  17. Pre-migration planning and depression among new migrants to Hong Kong: the moderating role of social support.

    PubMed

    Chou, Kee-Lee

    2009-04-01

    Although it is a well-known fact that migration is a risk factor contributing to psychopathology, little is known about how pre-migration factors may lead to depression among migrants. The present study examined the relationship between poorly planned migration and depressive symptoms, and evaluated the moderating roles of optimism, sense of control, and social support in the relationship between pre-migration planning and depression among new immigrants from Mainland China to Hong Kong. A representative sample of 449 migrants aged 18 and above were interviewed in 2007 using a face-to-face format. The 20-item Center for Epidemiological Studies of Depression (CES-D) scale was used to measure depressive symptoms, and a series of questions regarding socio-demographic characteristics (age, gender, marital status, education, and household income), optimism, sense of control, and social support were also included. A total of 26.5% of our sample scored 16 or above on the CES-D scale, which indicated a clinically significant case of depression. Poor migration planning was significantly related to CES-D scores after adjusting for all socio-demographic variables and three psycho-social factors. In addition, optimism, sense of control, and social support were also significantly related to the CES-D score. It was also found that social support reduced the harmful impact of poor migration planning on depressive symptoms. New immigrants to Hong Kong from Mainland China are at risk for depressive symptoms, especially those who are not well prepared for migration; therefore, prevention measures, particularly strengthening their social support in Hong Kong, should be considered seriously by policy makers.

  18. Raf-1 levels determine the migration rate of primary endometrial stromal cells of patients with endometriosis

    PubMed Central

    Yotova, Iveta; Quan, Ping; Gaba, Aulona; Leditznig, Nadja; Pateisky, Petra; Kurz, Christine; Tschugguel, Walter

    2012-01-01

    Endometriosis is a disease characterized by the localization of endometrial tissue outside the uterine cavity. The differences observed in migration of human endometrial stromal cells (hESC) obtained from patients with endometriosis versus healthy controls were proposed to correlate with the abnormal activation of Raf-1/ROCKII signalling pathway. To evaluate the mechanism by which Raf-1 regulates cytoskeleton reorganization and motility, we used primary eutopic (Eu-, n = 16) and ectopic (Ec-, n = 8; isolated from ovarian cysts) hESC of patients with endometriosis and endometriosis-free controls (Co-hESC, n = 14). Raf-1 siRNA knockdown in Co- and Eu-hESC resulted in contraction and decreased migration versus siRNA controls. This phenotype was reversed following the re-expression of Raf-1 in these cells. Lowest Raf-1 levels in Ec-hESC were associated with hyperactivated ROCKII and ezrin/radixin/moesin (E/R/M), impaired migration and a contracted phenotype similar to Raf-1 knockdown in Co- and Eu-hESC. We further show that the mechanism by which Raf-1 mediates migration in hESC includes direct myosin light chain phosphatase (MYPT1) phosphorylation and regulation of the levels of E/R/M, paxillin, MYPT1 and myosin light chain (MLC) phosphorylation indirectly via the hyperactivation of ROCKII kinase. Furthermore, we suggest that in contrast to Co-and Eu-hESC, where the cellular Raf-1 levels regulate the rate of migration, the low cellular Raf-1 content in Ec-hESC, might ensure their restricted migration by preserving the contracted cellular phenotype. In conclusion, our findings suggest that cellular levels of Raf-1 adjust the threshold of hESC migration in endometriosis. PMID:22225925

  19. Multi-Cellular Logistics of Collective Cell Migration

    PubMed Central

    Yamao, Masataka; Naoki, Honda; Ishii, Shin

    2011-01-01

    During development, the formation of biological networks (such as organs and neuronal networks) is controlled by multicellular transportation phenomena based on cell migration. In multi-cellular systems, cellular locomotion is restricted by physical interactions with other cells in a crowded space, similar to passengers pushing others out of their way on a packed train. The motion of individual cells is intrinsically stochastic and may be viewed as a type of random walk. However, this walk takes place in a noisy environment because the cell interacts with its randomly moving neighbors. Despite this randomness and complexity, development is highly orchestrated and precisely regulated, following genetic (and even epigenetic) blueprints. Although individual cell migration has long been studied, the manner in which stochasticity affects multi-cellular transportation within the precisely controlled process of development remains largely unknown. To explore the general principles underlying multicellular migration, we focus on the migration of neural crest cells, which migrate collectively and form streams. We introduce a mechanical model of multi-cellular migration. Simulations based on the model show that the migration mode depends on the relative strengths of the noise from migratory and non-migratory cells. Strong noise from migratory cells and weak noise from surrounding cells causes “collective migration,” whereas strong noise from non-migratory cells causes “dispersive migration.” Moreover, our theoretical analyses reveal that migratory cells attract each other over long distances, even without direct mechanical contacts. This effective interaction depends on the stochasticity of the migratory and non-migratory cells. On the basis of these findings, we propose that stochastic behavior at the single-cell level works effectively and precisely to achieve collective migration in multi-cellular systems. PMID:22205934

  20. Uniqueness of polymorphism for a discrete, selection-migration model with genetic dominance

    Treesearch

    James F. Selgrade; James H. Roberds

    2009-01-01

    The migration into a natural population of a controlled population, e.g., a transgenic population, is studied using a one island selection-migration model. A 2-dimensional system of nonlinear difference equations describes changes in allele frequency and population size between generations. Biologically reasonable conditions are obtained which guarantee the existence...

  1. Boundary migration and disappearance of voids in Alpha-Al2O3 at 2000 deg C

    NASA Technical Reports Server (NTRS)

    Komatsu, M.; Fujita, H.

    1984-01-01

    A series of photographs taken with Osaka University's high temperature 3MV electron microscope of alpha-A1(z)O(3) at 2000 C is presented. The dynamic study shows grain boundary migration in progress and demonstrates that disappearance of voids is controlled by boundary migration.

  2. 76 FR 9849 - 30-Day Notice of Proposed Information Collection: Refugee Biographic Data, OMB Control Number...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-22

    ... Originating Office: Bureau of Population, Refugees, and Migration, PRM/A Form Number: N/A Respondents: Refugee... Migration. Methodology: Biographic information is collected in a face-to-face interview of the applicant.... Lawrence Bartlett, Acting Director, Office of Admissions, Bureau of Population, Refugees, and Migration...

  3. 75 FR 3726 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-22

    ...- Migration' Variances (Renewal), EPA ICR Number 1353.09, OMB Control Number 2050-0062 AGENCY: Environmental... docket, go to http://www.regulations.gov . Title: Land Disposal Restrictions `No-Migration' Variances... migration.'' The applicant must demonstrate that hazardous wastes can be managed safely in a particular land...

  4. Intertwined effects of gender and migration status on persistence in SET study programmes

    NASA Astrophysics Data System (ADS)

    Guenther, Elisabeth Anna; Koeszegi, Sabine Theresia

    2017-11-01

    This paper explores the intersectional interference of gender and migration status on students' persistence at an Austrian University of Technology. While controlling for the pre-university education and performance indicators, we estimate the odds for the persistence of male and female students, as well as of students with diverse migration statuses. We use the enrolment data of students from 1998 to 2010. The analysis reveals remarkable and significant effects of gender and migration status, as well as intersectional interference effects from both social categories on persistence. Female and students with immigration status are less likely to persist, even if performance and previous relevant experiences are controlled. A segregated analysis of the student population sheds further light on the interlocked and entangled effects of the social ascriptions underlying gender and migration status. The analysis supports the proposition of the accumulation of (dis-)advantages along students' careers. The profound quantification of gender and migration status effects can be utilised as basis for further research and purposeful policy measures to increase persistence in Science, Engineering and Technology for students with diverse backgrounds.

  5. Prohibitin, relocated to the front ends, can control the migration directionality of colorectal cancer cells

    PubMed Central

    Guo, Li-Li; Hu, Chun-Ting; Huang, Ying-Xin; Huang, Guan; Jing, Fang-Yan; Liu, Chao; Li, Zhuo-Yi; Zhou, Na; Yan, Qian-Wen; Lei, Yan; Zhu, Shi-Jie; Cheng, Zhi-Qiang; Cao, Guang-Wen; Deng, Yong-Jian; Ding, Yan-Qing

    2017-01-01

    Directional migration is a cost-effective movement allowing invasion and metastatic spread of cancer cells. Although migration related to cytoskeletal assembly and microenvironmental chemotaxis has been elucidated, little is known about interaction between extracellular and intracellular molecules for controlling the migrational directionality. A polarized expression of prohibitin (PHB) in the front ends of CRC cells favors metastasis and is correlated with poor prognosis for 545 CRC patients. A high level of vascular endothelial growth factor (VEGF) in the interstitial tissue of CRC patients is associated with metastasis. VEGF bound to its receptor, neuropilin-1, can stimulate the activation of cell division cycle 42, which recruits intra-mitochondrial PHB to the front end of a CRC cell. This intracellular relocation of PHB results in the polymerization and reorganization of filament actin extending to the front end of the cell. As a result, the migration directionality of CRC cells is targeted towards VEGF. Together, these findings identify PHB as a key modulator of directional migration of CRC cells and a target for metastasis. PMID:29100316

  6. 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.

  7. Androgen-Induced Cell Migration: Role of Androgen Receptor/Filamin A Association

    PubMed Central

    Castoria, Gabriella; D'Amato, Loredana; Ciociola, Alessandra; Giovannelli, Pia; Giraldi, Tiziana; Sepe, Leandra; Paolella, Giovanni; Barone, Maria Vittoria; Migliaccio, Antimo; Auricchio, Ferdinando

    2011-01-01

    Background Androgen receptor (AR) controls male morphogenesis, gametogenesis and prostate growth as well as development of prostate cancer. These findings support a role for AR in cell migration and invasiveness. However, the molecular mechanism involved in AR-mediated cell migration still remains elusive. Methodology/Principal Findings Mouse embryo NIH3T3 fibroblasts and highly metastatic human fibrosarcoma HT1080 cells harbor low levels of transcriptionally incompetent AR. We now report that, through extra nuclear action, AR triggers migration of both cell types upon stimulation with physiological concentrations of the androgen R1881. We analyzed the initial events leading to androgen-induced cell migration and observed that challenging NIH3T3 cells with 10 nM R1881 rapidly induces interaction of AR with filamin A (FlnA) at cytoskeleton. AR/FlnA complex recruits integrin beta 1, thus activating its dependent cascade. Silencing of AR, FlnA and integrin beta 1 shows that this ternary complex controls focal adhesion kinase (FAK), paxillin and Rac, thereby driving cell migration. FAK-null fibroblasts migrate poorly and Rac inhibition by EHT impairs motility of androgen-treated NIH3T3 cells. Interestingly, FAK and Rac activation by androgens are independent of each other. Findings in human fibrosarcoma HT1080 cells strengthen the role of Rac in androgen signaling. The Rac inhibitor significantly impairs androgen-induced migration in these cells. A mutant AR, deleted of the sequence interacting with FlnA, fails to mediate FAK activation and paxillin tyrosine phosphorylation in androgen-stimulated cells, further reinforcing the role of AR/FlnA interaction in androgen-mediated motility. Conclusions/Significance The present report, for the first time, indicates that the extra nuclear AR/FlnA/integrin beta 1 complex is the key by which androgen activates signaling leading to cell migration. Assembly of this ternary complex may control organ development and prostate cancer metastasis. PMID:21359179

  8. Politics and ideology in migration policy formulation: the case of Kuwait.

    PubMed

    Russell, S S

    1989-01-01

    In 1716, 3 prominent families of the original Kuwaitis agreed that 1 family would control finance and commerce, another seafaring activities, and the 3rd the government. This continued allegiance has been instrumental in shaping migration policy in Kuwait. Migration to Kuwait began in the 1930s-1940s to meet labor needs of the oil industry and the social infrastructure. This began a steady increase, with several setbacks in the early 1970s, of the migrant population. Between (1959-1964), Kuwait had to determine how it would exist and operate as an independent state. The new state established migration policy based on a need for national identity and on weighing the interests of 4 political groups: the ruling family; the wealthy merchants; the Arab Nationalist Movement; and Kuwaiti Nationalists. 3 migration laws emerged which satisfied the 4 groups and in some form continued into the 1980s. These laws basically allowed the continuation of free immigration of labor with the government controlling entry, movement, rights, and employment of the migrants while stressing neutrality and reciprocity with other states, especially Arab states. 1 law greatly limited the number of citizenships to nonKuwaitis and guaranteed economic control and major share of profits to Kuwaitis. Between 1965-1984, many changes to migration policy occurred for political, demographic, and economic reasons. 1 such change was an amendment restricting naturalization to Muslims, thereby not allowing naturalization of the growing Asian migration population, to preserve their cultural authenticity. By 1984, following 1 rebalance of the distribution of Kuwaitis and nonKuwaitis, economic declines, and security threats, migration policy shifted back to population balance. Kuwaiti history shows, however, that experimenting with migration policy and population balance cannot establish internal political and social cohesion. This is a revised version of a paper originally presented at the 1987 Annual Meeting of the Population Association of America (see Population Index, Vol. 53, No. 3, Fall 1987, p. 409).

  9. Cryogenic Control System Migration and Developments towards the UNICOS CERN Standard at INFN

    NASA Astrophysics Data System (ADS)

    Modanese, Paolo; Calore, Andrea; Contran, Tiziano; Friso, Alessandro; Pengo, Marco; Canella, Stefania; Burioli, Sergio; Gallese, Benedetto; Inglese, Vitaliano; Pezzetti, Marco; Pengo, Ruggero

    The cryogenic control systems at Laboratori Nazionali di Legnaro (LNL) are undergoing an important and radical modernization, allowing all the plants controls and supervision systems to be renewed in a homogeneous way towards the CERN-UNICOS standard. Before the UNICOS migration project started there were as many as 7 different types of PLC and 7 different types of SCADA, each one requiring its own particular programming language. In these conditions, even a simple modification and/or integration on the program or on the supervision, required the intervention of a system integrator company, specialized in its specific control system. Furthermore it implied that the operators have to be trained to learn the different types of control systems. The CERN-UNICOS invented for LHC [1] has been chosen due to its reliability and planned to run and be maintained for decades on. The complete migration is part of an agreement between CERN and INFN.

  10. Improving health care delivery to aging adults with disabilities: social work with dual eligibles in a climate of health care reform.

    PubMed

    Bachman, Sara S; Gonyea, Judith G

    2012-01-01

    Adults aging with disabilities comprise a diverse group. In this article, we identify the prevalence and characteristics of this target population, focusing on adults who are dually eligible for Medicare and Medicaid. We articulate challenges in the delivery of health, social, and support services to adults aging with disabilities, particularly how existing health care policy and financing contributes to fragmentation of care. Finally, we identify opportunities for social workers to advocate for and promote system improvements in the delivery of care for aging adults with disabilities in the current climate of health care reform.

  11. Utilization and expenditures under Medicaid for Supplemental Security Income disabled

    PubMed Central

    Adams, E. Kathleen; Ellwood, Marilyn Rymer; Pine, Penelope L.

    1989-01-01

    Recently available data on major disabling conditions of the Supplemental Security Income disabled are used to examine 1984 patterns of Medicaid expenditures in California, Georgia, Michigan, and Tennessee. Results indicate that 37-58 percent of these expenditures are for enrollees whose major disabling condition involves mental retardation or other mental disorders. This pattern occurs because a high proportion of disabled enrollees have these conditions, rather than high expenses per enrollee. Annual Medicaid expenditures per enrollee were highest for the disabled with neoplasms, blood disorders, and genitourinary conditions. Expenditures per enrollee were higher for younger enrollees and lower for those dually enrolled in Medicare. PMID:10318336

  12. Low-Melt Polyamic Acid Based Powder Coatings

    NASA Technical Reports Server (NTRS)

    Jolley, Scott T. (Inventor)

    2017-01-01

    The present invention is directed to a method for powder coating a metal substrate using a low-melt polyamic acid (PAA) polymer that readily imidizes to polyimides. These low-melt PAAs have been shown to be useful in resins applied as powder coatings to metal surfaces. The resin includes an end-capping material capable of providing crosslinking functionality to at least one end of the low-melt PAA polymer. The end-capping material functions dually as a polymerization chain terminator and crosslinking agent, thus producing resins that have molecular weights low enough to flow well and form good cured films applicable for use in powder coating.

  13. Dual-eligibles with Mental Disorders and Medicare Part D: How are they faring?

    PubMed Central

    Donohue, Julie M.; Huskamp, Haiden A.; Zuvekas, Samuel H.

    2009-01-01

    In 2006, 6 million beneficiaries who were dually eligible for Medicare and Medicaid switched from Medicaid to Medicare Part D coverage of their prescription drugs. This change led to a significant expansion of Medicare’s role in financing psychotropic medications for this group. A reduction in the number of plans serving dual-eligibles and an increase in utilization restrictions for some psychotropics since 2006 raises concerns about medication access for dual-eligibles with mental disorders and point to potential problems with adverse selection. To improve access to medication for this population, Medicare might consider changes to the enrollment and risk-sharing systems. PMID:19414883

  14. The causes of international labor migrations--a demand-determined approach.

    PubMed

    Straubhaar, T

    1986-01-01

    The author first studies the reasons why people migrate using a neoclassical approach concerning income differentials. He tests this approach empirically and demonstrates its limits. A demand-determination approach based on human capital theory is then outlined to overcome these limits and to take into account restrictive immigration controls. Migration from Italy, Spain, Greece, Portugal, and Turkey to the European Community destination countries is examined. It is concluded that "the demand for immigrants in the destination country is the decisive condition for the phenomenon of international labor migration, and the supply of migration-willing workers is only a necessary condition." excerpt

  15. The effect of pulsed electric fields on the electrotactic migration of human neural progenitor cells through the involvement of intracellular calcium signaling.

    PubMed

    Hayashi, Hisamitsu; Edin, Fredrik; Li, Hao; Liu, Wei; Rask-Andersen, Helge

    2016-12-01

    Endogenous electric fields (EFs) are required for the physiological control of the central nervous system development. Application of the direct current EFs to neural stem cells has been studied for the possibility of stem cell transplantation as one of the therapies for brain injury. EFs generated within the nervous system are often associated with action potentials and synaptic activity, apparently resulting in a pulsed current in nature. The aim of this study is to investigate the effect of pulsed EF, which can reduce the cytotoxicity, on the migration of human neural progenitor cells (hNPCs). We applied the mono-directional pulsed EF with a strength of 250mV/mm to hNPCs for 6h. The migration distance of the hNPCs exposed to pulsed EF was significantly greater compared with the control not exposed to the EF. Pulsed EFs, however, had less of an effect on the migration of the differentiated hNPCs. There was no significant change in the survival of hNPCs after exposure to the pulsed EF. To investigate the role of Ca 2+ signaling in electrotactic migration of hNPCs, pharmacological inhibition of Ca 2+ channels in the EF-exposed cells revealed that the electrotactic migration of hNPCs exposed to Ca 2+ channel blockers was significantly lower compared to the control group. The findings suggest that the pulsed EF induced migration of hNPCs is partly influenced by intracellular Ca 2+ signaling. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Comparing internal migration across the countries of Latin America: A multidimensional approach

    PubMed Central

    Bernard, Aude; Rowe, Francisco; Bell, Martin; Ueffing, Philipp; Charles-Edwards, Elin

    2017-01-01

    While considerable progress has been made in understanding the way particular aspects of internal migration, such as its intensity, age profile and spatial impact, vary between countries around the world, little attention to date has been given to establishing how these dimensions of migration interact in different national settings. We use recently developed measures of internal migration that are scale-independent to compare the overall intensity, age composition, spatial impact, and distance profile of internal migration in 19 Latin American countries. Comparisons reveal substantial cross-national variation but cluster analysis suggests the different dimensions of migration evolve systematically to form a broad sequence characterised by low intensities, young ages at migration, unbalanced flows and high friction of distance at lower levels of development, trending to high intensities, an older age profile of migration, more closely balanced flows and lower friction of distance at later stages of development. However, the transition is not linear and local contingencies, such as international migration and political control, often distort the migration-development nexus, leading to unique migration patterns in individual national contexts. PMID:28328932

  17. Measurements of fluid transport by controllable vertical migrations of plankton

    NASA Astrophysics Data System (ADS)

    Houghton, Isabel A.; Dabiri, John O.

    2016-11-01

    Diel vertical migration of zooplankton has been proposed to be a significant contributor to local and possibly large-scale fluid transport in the ocean. However, studies of this problem to date have been limited to order-of-magnitude estimates based on first principles and a small number of field observations. In this work, we leverage the phototactic behavior of zooplankton to stimulate controllable vertical migrations in the laboratory and to study the associated fluid transport and mixing. Building upon a previous prototype system, a laser guidance system induces vertical swimming of brine shrimp (Artemia salina) in a 2.1 meter tall, density-stratified water tank. The animal swimming speed and spacing during the controlled vertical migration is characterized with video analysis. A schlieren imaging system is utilized to visualize density perturbations to a stable stratification for quantification of fluid displacement length scales and restratification timescales. These experiments can add to our understanding of the dynamics of active particles in stratified flows. NSF and US-Israel Binational Science Foundation.

  18. Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling.

    PubMed

    Borrell, Víctor; Marín, Oscar

    2006-10-01

    Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.

  19. Return migration and the health of older aged parents: evidence from rural Thailand.

    PubMed

    Zimmer, Zachary; Knodel, John

    2010-10-01

    To examine the extent to which an association exists between health of older parents and return migration of children in rural Thailand. Data come from the 2006 Migration Impact Survey specifically designed to obtain information on the impact of migration on older adults in rural areas. Associations are examined from both the perspectives of parents (N = 883) and migrating children (N = 2,150) using equations that adjust for demographic characteristics of parents and children and factors that may indicate unmet support needs. A robust association with poor health promoting migration returns from both parent and child perspective exists and remains even with controls that might attenuate the relationship. Although media discussions have pointed out dangers of out-migration for older adults, little systematic evidence exists. This study supports the viewpoint that accommodations for older adults can be made despite social changes promoting out-migration and demographic aging of the population.

  20. Drebrin-mediated microtubule–actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection

    DOE PAGES

    Trivedi, Niraj; Stabley, Daniel R.; Cain, Blake; ...

    2017-02-23

    Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule–actomyosin crosstalk is required for a neuron’s ‘two-stroke’ nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule–actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration. Lattice light-sheet and structured illumination microscopy reveal a proximal leading process nanoscale architecture wherein f-actin and drebrin intervene between microtubules and the plasma membrane. Functional perturbationsmore » of drebrin demonstrate that proximal leading process microtubule–actomyosin coupling steers the direction of centrosome and somal migration, as well as the switch from tangential to radial migration. Finally, the Siah2 E3 ubiquitin ligase antagonizes drebrin function, suggesting a model for control of the microtubule–actomyosin interfaces during neuronal differentiation.« less

  1. Drebrin-mediated microtubule–actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection

    PubMed Central

    Trivedi, Niraj; Stabley, Daniel R.; Cain, Blake; Howell, Danielle; Laumonnerie, Christophe; Ramahi, Joseph S.; Temirov, Jamshid; Kerekes, Ryan A.; Gordon-Weeks, Phillip R.; Solecki, David J.

    2017-01-01

    Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule–actomyosin crosstalk is required for a neuron's ‘two-stroke' nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule–actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration. Lattice light-sheet and structured illumination microscopy reveal a proximal leading process nanoscale architecture wherein f-actin and drebrin intervene between microtubules and the plasma membrane. Functional perturbations of drebrin demonstrate that proximal leading process microtubule–actomyosin coupling steers the direction of centrosome and somal migration, as well as the switch from tangential to radial migration. Finally, the Siah2 E3 ubiquitin ligase antagonizes drebrin function, suggesting a model for control of the microtubule–actomyosin interfaces during neuronal differentiation. PMID:28230156

  2. Reduced Healthcare Use and Apparent Savings with Passive Home Monitoring Technology: A Pilot Study.

    PubMed

    Finch, Michael; Griffin, Kristen; Pacala, James T

    2017-06-01

    To conduct a cost analysis of ambient assisted living technology, which is promising for improving the ability of individuals and care providers to monitor daily activities and gain better awareness through proactive management of health and safety. Three-arm cohort study. Homes of enrollees of a state-based healthcare plan for older adults. Enrollees dually eligible for Medicare and Medicaid (N = 268). Health and safety passive remote patient monitoring (PRPM) systems were installed in enrollees' homes (the intervention group) with monitoring and proactive intervention of a case manager when deviation from baseline subject behavior was detected. Claims data were collected over 12 months to assess healthcare use and costs in the intervention group and to compare use and costs with those of two control groups: a concurrent group of enrollees who declined the technology and a historical cohort matched on age to the participation group. Although the small sample size precluded cost differences that were statistically significant, the participant group used substantially less custodial care, emergency department (ED) services, inpatient stays, and ED costs than the two control groups. In this pilot study, the PRPM system was associated with apparent healthcare cost savings. Although more cost analyses are warranted, ambient assisted living technologies are a potentially valuable investment for older adult care. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

  3. List Memory in Young Adults With Language Learning Disability

    PubMed Central

    Byrd, Courtney T.; McGregor, Karla K.; Zimmerman, Hannah; Bludau, Kadee

    2015-01-01

    Purpose The purpose of this study was to characterize the verbal memory limitations of young adults with language learning disability (LLD). Method Sixteen young adults with LLD and 34 age- and education-matched controls with typical language participated in a Deese–Roediger–McDermott (DRM; Deese, 1959; Roediger & McDermott, 1995) list recall experiment. Participants listened to 12-item word lists that converged on a nonpresented critical item (e.g., rain) semantically (umbrella, drench, weather, hail), phonologically (train, main, ran, wren), or dually in a hybrid list (umbrella, train, drench, main) and recalled words in no particular order. Group comparisons were made on veridical recall (i.e., words that were presented) and false recall of nonpresented critical items. Recall performance was analyzed by list type and list position to examine potential differences in the quality of memorial processes. Results The LLD group produced fewer veridical recalls than the controls. Both groups demonstrated list type and list position effects in veridical recall. False recall of the critical items was comparable in the 2 groups and varied by list type in predictable ways. Conclusion Young adults with LLD have verbal memory limitations characterized by quantitatively low levels of accurate recall. Qualitative patterns of recall are similar to those of unaffected peers. Therefore, the memory problem is characterized by limited capacity; memorial processes appear to be intact. PMID:25652445

  4. Paxillin Mediates Sensing of Physical Cues and Regulates Directional Cell Motility by Controlling Lamellipodia Positioning

    PubMed Central

    Sero, Julia E.; Thodeti, Charles K.; Mammoto, Akiko; Bakal, Chris; Thomas, Sheila; Ingber, Donald E.

    2011-01-01

    Physical interactions between cells and the extracellular matrix (ECM) guide directional migration by spatially controlling where cells form focal adhesions (FAs), which in turn regulate the extension of motile processes. Here we show that physical control of directional migration requires the FA scaffold protein paxillin. Using single-cell sized ECM islands to constrain cell shape, we found that fibroblasts cultured on square islands preferentially activated Rac and extended lamellipodia from corner, rather than side regions after 30 min stimulation with PDGF, but that cells lacking paxillin failed to restrict Rac activity to corners and formed small lamellipodia along their entire peripheries. This spatial preference was preceded by non-spatially constrained formation of both dorsal and lateral membrane ruffles from 5–10 min. Expression of paxillin N-terminal (paxN) or C-terminal (paxC) truncation mutants produced opposite, but complementary, effects on lamellipodia formation. Surprisingly, pax−/− and paxN cells also formed more circular dorsal ruffles (CDRs) than pax+ cells, while paxC cells formed fewer CDRs and extended larger lamellipodia even in the absence of PDGF. In a two-dimensional (2D) wound assay, pax−/− cells migrated at similar speeds to controls but lost directional persistence. Directional motility was rescued by expressing full-length paxillin or the N-terminus alone, but paxN cells migrated more slowly. In contrast, pax−/− and paxN cells exhibited increased migration in a three-dimensional (3D) invasion assay, with paxN cells invading Matrigel even in the absence of PDGF. These studies indicate that paxillin integrates physical and chemical motility signals by spatially constraining where cells will form motile processes, and thereby regulates directional migration both in 2D and 3D. These findings also suggest that CDRs may correspond to invasive protrusions that drive cell migration through 3D extracellular matrices. PMID:22194823

  5. Stress and food deprivation: linking physiological state to migration success in a teleost fish.

    PubMed

    Midwood, Jonathan D; Larsen, Martin H; Aarestrup, Kim; Cooke, Steven J

    2016-12-01

    Food deprivation is a naturally occurring stressor that is thought to influence the ultimate life-history strategy of individuals. Little is known about how food deprivation interacts with other stressors to influence migration success. European populations of brown trout (Salmo trutta) exhibit partial migration, whereby a portion of the population smoltifies and migrates to the ocean, and the rest remain in their natal stream. This distinct, natural dichotomy of life-history strategies provides an excellent opportunity to explore the roles of energetic state (as affected by food deprivation) and activation of the glucocorticoid stress response in determining life-history strategy and survival of a migratory species. Using an experimental approach, the relative influences of short-term food deprivation and experimental cortisol elevation (i.e. intra-coelomic injection of cortisol suspended in cocoa butter) on migratory status, survival and growth of juvenile brown trout relative to a control were evaluated. Fewer fish migrated in both the food deprivation and cortisol treatments; however, migration of fish in cortisol and control treatments occurred at the same time while that of fish in the food deprivation treatment was delayed for approximately 1 week. A significantly greater proportion of trout in the food deprivation treatment remained in their natal stream, but unlike the cortisol treatment, there were no long-term negative effects of food deprivation on growth, relative to the control. Overall survival rates were comparable between the food deprivation and control treatments, but significantly lower for fish in the cortisol treatment. Food availability and individual energetic state appear to dictate the future life-history strategy (migrate or remain resident) of juvenile salmonids while experimental elevation of the stress hormone cortisol causes impaired growth and reduced survival of both resident and migratory individuals. © 2016. Published by The Company of Biologists Ltd.

  6. Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

    PubMed

    Burgos, Jose L; Patterson, Thomas L; Graff-Zivin, Joshua S; Kahn, James G; Rangel, M Gudelia; Lozada, M Remedios; Staines, Hugo; Strathdee, Steffanie A

    2016-01-01

    We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310-$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104-$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component.

  7. Consumer responses to the Wisconsin Partnership Program for Elderly Persons: a variation on the PACE Model.

    PubMed

    Kane, Robert L; Homyak, Patricia; Bershadsky, Boris; Lum, Yat-Sang

    2002-04-01

    The Wisconsin Partnership Program (WPP) is a variation on the Program for All-inclusive Care of the Elderly (PACE) model that is designed to be more flexible by allowing frail elderly dual-eligible (for both Medicare and Medicaid) clients to use their regular primary care physicians instead of relying on the physician hired by PACE. Case management is provided by a team of nurse, social worker, and nurse practitioner. The latter is charged with communicating with the client's primary physician. We compared the functional status and satisfaction of WPP elderly enrollees with those of two sets of dually eligible controls drawn from the Medicaid waiver rosters. One set of controls came from persons in the same county who opted not to enroll in WPP. The second came from matched counties that did not have access to the WPP. Enrollees were interviewed in person. Family members were interviewed by telephone. The prevalence of activities of daily living (ADLs) and instrumental activities of daily living (IADLs) dependency was lower for the WPP sample than that for the controls. The pattern of unmet needs was generally comparable. About half of each sample had a written advance directive. Overall, there were few areas of significant difference in beneficiaries' satisfaction. The WPP families were more satisfied than either control group that services were provided when needed and were better coordinated. There were no significant differences in the prevalence of any aspect of care burden. The impact of WPP seems limited. There is some evidence that families perceive better coordinated care. A more complete evaluation will await the analysis of the differences in utilization patterns between WPP and the controls.

  8. [Glyburide prevents pulmonary artery smooth muscle cell proliferation and migration via inhibiting NLRP3 activation].

    PubMed

    Liu, Y F; Wang, W; Liu, T; Zhang, W; Liu, J; Wang, J

    2017-06-12

    Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot. Results: Compared with the control group, the protein expressions of NLRP3, caspase-1 and IL-1β in PASMCs were increased to (1.38±0.09, t =3.998, P <0.001), (1.32±0.1, t =3.268, P <0.01)and(1.43±0.19) ( t =2.096, P <0.05) folds in the PDGF group. Glyburide had no effect on NLRP3, caspase-1 and IL-1β expression as compared with the control group, while the NLRP3, caspase-1 and IL-1β were decreased by(20.49±7.6)% ( t =2.862, P <0.01), (32.94±3.44)% ( t =4.154, P <0.001) and (24.67±5.29)% ( t =2.335, P <0.05) in the PDGF+ glyburide group, respectively, as compared with the PDGF group. Compared with the control group, the PASMCs proliferation and migration in the PDGF group were significantly increased to (1.74±0.23, t =4.717, P <0.001) and (3.12±0.8, t =5.249, P <0.001) folds, respectively. Compared with the control group, glyburide had no effect on PASMCs proliferation and migration. In PDGF+ glyburide group, cell proliferation was reduced by (50.5±4.27)% ( t =4.462, P <0.001) and cell migration count was lower than in the PDGF group (42.77±2.84)% ( t =3.716, P <0.001). Conclusion: Glyburide could ameliorate PDGF-induced PASMCs proliferation and migration by inhibiting NLRP3 inflammasome activation.

  9. In-situ study of migration and transformation of nitrogen in groundwater based on continuous observations at a contaminated desert site

    NASA Astrophysics Data System (ADS)

    Zuo, Rui; Jin, Shuhe; Chen, Minhua; Guan, Xin; Wang, Jinsheng; Zhai, Yuanzheng; Teng, Yanguo; Guo, Xueru

    2018-04-01

    The objective of this study was to explore the controlling factors on the migration and transformation of nitrogenous wastes in groundwater using long-term observations from a contaminated site on the southwestern edge of the Tengger Desert in northwestern China. Contamination was caused by wastewater discharge rich in ammonia. Two long-term groundwater monitoring wells (Wells 1# and 2#) were constructed, and 24 water samples were collected. Five key indicators were tested: ammonia, nitrate, nitrite, dissolved oxygen, and manganese. A numerical method was used to simulate the migration process and to determine the migration stage of the main pollutant plume in groundwater. The results showed that at Well 1# the nitrogenous waste migration process had essentially been completed, while at Well 2# ammonia levels were still rising and gradually transitioning to a stable stage. The differences for Well 1# and Well 2# were primarily caused by differences in groundwater flow. The change in ammonia concentration was mainly controlled by the migration of the pollution plume under nitrification in groundwater. The nitrification rate was likely affected by changes in dissolved oxygen and potentially manganese.

  10. Impact of modeled microgravity on migration, differentiation, and cell cycle control of primitive human hematopoietic progenitor cells.

    PubMed

    Plett, P Artur; Abonour, Rafat; Frankovitz, Stacy M; Orschell, Christie M

    2004-08-01

    Migration, proliferation, and differentiation of bone marrow (BM) hematopoietic stem cells (HSC) are important factors in maintaining hematopoietic homeostasis. Homeostatic control of erythrocytes and lymphocytes is perturbed in humans exposed to microgravity (micro-g), resulting in space flight-induced anemia and immunosuppression. We sought to determine whether any of these anomalies can be explained by micro-g-induced changes in migration, proliferation, and differentiation of human BM CD34+ cells, and whether such changes can begin to explain any of the shifts in hematopoietic homeostasis observed in astronauts. BM CD34+ cells were cultured in modeled micro-g (mmicro-g) using NASA's rotating wall vessels (RWV), or in control cultures at earth gravity for 2 to 18 days. Cells were harvested at different times and CD34+ cells assessed for migration potential, cell-cycle kinetics and regulatory proteins, and maturation status. Culture of BM CD34+ cells in RWV for 2 to 3 days resulted in a significant reduction of stromal cell-derived factor 1 (SDF-1alpha)-directed migration, which correlated with decreased expression of F-actin. Modeled micro-g induced alterations in cell-cycle kinetics that were characterized by prolonged S phase and reduced cyclin A expression. Differentiation of primitive CD34+ cells cultured for 14 to 18 days in RWV favored myeloid cell development at the expense of erythroid development, which was significantly reduced compared to controls. These results illustrate that mmicro-g significantly inhibits the migration potential, cell-cycle progression, and differentiation patterns of primitive BM CD34+ cells, which may contribute to some of the hematologic abnormalities observed in humans during space flight.

  11. 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

  12. The effect of thyroid antigens on the in vitro migration of leucocytes from patients with Hashimoto thyroiditis

    PubMed Central

    Calder, Elizabeth A.; McLeman, Dena; Barnes, E. W.; Irvine, W. J.

    1972-01-01

    A total of fifty-two patients with Hashimoto thyroiditis were tested for delayed hypersensitivity to thyroid antigens using the leucocyte migration test. The percentage of patients showing abnormal migration in the presence of crude thyroid extract, thyroglobulin, thyroid mitochondria and thyroid microsomes was 75, 44, 54 and 34% respectively. Fifty-three control patients were studied concurrently with the same antigens and the percentage showing abnormal migration was 4, 6, 6 and 6% respectively. The antigenic activity of the mitochondrial fraction was not organ specific; both liver and kidney mitochondria interfered with the migration of leucocytes from patients with Hashimoto thyroiditis. PMID:4568149

  13. Contamination in food from packaging material.

    PubMed

    Lau, O W; Wong, S K

    2000-06-16

    Packaging has become an indispensible element in the food manufacturing process, and different types of additives, such as antioxidants, stabilizers, lubricants, anti-static and anti-blocking agents, have also been developed to improve the performance of polymeric packaging materials. Recently the packaging has been found to represent a source of contamination itself through the migration of substances from the packaging into food. Various analytical methods have been developed to analyze the migrants in the foodstuff, and migration evaluation procedures based on theoretical prediction of migration from plastic food contact material were also introduced recently. In this paper, the regulatory control, analytical methodology, factors affecting the migration and migration evaluation are reviewed.

  14. Numerical examination of the factors controlling DNAPL migration through a single fracture.

    PubMed

    Reynolds, D A; Kueper, B H

    2002-01-01

    The migration of five dense nonaqueous phase liquids (DNAPLs) through a single fracture in a clay aquitard was numerically simulated with the use of a compositional simulator. The effects of fracture aperture, fracture dip, matrix porosity, and matrix organic carbon content on the migration of chlorobenzene, 1,2-dichloroethylene, trichloroethylene, tetra-chloroethylene, and 1,2-dibromoethane were examined. Boundary conditions were chosen such that DNAPL entry into the system was allowed to vary according to the stresses applied. The aperture is the most important factor of those studied controlling the migration rate of DNAPL through a single fracture embedded in a clay matrix. Loss of mass to the matrix through diffusion does not significantly retard the migration rate of the DNAPL, particularly in larger aperture fractures (e.g., 50 microm). With time, the ratio of diffusive loss to the matrix to DNAPL flux into the fracture approaches an asymptotic value lower than unity. The implication is that matrix diffusion cannot arrest the migration of DNAPL in a single fracture. The complex relationships between density, viscosity, and solubility that, to some extent, govern the migration of DNAPL through these systems prevent accurate predictions without the use of numerical models. The contamination potential of the migrating DNAPL is significantly increased through the transfer of mass to the matrix. The occurrence of opposite concentration gradients within the matrix can cause dissolved phase contamination to exist in the system for more than 1000 years after the DNAPL has been completely removed from the fracture.

  15. Controlled levels of canonical Wnt signaling are required for neural crest migration.

    PubMed

    Maj, Ewa; Künneke, Lutz; Loresch, Elisabeth; Grund, Anita; Melchert, Juliane; Pieler, Tomas; Aspelmeier, Timo; Borchers, Annette

    2016-09-01

    Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Relationship between Migration and HIV Risky Behavior: a Comparative Study of Returning Migrants and Non Migrants Based on Rural Out-of-school Youth in Jilin, China.

    PubMed

    Zhu, Guang Rong; Ji, Cheng Ye; Yang, Xing Hua

    2015-06-01

    To estimate the relationship between migration and HIV risky behavior when controlling for gender, age, and educational levels and to evaluate the gender differences in migration, HIV knowledge, and HIV risky behaviors among rural youth in China. A cross-sectional, anonymous, investigative questionnaire for 1710 unmarried, out-of-school rural youth, aged between 15 and 24 years, was handed out in Gongzhuling county of Jilin province, China. 58.5% of participants had a history of migration, irrespective of gender. There were gender differences observed in other factors such as drug abuse (4.3% for males and 5.5% for females, P<0.01), multiple sexual partners (24.1% for males and 44.1% for females, P<0.01), and HIV knowledge rate (35.2% for males and 25.5% for females, P<0.001). While controlling for gender, age, and educational levels, the relationships between migration and drug abuse, selling sex, and non usage of condoms during last instance of sexual activity were found to be significant. The cases of premarital sex and multiple sexual partners were both not found to be related to migration. Among rural youth, the HIV risky behavior such as drug abuse, selling sex, and lack of condom use, is significantly related to migration, while premarital sex and multiple sexual partners seem unrelated to migration. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  17. Cdk5 phosphorylation of WAVE2 regulates oligodendrocyte precursor cell migration through nonreceptor tyrosine kinase Fyn.

    PubMed

    Miyamoto, Yuki; Yamauchi, Junji; Tanoue, Akito

    2008-08-13

    Myelin formation of the CNS is a complex and dynamic process. Before the onset of myelination, oligodendrocytes (OLs), the myelin-forming glia of the CNS, proliferate and migrate along axons. Little is known about the molecular mechanisms underlying the early myelination processes. Here, we show that platelet-derived growth factor (PDGF), the crucial physiological ligand in early OL development, controls the migration of oligodendrocyte precursor cells (OPCs) through cyclin-dependent kinase 5 (Cdk5). PDGF stimulates Cdk5 activity in a time-dependent manner, whereas suppression of Cdk5 by the specific inhibitor roscovitine or by the retrovirus encoding short-hairpin RNA for Cdk5 impairs PDGF-dependent OPC migration. The activation of Cdk5 by PDGF is mediated by the phosphorylation of the nonreceptor tyrosine kinase, Fyn, whose inhibition reduces PDGF-dependent OPC migration. Furthermore, Cdk5 regulates PDGF-dependent OPC migration through the direct phosphorylation of WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein 2 (WAVE2). Cdk5 phosphorylates WAVE2 at Ser-137 in vitro. Infection of the WAVE2 construct harboring the Ser-137-to-Ala reduces PDGF-dependent migration. Together, PDGF regulates OPC migration through an as-yet-unidentified signaling cascade coupling Fyn kinase to Cdk5 phosphorylation of WAVE2. These results provide new insights into both the role of Cdk5 in glial cells and the molecular mechanisms controlling the early developmental stage of OLs.

  18. Redundant control of migration and adhesion by ERM proteins in vascular smooth muscle cells

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

    Baeyens, Nicolas; Latrache, Iman; Yerna, Xavier

    Highlights: •The three ERM proteins are expressed in vascular smooth muscle cell. •ERM depletion inhibited PDGF-evoked migration redundantly. •ERM depletion increased cell adhesion redundantly. •ERM depletion did not affect PDGF-evoked Ca signal, Rac1 activation, proliferation. •ERM proteins control PDGF-induced migration by regulating adhesion. -- Abstract: Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the rolemore » of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis. We used primary cultured VSMC obtained from rat aorta, which express the three ERM proteins. Simultaneous depletion of the three ERM proteins with specific siRNAs abolished the effects of PDGF on cell architecture and migration and markedly increased cell adhesion and focal adhesion size, while these parameters were only slightly affected by depletion of ezrin, radixin or moesin alone. Rac1 activation, cell proliferation, and Ca{sup 2+} signal in response to PDGF were unaffected by ERM depletion. These results indicate that ERM proteins exert a redundant control on PDGF-induced VSMC migration by regulating focal adhesion turn-over and cell adhesion to substrate.« less

  19. A Novel Single-Strand RNAi Therapeutic Agent Targeting the (Pro)renin Receptor Suppresses Ocular Inflammation.

    PubMed

    Kanda, Atsuhiro; Ishizuka, Erdal Tan; Shibata, Atsushi; Matsumoto, Takahiro; Toyofuku, Hidekazu; Noda, Kousuke; Namba, Kenichi; Ishida, Susumu

    2017-06-16

    The receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to the (pro)renin receptor [(P)RR] dually activates the tissue renin-angiotensin system (RAS) and RAS-independent intracellular signaling. Here we revealed significant upregulation of prorenin and soluble (P)RR levels in the vitreous fluid of patients with uveitis compared to non-inflammatory controls, together with a positive correlation between these RAPS components and monocyte chemotactic protein-1 among several upregulated cytokines. Moreover, we developed a novel single-strand RNAi agent, proline-modified short hairpin RNA directed against human and mouse (P)RR [(P)RR-PshRNA], and we determined its safety and efficacy in vitro and in vivo. Application of (P)RR-PshRNA in mice caused significant amelioration of acute (uveitic) and chronic (diabetic) models of ocular inflammation with no apparent adverse effects. Our findings demonstrate the significant implication of RAPS in the pathogenesis of human uveitis and the potential usefulness of (P)RR-PshRNA as a therapeutic agent to reduce ocular inflammation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Alteration of corneal epithelial ion transport by sympathectomy.

    PubMed

    Klyce, S D; Beuerman, R W; Crosson, C E

    1985-04-01

    The cornea is dually innervated, receiving afferent nerves from the trigeminal ganglion and efferent nerves from the superior cervical ganglion. This study examines the specific effects of superior cervical ganglionectomy (SCGX) on the in vitro ion transport characteristics of the rabbit corneal epithelium. Two weeks after SCGX, epithelial Cl--dependent transport and total ionic conductance were increased in comparison to values obtained in paired control eyes. This increased transport level appeared to be independent of membrane receptor activity as demonstrated by lack of responsiveness to alpha-adrenergic, beta-adrenergic, serotonergic, dopaminergic, nicotinic cholinergic, or muscarinic cholinergic blockade. Nevertheless, SCGX produced a supersensitivity to epinephrine-stimulated transport as measured by the responsiveness of the ion transport current. Furthermore, SCGX abolished the responsiveness of the epithelium to serotonin. On the basis of these and earlier findings, the authors conclude that corneal sympathetic innervation influences membrane and receptor properties. Autonomic neurotrophic effects in the corneal epithelium include suppression of apical membrane Cl- permeability and of beta-adrenoreceptor sensitivity to biogenic amines. It is proposed that the corneal serotonergic receptors that activate Cl- transport lie on the sympathetic nerve terminals and stimulate this transport process by causing the neural release of a catecholamine.

  1. The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code

    PubMed Central

    Hofhuis, Julia; Schueren, Fabian; Nötzel, Christopher; Lingner, Thomas; Gärtner, Jutta; Jahn, Olaf

    2016-01-01

    Translational readthrough gives rise to C-terminally extended proteins, thereby providing the cell with new protein isoforms. These may have different properties from the parental proteins if the extensions contain functional domains. While for most genes amino acid incorporation at the stop codon is far lower than 0.1%, about 4% of malate dehydrogenase (MDH1) is physiologically extended by translational readthrough and the actual ratio of MDH1x (extended protein) to ‘normal' MDH1 is dependent on the cell type. In human cells, arginine and tryptophan are co-encoded by the MDH1x UGA stop codon. Readthrough is controlled by the 7-nucleotide high-readthrough stop codon context without contribution of the subsequent 50 nucleotides encoding the extension. All vertebrate MDH1x is directed to peroxisomes via a hidden peroxisomal targeting signal (PTS) in the readthrough extension, which is more highly conserved than the extension of lactate dehydrogenase B. The hidden PTS of non-mammalian MDH1x evolved to be more efficient than the PTS of mammalian MDH1x. These results provide insight into the genetic and functional co-evolution of these dually localized dehydrogenases. PMID:27881739

  2. Serum fructosamine concentrations in 59 dogs naturally Infected with Angiostrongylus vasorum.

    PubMed

    Willesen, J L; Jensen, A L; Kristensen, A T; Kjelgaard-Hansen, M; Jessen, R; Koch, J

    2006-06-01

    Retrospectively, 89 cases of dogs infected with Angiostrongylus vasorum were examined. Fifty-nine of these 89 dogs fulfilled the criteria of not being dually infected with Crenosoma vulpis as well as having a full biochemistry profile including serum fructosamine available. The mean serum fructosamine value of the 59 dogs was 236 micromol/l (reference value 258-348 micromol/l) and significantly lower than the serum fructosamine level of 314 micromol/l in a control group of 42 clinically healthy dogs. Eleven dogs were available for follow up after successful treatment of angiostrongylosis. In this group, the serum fructosamine value rose from a mean of 244 micromol/l to a mean of 320 micromol/l following treatment. Serum glucose, albumin and protein were all within the respective reference ranges at all sampling points. The results indicate that serum fructosamine could be affected by infection with A. vasorum. Furthermore, this change cannot be explained by measurable changes in the level of glucose, albumin or protein. The clinical impact of this study is that a low fructosamine value may indicate infection with A. vasorum thereby suggesting a Baermann test to be performed.

  3. Cadherin-2 Is Required Cell Autonomously for Collective Migration of Facial Branchiomotor Neurons.

    PubMed

    Rebman, Jane K; Kirchoff, Kathryn E; Walsh, Gregory S

    2016-01-01

    Collective migration depends on cell-cell interactions between neighbors that contribute to their overall directionality, yet the mechanisms that control the coordinated migration of neurons remains to be elucidated. During hindbrain development, facial branchiomotor neurons (FBMNs) undergo a stereotypic tangential caudal migration from their place of birth in rhombomere (r)4 to their final location in r6/7. FBMNs engage in collective cell migration that depends on neuron-to-neuron interactions to facilitate caudal directionality. Here, we demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for directional and collective migration of FBMNs. We generated stable transgenic zebrafish expressing dominant-negative Cadherin-2 (Cdh2ΔEC) driven by the islet1 promoter. Cell-autonomous inactivation of Cadherin-2 function led to non-directional migration of FBMNs and a defect in caudal tangential migration. Additionally, mosaic analysis revealed that Cdh2ΔEC-expressing FBMNs are not influenced to migrate caudally by neighboring wild-type FBMNs due to a defect in collective cell migration. Taken together, our data suggest that Cadherin-2 plays an essential cell-autonomous role in mediating the collective migration of FBMNs.

  4. Experimental study to control the upstream migration of invasive alien fish species by submerged weir

    NASA Astrophysics Data System (ADS)

    Sakuma, Masami; Kunimatsu, Fumihiro; Tsuchiya, Taku; Kawamura, Makiko; Fujita, Hiroshi

    Largemouth bass and Bluegill, major invasive alien fish species in Japan, have been extending their habitat ranges over not only Lake Biwa and the lagoons but also surrounding waters connected to them through small rivers and canals. Their increasing number is bringing about the reduction in the number of native fish species. To prevent the spread of these alien species through small rivers and canals during breeding season of the native fish (crucian carp), this study experimentally examined the effect of a submerged weir on controlling upstream migration of the alien species and the native fish. As a result of the experiment, the ratio of the alien species migrating upstream decreased as the weir height rose, whereas the ratio did not show the same trend in the case of the native fish. The ratio of the alien species also decreased as the overflow velocity over the weir rose. On the other hand, the ratio of the native fish increased as the overflow velocity rose up to 1.0m/s and decreased thereafter. These results suggest that the submerged weir may control upstream migration of the alien species to surrounding waters through small rivers and canals without interfering with the reproductive migration of the native fish.

  5. Magneto-ionic control of interfacial magnetism

    NASA Astrophysics Data System (ADS)

    Bauer, Uwe; Yao, Lide; Tan, Aik Jun; Agrawal, Parnika; Emori, Satoru; Tuller, Harry L.; van Dijken, Sebastiaan; Beach, Geoffrey S. D.

    2015-02-01

    In metal/oxide heterostructures, rich chemical, electronic, magnetic and mechanical properties can emerge from interfacial chemistry and structure. The possibility to dynamically control interface characteristics with an electric field paves the way towards voltage control of these properties in solid-state devices. Here, we show that electrical switching of the interfacial oxidation state allows for voltage control of magnetic properties to an extent never before achieved through conventional magneto-electric coupling mechanisms. We directly observe in situ voltage-driven O2- migration in a Co/metal-oxide bilayer, which we use to toggle the interfacial magnetic anisotropy energy by >0.75 erg cm-2 at just 2 V. We exploit the thermally activated nature of ion migration to markedly increase the switching efficiency and to demonstrate reversible patterning of magnetic properties through local activation of ionic migration. These results suggest a path towards voltage-programmable materials based on solid-state switching of interface oxygen chemistry.

  6. Control of the collective migration of enteric neural crest cells by the Complement anaphylatoxin C3a and N-cadherin

    PubMed Central

    Broders-Bondon, Florence; Paul-Gilloteaux, Perrine; Gazquez, Elodie; Heysch, Julie; Piel, Matthieu; Mayor, Roberto; Lambris, John D.; Dufour, Sylvie

    2016-01-01

    We analyzed the cellular and molecular mechanisms governing the adhesive and migratory behavior of enteric neural crest cells (ENCCs) during their collective migration within the developing mouse gut. We aimed to decipher the role of the complement anaphylatoxin C3a during this process, because this well-known immune system attractant has been implicated in cephalic NCC co-attraction, a process controlling directional migration. We used the conditional Ht-PA-cre transgenic mouse model allowing a specific ablation of the N-cadherin gene and the expression of a fluorescent reporter in migratory ENCCs without affecting the central nervous system. We performed time-lapse videomicroscopy of ENCCs from control and N-cad-herin mutant gut explants cultured on fibronectin (FN) and micropatterned FN-stripes with C3a or C3aR antagonist, and studied cell migration behavior with the use of triangulation analysis to quantify cell dispersion. We performed ex vivo gut cultures with or without C3aR antagonist to determine the effect on ENCC behavior. Confocal microscopy was used to analyze the cell-matrix adhesion properties. We provide the first demonstration of the localization of the complement anaphylatoxin C3a and its receptor on ENCCs during their migration in the embryonic gut. C3aR receptor inhibition alters ENCC adhesion and migration, perturbing directionality and increasing cell dispersion both in vitro and ex vivo. N-cad-herin-null ENCCs do not respond to C3a co-attraction. These findings indicate that C3a regulates cell migration in a N-cadherin-dependent process. Our results shed light on the role of C3a in regulating collective and directional cell migration, and in ganglia network organization during enteric nervous system ontogenesis. The detection of an immune system chemokine in ENCCs during ENS development may also shed light on new mechanisms for gastrointestinal disorders. PMID:27041467

  7. Spatial control of active CDC-42 during collective migration of hypodermal cells in Caenorhabditis elegans.

    PubMed

    Ouellette, Marie-Hélène; Martin, Emmanuel; Lacoste-Caron, Germain; Hamiche, Karim; Jenna, Sarah

    2016-08-01

    Collective epithelial cell migration requires the maintenance of cell-cell junctions while enabling the generation of actin-rich protrusions at the leading edge of migrating cells. Ventral enclosure of Caenorhabditis elegans embryos depends on the collective migration of anterior-positioned leading hypodermal cells towards the ventral midline where they form new junctions with their contralateral neighbours. In this study, we characterized the zygotic function of RGA-7/SPV-1, a CDC-42/Cdc42 and RHO-1/RhoA-specific Rho GTPase-activating protein, which controls the formation of actin-rich protrusions at the leading edge of leading hypodermal cells and the formation of new junctions between contralateral cells. We show that RGA-7 controls these processes in an antagonistic manner with the CDC-42's effector WSP-1/N-WASP and the CDC-42-binding proteins TOCA-1/2/TOCA1. RGA-7 is recruited to spatially distinct locations at junctions between adjacent leading cells, where it promotes the accumulation of clusters of activated CDC-42. It also inhibits the spreading of these clusters towards the leading edge of the junctions and regulates their accumulation and distribution at new junctions formed between contralateral leading cells. Our study suggests that RGA-7 controls collective migration and junction formation between epithelial cells by spatially restricting active CDC-42 within cell-cell junctions. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  8. [Migration of eight harmful elements from household products made with synthetic resin that infants may swallow by mistake].

    PubMed

    Isama, Kazuo; Kawakami, Tsuyoshi; Nishimura, Tetsuji

    2011-01-01

    Harmful elements are used as stabilizers and colorants in synthetic resin products. Accidental ingestion of harmful elements from such synthetic resins by infants is a dangerous health hazard. The Japanese Food Sanitation Law and the International Standard ISO 8124-3 "Safety of toys-Part 3: Migration of certain elements" control the levels of migrated harmful elements, such as lead or cadmium, from infants toys. However, the levels of migrated harmful elements from household products that are not infants toys are not controlled, since they are not covered by the law or standard. Therefore, we investigated the level of eight harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) migrated from household products made of synthetic resin that infants may swallow by mistake. The extraction test of ISO 8124-3: 2010 was executed in 135 products (total 150 specimens), and the concentration of these elements was measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result, 1810 mg/kg and 1660 mg/kg of lead, exceeding the maximum acceptable level of the ISO standard, migrated from two products. In addition, lead and/or chromium at levels more than 1/10 of the maximum acceptable levels of the ISO standard migrated from four products. Household products that infants may swallow by mistake should ideally not release harmful elements such as lead and chromium.

  9. Rural-to-Urban Migration, Strain, and Juvenile Delinquency: A Study of Eighth-Grade Students in Guangzhou, China.

    PubMed

    Lo, Celia C; Cheng, Tyrone C; Bohm, Maggie; Zhong, Hua

    2018-02-01

    This examination of minor and serious delinquency among eighth graders in a large southern Chinese city, Guangzhou, also compared groups of these students, observing differences between the delinquency of migrants and that of urban natives. Data used were originally collected for the study "Stuck in the City: Migration and Delinquency Among Migrant Adolescents in Guangzhou." The present study asked whether and how various sources of strain and social control factors explained students' delinquency, questioning how meaningfully migration status moderated several of the observed delinquency relationships. Of students in the sample, 741 reported being natives of Guangzhou, and 497 reported migrating to Guangzhou from a rural area. The study conceptualized internal migration as a strain factor leading to delinquency, but the analyses did not suggest direct association between internal migration and delinquency. Results generally supported Agnew's theory, and, what's more, they tended to confirm that migration status moderated juvenile delinquency.

  10. Socioeconomic context and the association between marriage and Mexico-U.S. migration.

    PubMed

    Riosmena, Fernando

    2009-06-01

    In this paper, I analyze how the association between Mexico-U.S. migration and marriage varies across socioeconomic settings in origins. Using Mexican Migration Project data and employing bilevel survival analysis with controls for socioeconomic, migrant network, and marriage market characteristics and family size, I find that single people are most likely to migrate relative to those married in areas of recent industrialization, where the Mexican patriarchal system is weaker and economic opportunities for both men and women make post-marital migration less attractive. Marital status is not significant in agriculture-dependent areas, where the bargaining power of husbands might be higher relative to other settings; their age-profiles of earnings flatter; and remunerated female work scarcer, making migration attractive later in the life course.

  11. Socioeconomic context and the association between marriage and Mexico–U.S. migration

    PubMed Central

    Riosmena, Fernando

    2009-01-01

    In this paper, I analyze how the association between Mexico–U.S. migration and marriage varies across socioeconomic settings in origins. Using Mexican Migration Project data and employing bilevel survival analysis with controls for socioeconomic, migrant network, and marriage market characteristics and family size, I find that single people are most likely to migrate relative to those married in areas of recent industrialization, where the Mexican patriarchal system is weaker and economic opportunities for both men and women make post-marital migration less attractive. Marital status is not significant in agriculture-dependent areas, where the bargaining power of husbands might be higher relative to other settings; their age-profiles of earnings flatter; and remunerated female work scarcer, making migration attractive later in the life course. PMID:19756216

  12. Micropatterned Protective Membranes Inhibit Lens Epithelial Cell Migration in Posterior Capsule Opacification Model

    PubMed Central

    Magin, Chelsea M.; May, Rhea M.; Drinker, Michael C.; Cuevas, Kevin H.; Brennan, Anthony B.; Reddy, Shravanthi T.

    2015-01-01

    Purpose To evaluate the ability of Sharklet (SK) micropatterns to inhibit lens epithelial cell (LEC) migration. Sharklet Technologies, Inc. (STI) and InSight Innovations, LLC have proposed to develop a Sharklet-patterned protective membrane (PM) to be implanted in combination with a posterior chamber intraocular lens (IOL) to inhibit cellular migration across the posterior capsule, and thereby reduce rates of posterior capsular opacification (PCO). Methods A variety of STI micropatterns were evaluated versus smooth (SM) controls in a modified scratch wound assay for the ability to reduce or inhibit LEC migration. The best performing topography was selected, translated to a radial design, and applied to PM prototypes. The PM prototypes were tested in an in vitro PCO model for reduction of cell migration behind an IOL versus unpatterned prototypes and IOLs with no PM. In both assays, cell migration was analyzed with fluorescent microscopy. Results All SK micropatterns significantly reduced LEC migration compared with SM controls. Micropatterns that protruded from the surface reduced migration more than recessed features. The best performing micropattern reduced LEC coverage by 80%, P = 0.0001 (ANOVA, Tukey Test). Micropatterned PMs reduced LEC migration in a PCO model by 50%, P = 0.0005 (ANOVA, Tukey Test) compared with both IOLs with no PM and IOLs with SM PMs. Conclusions Collectively, in vitro results indicate the implantation of micropatterned PMs in combination with posterior chamber IOLs could significantly reduce rates of clinically relevant PCO. This innovative technology is a globally accessible solution to high PCO rates. Translational Relevance A novel IOL incorporating the SK micropattern in a membrane design surrounding the optic may help increase the success of cataract surgery by reducing secondary cataract, or PCO. PMID:25883876

  13. Control of lateral migration and germ cell elimination by the Drosophila melanogaster lipid phosphate phosphatases Wunen and Wunen 2

    PubMed Central

    Sano, Hiroko; Renault, Andrew D.; Lehmann, Ruth

    2005-01-01

    In most organisms, primordial germ cells (PGCs) arise far from the region where somatic gonadal precursors (SGPs) are specified. Although PGCs in general originate as a single cluster of cells, the somatic parts of the gonad form on each site of the embryo. Thus, to reach the gonad, PGCs not only migrate from their site of origin but also split into two groups. Taking advantage of high-resolution real-time imaging, we show that in Drosophila melanogaster PGCs are polarized and migrate directionally toward the SGPs, avoiding the midline. Unexpectedly, neither PGC attractants synthesized in the SGPs nor known midline repellents for axon guidance were required to sort PGCs bilaterally. Repellent activity provided by wunen (wun) and wunen-2 (wun-2) expressed in the central nervous system, however, is essential in this migration process and controls PGC survival. Our results suggest that expression of wun/wun-2 repellents along the migratory paths provides faithful control over the sorting of PGCs into two gonads and eliminates PGCs left in the middle of the embryo. PMID:16301333

  14. Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

    PubMed Central

    Morgan, Mark R.; Hamidi, Hellyeh; Bass, Mark D.; Warwood, Stacey; Ballestrem, Christoph; Humphries, Martin J.

    2013-01-01

    Summary Precise spatiotemporal coordination of integrin adhesion complex dynamics is essential for efficient cell migration. For cells adherent to fibronectin, differential engagement of α5β1 and αVβ3 integrins is used to elicit changes in adhesion complex stability, mechanosensation, matrix assembly, and migration, but the mechanisms responsible for receptor regulation have remained largely obscure. We identify phosphorylation of the membrane-intercalated proteoglycan syndecan-4 as an essential switch controlling integrin recycling. Src phosphorylates syndecan-4 and, by driving syntenin binding, leads to suppression of Arf6 activity and recycling of αVβ3 to the plasma membrane at the expense of α5β1. The resultant elevation in αVβ3 engagement promotes stabilization of focal adhesions. Conversely, abrogation of syndecan-4 phosphorylation drives surface expression of α5β1, destabilizes adhesion complexes, and disrupts cell migration. These data identify the dynamic spatiotemporal regulation of Src-mediated syndecan-4 phosphorylation as an essential switch controlling integrin trafficking and adhesion dynamics to promote efficient cell migration. PMID:23453597

  15. Transparency in Distributed File Systems

    DTIC Science & Technology

    1989-01-01

    ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK Computer Science Department AREA & WORK UNIT NUMBERS 734 Comouter Studies Bldc . University of...sistency control , file and director) placement, and file and directory migration in a way that pro- 3 vides full network transparency. This transparency...areas of naming, replication, con- sistency control , file and directory placement, and file and directory migration in a way that pro- 3 vides full

  16. Pre-migration Trauma Exposure and Psychological Distress for Asian American Immigrants: Linking the Pre- and Post-migration Contexts.

    PubMed

    Li, Miao; Anderson, James G

    2016-08-01

    Drawing on the life course perspective and the assumptive world theory, this paper examines whether pre-migration trauma exposure is associated with psychological distress through post-migration perceived discrimination for Asian American immigrants. The study is based on cross-sectional data from the National Latino and Asian American Study (N = 1639). Structural equation model is used to estimate the relationship between pre-migration trauma, post-migration perceived discrimination, and psychological distress. Additional models are estimated to explore possible variations across ethnic groups as well as across different types of pre-migration trauma experience. Pre-migration trauma exposure is associated with higher levels of psychological distress, both directly and indirectly through higher level of perceived discrimination, even after controlling for demographic/acculturative factors and post-migration trauma exposure. This pattern holds for the following sub-types of pre-migration trauma: political trauma, crime victimization, physical violence, accidental trauma, and relational trauma. Multi-group analyses show that this pattern holds for all Asian immigrant subgroups except the Vietnamese. Studies of immigrant mental health primarily focus on post-migration stressors. Few studies have considered the link between pre- and post-migration contexts in assessing mental health outcomes. The study illustrates the usefulness of bridging the pre- and post-migration context in identifying the mental health risks along the immigrant life course.

  17. A Programmable SDN+NFV Architecture for UAV Telemetry Monitoring

    NASA Technical Reports Server (NTRS)

    White, Kyle J. S.; Pezaros, Dimitrios P.; Denney, Ewen; Knudson, Matt D.

    2017-01-01

    With the explosive growth in UAV numbers forecast worldwide, a core concern is how to manage the ad-hoc network configuration required for mobility management. As UAVs migrate among ground control stations, associated network services, routing and operational control must also rapidly migrate to ensure a seamless transition. In this paper, we present a novel, lightweight and modular architecture which supports high mobility, resilience and flexibility through the application of SDN and NFV principles on top of the UAV infrastructure. By combining SDN programmability and Network Function Virtualization we can achieve resilient infrastructure migration of network services, such as network monitoring and anomaly detection, coupled with migrating UAVs to enable high mobility management. Our container-based monitoring and anomaly detection Network Functions (NFs) can be tuned to specific UAV models providing operators better insight during live, high-mobility deployments. We evaluate our architecture against telemetry from over 80flights from a scientific research UAV infrastructure.

  18. A role for social workers in improving care setting transitions: a case study.

    PubMed

    Barber, Ruth D; Coulourides Kogan, Alexis; Riffenburgh, Anne; Enguidanos, Susan

    2015-01-01

    High 30-day readmission rates are a major burden to the American medical system. Much attention is on transitional care to decrease financial costs and improve patient outcomes. Social workers may be uniquely qualified to improve care transitions and have not previously been used in this role. We present a case study of an older, dually eligible Latina woman who received a social work-driven transition intervention that included in-home and telephone contacts. The patient was not readmitted during the six-month study period, mitigated her high pain levels, and engaged in social outings once again. These findings suggest the value of a social worker in a transitional care role.

  19. Impacts of a disease management program for dually eligible beneficiaries.

    PubMed

    Esposito, Dominick; Brown, Randall; Chen, Arnold; Schore, Jennifer; Shapiro, Rachel

    2008-01-01

    The LifeMasters Supported SelfCare demonstration program provides disease management (DM) services to Florida Medicare beneficiaries who are also enrolled in Medicaid and have congestive heart failure (CHF), diabetes, or coronary artery disease (CAD). The population-based program provides primarily telephonic patient education and monitoring services. Findings from the randomized, intent-to-treat design over the first 18 months of operations show virtually no overall impacts on hospital or emergency room (ER) use, Medicare expenditures, quality of care, or prescription drug use for the 33,000 enrollees. However, for beneficiaries with CHF who resided in high-cost South Florida counties, the program reduced Medicare expenditures by 9.6 percent.

  20. Coverage and prior authorization of psychotropic drugs under Medicare Part D.

    PubMed

    Huskamp, Haiden A; Stevenson, David G; Donohue, Julie M; Newhouse, Joseph P; Keating, Nancy L

    2007-03-01

    This study examined formulary coverage and use of utilization management tools for three classes of psychotropic medications (antidepressants, antipsychotics, and anticonvulsants) among Medicare Part D prescription drug plans serving individuals dually eligible for the Medicare and Medicaid programs. Plans must cover "all or substantially all" molecules (distinct drugs) in these classes. Plans serving "dual eligibles" generally covered at least one formulation of all molecules in the three classes. However, certain product formulations were not covered by a number of plans, and use of prior authorization was common for a minority of plans. The effect of Part D will depend on the restrictiveness of the prior authorization and appeals processes, which is currently unknown.

  1. Reversible Redox Activity by Ion-pH Dually Modulated Duplex Formation of i-Motif DNA with Complementary G-DNA.

    PubMed

    Chang, Soyoung; Kilic, Tugba; Lee, Chang Kee; Avci, Huseyin; Bae, Hojae; Oskui, Shirin Mesbah; Jung, Sung Mi; Shin, Su Ryon; Kim, Seon Jeong

    2018-04-08

    The unique biological features of supramolecular DNA have led to an increasing interest in biomedical applications such as biosensors. We have developed an i-motif and G-rich DNA conjugated single-walled carbon nanotube hybrid materials, which shows reversible conformational switching upon external stimuli such as pH (5 and 8) and presence of ions (Li⁺ and K⁺). We observed reversible electrochemical redox activity upon external stimuli in a quick and robust manner. Given the ease and the robustness of this method, we believe that pH- and ion-driven reversible DNA structure transformations will be utilized for future applications for developing novel biosensors.

  2. The Influence of Seal Properties on Pressure Buildup and Leakage of Carbon Dioxide from Sequestration Reservoirs (Invited)

    NASA Astrophysics Data System (ADS)

    Benson, S. M.; Chabora, E.

    2009-12-01

    The transport properties of seals, namely permeability, relative permeability, and capillary pressure control both migration of carbon dioxide and brine through the seal. Only recently has the the importance of brine migration emerged as key issue in the environmental performance of carbon dioxide sequestration projects. In this study we use numerical simulation to show that brine migration through the seal can be either advantageous or deleterious to the environmental performance of a carbon dioxide sequestration project. Brine migration through the seal can lower the pressure buildup in the storage reservoir, thereby reducing the risk of leakage or geomechanical stresses on the seal. On the other hand, if the seal is penetrated by a permeable fault it can lead to focused flow up a fault, which could lead to brine migration into drinking water aquifers. We also show that as the carbon dioxide plume grows, brine flow undergoes a complex evolution from upward flow to downward flows driven by countercurrent migration of carbon dioxide and brine in the seal and capillary pressure gradients at the base of the seal. Finally, we discuss desirable attributes seals, taking into account both carbon dioxide and brine migration through the seal. In particular, identifying seals that provide an effective capillary barrier to block the flow of carbon dioxide while allowing some brine migration through the seal can help to control pressure buildup and allow more efficient utilization of a sequestration reservoir. This could be particularly important in those settings that may be limited by the maximum allowable pressure buildup.

  3. 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.

  4. Surface micro- and nano-texturing of stainless steel by femtosecond laser for the control of cell migration.

    PubMed

    Martínez-Calderon, M; Manso-Silván, M; Rodríguez, A; Gómez-Aranzadi, M; García-Ruiz, J P; Olaizola, S M; Martín-Palma, R J

    2016-11-02

    The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials.

  5. Surface micro- and nano-texturing of stainless steel by femtosecond laser for the control of cell migration

    PubMed Central

    Martínez-Calderon, M.; Manso-Silván, M.; Rodríguez, A.; Gómez-Aranzadi, M.; García-Ruiz, J. P.; Olaizola, S. M.; Martín-Palma, R. J.

    2016-01-01

    The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials. PMID:27805063

  6. 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

  7. 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.

  8. Disruption, not displacement: Environmental variability and temporary migration in Bangladesh

    PubMed Central

    Gray, Clark; Yunus, Mohammad; Emch, Michael

    2018-01-01

    Mass migration is one of the most concerning potential outcomes of global climate change. Recent research into environmentally induced migration suggests that relationship is much more complicated than originally posited by the ‘environmental refugee’ hypothesis. Climate change is likely to increase migration in some cases and reduce it in others, and these movements will more often be temporary and short term than permanent and long term. However, few large-sample studies have examined the evolution of temporary migration under changing environmental conditions. To address this gap, we measure the extent to which temperature, precipitation, and flooding can predict temporary migration in Matlab, Bangladesh. Our analysis incorporates high-frequency demographic surveillance data, a discrete time event history approach, and a range of sociodemographic and contextual controls. This approach reveals that migration declines immediately after flooding but quickly returns to normal. In contrast, optimal precipitation and high temperatures have sustained positive effects on temporary migration that persist over one to two year periods. Building on previous studies of long-term migration, these results challenge the common assumption that flooding, precipitation extremes and high temperatures will consistently increase temporary migration. Instead, our results are consistent with a livelihoods interpretation of environmental migration in which households draw on a range of strategies to cope with environmental variability. PMID:29375196

  9. Disruption, not displacement: Environmental variability and temporary migration in Bangladesh.

    PubMed

    Call, Maia A; Gray, Clark; Yunus, Mohammad; Emch, Michael

    2017-09-01

    Mass migration is one of the most concerning potential outcomes of global climate change. Recent research into environmentally induced migration suggests that relationship is much more complicated than originally posited by the 'environmental refugee' hypothesis. Climate change is likely to increase migration in some cases and reduce it in others, and these movements will more often be temporary and short term than permanent and long term. However, few large-sample studies have examined the evolution of temporary migration under changing environmental conditions. To address this gap, we measure the extent to which temperature, precipitation, and flooding can predict temporary migration in Matlab, Bangladesh. Our analysis incorporates high-frequency demographic surveillance data, a discrete time event history approach, and a range of sociodemographic and contextual controls. This approach reveals that migration declines immediately after flooding but quickly returns to normal. In contrast, optimal precipitation and high temperatures have sustained positive effects on temporary migration that persist over one to two year periods. Building on previous studies of long-term migration, these results challenge the common assumption that flooding, precipitation extremes and high temperatures will consistently increase temporary migration. Instead, our results are consistent with a livelihoods interpretation of environmental migration in which households draw on a range of strategies to cope with environmental variability.

  10. Synergistic Effects of SAM and Selenium Compounds on Proliferation, Migration and Adhesion of HeLa Cells.

    PubMed

    Sun, Licui; Zhang, Jianxin; Yang, Qiu; Si, Yang; Liu, Yiqun; Wang, Qin; Han, Feng; Huang, Zhenwu

    2017-08-01

    To determine the antitumor activities and molecular mechanism of selenium compounds in HeLa cells. Western blotting was used to detect ERK and AKT activation in HeLa cells induced by selenium compounds selenomethionine (SeMet), methylselenocysteine (MeSeCys) and methylseleninic acids (MeSeA). Using MTT, wound-healing and Matrigel adhesion assays, the antitumor effects of SAM and selenium compounds were evaluated in HeLa cells. MeSeA inhibited ERK and AKT signaling pathways and suppressed the proliferation (p<0.05 vs. HeLa control), migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. MeSeCys and SeMet inhibited AKT signaling pathways and the migration (p<0.05 vs. HeLa control) and adhesion (p<0.01 vs. HeLa control) of HeLa cells. The synergistic action of MeSeA with SAM led to a statistically significant inhibition of proliferation, migration and adhesion of HeLa cells. MeSeA, MeSeCys and SeMet exert different antitumor activities by inhibiting ERK and AKT signaling pathways. The combination of MeSeA and SAM exhibited better antitumor effects compared to the other treatments. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. [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.

  12. Polymorphonuclear cell motility, ankylosing spondylitis, and HLA B27.

    PubMed Central

    Pease, C T; Fordham, J N; Currey, H L

    1984-01-01

    Polymorphonuclear leucocyte (PMN) function was studied in 29 subjects with ankylosing spondylitis (AS). Of these, 20 were HLA B27+ve and 9 B27-ve. There were 30 controls and, of these, 15 were B27+ve. Random and directed cell migration was measured by 2 techniques: migration through a micropore filter and migration under an agar film. The chemo-attractant was either case in-activated serum or zymosan-activated serum. By both techniques directed motility was increased in subjects with B27 or with AS when compared to the B27-ve controls. This suggests that the disease AS and the possession of B27 are both associated with increased PMN motility. PMID:6608924

  13. [Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

    PubMed

    Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

    2011-10-01

    To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

  14. Development of three-dimensional collagen scaffolds with controlled architecture for cell migration studies using breast cancer cell lines.

    PubMed

    Campbell, Jonathan J; Husmann, Anke; Hume, Robert D; Watson, Christine J; Cameron, Ruth E

    2017-01-01

    Cancer is characterized by cell heterogeneity and the development of 3D in vitro assays that can distinguish more invasive or migratory phenotypes could enhance diagnosis or drug discovery. 3D collagen scaffolds have been used to develop analogues of complex tissues in vitro and are suited to routine biochemical and immunological assays. We sought to increase 3D model tractability and modulate the migration rate of seeded cells using an ice-templating technique to create either directional/anisotropic or non-directional/isotropic porous architectures within cross-linked collagen scaffolds. Anisotropic scaffolds supported the enhanced migration of an invasive breast cancer cell line MDA-MB-231 with an altered spatial distribution of proliferative cells in contrast to invasive MDA-MB-468 and non-invasive MCF-7 cells lines. In addition, MDA-MB-468 showed increased migration upon epithelial-to-mesenchymal transition (EMT) in anisotropic scaffolds. The provision of controlled architecture in this system may act both to increase assay robustness and as a tuneable parameter to capture detection of a migrated population within a set time, with consequences for primary tumour migration analysis. The separation of invasive clones from a cancer biomass with in vitro platforms could enhance drug development and diagnosis testing by contributing assay metrics including migration rate, as well as modelling cell-cell and cell-matrix interaction in a system compatible with routine histopathological testing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. 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.

  16. Controlled surface topography regulates collective 3D migration by epithelial-mesenchymal composite embryonic tissues.

    PubMed

    Song, Jiho; Shawky, Joseph H; Kim, YongTae; Hazar, Melis; LeDuc, Philip R; Sitti, Metin; Davidson, Lance A

    2015-07-01

    Cells in tissues encounter a range of physical cues as they migrate. Probing single cell and collective migratory responses to physically defined three-dimensional (3D) microenvironments and the factors that modulate those responses are critical to understanding how tissue migration is regulated during development, regeneration, and cancer. One key physical factor that regulates cell migration is topography. Most studies on surface topography and cell mechanics have been carried out with single migratory cells, yet little is known about the spreading and motility response of 3D complex multi-cellular tissues to topographical cues. Here, we examine the response to complex topographical cues of microsurgically isolated tissue explants composed of epithelial and mesenchymal cell layers from naturally 3D organized embryos of the aquatic frog Xenopus laevis. We control topography using fabricated micropost arrays (MPAs) and investigate the collective 3D migration of these multi-cellular systems in these MPAs. We find that the topography regulates both collective and individual cell migration and that dense MPAs reduce but do not eliminate tissue spreading. By modulating cell size through the cell cycle inhibitor Mitomycin C or the spacing of the MPAs we uncover how 3D topographical cues disrupt collective cell migration. We find surface topography can direct both single cell motility and tissue spreading, altering tissue-scale processes that enable efficient conversion of single cell motility into collective movement. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Controlling the migration behaviors of vascular smooth muscle cells by methoxy poly(ethylene glycol) brushes of different molecular weight and density.

    PubMed

    Wu, Jindan; Mao, Zhengwei; Gao, Changyou

    2012-01-01

    Cell migration is an important biological activity. Regulating the migration of vascular smooth muscle cells (VSMCs) is critical in tissue engineering and therapy of cardiovascular disease. In this work, methoxy poly(ethylene glycol) (mPEG) brushes of different molecular weight (Mw 2 kDa, 5 kDa and 10 kDa) and grafting mass (0-859 ng/cm(2)) were prepared on aldehyde-activated glass slides, and were characterized by X-ray photoelectron spectrometer (XPS) and quartz crystal microbalance with dissipation (QCM-d). Adhesion and migration processes of VSMCs were studied as a function of different mPEG Mw and grafting density. We found that these events were mainly regulated by the grafting mass of mPEG regardless of mPEG Mw and grafting density. The VSMCs migrated on the surfaces randomly without a preferential direction. Their migration rates increased initially and then decreased along with the increase of mPEG grafting mass. The fastest rates (~24 μm/h) appeared on the mPEG brushes with grafting mass of 300-500 ng/cm(2) depending on the Mw. Cell adhesion strength, arrangement of cytoskeleton, and gene and protein expression levels of adhesion related proteins were studied to unveil the intrinsic mechanism. It was found that the cell-substrate interaction controlled the cell mobility, and the highest migration rate was achieved on the surfaces with appropriate adhesion force. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. A model for migration and accumulation of hydrocarbons in the Thamama and Arab reservoirs in Abu Dhabi, U.A.E.

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

    Hawas, M.F.; Takezaki, H.

    1995-08-01

    The distribution of hydrocarbons in the Lower Cretaceous Thamama Group and Upper Jurassic Arab Formation in Abu Dhabi is influenced by the development of the intervening Hith anhydrites. The geochemical analysis of Thamama and Arab hydrocarbons indicate that they were generated from a common source rock: the Upper Jurassic Diyab Formation. Studies carried out on the Miocene sabkha anhydrites in the coastal flat west of Abu Dhabi supported a model for vertical migration through the Hith anhydrites under certain conditions. The established model implies that the Diyab oil and gas had migrated essentially vertically and individually which means that themore » oil migrated prior to the gas and their distribution is controlled by the differential sealing potential of the anhydrites at each migration phase: a Hith anhydrite bed of more than 30 feet (ft.) thick was a perfect seal for hydrocarbon migration into the Arab reservoirs. In this case, oils could not break through to the overlying Thamama group. But where the anhydride bed thicknesses dropped below 30 ft. thick, this permitted oil migration through to the overlying Thamama reservoirs during the oil generation phase in the Turonian time. At a later stage, with additional depth of burial and progressive diagenesis anhydrite beds as thin as 8 ft. thick became effective seals. These controlled the distribution of the gas during the gas generation phase in the Eocene time.« less

  19. Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration

    PubMed Central

    Karunarathne, W. K. Ajith; Giri, Lopamudra; Patel, Anilkumar K.; Venkatesh, Kareenhalli V.; Gautam, N.

    2013-01-01

    There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein–coupled receptor network control of other cell behaviors. PMID:23569254

  20. Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration.

    PubMed

    Karunarathne, W K Ajith; Giri, Lopamudra; Patel, Anilkumar K; Venkatesh, Kareenhalli V; Gautam, N

    2013-04-23

    There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein-coupled receptor network control of other cell behaviors.

  1. Observation method to predict meander migration and vertical degradation of rivers.

    DOT National Transportation Integrated Search

    2014-05-01

    Meander migration and vertical degradation of river bed are processes that have been studied for years. : Different methods have been proposed to make predictions of the behavior of rivers with respect to these : processes. These two erosion controll...

  2. Control of Subsurface Contaminant Migration by Vertical Engineered Barriers

    EPA Science Inventory

    This Fact Sheet is intended to provide remedial project managers (RPMs), on-scene coordinators (OSCs), contractors, and other remediation stakeholders with a basic overview of hazardous waste containment systems constructed to prevent or limit the migration of contamination in gr...

  3. The Influence of Physical Forces on Progenitor Cell Migration, Proliferation and Differentiation in Fracture Repair

    DTIC Science & Technology

    2009-11-01

    The Influence of Physical Forces on Progenitor Cell Migration, Proliferation and Differentiation in Fracture Repair PRINCIPAL INVESTIGATOR...REPORT TYPE Final 3. DATES COVERED (From - To) 11/1/05 – 10/31/09 4. TITLE AND SUBTITLE The Influence of Physical Forces on Progenitor Cell Migration...SUPPLEMENTARY NOTES 14. ABSTRACT The goal of this program is to investigate the influence of controlled mechanical stimulation on the behavior of

  4. Myosin-II controls cellular branching morphogenesis and migration in 3D by minimizing cell surface curvature

    PubMed Central

    Elliott, Hunter; Fischer, Robert A.; Myers, Kenneth A.; Desai, Ravi A.; Gao, Lin; Chen, Christopher S.; Adelstein, Robert; Waterman, Clare M.; Danuser, Gaudenz

    2014-01-01

    In many cases cell function is intimately linked to cell shape control. We utilized endothelial cell branching morphogenesis as a model to understand the role of myosin-II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell surface curvature. We find that Rho/ROCK-stimulated myosin-II contractility minimizes cell-scale branching by recognizing and minimizing local cell surface curvature. Utilizing micro-fabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin-II cortical association, where it acts to maintain minimal curvature. The feedback between myosin-II regulation by and control of curvature drives cycles of localized cortical myosin-II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration. PMID:25621949

  5. Probing Leader Cells in Endothelial Collective Migration by Plasma Lithography Geometric Confinement

    PubMed Central

    Yang, Yongliang; Jamilpour, Nima; Yao, Baoyin; Dean, Zachary S.; Riahi, Reza; Wong, Pak Kin

    2016-01-01

    When blood vessels are injured, leader cells emerge in the endothelium to heal the wound and restore the vasculature integrity. The characteristics of leader cells during endothelial collective migration under diverse physiological conditions, however, are poorly understood. Here we investigate the regulation and function of endothelial leader cells by plasma lithography geometric confinement generated. Endothelial leader cells display an aggressive phenotype, connect to follower cells via peripheral actin cables and discontinuous adherens junctions, and lead migrating clusters near the leading edge. Time-lapse microscopy, immunostaining, and particle image velocimetry reveal that the density of leader cells and the speed of migrating clusters are tightly regulated in a wide range of geometric patterns. By challenging the cells with converging, diverging and competing patterns, we show that the density of leader cells correlates with the size and coherence of the migrating clusters. Collectively, our data provide evidence that leader cells control endothelial collective migration by regualting the migrating clusters. PMID:26936382

  6. 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.

  7. Confinement and low adhesion induce fast amoeboid migration of slow mesenchymal cells.

    PubMed

    Liu, Yan-Jun; Le Berre, Maël; Lautenschlaeger, Franziska; Maiuri, Paolo; Callan-Jones, Andrew; Heuzé, Mélina; Takaki, Tohru; Voituriez, Raphaël; Piel, Matthieu

    2015-02-12

    The mesenchymal-amoeboid transition (MAT) was proposed as a mechanism for cancer cells to adapt their migration mode to their environment. While the molecular pathways involved in this transition are well documented, the role of the microenvironment in the MAT is still poorly understood. Here, we investigated how confinement and adhesion affect this transition. We report that, in the absence of focal adhesions and under conditions of confinement, mesenchymal cells can spontaneously switch to a fast amoeboid migration phenotype. We identified two main types of fast migration--one involving a local protrusion and a second involving a myosin-II-dependent mechanical instability of the cell cortex that leads to a global cortical flow. Interestingly, transformed cells are more prone to adopt this fast migration mode. Finally, we propose a generic model that explains migration transitions and predicts a phase diagram of migration phenotypes based on three main control parameters: confinement, adhesion, and contractility. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Lateral migration of dual droplet trains in a double spiral microchannel

    NASA Astrophysics Data System (ADS)

    Xue, ChunDong; Chen, XiaoDong; Liu, Chao; Hu, GuoQing

    2016-07-01

    Microfluidic droplets have emerged as novel platforms for chemical and biological applications. Manipulation of droplets has thus attracted increasing attention. Different from solid particles, deformable droplets cannot be efficiently controlled by inertia-driven approaches. Here, we report a study on the lateral migration of dual droplet trains in a double spiral microchannel at low Reynolds numbers. The dominant driving mechanism is elucidated as wall effect originated from the droplet deformation. Three types of migration modes are observed with varying Reynolds numbers and the size-dependent mode is intensively investigated. We obtain empirical formulas by relating the migration to Reynolds numbers and droplet sizes. The effect of droplet deformability on the migration and the detailed migration behavior along the double spiral channel are discussed. Numerical simulations are also performed and yielded in qualitative agreement with the experiments. This proposed low Re approach based on lateral migration could be a promising alternative to existing inertia-driven approaches especially concerning deformable entities and susceptible bio-particles.

  9. Probing Leader Cells in Endothelial Collective Migration by Plasma Lithography Geometric Confinement.

    PubMed

    Yang, Yongliang; Jamilpour, Nima; Yao, Baoyin; Dean, Zachary S; Riahi, Reza; Wong, Pak Kin

    2016-03-03

    When blood vessels are injured, leader cells emerge in the endothelium to heal the wound and restore the vasculature integrity. The characteristics of leader cells during endothelial collective migration under diverse physiological conditions, however, are poorly understood. Here we investigate the regulation and function of endothelial leader cells by plasma lithography geometric confinement generated. Endothelial leader cells display an aggressive phenotype, connect to follower cells via peripheral actin cables and discontinuous adherens junctions, and lead migrating clusters near the leading edge. Time-lapse microscopy, immunostaining, and particle image velocimetry reveal that the density of leader cells and the speed of migrating clusters are tightly regulated in a wide range of geometric patterns. By challenging the cells with converging, diverging and competing patterns, we show that the density of leader cells correlates with the size and coherence of the migrating clusters. Collectively, our data provide evidence that leader cells control endothelial collective migration by regualting the migrating clusters.

  10. Dcx Re-expression Reduces Subcortical Band Heterotopia and Seizure Threshold in an Animal Model of Neuronal Migration Disorder

    PubMed Central

    Manent, Jean-Bernard; Wang, Yu; Chang, YoonJeung; Paramasivam, Murugan; LoTurco, Joseph J

    2009-01-01

    Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration, and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNAi of Dcx, that aberrantly positioned neurons can be stimulated to migrate by re-expressing Dcx after birth. Re-starting migration in this way both reduces neocortical malformations and restores neuronal patterning. We find further that the capacity to reduce SBH has a critical period in early postnatal development. Moreover, intervention after birth reduces convulsant-induced seizure threshold to levels similar to that of malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by re-engaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk. PMID:19098909

  11. Biarsenical labeling of vesicular stomatitis virus encoding tetracysteine-tagged m protein allows dynamic imaging of m protein and virus uncoating in infected cells.

    PubMed

    Das, Subash C; Panda, Debasis; Nayak, Debasis; Pattnaik, Asit K

    2009-03-01

    A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) in place of P and a fusion matrix protein (monomeric red fluorescent protein fused in frame at the carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type (wt) M protein in its normal location, was recovered, but the MmRFP was not incorporated into the virions. Subsequently, we generated recombinant viruses (VSV-PeGFP-DeltaM-Mtc and VSV-DeltaM-Mtc) encoding M protein with a carboxy-terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant viruses incorporated Mtc at levels similar to M in wt VSV, demonstrating recovery of infectious rhabdoviruses encoding and incorporating a tagged M protein. Virions released from cells infected with VSV-PeGFP-DeltaM-Mtc and labeled with the biarsenical red dye (ReAsH) were dually fluorescent, fluorescing green due to incorporation of PeGFP in the nucleocapsids and red due to incorporation of ReAsH-labeled Mtc in the viral envelope. Transport and subsequent association of M protein with the plasma membrane were shown to be independent of microtubules. Sequential labeling of VSV-DeltaM-Mtc-infected cells with the biarsenical dyes ReAsH and FlAsH (green) revealed that newly synthesized M protein reaches the plasma membrane in less than 30 min and continues to accumulate there for up to 2 1/2 hours. Using dually fluorescent VSV, we determined that following adsorption at the plasma membrane, the time taken by one-half of the virus particles to enter cells and to uncoat their nucleocapsids in the cytoplasm is approximately 28 min.

  12. Aspects of T-Dually Extended Superspaces

    NASA Astrophysics Data System (ADS)

    Polacek, Martin

    This dissertation is divided into three main parts where we derive various properties of the T-dually extended superspaces. In the first part we reformulate the manifestly T-dual description of the massless sector of the closed bosonic string, directly from the geometry associated with the (left and right) affine Lie algebra of the coset space Poincare/Lorentz. This construction initially doubles not only the (space-time) coordinates for translations but also those for Lorentz transformations (and their "dual"). As a result, the Lorentz connection couples directly to the string (as does the vielbein), rather than being introduced indirectly through covariant derivatives as previously. This not only reproduces the old definition of T-dual torsion, but automatically gives a general, covariant definition of T-dual curvature (but still with some undetermined connections). In the second part we give the manifestly T-dual formulation of the massless sector of the classical 3D Type II superstring in off-shell 3D N = 2 superspace, including the action. It has a simple relation to the known superspace of 4D N = 1 supergravity in 4D M-theory via 5D F-theory. The pre-potential appears as part of the vielbein, without derivatives. In the last and the most involved part we find the pre-potential in the superspace with AdS5 x S5 background. The pre-potential appears as part of the vielbeins, without derivatives. In both subspaces (AdS5 and S 5) we use Poincare coordinates. We pick one bulk coordinate in AdS5 and one bulk coordinate in S 5 to define the space-cone gauge. Such space-cone gauge destroys the bulk Lorentz covariance. However, it still preserves boundary Lorentz covariance (and gives projective superspace) SO ( 3, 1) ⊗ SO (4) and so symmetries of boundary CFT are manifest.

  13. Tracking Mallards (Anas platyrhynchos) with GPS Satellite Transmitters Along Their Migration Route Through Northeast Asia.

    PubMed

    Shin, Jeong-Hwa; Lee, Ki-Sup; Kim, Seol-Hee; Hwang, Jong-Kyung; Woo, Chanjin; Kim, Jiyeon; Kim, Jung-Hyun; Suh, Jae-Hwa; Jeong, Jipseol; Wang, Seung-Jun; Chung, Hyen-Mi; Yu, Seung-do; Choi, Kyung-Hee; Mo, In-Pil

    2016-05-01

    In this study, Global Positioning System satellite transmitters were attached to three mallards (Anas platyrhynchos) wintering in South Korea to track their migration routes, stopover sites, breeding sites, and migration patterns. We successfully tracked only one mallard (no. 108917) from November 15, 2011, to November 29, 2013, and determined separate migration routes in two cases of spring migration and one case of fall migration. The mallard repeatedly migrated to the same final destination, even though the travel path varied. We identified six stopover sites: Hunhe River, Liaohe River, Yinma River, Yalu River, Songjeon Bay, and Dahuofang Reservoir in China and South Korea. The wintering sites of two migration cases were discovered to be identical (Gokgyo River in Asan, South Korea). The terminal sites, which were presumed to be breeding grounds, were the same in both cases (Hinggan League in Inner Mongolia Autonomous Region, China). On the basis of the migration routes identified in this study, we suggest that future efforts to control highly pathogenic avian influenza (HPAI) should not only include avian influenza surveillance but also implement flyway-based strategies, with regard to all countries affected by potential HPAI outbreaks.

  14. Functionalized iron oxide nanoparticles for controlling the movement of immune cells

    NASA Astrophysics Data System (ADS)

    White, Ethan E.; Pai, Alex; Weng, Yiming; Suresh, Anil K.; van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

    2015-04-01

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed ``cell box'' was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. Electronic supplementary information (ESI) available: Transmission electron microscopy images of the particles, additional independent experiments for the NFκB activity and exocytosis assays, TEM images for the SPION untreated cells, bright field microscopy images of the cells alone in the presence and absence of magnet, images of the magnetic movement experiments at higher doses of SPION, full uncropped images of the post-migration LIVE/DEAD assay, and a video file of cell movement. See DOI: 10.1039/c3nr04421a

  15. Effects of abdominally implanted radiotransmitters with percutaneous antennas on migration, reproduction, and survival of Canada geese

    USGS Publications Warehouse

    Hupp, Jerry W.; Pearce, John M.; Mulcahy, Daniel M.; Miller, David A.

    2006-01-01

    Abdominally implanted radiotransmitters with percutaneous antennas are increasingly used to monitor movements, survival, and reproduction of waterbirds. However, there has been relatively little assessment of the effects of such radios on avian demographic parameters or migration. We implanted either a 26- or 35-g abdominal transmitter with percutaneous antenna in 198 adult female lesser Canada geese (Branta canadensis parvipes) in Anchorage, Alaska during 2000 and 2001. We compared migration chronology, reproductive effort, and survival of radiomarked females to 118 control females marked with leg bands. Arrival dates following spring migration were similar among females in different treatments in 2001. However, in 2002, wind direction during late migration was less favorable, and arrival of females with 35-g radiotransmitters lagged 1–2 days behind that of control females. Nest initiation dates, clutch size, and mean egg volume were similar for 152 nests of females that lacked radios and 62 nests of radiomarked females. Estimated nesting propensity for females with operable radiotransmitters was 61% and 72% in 2001 and 2002, respectively. Apparent annual survival (ϕ = 0.82, 95% confidence interval: 0.76 to 0.87) was similar among treatments in the first year after geese were marked. In the second and third years after marking, model-averaged estimates for survival of females with large radiotransmitters were 10% lower than estimates for control females. However, the effect of large radios on long-term survival was equivocal because of uncertainty surrounding treatment estimates. We conclude that abdominally implanted radiotransmitters with percutaneous antennas had small effects on migration chronology but no apparent effects on fecundity. Abdominal transmitters can provide unbiased estimates of anserine survival in the first year after deployment. Because of the potentially greater effects of larger transmitters on migration and long-term survival, we recommend that biologists minimize the size of implanted transmitters and deploy radios with caution if long-term survival of marked birds is a concern.

  16. Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

    PubMed

    Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

    2017-09-01

    Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Migration and persistence of human influenza A viruses, Vietnam, 2001-2008.

    PubMed

    Le, Mai Quynh; Lam, Ha Minh; Cuong, Vuong Duc; Lam, Tommy Tsan-Yuk; Halpin, Rebecca A; Wentworth, David E; Hien, Nguyen Tran; Thanh, Le Thi; Phuong, Hoang Vu Mai; Horby, Peter; Boni, Maciej F

    2013-11-01

    Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001-2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year.

  18. 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

  19. Migration Background Influences Consumption Patterns Based on Dietary Recommendations of Food Bank Users in Germany.

    PubMed

    Stroebele-Benschop, Nanette; Depa, Julia; Gyngell, Fiona; Müller, Annalena; Eleraky, Laila; Hilzendegen, Carolin

    2018-03-29

    People with low income tend to eat less balanced than people with higher income. This seems to be particularly the case for people with migration background. This cross-sectional study examined the relation of consumption patterns of 597 food bank users with different migration background in Germany. Questionnaires were distributed assessing sociodemographic information and consumption patterns. Analyses were conducted using binary logistic regressions. Models were controlled for age, gender, type of household and education. The group of German food bank users consumed fewer fruits and vegetables and less fish compared to all other groups with migration background (former USSR, Balkan region, Middle East). A significant predictor for fruit and vegetable consumption was migration status. Participants from the former USSR consumed less often SSBs compared to the other groups. Dietary recommendations for low income populations should take into consideration other aspects besides income such as migration status.

  20. STRUCTURAL ECONOMIC CHANGE AND INTERNATIONAL MIGRATION FROM MEXICO AND POLAND

    PubMed Central

    Massey, Douglas S.; Kalter, Frank; Pren, Karen A.

    2010-01-01

    In this article we use uniquely comparable data sets from two very different settings to examine how exogenous economic transformations affect the likelihood and selectivity of international out-migration. Specifically, we use data from the Mexican Migration Project to construct event history files predicting first U.S. trips from seven communities in the state of Veracruz, which until recently sent very few migrants abroad. Similarly, using data from the Polish Migration Project, we derive comparable event history files predicting first trips to Germany from four Polish communities, which also sent few migrants abroad before the 1980s. Our analyses suggest that the onset of structural adjustment in both places had a significant effect in raising the probability of international migration, even when controlling for a set of standard variables specified by other theories to influence migration propensity, such as the size of the binational income gap and various indicators of human and social capital. PMID:21765550

  1. Investigating Electrostatic Precipitator Design Parameters for Efficient Control of Particulate Matter in Thermal Power Plant: A Case Study

    NASA Astrophysics Data System (ADS)

    Rai, P.; Gautam, N.; Chandra, H.

    2018-06-01

    This work deals with the analysis and modification of operational parameters for meeting the emission standards, set by Central Pollution Control Board (CPCB)/State Pollution Control Board (SPCB) from time to time of electrostatic precipitator (ESP). The analysis is carried out by using standard chemical analysis supplemented by the relevant data collected from Korba East Phase (Ph)-III thermal power plant, under Chhattisgarh State Electricity Board (CSEB) operating at Korba, Chhattisgarh. Chemical analysis is used to predict the emission level for different parameters of ESP. The results reveal that for a constant outlet PM concentration and fly ash percentage, the total collection area decreases with the increase in migration velocity. For constant migration velocity and outlet PM concentration, the total collection area increases with the increase in the fly ash percent. For constant migration velocity and outlet e PM concentration, the total collection area increases with the ash content in the coal. i.e. from minimum ash to maximum ash. As far as the efficiency is concerned, it increases with the fly ash percent, ash content and the inlet dust concentration but decreases with the outlet PM concentration at constant migration velocity, fly ash and ash content.

  2. Platelet-Rich Fibrin Lysate Can Ameliorate Dysfunction of Chronically UVA-Irradiated Human Dermal Fibroblasts.

    PubMed

    Wirohadidjojo, Yohanes Widodo; Budiyanto, Arief; Soebono, Hardyanto

    2016-09-01

    To determine whether platelet-rich fibrin lysate (PRF-L) could restore the function of chronically ultraviolet-A (UVA)-irradiated human dermal fibroblasts (HDFs), we isolated and sub-cultured HDFs from six different human foreskins. HDFs were divided into two groups: those that received chronic UVA irradiation (total dosages of 10 J cm⁻²) and those that were not irradiated. We compared the proliferation rates, collagen deposition, and migration rates between the groups and between chronically UVA-irradiated HDFs in control and PRF-L-treated media. Our experiment showed that chronic UVA irradiation significantly decreased (p<0.05) the proliferation rates, migration rates, and collagen deposition of HDFs, compared to controls. Compared to control media, chronically UVA-irradiated HDFs in 50% PRF-L had significantly increased proliferation rates, migration rates, and collagen deposition (p<0.05), and the migration rates and collagen deposition of chronically UVA-irradiated HDFs in 50% PRF-L were equal to those of normal fibroblasts. Based on this experiment, we concluded that PRF-L is a good candidate material for treating UVA-induced photoaging of skin, although the best method for its clinical application remains to be determined.

  3. Investigating Electrostatic Precipitator Design Parameters for Efficient Control of Particulate Matter in Thermal Power Plant: A Case Study

    NASA Astrophysics Data System (ADS)

    Rai, P.; Gautam, N.; Chandra, H.

    2018-02-01

    This work deals with the analysis and modification of operational parameters for meeting the emission standards, set by Central Pollution Control Board (CPCB)/State Pollution Control Board (SPCB) from time to time of electrostatic precipitator (ESP). The analysis is carried out by using standard chemical analysis supplemented by the relevant data collected from Korba East Phase (Ph)-III thermal power plant, under Chhattisgarh State Electricity Board (CSEB) operating at Korba, Chhattisgarh. Chemical analysis is used to predict the emission level for different parameters of ESP. The results reveal that for a constant outlet PM concentration and fly ash percentage, the total collection area decreases with the increase in migration velocity. For constant migration velocity and outlet PM concentration, the total collection area increases with the increase in the fly ash percent. For constant migration velocity and outlet e PM concentration, the total collection area increases with the ash content in the coal. i.e. from minimum ash to maximum ash. As far as the efficiency is concerned, it increases with the fly ash percent, ash content and the inlet dust concentration but decreases with the outlet PM concentration at constant migration velocity, fly ash and ash content.

  4. Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

    PubMed Central

    Burgos, Jose L.; Patterson, Thomas L.; Graff-Zivin, Joshua S.; Kahn, James G.; Rangel, M. Gudelia; Lozada, M. Remedios; Staines, Hugo; Strathdee, Steffanie A.

    2016-01-01

    Background We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008–2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. Methods A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY) over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER), defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs) compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP) in Mexico (equivalent to US$10,300). Findings For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER) of US$4,360 ($310–$7,200) per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310–$7,200) compared with the mixed approach. For TJ, the combination of interactive safer sex/didactic safer injection had an ICER of US$5,921 ($104–$9,500) per QALY compared with dually didactic. Strategies using the interactive safe injection intervention were dominated due to lack of efficacy advantage. The multivariate sensitivity analysis showed a 95% certainty that in both CJ and TJ the ICER for the mixed approach (interactive safer sex didactic safer injection intervention) was less than the GDP per capita for Mexico. The dual interactive approach met this threshold consistently in CJ, but not in TJ. Interpretation In the absence of an expanded NEP in CJ, the combined-interactive formats of the MMS behavioral intervention is highly cost-effective. In contrast, in TJ where NEP expansion suggests that improved access to sterile syringes significantly reduced injection-related risks, the interactive safer-sex combined didactic safer-injection was highly cost-effective compared with the combined didactic versions of the safer-sex and safer-injection formats of the MMS, with no added benefit from the interactive safer-injection component. PMID:26890001

  5. Closing service system gaps for homeless clients with a dual diagnosis: integrated teams and interagency cooperation.

    PubMed

    Rosenheck, Robert A; Resnick, Sandra G; Morrissey, Joseph P

    2003-06-01

    There is great concern about fragmentation of mental health service delivery, especially for dually diagnosed homeless people, and apprehension that such fragmentation adversely affects service access and outcomes. This study first seeks to articulate two alternative approaches to the integration of psychiatric and substance abuse services, one involving an integrated team model and the other a collaborative relationship between agencies. It then applies this conceptualization to a sample of dually diagnosed homeless people who participated in the ACCESS demonstration. Longitudinal outcome data were obtained through interviews at baseline, 3 months, and 12 months with homeless clients with a dual diagnosis (N = 1074) who received ACT-like case management services through the ACCESS demonstration. A survey of ACCESS case managers was conducted to obtain information on: (i) the proportion of clients who received substance abuse services directly from ACCESS case management teams, and the proportion who received services from other agencies; and (ii) the perceived quality of the relationship (i.e. communication, cooperation and trust) between providers--both within the same teams and between agencies. Hierarchical linear modeling was then used to examine the relationship of these two factors to service use and outcome with mixed-model regression analysis. Significant (p<.05) and positive relationships were observed in 4 of the 20 analyses of the association of service use and measures of communication, cooperation, and trust (either intrateam or inter-agency) while none were significant and negative. At 12 months, receipt of a higher proportion of services from agencies other than the ACCESS team was associated with fewer days homeless, and greater reduction of psychiatric symptoms, contradicting the hypothesis that integrated team care is more effective than interagency collaborations. This study broadens the conceptual framework for addressing service system fragmentation by considering both single team integration and interagency coordination, and by considering both program structure and the quality of relationships between providers. Data from a multi-site outcome study demonstrated suggestive associations between perceptions of communication, cooperation and measures of clinical service use. However, the proportion of clients treated entirely within a single team was associated with poorer housing and psychiatric outcomes. These empirical results must be regarded as illustrative rather than conclusive because of the use of a non-experimental study design, imperfections in the available measures, and the incomplete sampling of case managers. This study suggests that fragmentation of services for dually diagnosed clients may be reduced by improving the interactions within and between agencies providing these services. While primary emphasis has been placed on developing integrated teams, interagency approaches should not be prematurely excluded. Research on approaches to reducing system fragmentation have focused on either global efforts to integrate numerous agencies in a community or highly focused efforts to develop specialized teams. Future research should also focus on the possibility of fostering constructive relationships between selected pairs or subsets of agencies. Research in this area will also benefit from the further development measures of team integration and of both intra-team and inter-agency communication, collaboration, and trust.

  6. Molecular imaging of drug-modulated protein-protein interactions in living subjects.

    PubMed

    Paulmurugan, Ramasamy; Massoud, Tarik F; Huang, Jing; Gambhir, Sanjiv S

    2004-03-15

    Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

  7. Production of migration inhibitory factor in response to bacterial and fungal antigens in patients with untreated Graves' disease

    PubMed Central

    Wall, Jack R.; Ryan, E. Ann

    1980-01-01

    Tests for the production of migration inhibitory factor by peripheral blood leukocytes in response to ubiquitous bacterial and fungal antigens were carried out in patients with untreated Graves' disease and in healthy control subjects. Dose-response studies, tests for the production of this factor after 72 hours' stimulation with phytohemagglutinin as a test for reserve, and tests before and after 24 hours' preculture to deplete suppressor cells were also performed in some patients. The antigens used were Candida, Trichophyton-Oidiomyces-Epidermophyton, mumps live attenuated virus and purified protein derivative of tuberculin. The production of migration inhibitory factor was measured by the agarose microdroplet method. The production of migration inhibitory factor in response to all the antigens except mumps virus was slightly greater in the patients than in the control subjects, although the differences were not significant. The dose-response characteristics and the production of migration inhibitory factor after stimulation with phytohemagglutinin were similar in the two groups. The production of migration inhibitory factor in response to suboptimal concentrations of Candida, Trichophyton-Oidiomyces-Epidermophyton and mumps virus was not enhanced in either group after 24 hours' preculture apart from a slight increase in response to mumps virus in the patients. These results fail to support the suggestion that patients with Graves' disease have a deficiency of suppressor cells. PMID:6446374

  8. Monocyte function in infectious mononucleosis: evidence for a reversible cellular defect.

    PubMed

    Britton, S

    1976-10-01

    Migration of blood monocytes from patients with acute infectious mononucleosis and from normal controls was measured against chemotactic factors in serum. Moncytes from patients with acute infectious mononucleosis showed decreased migration as compared with that of control monocytes. However, serum from patients with infectious mononucleosis contained normal or above normal amounts of chemotaxins for monocytes. The migratory defect of monocytes from patients with infectious mononucleosis was reversible within three months after the onset of diesease. The cause of this monocyte migration defect in infectious mononucleosis is though to be an in vivo blockade of receptors on monocytes for chemotaxins, and it is speculated that this defect can partially explain the explain the ablated delayed-hypersensitivity skin reactions in this disease.

  9. Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations.

    PubMed

    Petrie Aronin, Caren E; Zhao, Yun M; Yoon, Justine S; Morgan, Nicole Y; Prüstel, Thorsten; Germain, Ronald N; Meier-Schellersheim, Martin

    2017-11-21

    Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments. Published by Elsevier Inc.

  10. Prospect theory and the decision to move or stay.

    PubMed

    Clark, William A V; Lisowski, William

    2017-09-05

    Migration has always involved stress and risk. More risk-averse households are less likely to move, while less risk-averse households will seek out opportunities and migrate. We investigate how the theoretical contributions of prospect theory, and specifically the endowment effect, can provide new understanding about decisions whether to migrate or not. We test the hypothesis that risk aversion extends the length of stay in the dwelling and, by extension, in the local labor and housing markets. How long people remain in place is a function, we hypothesize, of their independently self-assessed propensity to take risks, after controlling for a range of demographic and socioeconomic characteristics. We use the theoretical insights of prospect theory and the endowment effect (the notion of the "use value" differing from the "exchange value") to explain the likelihood of staying after controlling for life-course events. The results confirm the explanatory power of self-assessed risk in the decision to migrate or stay and, equally important, confirm the role of the endowment effect.

  11. Prospect theory and the decision to move or stay

    PubMed Central

    Clark, William A. V.

    2017-01-01

    Migration has always involved stress and risk. More risk-averse households are less likely to move, while less risk-averse households will seek out opportunities and migrate. We investigate how the theoretical contributions of prospect theory, and specifically the endowment effect, can provide new understanding about decisions whether to migrate or not. We test the hypothesis that risk aversion extends the length of stay in the dwelling and, by extension, in the local labor and housing markets. How long people remain in place is a function, we hypothesize, of their independently self-assessed propensity to take risks, after controlling for a range of demographic and socioeconomic characteristics. We use the theoretical insights of prospect theory and the endowment effect (the notion of the “use value” differing from the “exchange value”) to explain the likelihood of staying after controlling for life-course events. The results confirm the explanatory power of self-assessed risk in the decision to migrate or stay and, equally important, confirm the role of the endowment effect. PMID:28827341

  12. Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.

    PubMed

    Mizoguchi, Takamasa; Ikeda, Shoko; Watanabe, Saori; Sugawara, Michiko; Itoh, Motoyuki

    2017-10-31

    Persistent directional cell migration is involved in animal development and diseases. The small GTPase Rac1 is involved in F-actin and focal adhesion dynamics. Local Rac1 activity is required for persistent directional migration, whereas global, hyperactivated Rac1 enhances random cell migration. Therefore, precise control of Rac1 activity is important for proper directional cell migration. However, the molecular mechanism underlying the regulation of Rac1 activity in persistent directional cell migration is not fully understood. Here, we show that the ubiquitin ligase mind bomb 1 (Mib1) is involved in persistent directional cell migration. We found that knockdown of MIB1 led to an increase in random cell migration in HeLa cells in a wound-closure assay. Furthermore, we explored novel Mib1 substrates for cell migration and found that Mib1 ubiquitinates Ctnnd1. Mib1-mediated ubiquitination of Ctnnd1 K547 attenuated Rac1 activation in cultured cells. In addition, we found that posterior lateral line primordium cells in the zebrafish mib1 ta52b mutant showed increased random migration and loss of directional F-actin-based protrusion formation. Knockdown of Ctnnd1 partially rescued posterior lateral line primordium cell migration defects in the mib1 ta52b mutant. Taken together, our data suggest that Mib1 plays an important role in cell migration and that persistent directional cell migration is regulated, at least in part, by the Mib1-Ctnnd1-Rac1 pathway. Published under the PNAS license.

  13. A versatile microfluidic platform for the study of cellular interactions between endothelial cells and neutrophils.

    PubMed

    Wu, Xiaojie; Newbold, Molly A; Gao, Zhe; Haynes, Christy L

    2017-05-01

    Endothelial migration is a critical physiological process during vascular angiogenesis, growth and development, as well as in various disease conditions, such as cancer and cardiovascular diseases. Neutrophil migration, known as the important characteristic of immune responses, is also recognized as a contributor to the diseases involving endothelial migration. Herein, the mutually dependent relationship between neutrophil recruitment and endothelial migration was studied on a microfluidic platform for the first time. An in vivo-like microenvironment is created inside microfluidic devices by embedding a gel scaffold into the micro-chambers. This approach, with controllable stable chemical gradients and the ability to quantitate interaction characteristics, overcomes the limitations of the current in vivo and in vitro assays for cell migration studies. The number of neutrophils migrating through the endothelial cell layer is heavily influenced by the concentration of vascular endothelial growth factor (VEGF) that induces endothelial cell migration in the gel scaffold, and is not as correlated to the concentration of chemokine solution used for initiating neutrophil migration. More importantly, neutrophil migration diminishes the effects of the drug that inhibits endothelial migration and this process is regulated by the concentration of chemokine molecules instead of VEGF concentration. The results presented herein demonstrate the complicated cellular interactions between endothelial cells and neutrophils: endothelial migration delicately regulates neutrophil migration while the presence of neutrophils stabilizes the structures of endothelial migration. This study provides deeper understanding of the dynamic cellular interactions between neutrophils and endothelial cells as well as the pathogenesis of relevant diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Rac1 mediates laminar shear stress-induced vascular endothelial cell migration

    PubMed Central

    Huang, Xianliang; Shen, Yang; Zhang, Yi; Wei, Lin; Lai, Yi; Wu, Jiang; Liu, Xiaojing; Liu, Xiaoheng

    2013-01-01

    The migration of endothelial cells (ECs) plays an important role in vascular remodeling and regeneration. ECs are constantly subjected to shear stress resulting from blood flow and are able to convert mechanical stimuli into intracellular signals that affect cellular behaviors and functions. The aim of this study is to elucidate the effects of Rac1, which is the member of small G protein family, on EC migration under different laminar shear stress (5.56, 10.02, and 15.27 dyn/cm2). The cell migration distance under laminar shear stress increased significantly than that under the static culture condition. Especially, under relative high shear stress (15.27 dyn/cm2) there was a higher difference at 8 h (P < 0.01) and 2 h (P < 0.05) compared with static controls. RT-PCR results further showed increasing mRNA expression of Rac1 in ECs exposed to laminar shear stress than that exposed to static culture. Using plasmids encoding the wild-type (WT), an activated mutant (Q61L), and a dominant-negative mutant (T17N), plasmids encoding Rac1 were transfected into EA.hy 926 cells. The average net migration distance of Rac1Q61L group increased significantly, while Rac1T17N group decreased significantly in comparison with the static controls. These results indicated that Rac1 mediated shear stress-induced EC migration. Our findings conduce to elucidate the molecular mechanisms of EC migration induced by shear stress, which is expected to understand the pathophysiological basis of wound healing in health and diseases. PMID:24430179

  15. Proceedings of the Annual Environmental Systems Symposium (11th) Held at Arlington, Virginia on 19-20 November 1980,

    DTIC Science & Technology

    1980-11-20

    PROGRAMS TO CONTROL ENVIRONMENTAL CONTAMINATION FROM PAST ACTIVITIES. * THEN, I WILL PRESENT OUR MAJOR PROGRAM TO IMtPLEMENT WITHIN THE DEPARTMENT OF...OF DOD’S HAZARDOUS WASTE DISPOSAL PROGRAM AND OUR PROGRAM TO ABATE MIGRATION OF CONTAMINANTS FROM DEFENSE INSTALLATIONS. THE INTENSE QUESTIONS FROM THE...INDUSTRY AND MOST OF THE GOVERNMENT. SINCE 1975, DEFENSE HAS HAD ITS INSTALLATION RESTORATION PROGRAM TO ASSESS AND CONTROL ANY POSSIBLE MIGRATION OF

  16. Enhancing Readiness-to-Change Substance Abuse in Persons with Schizophrenia

    PubMed Central

    Carey, Kate B.; Purnine, Daniel M.; Maisto, Stephen A.; Carey, Michael P.

    2008-01-01

    This article describes a four-session intervention designed for persons with co-occurring substance abuse and schizophrenia-spectrum disorders, to be administered as an add-on module to supplement ongoing mental health treatment in an outpatient setting. The intervention targets those dually diagnosed individuals with low readiness-to-change as indicated by current use, and/or low level of engagement in treatment for substance abuse. The intervention is designed to increase problem recognition, to enhance motivation to change maladaptive patterns of substance use, and to facilitate engagement in substance abuse. To achieve these goals, we have adopted constructs from the Transtheoretical Model of Change and utilize principles of motivational and harm reduction interventions, and tailored them to the target population. PMID:11428245

  17. Excited State Intramolecular Proton Transfer of 2,5-bis(5-ethyl-2-benzoxazolyl)-hydroquinone and its OH/OD-isotopomers studied in supersonic jets

    NASA Astrophysics Data System (ADS)

    Peukert, Sebastian; Gil, Michał; Kijak, Michał; Sepioł, Jerzy

    2015-11-01

    The Excited State Intramolecular Proton Transfer (ESIPT) reactions of dually fluorescent 2,5-bis(5-ethyl-2-benzoxazolyl)-hydroquinone (DE-BBHQ) and its isotopomers have been studied in the supersonic jet applying laser induced fluorescence (LIF) and fluorescence-depletion (F-D) spectroscopy. LIF-spectra measured at photo-tautomeric (red) fluorescence exhibit a characteristic triplet pattern of vibronic bands, which gradually collapses upon successive deuteration. Complementary TDDFT calculations indicate the possibility of 2 consecutive ESIPT reactions yielding an excited state diketo-tautomer. However, concerning this matter the present experimental results are not unambiguous and could be also rationalized without assuming the formation of an additional photo-tautomer.

  18. The Social Determinants of Refugee Mental Health in the Post-Migration Context: A Critical Review.

    PubMed

    Hynie, Michaela

    2018-05-01

    With the global increase in the number of refugees and asylum seekers, mental health professionals have become more aware of the need to understand and respond to the mental health needs of forced migrants. This critical review summarizes the findings of recent systematic reviews and primary research on the impact of post-migration conditions on mental disorders and PTSD among refugees and asylum seekers. Historically, the focus of mental health research and interventions with these populations has been on the impact of pre-migration trauma. Pre-migration trauma does predict mental disorders and PTSD, but the post-migration context can be an equally powerful determinant of mental health. Moreover, post-migration factors may moderate the ability of refugees to recover from pre-migration trauma. The importance of post-migration stressors to refugee mental health suggests the need for therapeutic interventions with psychosocial elements that address the broader conditions of refugee and asylum seekers' lives. However, there are few studies of multimodal interventions with refugees, and even fewer with control conditions that allow for conclusions about their effectiveness. These findings are interpreted using a social determinants of health framework that connects the risk and protective factors in the material and social conditions of refugees' post-migration lives to broader social, economic and political factors.

  19. Technical Advance: New in vitro method for assaying the migration of primary B cells using an endothelial monolayer as substrate.

    PubMed

    Stewart-Hutchinson, Phillip J; Szasz, Taylor P; Jaeger, Emily R; Onken, Michael D; Cooper, John A; Morley, Sharon Celeste

    2017-09-01

    Migration of B cells supports their development and recruitment into functional niches. Therefore, defining factors that control B cell migration will lead to a better understanding of adaptive immunity. In vitro cell migration assays with B cells have been limited by poor adhesion of cells to glass coated with adhesion molecules. We have developed a technique using monolayers of endothelial cells as the substrate for B cell migration and used this technique to establish a robust in vitro assay for B cell migration. We use TNF-α to up-regulate surface expression of the adhesion molecule VCAM-1 on endothelial cells. The ligand VLA-4 is expressed on B cells, allowing them to interact with the endothelial monolayer and migrate on its surface. We tested our new method by examining the role of L-plastin (LPL), an F-actin-bundling protein, in B cell migration. LPL-deficient (LPL -/- ) B cells displayed decreased speed and increased arrest coefficient compared with wild-type (WT) B cells, following chemokine stimulation. However, the confinement ratios for WT and LPL -/- B cells were similar. Thus, we demonstrate how the use of endothelial monolayers as a substrate will support future interrogation of molecular pathways essential to B cell migration. © Society for Leukocyte Biology.

  20. Photoevaporation Does Not Create a Pileup of Giant Planets at 1 au

    NASA Astrophysics Data System (ADS)

    Wise, A. W.; Dodson-Robinson, S. E.

    2018-03-01

    The semimajor axis distribution of giant exoplanets appears to have a pileup near 1 au. Photoevaporation opens a gap in the inner few au of gaseous disks before dissipating them. Here, we investigate if photoevaporation can significantly affect the final distribution of giant planets by modifying gas surface density and hence Type II migration rates near the photoevaporation gap. We first use an analytic disk model to demonstrate that newly formed giant planets have a long migration epoch before photoevaporation can significantly alter their migration rates. Next, we present new 2D hydrodynamic simulations of planets migrating in photoevaporating disks, in which each are paired with a control simulation of migration in an otherwise identical disk without photoevaporation. We show that in disks with surface densities near the minimum threshold for forming giant planets, photoevaporation alters the final semimajor axis of a migrating gas giant by at most 5% over the course of 0.1 Myr of migration. Once the disk mass has become low enough for photoevaporation to carve a sharp gap, migration has almost completely stalled due to the low surface density of gas at the Lindblad resonances. We find that photoevaporation modifies migration rates so little that it is unlikely to leave a significant signature on the distribution of giant exoplanets.

  1. HOW JOB CHARACTERISTICS AFFECT INTERNATIONAL MIGRATION: THE ROLE OF INFORMALITY IN MEXICO

    PubMed Central

    Blanchard, Sarah

    2016-01-01

    Despite the importance given to employment opportunities as a primary motive for migration, previous studies have paid insufficient attention to the kinds of jobs that are more likely to retain workers in their countries of origin. We use information from a panel survey of Mexican adults to examine how job characteristics affect the risk of international migration. The sampling strategy and overall size of the survey allow us to analyze the effect of employment characteristics on migration from urban areas, which have much greater labor market diversity, and to separate our analysis by gender. We also distinguish migrants according to whether they migrate for work or for other reasons. We find informality to be a significant predictor of international migration. Even after controlling for individual factors including workers’ wages, as well as various household- and community-level predictors, we find that workers employed in the informal sector have significantly higher odds of migrating than their counterparts in the formal sector. The pervasive nature of informality in many developing countries from which a high proportion of international migrants originate may therefore create a constant supply of workers who are predisposed to migrate. Our findings thus have important implications for a proper understanding of the effects of economic development on migration. PMID:23073750

  2. How job characteristics affect international migration: the role of informality in Mexico.

    PubMed

    Villarreal, Andrés; Blanchard, Sarah

    2013-04-01

    Despite the importance given to employment opportunities as a primary motive for migration, previous studies have paid insufficient attention to the kinds of jobs that are more likely to retain workers in their countries of origin. We use information from a panel survey of Mexican adults to examine how job characteristics affect the risk of international migration. The sampling strategy and overall size of the survey allow us to analyze the effect of employment characteristics on migration from urban areas, which have much greater labor market diversity, and to separate our analysis by gender. We also distinguish migrants according to whether they migrate for work or for other reasons. We find informality to be a significant predictor of international migration. Even after controlling for individual factors including workers' wages, as well as various household- and community-level predictors, we find that workers employed in the informal sector have significantly higher odds of migrating than their counterparts in the formal sector. The pervasive nature of informality in many developing countries from which a high proportion of international migrants originate may therefore create a constant supply of workers who are predisposed to migrate. Our findings thus have important implications for a proper understanding of the effects of economic development on migration.

  3. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  4. Predicting Bison Migration out of Yellowstone National Park Using Bayesian Models

    PubMed Central

    Geremia, Chris; White, P. J.; Wallen, Rick L.; Watson, Fred G. R.; Treanor, John J.; Borkowski, John; Potter, Christopher S.; Crabtree, Robert L.

    2011-01-01

    Long distance migrations by ungulate species often surpass the boundaries of preservation areas where conflicts with various publics lead to management actions that can threaten populations. We chose the partially migratory bison (Bison bison) population in Yellowstone National Park as an example of integrating science into management policies to better conserve migratory ungulates. Approximately 60% of these bison have been exposed to bovine brucellosis and thousands of migrants exiting the park boundary have been culled during the past two decades to reduce the risk of disease transmission to cattle. Data were assimilated using models representing competing hypotheses of bison migration during 1990–2009 in a hierarchal Bayesian framework. Migration differed at the scale of herds, but a single unifying logistic model was useful for predicting migrations by both herds. Migration beyond the northern park boundary was affected by herd size, accumulated snow water equivalent, and aboveground dried biomass. Migration beyond the western park boundary was less influenced by these predictors and process model performance suggested an important control on recent migrations was excluded. Simulations of migrations over the next decade suggest that allowing increased numbers of bison beyond park boundaries during severe climate conditions may be the only means of avoiding episodic, large-scale reductions to the Yellowstone bison population in the foreseeable future. This research is an example of how long distance migration dynamics can be incorporated into improved management policies. PMID:21340035

  5. Advances and Environmental Conditions of Spring Migration Phenology of American White Pelicans

    NASA Astrophysics Data System (ADS)

    King, D. Tommy; Wang, Guiming; Yang, Zhiqiang; Fischer, Justin W.

    2017-01-01

    Spring migration phenology of birds has advanced under warming climate. Migration timing of short-distance migrants is believed to be responsive to environmental changes primarily under exogenous control. However, understanding the ecological causes of the advancement in avian spring migration phenology is still a challenge due to the lack of long-term precise location data. We used 11 years of Global Positioning System relocation data to determine four different migration dates of the annual migration cycle of the American white pelican (Pelecanus erythrorhynchos), a short-distance migrant. We also tested the hypothesis that increases in winter temperature and precipitation on the wintering grounds would advance pelican spring migration. Pelican spring departures and arrivals advanced steadily from 2002 to 2011. Spring departure timing exhibited high repeatability at the upper end of migration timing repeatability reported in literature. However, individual spring departure and arrival dates were not related to winter daily temperature, total winter precipitation, and detrended vegetation green-up dates indexed by the normalized difference vegetation index. Despite high repeatability, the observed between-year variation of spring departure dates was still sufficient for the advancement of spring departure timing.

  6. Advances and Environmental Conditions of Spring Migration Phenology of American White Pelicans.

    PubMed

    King, D Tommy; Wang, Guiming; Yang, Zhiqiang; Fischer, Justin W

    2017-01-16

    Spring migration phenology of birds has advanced under warming climate. Migration timing of short-distance migrants is believed to be responsive to environmental changes primarily under exogenous control. However, understanding the ecological causes of the advancement in avian spring migration phenology is still a challenge due to the lack of long-term precise location data. We used 11 years of Global Positioning System relocation data to determine four different migration dates of the annual migration cycle of the American white pelican (Pelecanus erythrorhynchos), a short-distance migrant. We also tested the hypothesis that increases in winter temperature and precipitation on the wintering grounds would advance pelican spring migration. Pelican spring departures and arrivals advanced steadily from 2002 to 2011. Spring departure timing exhibited high repeatability at the upper end of migration timing repeatability reported in literature. However, individual spring departure and arrival dates were not related to winter daily temperature, total winter precipitation, and detrended vegetation green-up dates indexed by the normalized difference vegetation index. Despite high repeatability, the observed between-year variation of spring departure dates was still sufficient for the advancement of spring departure timing.

  7. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    PubMed

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2018-03-01

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  8. Universal cements: dual activated and chemically activated

    PubMed Central

    de Lima, Eliane; Santos, Ricardo; Durão, Márcia; Nascimento, Armiliana; Braz, Rodivan

    2016-01-01

    Abstract Objective: The aim of the present study was to assess the bond strength of universal cements cured either dually or chemically only. Methods: Three cements were assessed using different types of application: dual activated (DA) or chemically activated (CA). In total 80 dentin blocks were used, obtained through the enamel wear of the lingual and buccal surfaces of bovine incisors. Standard cone-shaped cavity preparations were created using diamond burs. Subsequently, indirect restoration blocks were designed with Filtek Z350 (3M ESPE) composite resin. The teeth were divided into two groups (DA and CA) and then subdivided into four subgroups (n = 10) prior to cementation with the respective products: Duo-Link (Bisco); RelyX Ultimate (3M ESPE); Nexus 3 (Kerr) and conventional RelyX ARC (3M ESPE) as the control. The cementation in the PA group was applied following the manufacturer’s instructions. The CA group was cemented in a darkroom to avoid exposure to light. They were stored in distilled water at 37 °C for 24 h and submitted to the push-out test. Data were analyzed by two-way ANOVA and Tukey’s post-hoc test (p < .05). Results: The greatest bond strength results were obtained for photoactivated universal cements. Conclusion: Chemical activation is not sufficient to ensure acceptable bond strength. PMID:28642922

  9. Verbal fluency, clustering, and switching in patients with psychosis following traumatic brain injury (PFTBI).

    PubMed

    Batty, Rachel; Francis, Andrew; Thomas, Neil; Hopwood, Malcolm; Ponsford, Jennie; Johnston, Lisa; Rossell, Susan

    2015-06-30

    Verbal fluency in patients with psychosis following traumatic brain injury (PFTBI) has been reported as comparable to healthy participants. This finding is counterintuitive given the prominent fluency impairments demonstrated post-traumatic brain injury (TBI) and in psychotic disorders, e.g. schizophrenia. We investigated phonemic (executive) fluency (3 letters: 'F' 'A' and 'S'), and semantic fluency (1 category: fruits and/or vegetables) in four matched groups; PFTBI (N=10), TBI (N=10), schizophrenia (N=23), and healthy controls (N=23). Words produced (minus perseverations and errors), and clustering and switching scores were compared for the two fluency types across the groups. The results confirmed that PFTBI patients do show impaired fluency, aligned with existing evidence in TBI and schizophrenia. PFTBI patients produced the least amount of words on the phonemic fluency ('A') trial and total score, and demonstrated reduced switching on both phonemic and semantic tasks. No significant differences in clustering performance were found. Importantly, the pattern of results suggested that PFTBI patients share deficits with their brain-injured (primarily executive), and psychotic (executive and semantic), counterparts, and that these are exacerbated by their dual-diagnosis. These findings add to a very limited literature by providing novel evidence of the nature of fluency impairments in dually-diagnosed PFTBI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Migration Factors in West African Immigrant Parents' Perceptions of Their Children's Neighborhood Safety.

    PubMed

    Rasmussen, Andrew; Cissé, Aïcha; Han, Ying; Roubeni, Sonia

    2018-02-12

    Immigrants make up large proportions of many low-income neighborhoods, but have been largely ignored in the neighborhood safety literature. We examined perceived safety's association with migration using a six-item, child-specific measure of parents' perceptions of school-aged (5-12 years of age) children's safety in a sample of 93 West African immigrant parents in New York City. Aims of the study were (a) to identify pre-migration correlates (e.g., trauma in home countries), (b) to identify migration-related correlates (e.g., immigration status, time spent separated from children during migration), and (c) to identify pre-migration and migration correlates that accounted for variance after controlling for non-migration-related correlates (e.g., neighborhood crime, parents' psychological distress). In a linear regression model, children's safety was associated with borough of residence, greater English ability, less emotional distress, less parenting difficulty, and a history of child separation. Parents' and children's gender, parents' immigration status, and the number of contacts in the U.S. pre-migration and pre-migration trauma were not associated with children's safety. That child separation was positively associated with safety perceptions suggests that the processes that facilitate parent-child separation might be reconceptualized as strengths for transnational families. Integrating migration-related factors into the discussion of neighborhood safety for immigrant populations allows for more nuanced views of immigrant families' well-being in host countries. © Society for Community Research and Action 2018.

  11. Conservation physiology of animal migration

    PubMed Central

    Lennox, Robert J.; Chapman, Jacqueline M.; Souliere, Christopher M.; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D.; Cooke, Steven J.

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals. PMID:27293751

  12. Conservation physiology of animal migration.

    PubMed

    Lennox, Robert J; Chapman, Jacqueline M; Souliere, Christopher M; Tudorache, Christian; Wikelski, Martin; Metcalfe, Julian D; Cooke, Steven J

    2016-01-01

    Migration is a widespread phenomenon among many taxa. This complex behaviour enables animals to exploit many temporally productive and spatially discrete habitats to accrue various fitness benefits (e.g. growth, reproduction, predator avoidance). Human activities and global environmental change represent potential threats to migrating animals (from individuals to species), and research is underway to understand mechanisms that control migration and how migration responds to modern challenges. Focusing on behavioural and physiological aspects of migration can help to provide better understanding, management and conservation of migratory populations. Here, we highlight different physiological, behavioural and biomechanical aspects of animal migration that will help us to understand how migratory animals interact with current and future anthropogenic threats. We are in the early stages of a changing planet, and our understanding of how physiology is linked to the persistence of migratory animals is still developing; therefore, we regard the following questions as being central to the conservation physiology of animal migrations. Will climate change influence the energetic costs of migration? Will shifting temperatures change the annual clocks of migrating animals? Will anthropogenic influences have an effect on orientation during migration? Will increased anthropogenic alteration of migration stopover sites/migration corridors affect the stress physiology of migrating animals? Can physiological knowledge be used to identify strategies for facilitating the movement of animals? Our synthesis reveals that given the inherent challenges of migration, additional stressors derived from altered environments (e.g. climate change, physical habitat alteration, light pollution) or interaction with human infrastructure (e.g. wind or hydrokinetic turbines, dams) or activities (e.g. fisheries) could lead to long-term changes to migratory phenotypes. However, uncertainty remains because of the complexity of biological systems, the inherently dynamic nature of the environment and the scale at which many migrations occur and associated threats operate, necessitating improved integration of physiological approaches to the conservation of migratory animals.

  13. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force.

    PubMed

    Wolf, Katarina; Te Lindert, Mariska; Krause, Marina; Alexander, Stephanie; Te Riet, Joost; Willis, Amanda L; Hoffman, Robert M; Figdor, Carl G; Weiss, Stephen J; Friedl, Peter

    2013-06-24

    Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical tissue constraints. Migration rates are further governed by the capacity to degrade ECM by proteolytic enzymes, particularly matrix metalloproteinases (MMPs), and integrin- and actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify the limits of cell migration by physical arrest. MMP-independent migration declined as linear function of pore size and with deformation of the nucleus, with arrest reached at 10% of the nuclear cross section (tumor cells, 7 µm²; T cells, 4 µm²; neutrophils, 2 µm²). Residual migration under space restriction strongly depended upon MMP-dependent ECM cleavage by enlarging matrix pore diameters, and integrin- and actomyosin-dependent force generation, which jointly propelled the nucleus. The limits of interstitial cell migration thus depend upon scaffold porosity and deformation of the nucleus, with pericellular collagenolysis and mechanocoupling as modulators.

  14. Changes in leucocyte migration after renal transplantation

    PubMed Central

    Smith, M. G. M.; Eddleston, A. L. W. F.; Dominguez, J. A.; Evans, D. B.; Bewick, M.; Williams, Roger

    1969-01-01

    The leucocyte migration test, an in-vitro measure of cellular immunity, has been used to follow the changes in cell-mediated hypersensitivity to kidney and histocompatibility antigens in three patients after renal transplantation. Inhibition of leucocyte migration, indicating strong sensitization to the antigens used, occurred in each patient, starting five to seven days after transplantation. Satisfactory renal function had not been established in any of the patients at this time. In one case inhibition of leucocyte migration persisted almost continuously until the 24th day and was associated with poor renal function proved histologically to be due to rejection. Treatment with increased dosage of prednisone was associated with a rapid reversion to normal of the migration index and improvement in renal function. Later, inhibition of migration occurred again, and shortly afterwards the graft ceased to function. In the other two cases the migration index became normal without alteration in immunosuppressive therapy and a satisfactory diuresis followed. It is suggested that this simple test should prove useful in the specific diagnosis of rejection and in control of immunosuppressive therapy. ImagesFig. 3Fig. 4 PMID:4899455

  15. Slits Affect the Timely Migration of Neural Crest Cells via Robo Receptor

    PubMed Central

    Giovannone, Dion; Reyes, Michelle; Reyes, Rachel; Correa, Lisa; Martinez, Darwin; Ra, Hannah; Gomez, Gustavo; Kaiser, Josh; Ma, Le; Stein, Mary-Pat; de Bellard, Maria Elena

    2013-01-01

    SUMMARY Background Neural crest cells emerge by delamination from the dorsal neural tube and give rise to various components of the peripheral nervous system in vertebrate embryos. These cells change from non-motile into highly motile cells migrating to distant areas before further differentiation. Mechanisms controlling delamination and subsequent migration of neural crest cells are not fully understood. Slit2, a chemorepellant for axonal guidance that repels and stimulates motility of trunk neural crest cells away from the gut has recently been suggested to be a tumor suppressor molecule. The goal of this study was to further investigate the role of Slit2 in trunk neural crest cell migration by constitutive expression in neural crest cells. Results We found that Slit gain-of-function significantly impaired neural crest cell migration while Slit loss-of-function favored migration. In addition, we observed that the distribution of key cytoskeletal markers was disrupted in both gain and loss of function instances. Conclusions These findings suggest that Slit molecules might be involved in the processes that allow neural crest cells to begin migration and transitioning to a mesenchymal type. PMID:22689303

  16. Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

    PubMed Central

    Vargas, Pablo; Maiuri, Paolo; Bretou, Marine; Sáez, Pablo J.; Pierobon, Paolo; Maurin, Mathieu; Chabaud, Mélanie; Lankar, Danielle; Obino, Dorian; Terriac, Emmanuel; Raab, Matthew; Thiam, Hawa-Racine; Brocker, Thomas; Kitchen-Goosen, Susan M.; Alberts, Arthur S.; Sunareni, Praveen; Xia, Sheng; Li, Rong; Voituriez, Raphael; Piel, Matthieu; Lennon-Duménil, Ana-Maria

    2018-01-01

    Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4–MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function. PMID:26641718

  17. Morphological constraints on changing avian migration phenology.

    PubMed

    Møller, A P; Rubolini, D; Saino, N

    2017-06-01

    Many organisms at northern latitudes have responded to climate warming by advancing their spring phenology. Birds are known to show earlier timing of spring migration and reproduction in response to warmer springs. However, species show heterogeneous phenological responses to climate warming, with those that have not advanced or have delayed migration phenology experiencing population declines. Although some traits (such as migration distance) partly explain heterogeneity in phenological responses, the factors affecting interspecies differences in the responsiveness to climate warming have yet to be fully explored. In this comparative study, we investigate whether variation in wing aspect ratio (reflecting relative wing narrowness), an ecomorphological trait that is strongly associated with flight efficiency and migratory behaviour, affects the ability to advance timing of spring migration during 1960-2006 in a set of 80 European migratory bird species. Species with larger aspect ratio (longer and narrower wings) showed smaller advancement of timing of spring migration compared to species with smaller aspect ratio (shorter and wider wings) while controlling for phylogeny, migration distance and other life-history traits. In turn, migration distance positively predicted aspect ratio across species. Hence, species that are better adapted to migration appear to be more constrained in responding phenologically to rapid climate warming by advancing timing of spring migration. Our findings corroborate the idea that aspect ratio is a major evolutionary correlate of migration, and suggest that selection for energetically efficient flights, as reflected by high aspect ratio, may hinder phenotypically plastic/microevolutionary adjustments of migration phenology to ongoing climatic changes. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  18. If and when: intrinsic differences and environmental stressors influence migration in brown trout (Salmo trutta).

    PubMed

    Peiman, Kathryn S; Birnie-Gauvin, Kim; Midwood, Jonathan D; Larsen, Martin H; Wilson, Alexander D M; Aarestrup, Kim; Cooke, Steven J

    2017-06-01

    Partial migration is a common phenomenon, yet the causes of individual differences in migratory propensity are not well understood. We examined factors that potentially influence timing of migration and migratory propensity in a wild population of juvenile brown trout (Salmo trutta) by combining experimental manipulations with passive integrated transponder telemetry. Individuals were subjected to one of six manipulations: three designed to mimic natural stressors (temperature increase, food deprivation, and chase by a simulated predator), an injection of exogenous cortisol designed to mimic an extreme physiological challenge, a sham injection, and a control group. By measuring length and mass of 923 individuals prior to manipulation and by monitoring tagged individuals as they left the stream months later, we assessed whether pre-existing differences influenced migratory tendency and timing of migration, and whether our manipulations affected growth, condition, and timing of migration. We found that pre-existing differences predicted migration, with smaller individuals and individuals in poor condition having a higher propensity to migrate. Exogenous cortisol manipulation had the largest negative effect on growth and condition, and resulted in an earlier migration date. Additionally, low-growth individuals within the temperature and food deprivation treatments migrated earlier. By demonstrating that both pre-existing differences in organism state and additional stressors can affect whether and when individuals migrate, we highlight the importance of understanding individual differences in partial migration. These effects may carry over to influence migration success and affect the evolutionary dynamics of sub-populations experiencing different levels of stress, which is particularly relevant in a changing world.

  19. Polyamine-dependent migration of retinal pigment epithelial cells.

    PubMed

    Johnson, Dianna A; Fields, Carolyn; Fallon, Amy; Fitzgerald, Malinda E C; Viar, Mary Jane; Johnson, Leonard R

    2002-04-01

    Migration of retinal pigment epithelial (RPE) cells can be triggered by disruption of the RPE monolayer or injury to the neural retina. Migrating cells may re-establish a confluent monolayer, or they may invade the neural retina and disrupt visual function. The purpose of this study was to examine the role of endogenous polyamines in mechanisms of RPE migration. Endogenous polyamine levels were determined in an immortalized RPE cell line, D407, using HPLC. Activities of the two rate-limiting enzymes for polyamine synthesis, ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (SAMdc), were measured by liberation of ((14)CO(2))(.) Migration was assessed in confluent cultures by determining the number of cells migrating into a mechanically denuded area. All measurements were obtained both in control cultures and in cultures treated with synthesis inhibitors that deplete endogenous polyamines. Subcellular localization of endogenous polyamines was determined using a polyamine antibody. The polyamines, spermidine and spermine, as well as their precursor, putrescine, were normal constituents of RPE cells. The two rate-limiting synthetic enzymes were also present, and their activities were stimulated dramatically by addition of serum to the culture medium. Cell migration was similarly stimulated by serum exposure. When endogenous polyamines were depleted, migration was blocked. When polyamines were replenished through uptake, migration was restored. Polyamine immunoreactivity was limited to membrane patches in quiescent cells. In actively migrating and dividing cells, immunoreactivity was enhanced throughout the cytoplasm. Polyamines are essential for RPE migration. Pharmacologic manipulation of the polyamine pathway could provide a therapeutic strategy for regulating anomalous migration.

  20. North-South Migration of West Coast Low Pressure Centers

    ERIC Educational Resources Information Center

    McIntosh, C. Barron

    1974-01-01

    Monthly maps of low pressure centers are presented here to attempt a concrete representation that may help students to understand the seasonal change from dry months to wet months along the mid-latitude west coast as a seasonal north-south migration of factors controlling rain and drought. (Author/JH)

  1. 76 FR 4485 - Privacy Act of 1974; Report of Modified or Altered System of Records

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Privacy Act of 1974; Report of Modified or Altered System of Records AGENCY: Division of Global Migration and... Infectious Diseases (CCID), Division of Global Migration and Quarantine, National Center for the Preparedness...

  2. Absence of bundle structure in the neocortex of the reeler mouse at the embryonic stage. Studies by scanning electron microscopic fractography.

    PubMed

    Mikoshiba, K; Nishimura, Y; Tsukada, Y

    The reeler mutant mouse is characterized by a derangement of the cerebral cortical structure due to abnormalities during the migration step at the embryonic stage. We have analyzed both the control and reeler cerebral cortex by means of scanning electron microscopic fractography. In the control cerebral cortex, the bundle formation was composed of fine fibers on which the migrating neuroblasts were attached perpendicular to the pial surface, whereas no bundle formation was observed in the reeler; instead, there was a fine meshwork of fibers surrounding the neuroblasts. The possible role of bundle formation in the normal cerebral cortex and the correlation between the inability of cells to migrate and the absence of bundle formation in the reeler is discussed.

  3. Migrated Essure permanent birth control device: sonographic findings.

    PubMed

    Khati, Nadia Juliet; Gorodenker, Joseph; Brindle, Kathleen Ann

    2014-05-01

    We report a case of a migrated Essure permanent birth control device. The correct diagnosis was made on conventional two-dimensional and three-dimensional pelvic sonography 7 years after placement of the device when the patient presented with persistent right-sided pain. The 3-month post placement hysterosalpingogram had shown an appropriately occluded right fallopian tube but had overlooked the abnormal position of the right Essure device, which was too proximal and extending slightly in the uterine cavity. Copyright © 2013 Wiley Periodicals, Inc.

  4. Object migration and authentication. [in computer operating systems design

    NASA Technical Reports Server (NTRS)

    Gligor, V. D.; Lindsay, B. G.

    1979-01-01

    The paper presents a mechanism permitting a type manager to fabricate a migrated object representation which can be entrusted to other subsystems or transmitted outside of the control of a local computer system. The migrated object representation is signed by the type manager in such a way that the type manager's signature cannot be forged and the manager is able to authenticate its own signature. Subsequently, the type manager can retrieve the migrated representation and validate its contents before reconstructing the object in its original representation. This facility allows type managers to authenticate the contents of off-line or network storage and solves problems stemming from the hierarchical structure of the system itself.

  5. Integrative Mechanisms of Oriented Neuronal Migration in the Developing Brain

    PubMed Central

    Evsyukova, Irina; Plestant, Charlotte; Anton, E.S.

    2014-01-01

    The emergence of functional neuronal connectivity in the developing cerebral cortex depends on neuronal migration. This process enables appropriate positioning of neurons and the emergence of neuronal identity so that the correct patterns of functional synaptic connectivity between the right types and numbers of neurons can emerge. Delineating the complexities of neuronal migration is critical to our understanding of normal cerebral cortical formation and neurodevelopmental disorders resulting from neuronal migration defects. For the most part, the integrated cell biological basis of the complex behavior of oriented neuronal migration within the developing mammalian cerebral cortex remains an enigma. This review aims to analyze the integrative mechanisms that enable neurons to sense environmental guidance cues and translate them into oriented patterns of migration toward defined areas of the cerebral cortex. We discuss how signals emanating from different domains of neurons get integrated to control distinct aspects of migratory behavior and how different types of cortical neurons coordinate their migratory activities within the developing cerebral cortex to produce functionally critical laminar organization. PMID:23937349

  6. Migration and Persistence of Human Influenza A Viruses, Vietnam, 2001–2008

    PubMed Central

    Le, Mai Quynh; Lam, Ha Minh; Cuong, Vuong Duc; Lam, Tommy Tsan-Yuk; Halpin, Rebecca A; Wentworth, David E; Hien, Nguyen Tran; Thanh, Le Thi; Phuong, Hoang Vu Mai; Horby, Peter

    2013-01-01

    Understanding global influenza migration and persistence is crucial for vaccine strain selection. Using 240 new human influenza A virus whole genomes collected in Vietnam during 2001–2008, we looked for persistence patterns and migratory connections between Vietnam and other countries. We found that viruses in Vietnam migrate to and from China, Hong Kong, Taiwan, Cambodia, Japan, South Korea, and the United States. We attempted to reduce geographic bias by generating phylogenies subsampled at the year and country levels. However, migration events in these phylogenies were still driven by the presence or absence of sequence data, indicating that an epidemiologic study design that controls for prevalence is required for robust migration analysis. With whole-genome data, most migration events are not detectable from the phylogeny of the hemagglutinin segment alone, although general migratory relationships between Vietnam and other countries are visible in the hemagglutinin phylogeny. It is possible that virus lineages in Vietnam persisted for >1 year. PMID:24188643

  7. Carbon Ion Irradiation Inhibits Glioma Cell Migration Through Downregulation of Integrin Expression

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

    Rieken, Stefan, E-mail: Stefan.Rieken@med.uni-heidelberg.de; Habermehl, Daniel; Wuerth, Lena

    2012-05-01

    Purpose: To investigate the effect of carbon ion irradiation on glioma cell migration. Methods and Materials: U87 and Ln229 glioma cells were irradiated with photons and carbon ions. Migration was analyzed 24 h after irradiation. Fluorescence-activated cell sorting analysis was performed in order to quantify surface expression of integrins. Results: Single photon doses of 2 Gy and 10 Gy enhanced {alpha}{sub {nu}}{beta}{sub 3} and {alpha}{sub {nu}}{beta}{sub 5} integrin expression and caused tumor cell hypermigration on both vitronectin (Vn) and fibronectin (Fn). Compared to integrin expression in unirradiated cells, carbon ion irradiation caused decreased integrin expression and inhibited cell migration onmore » both Vn and Fn. Conclusion: Photon radiotherapy (RT) enhances the risk of tumor cell migration and subsequently promotes locoregional spread via photon induction of integrin expression. In contrast to photon RT, carbon ion RT causes decreased integrin expression and suppresses glioma cell migration on both Vn and Fn, thus promising improved local control.« less

  8. Gas migration through Opouawe Bank at the Hikurangi margin offshore New Zealand

    NASA Astrophysics Data System (ADS)

    Koch, Stephanie; Schroeder, Henning; Haeckel, Matthias; Berndt, Christian; Bialas, Joerg; Papenberg, Cord; Klaeschen, Dirk; Plaza-Faverola, Andreia

    2016-06-01

    This study presents 2D seismic reflection data, seismic velocity analysis, as well as geochemical and isotopic porewater compositions from Opouawe Bank on New Zealand's Hikurangi subduction margin, providing evidence for essentially pure methane gas seepage. The combination of geochemical information and seismic reflection images is an effective way to investigate the nature of gas migration beneath the seafloor, and to distinguish between water advection and gas ascent. The maximum source depth of the methane that migrates to the seep sites on Opouawe Bank is 1,500-2,100 m below seafloor, generated by low-temperature degradation of organic matter via microbial CO2 reduction. Seismic velocity analysis enabled identifying a zone of gas accumulation underneath the base of gas hydrate stability (BGHS) below the bank. Besides structurally controlled gas migration along conduits, gas migration also takes place along dipping strata across the BGHS. Gas migration on Opouawe Bank is influenced by anticlinal focusing and by several focusing levels within the gas hydrate stability zone.

  9. The Ldb1 and Ldb2 Transcriptional Cofactors Interact with the Ste20-like Kinase SLK and Regulate Cell Migration

    PubMed Central

    Storbeck, Chris J.; Wagner, Simona; O'Reilly, Paul; McKay, Marlene; Parks, Robin J.; Westphal, Heiner

    2009-01-01

    Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses, and tissue repair. Here, we show that the microtubule-associated Ste20 kinase SLK, required for cell migration, interacts with the LIM domain binding transcriptional cofactor proteins Ldb1/CLIM2 and Ldb2/CLIM1/NLI. We demonstrate that Ldb1 and 2 bind directly to the SLK carboxy-terminal AT1-46 homology domain in vitro and in vivo. We find that Ldb1 and -2 colocalize with SLK in migrating cells and that both knockdown and overexpression of either factor results in increased motility. Supporting this, knockdown of Ldb1 increases focal adhesion turnover and enhances migration in fibroblasts. We propose that Ldb1/2 function to maintain SLK in an inactive state before its activation. These findings highlight a novel function for Ldb1 and -2 and expand their role to include the control of cell migration. PMID:19675209

  10. Corresponding long-term shifts in stream temperature and invasive fish migration

    USGS Publications Warehouse

    McCann, Erin L.; Johnson, Nicholas; Pangle, Kevin

    2018-01-01

    By investigating historic trapping records of invasive sea lamprey (Petromyzon marinus) throughout tributaries to the Laurentian Great Lakes, we found that upstream spawning migration timing was highly correlated with stream temperatures over large spatial and temporal scales. Furthermore, several streams in our study exceeded a critical spring thermal threshold (i.e., 15°C) and experienced peak spawning migration up to 30 days earlier since the 1980s, whereas others were relatively unchanged. Streams exhibiting warming trends and earlier migration were spatially clustered and generally found on the leeward side of the Great Lakes where the lakes most affect local climate. These findings highlight that all streams are not equally impacted by climate change and represent, to our knowledge, the first observation linking long-term changes in stream temperatures to shifts in migration timing of an invasive fish. Earlier sea lamprey migration in Great Lakes tributaries may improve young of the year growth and survival, but not limit their spatial distribution, making sea lamprey control more challenging.

  11. Impact of the corrin framework of vitamin B12 on the electrochemical carbon-skeleton rearrangement in comparison to an imine/oxime planar ligand; tuning selectivity in 1,2-migration of a functional group by controlling electrolysis potential.

    PubMed

    Tahara, Keishiro; Pan, Ling; Yamaguchi, Ryoko; Shimakoshi, Hisashi; Abe, Masaaki; Hisaeda, Yoshio

    2017-10-01

    Among the coenzyme B 12 -dependent enzymes, methylmalonyl-CoA mutase (MMCM) catalyzes the carbon-skeleton rearrangement reaction between R-methylmalonyl-CoA and succinyl-CoA. Diethyl 2-bromomethyl-2-phenylmalonate, an alkyl bromide substrate having two different migrating groups (phenyl and carboxylic ester groups) on the β-carbon, was applied to the electrolysis mediated by a hydrophobic vitamin B 12 model complex, heptamethyl cobyrinate perchlorate in this study. The electrolysis of the substrate at -1.0V vs. Ag-AgCl by light irradiation afforded the simple reduced product (diethyl 2-methyl-2-phenylmalonate) and the phenyl migrated product (diethyl 2-benzyl-2-phenylmalonate), as well as the electrolysis of the substrate at -1.5V vs. Ag-AgCl in the dark. The electrolysis of the substrate at -2.0V vs. Ag-AgCl afforded the carboxylic ester migrated product (diethyl phenylsuccinate) as the major product. The selectivity for the migrating group was successfully tuned by controlling the electrolysis potential. We clarified that the cathodic chemistry of the Co(III) alkylated heptamethyl cobyrinate is critical for the selectivity of the migrating group through mechanistic investigations and comparisons to the simple vitamin B 12 model complex, an imine/oxime-type cobalt complex. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Impact of ethnicity, violence and acculturation on displaced migrants: psychological distress and psychosomatic complaints among refugees in Sweden.

    PubMed

    Sundquist, J; Bayard-Burfield, L; Johansson, L M; Johansson, S E

    2000-06-01

    This study uses data collected in 1996 by the Swedish National Board of Health and Welfare. By means of interviews with 1980 foreign-born immigrants, an attempt was made to determine the impact of a) migration status (country of birth/ethnicity), b) exposure to violence, c) Antonovsky's sense of coherence, d) acculturation status (knowledge of Swedish), e) sense of control over one's life, f) economic difficulties, and g) education, both on psychological distress (using General Health Questionnaire 12) and psychosomatic complaints (daytime fatigue, sleeping difficulties, and headache/migraine). Iranians and Chileans (age-adjusted) were at great risk for psychological distress as compared with Poles, whereas Turks and Kurds exhibited no such risk. When the independent factors were included in the model, the migration status effect decreased to insignificance (with the exception of Iranian men). A low sense of coherence, poor acculturation (men only), poor sense of control, and economic difficulties were strongly associated with the outcomes, generally accounting for a convincing link between migration status and psychological distress. Furthermore, a low sense of coherence, poor acculturation (men only), poor sense of control, and economic difficulties in exile seemed to be stronger risk factors for psychological distress in this group than exposure to violence before migration.

  13. Striations, duration, migration and tidal response in deep tremor.

    PubMed

    Ide, Satoshi

    2010-07-15

    Deep tremor in subduction zones is thought to be caused by small repeating shear slip events on the plate interface with significant slow components. It occurs at a depth of about 30 kilometres and provides valuable information on deep plate motion and shallow stress accumulation on the fault plane of megathrust earthquakes. Tremor has been suggested to repeat at a regular interval, migrate at various velocities and be modulated by tidal stress. Here I show that some time-invariant interface property controls tremor behaviour, using precise location of tremor sources with event duration in western Shikoku in the Nankai subduction zone, Japan. In areas where tremor duration is short, tremor is more strongly affected by tidal stress and migration is inhibited. Where tremor lasts longer, diffusive migration occurs with a constant diffusivity of 10(4) m(2) s(-1). The control property may be the ratio of brittle to ductile areas, perhaps determined by the influence of mantle wedge serpentinization on the plate interface. The spatial variation of the controlling property seems to be characterized by striations in tremor source distribution, which follows either the current or previous plate subduction directions. This suggests that the striations and corresponding interface properties are formed through the subduction of inhomogeneous structure, such as seamounts, for periods as long as ten million years.

  14. Multiple testing of food contact materials: a predictive algorithm for assessing the global migration from silicone moulds.

    PubMed

    Elskens, Marc; Vloeberghs, Daniel; Van Elsen, Liesbeth; Baeyens, Willy; Goeyens, Leo

    2012-09-15

    For reasons of food safety, packaging and food contact materials must be submitted to migration tests. Testing of silicone moulds is often very laborious, since three replicate tests are required to decide about their compliancy. This paper presents a general modelling framework to predict the sample's compliance or non-compliance using results of the first two migration tests. It compares the outcomes of models with multiple continuous predictors with a class of models involving latent and dummy variables. The model's prediction ability was tested using cross and external validations, i.e. model revalidation each time a new measurement set became available. At the overall migration limit of 10 mg dm(-2), the relative uncertainty on a prediction was estimated to be ~10%. Taking the default values for α and β equal to 0.05, the maximum value that can be predicted for sample compliance was therefore 7 mg dm(-2). Beyond this limit the risk for false compliant results increases significantly, and a third migration test should be performed. The result of this latter test defines the sample's compliance or non-compliance. Propositions for compliancy control inspired by the current dioxin control strategy are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Migration of Older to New Digital Control Systems in Nuclear Power Plant Main Control Rooms

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

    Kovesdi, Casey Robert; Joe, Jeffrey Clark

    The United States (U.S.) Department of Energy (DOE) Office of Nuclear Energy (NE) has the primary mission to advance nuclear power by resolving socio-technical issues through research and development (R&D). One DOE-NE activity supporting this mission is the Light Water Reactor Sustainability (LWRS) program. LWRS has the overall objective to sustain the operation of existing commercial nuclear power plants (NPPs) through conducting R&D across multiple “pathways,” or R&D focus areas. The Advanced Instrumentation, Information, and Control (II&C) Systems Technologies pathway conducts targeted R&D to address aging and reliability concerns with the legacy instrumentation and control (I&C) and related information systemsmore » in operating U.S. NPPs. This work involves (1) ensuring that legacy analog II&C systems are not life-limiting issues for the LWR fleet, and (2) implementing digital II&C technology in a manner that enables broad innovation and business improvement in the NPP operating model. Under the LWRS Advanced II&C pathway, Human Factors experts at Idaho National Laboratory (INL) have been conducting R&D in support of NPP main control room (MCR) modernization activities. Work in prior years has focused on migrating analog I&C systems to new digital I&C systems (). In fiscal year 2016 (FY16), one new focus area for this research is migrating older digital I&C systems to new and advanced digital I&C systems. This report summarizes a plan for conducting a digital-to-digital migration of a legacy digital I&C system to a new digital I&C system in support of control room modernization activities.« less

  16. Use of a Fish Transportation Barge for Increasing Returns of Steelhead Imprinted for Homing, Final Report.

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

    Harmon, Jerrel R.

    1989-08-01

    The objective of this 7-year National Fisheries Service study, which began is 1982, was to determine if transporting juvenile steelhead (Oncorhynchus mykiss) by truck and barge from Dworshak National Fish Hatchery (NFH), on the Clearwater River, to a release site on the Columbia River below Bonneville Dam would result in increased returns of adults to the various fisheries and to the hatchery homing site. During 1982 and 1983, over 500,000 marked juvenile steelhead were serially released as controls from the hatchery or barged as test fish to below Bonneville Dam. Recoveries of marked adults to various recovery sites are complete.more » Fish released in 1983 showed a stronger homing ability and more rapid upstream migration than test fish released in 1982. Most adults from both control and test releases in 1983 and control releases in 1982 migrated a considerable distance upstream and overwintered in the Snake and Clearwater Rivers--behavior similar to Clearwater River fish previously transported from Lower Granite Dam. In contrast, many of the adults from test releases in 1982 failed to migrate upstream during the fall, overwintered in the Columbia River, and migrated upstream the following spring. Survival of control fish released at Dworshak NFH in late April 1982 was substantially higher than survival of those released in mid-May. Survival and homing of control fish released in late April and early May 1983 were over 10 times that for fish released in late May. Return of adults from normal hatchery releases in 1982 was the highest ever observed at Dworshak NFH.« less

  17. Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 (IFITM3) Dually Regulates Its Endocytosis and Ubiquitination*

    PubMed Central

    Chesarino, Nicholas M.; McMichael, Temet M.; Hach, Jocelyn C.; Yount, Jacob S.

    2014-01-01

    Interferon-inducible transmembrane protein 3 (IFITM3) is essential for innate defense against influenza virus in mice and humans. IFITM3 localizes to endolysosomes where it prevents virus fusion, although mechanisms controlling its trafficking to this cellular compartment are not fully understood. We determined that both mouse and human IFITM3 are phosphorylated by the protein-tyrosine kinase FYN on tyrosine 20 (Tyr20) and that mouse IFITM3 is also phosphorylated on the non-conserved Tyr27. Phosphorylation led to a cellular redistribution of IFITM3, including plasma membrane accumulation. Mutation of Tyr20 caused a similar redistribution of IFITM3 and resulted in decreased antiviral activity against influenza virus, whereas Tyr27 mutation of mouse IFITM3 showed minimal effects on localization or activity. Using FYN knockout cells, we also found that IFITM3 phosphorylation is not a requirement for its antiviral activity. Together, these results indicate that Tyr20 is part of an endocytosis signal that can be blocked by phosphorylation or by mutation of this residue. Further mutagenesis narrowed this endocytosis-controlling region to four residues conforming to a YXXΦ (where X is any amino acid and Φ is Val, Leu, or Ile) endocytic motif that, when transferred to CD4, resulted in its internalization from the cell surface. Additionally, we found that phosphorylation of IFITM3 by FYN and mutagenesis of Tyr20 both resulted in decreased IFITM3 ubiquitination. Overall, these results suggest that modification of Tyr20 may serve in a cellular checkpoint controlling IFITM3 trafficking and degradation and demonstrate the complexity of posttranslational regulation of IFITM3. PMID:24627473

  18. In vivo Postnatal Electroporation and Time-lapse Imaging of Neuroblast Migration in Mouse Acute Brain Slices

    PubMed Central

    Oudin, Madeleine Julie; Doherty, Patrick; Lalli, Giovanna

    2013-01-01

    The subventricular zone (SVZ) is one of the main neurogenic niches in the postnatal brain. Here, neural progenitors proliferate and give rise to neuroblasts able to move along the rostral migratory stream (RMS) towards the olfactory bulb (OB). This long-distance migration is required for the subsequent maturation of newborn neurons in the OB, but the molecular mechanisms regulating this process are still unclear. Investigating the signaling pathways controlling neuroblast motility may not only help understand a fundamental step in neurogenesis, but also have therapeutic regenerative potential, given the ability of these neuroblasts to target brain sites affected by injury, stroke, or degeneration. In this manuscript we describe a detailed protocol for in vivo postnatal electroporation and subsequent time-lapse imaging of neuroblast migration in the mouse RMS. Postnatal electroporation can efficiently transfect SVZ progenitor cells, which in turn generate neuroblasts migrating along the RMS. Using confocal spinning disk time-lapse microscopy on acute brain slice cultures, neuroblast migration can be monitored in an environment closely resembling the in vivo condition. Moreover, neuroblast motility can be tracked and quantitatively analyzed. As an example, we describe how to use in vivo postnatal electroporation of a GFP-expressing plasmid to label and visualize neuroblasts migrating along the RMS. Electroporation of shRNA or CRE recombinase-expressing plasmids in conditional knockout mice employing the LoxP system can also be used to target genes of interest. Pharmacological manipulation of acute brain slice cultures can be performed to investigate the role of different signaling molecules in neuroblast migration. By coupling in vivo electroporation with time-lapse imaging, we hope to understand the molecular mechanisms controlling neuroblast motility and contribute to the development of novel approaches to promote brain repair. PMID:24326479

  19. DHA-mediated regulation of lung cancer cell migration is not directly associated with Gelsolin or Vimentin expression.

    PubMed

    Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K

    2016-06-15

    Deaths associated with cancer metastasis have steadily increased making the need for newer, anti-metastatic therapeutics imparative. Gelsolin and vimentin, actin binding proteins expressed in metastatic tumors, participate in actin remodelling and regulate cell migration. Docosahexaenoic acid (DHA) limits cancer cell proliferation and adhesion but the mechanisms involved in reducing metastatic phenotypes are unknown. We aimed to investigate the effects of DHA on gelsolin and vimentin expression, and ultimately cell migration and proliferation, in this context. Non-invasive lung epithelial cells (MLE12) and invasive lung cancer cells (A549) were treated with DHA (30μmol/ml) or/and 8 bromo-cyclic adenosine monophosphate (8 Br-cAMP) (300μmol/ml) for 6 or 24h either before (pre-treatment) or after (post-treatment) plating in transwells. Migration was assessed by the number of cells that progressed through the transwell. Gelsolin and vimentin expression were measured by Western blot and confocal microscopy in cells, and by immunohistochemistry in human lung cancer biopsy samples. A significant decrease in cell migration was detected for A549 cells treated with DHA verses control but this same decrease was not seen in MLE12 cells. DHA and 8 Br-cAMP altered gelsolin and vimentin expression but no clear pattern of change was observed. Immunofluorescence staining indicated slightly higher vimentin expression in human lung tissue that was malignant compared to control. Collectively, our data indicate that DHA inhibits cancer cell migration and further suggests that vimentin and gelsolin may play secondary roles in cancer cell migration and proliferation, but are not the primary regulators. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. DHA-Mediated Regulation of Lung Cancer Cell Migration Is Not Directly Associated with Gelsolin or Vimentin Expression

    PubMed Central

    Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K.

    2016-01-01

    AIMS Deaths associated with cancer metastasis have steadily increased making the need for newer, anti-metastatic therapeutics imparative. Gelsolin and vimentin, actin binding proteins expressed in metastatic tumors, participate in actin remodelling and regulate cell migration. Docosahexaenoic acid (DHA) limits cancer cell proliferation and adhesion but the mechanisms involved in reducing metastatic phenotypes are unknown. We aimed to investigate the effects of DHA on gelsolin and vimentin expression, and ultimately cell migration and proliferation, in this context. MAIN METHODS Non-invasive lung epithelial cells (MLE12) and invasive lung cancer cells (A549) were treated with DHA (30 μmol/ml) or/and 8 bromo-cyclic adenosine monophosphate (8 Br-cAMP) (300 μmol/ml) for 6 or 24 h either before (pre-treatment) or after (post-treatment) plating in transwells. Migration was assessed by the number of cells that progressed through the transwell. Gelsolin and vimentin expression were measured by western blot and confocal microscopy in cells, and by immunohistochemistry in human lung cancer biospy samples. KEY FINDINGS A significant decrease in cell migration was detected for A549 cells treated with DHA verses control but this same decrease was not seen in MLE12 cells. DHA and 8 Br-cAMP altered gelsolin and vimentin expression but no clear pattern of change was observed. Immunoflorescence staining indicated slightly higher vimentin expression in human lung tissue that was malignant compared to control. SIGNIFICANCE Collectively, our data indicate that DHA inhibits cancer cell migration and further suggests that vimentin and gelsolin may play secondary roles in cancer cell migration and proliferation, but are not the primary regulators. PMID:27157519

  1. Resveratrol Prevents High Fluence Red Light-Emitting Diode Reactive Oxygen Species-Mediated Photoinhibition of Human Skin Fibroblast Migration.

    PubMed

    Mamalis, Andrew; Koo, Eugene; Isseroff, R Rivkah; Murphy, William; Jagdeo, Jared

    2015-01-01

    Skin fibrosis is a significant medical problem that leads to a functional, aesthetic, and psychosocial impact on quality-of-life. Light-emitting diode-generated 633-nm red light (LED-RL) is part of the visible light spectrum that is not known to cause DNA damage and is considered a safe, non-invasive, inexpensive, and portable potential alternative to ultraviolet phototherapy that may change the treatment paradigm of fibrotic skin disease. The goal of our study was to investigate the how reactive oxygen species (ROS) free radicals generated by high fluence LED-RL inhibit the migration of skin fibroblasts, the main cell type involved in skin fibrosis. Fibroblast migration speed is increased in skin fibrosis, and we studied cellular migration speed of cultured human skin fibroblasts as a surrogate measure of high fluence LED-RL effect on fibroblast function. To ascertain the inhibitory role of LED-RL generated ROS on migration speed, we hypothesized that resveratrol, a potent antioxidant, could prevent the photoinhibitory effects of high fluence LED-RL on fibroblast migration speed. High fluence LED-RL generated ROS were measured by flow cytometry analysis using dihydrorhodamine (DHR). For purposes of comparison, we assessed the effects of ROS generated by hydrogen peroxide (H2O2) on fibroblast migration speed and the ability of resveratrol, a well known antioxidant, to prevent LED-RL and H2O2 generated ROS-associated changes in fibroblast migration speed. To determine whether resveratrol could prevent the high fluence LED-RL ROS-mediated photoinhibition of human skin fibroblast migration, treated cells were incubated with resveratrol at concentrations of 0.0001% and 0.001% for 24 hours, irradiated with high fluences LED-RL of 480, 640, and 800 J/cm2. High fluence LED-RL increases intracellular fibroblast ROS and decreases fibroblast migration speed. LED-RL at 480, 640 and 800 J/cm2 increased ROS levels to 132.8%, 151.0%, and 158.4% relative to matched controls, respectively. These LED-RL associated increases in ROS were prevented by pretreating cells with 0.0001% or 0.001% resveratrol. Next, we quantified the effect of hydrogen peroxide (H2O2)-associated ROS on fibroblast migration speed, and found that while H2O2-associated ROS significantly decreased relative fibroblast migration speed, pretreatment with 0.0001% or 0.001% resveratrol significantly prevented the decreases in migration speed. Furthermore, we found that LED-RL at 480, 640 and 800 J/cm2 decreased fibroblast migration speed to 83.0%, 74.4%, and 68.6% relative to matched controls, respectively. We hypothesized that these decreases in fibroblast migration speed were due to associated increases in ROS generation. Pretreatment with 0.0001% and 0.001% resveratrol prevented the LED-RL associated decreases in migration speed. High fluence LED-RL increases ROS and is associated with decreased fibroblast migration speed. We provide mechanistic support that the decreased migration speed associated with high fluence LED-RL is mediated by ROS, by demonstrating that resveratrol prevents high fluence LED-RL associated migration speed change. These data lend support to an increasing scientific body of evidence that high fluence LED-RL has anti-fibrotic properties. We hypothesize that our findings may result in a greater understanding of the fundamental mechanisms underlying visible light interaction with skin and we anticipate clinicians and other researchers may utilize these pathways for patient benefit.

  2. Reversing the direction of galvanotaxis with controlled increases in boundary layer viscosity

    NASA Astrophysics Data System (ADS)

    Kobylkevich, Brian M.; Sarkar, Anyesha; Carlberg, Brady R.; Huang, Ling; Ranjit, Suman; Graham, David M.; Messerli, Mark A.

    2018-05-01

    Weak external electric fields (EFs) polarize cellular structure and direct most migrating cells (galvanotaxis) toward the cathode, making it a useful tool during tissue engineering and for healing epidermal wounds. However, the biophysical mechanisms for sensing weak EFs remain elusive. We have reinvestigated the mechanism of cathode-directed water flow (electro-osmosis) in the boundary layer of cells, by reducing it with neutral, viscous polymers. We report that increasing viscosity with low molecular weight polymers decreases cathodal migration and promotes anodal migration in a concentration dependent manner. In contrast, increased viscosity with high molecular weight polymers does not affect directionality. We explain the contradictory results in terms of porosity and hydraulic permeability between the polymers rather than in terms of bulk viscosity. These results provide the first evidence for controlled reversal of galvanotaxis using viscous agents and position the field closer to identifying the putative electric field receptor, a fundamental, outside-in signaling receptor that controls cellular polarity for different cell types.

  3. Reversing the direction of galvanotaxis with controlled increases in boundary layer viscosity.

    PubMed

    Kobylkevich, Brian M; Sarkar, Anyesha; Carlberg, Brady R; Huang, Ling; Ranjit, Suman; Graham, David M; Messerli, Mark A

    2018-03-09

    Weak external electric fields (EFs) polarize cellular structure and direct most migrating cells (galvanotaxis) toward the cathode, making it a useful tool during tissue engineering and for healing epidermal wounds. However, the biophysical mechanisms for sensing weak EFs remain elusive. We have reinvestigated the mechanism of cathode-directed water flow (electro-osmosis) in the boundary layer of cells, by reducing it with neutral, viscous polymers. We report that increasing viscosity with low molecular weight polymers decreases cathodal migration and promotes anodal migration in a concentration dependent manner. In contrast, increased viscosity with high molecular weight polymers does not affect directionality. We explain the contradictory results in terms of porosity and hydraulic permeability between the polymers rather than in terms of bulk viscosity. These results provide the first evidence for controlled reversal of galvanotaxis using viscous agents and position the field closer to identifying the putative electric field receptor, a fundamental, outside-in signaling receptor that controls cellular polarity for different cell types.

  4. [Biologic effects of different concentrations of putrescine on human umbilical vein endothelial cells].

    PubMed

    Chen, Jianxia; Rong, Xinzhou; Fan, Guicheng; Li, Songze; Zhang, Tao; Li, Qinghui

    2015-12-01

    To explore the effects of different concentrations of putrescine on proliferation, migration, and apoptosis of human umbilical vein endothelial cells (HUVECs). HUVECs were routinely cultured in vitro. The 3rd to the 5th passage of HUVECs were used in the following experiments. (1) Cells were divided into 500, 1 000, and 5 000 µg/mL putrescine groups according to the random number table (the same grouping method was used for following grouping), with 3 wells in each group, which were respectively cultured with complete culture solution containing putrescine in the corresponding concentration for 24 h. Morphology of cells was observed by inverted optical microscope. (2) Cells were divided into 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 500.0, 1 000.0 µg/mL putrescine groups, and control group, with 4 wells in each group. Cells in the putrescine groups were respectively cultured with complete culture solution containing putrescine in the corresponding concentration for 24 h, and cells in control group were cultured with complete culture solution with no additional putrescine for 24 h. Cell proliferation activity (denoted as absorption value) was measured by colorimetry. (3) Cells were divided (with one well in each group) and cultured as in experiment (2), and the migration ability was detected by transwell migration assay. (4) Cells were divided (with one flask in each group) and cultured as in experiment (2), and the cell apoptosis rate was determined by flow cytometer. Data were processed with one-way analysis of variance, Kruskal-Wallis test, and Dunnett test. (1) After 24-h culture, cell attachment was good in 500 µg/mL putrescine group, and no obvious change in the shape was observed; cell attachment was less in 1 000 µg/mL putrescine group and the cells were small and rounded; cells in 5 000 µg/mL putrescine group were in fragmentation without attachment. (2) The absorption values of cells in 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 500.0, 1 000.0 µg/mL putrescine groups, and control group were respectively 0.588 ± 0.055, 0.857 ± 0.031, 0.707 ± 0.031, 0.662 ± 0.023, 0.450 ± 0.019, 0.415 ± 0.014, 0.359 ± 0.020, 0.204 ± 0.030, and 0.447 ± 0.021, with statistically significant differences among them (χ(2) = 6.86, P = 0.009). The cell proliferation activity in 0.5, 1.0, 5.0, and 10.0 µg/mL putrescine groups was higher than that in control group (P < 0.05 or P < 0.01). The cell proliferation activity in 500.0 and 1 000.0 µg/mL putrescine groups was lower than that in control group (with P values below 0.01). The cell proliferation activity in 50.0 and 100.0 µg/mL putrescine groups was close to that in control group (with P values above 0.05). (3) There were statistically significant differences in the numbers of migrated cells between the putrescine groups and control group (F = 138.662, P < 0.001). The number of migrated cells was more in 1.0, 5.0, and 10.0 µg/mL putrescine groups than in control group (with P value below 0.01). The number of migrated cells was less in 500.0 and 1 000.0 µg/mL putrescine groups than in control group (with P value below 0.01). The number of migrated cells in 0.5, 50.0, and 100.0 µg/mL putrescine groups was close to that in control group (with P values above 0.05). (4) There were statistically significant differences in the apoptosis rate between the putrescine groups and control group (χ(2)=3.971, P=0.046). The cell apoptosis rate was lower in 0.5, 1.0, 5.0, and 10.0 µg/mL putrescine groups than in control group (with P values below 0.05). The cell apoptosis rate was higher in 500.0 and 1 000.0 µg/mL putrescine groups than in control group (with P values below 0.01). The cell apoptosis rates in 50.0 and 100.0 µg/mL putrescine groups were close to the cell apoptosis rate in control group (with P values above 0.05). Low concentration of putrescine can remarkably enhance the ability of proliferation and migration of HUVECs, while a high concentration of putrescine can obviously inhibit HUVECs proliferation and migration, and it induces apoptosis.

  5. EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

    PubMed

    Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J

    2016-11-01

    Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

  6. Testosterone, migration distance, and migratory timing in song sparrows Melospiza melodia.

    PubMed

    Lymburner, Alannah H; Kelly, Tosha R; Hobson, Keith A; MacDougall-Shackleton, Elizabeth A; MacDougall-Shackleton, Scott A

    2016-09-01

    In seasonally migratory animals, migration distance often varies substantially within populations such that individuals breeding at the same site may overwinter different distances from the breeding grounds. Shorter migration may allow earlier return to the breeding grounds, which may be particularly advantageous to males competing to acquire a breeding territory. However, little is known about potential mechanisms that may mediate migration distance. We investigated naturally-occurring variation in androgen levels at the time of arrival to the breeding site and its relationship to overwintering latitude in male and female song sparrows (Melospiza melodia). We used stable isotope analysis of hydrogen (δ(2)H) in winter-grown claw tissue to infer relative overwintering latitude (migration distance), combined with 14years of capture records from a long-term study population to infer the arrival timing of males versus females. Relative to females, males had higher circulating androgen levels, migrated shorter distances, and were more likely to be caught early in the breeding season. Males that migrate short distances may benefit from early arrival at the breeding grounds, allowing them to establish a breeding territory. Even after controlling for sex and date, androgen levels were highest in individuals that migrated shorter distances. Our findings indicate that androgens and migration distance are correlated traits within and between sexes that may reflect individual variation within an integrated phenotype in which testosterone has correlated effects on behavioral traits such as migration. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Surface wettability of plasma SiOx:H nanocoating-induced endothelial cells' migration and the associated FAK-Rho GTPases signalling pathways

    PubMed Central

    Shen, Yang; Wang, Guixue; Huang, Xianliang; Zhang, Qin; Wu, Jiang; Tang, Chaojun; Yu, Qingsong; Liu, Xiaoheng

    2012-01-01

    Vascular endothelial cell (EC) adhesion and migration are essential processes in re-endothelialization of implanted biomaterials. There is no clear relationship and mechanism between EC adhesion and migration behaviour on surfaces with varying wettabilities. As model substrates, plasma SiOx:H nanocoatings with well-controlled surface wettability (with water contact angles in the range of 98.5 ± 2.3° to 26.3 ± 4.0°) were used in this study to investigate the effects of surface wettability on cell adhesion/migration and associated protein expressions in FAK-Rho GTPases signalling pathways. It was found that EC adhesion/migration showed opposite behaviour on the hydrophilic and hydrophobic surfaces (i.e. hydrophobic surfaces promoted EC migration but were anti-adhesions). The number of adherent ECs showed a maximum on hydrophilic surfaces, while cells adhered to hydrophobic surfaces exhibited a tendency for cell migration. The focal adhesion kinase (FAK) inhibitor targeting the Y-397 site of FAK could significantly inhibit cell adhesion/migration, suggesting that EC adhesion and migration on surfaces with different wettabilities involve (p)FAK and its downstream signalling pathways. Western blot results suggested that the FAK-Rho GTPases signalling pathways were correlative to EC migration on hydrophobic plasma SiOx:H surfaces, but uncertain to hydrophilic surfaces. This work demonstrated that surface wettability could induce cellular behaviours that were associated with different cellular signalling events. PMID:21715399

  8. Migration Study of Butylated Hydroxytoluene and Irganox 1010 from Polypropylene Treated with Severe Processing Conditions.

    PubMed

    Kang, Kyungmo; Chang, Yoonjee; Choi, Jae Chun; Park, Se-Jong; Han, Jaejoon

    2018-04-01

    Safety concerns have emerged over the increased use of polypropylene (PP) in food-packaging markets. Some antioxidants in PP can migrate to foods and cause undesirable effects in humans. In this study, migration behaviors of butylated hydroxytoluene (BHT) and Irganox 1010 (I-1010) in PP sheets were determined according to the US FDA migration test conditions. In particular, we tested the effects of severe conditions of food processing and storage, such as autoclave heating (sterilization at about 121 °C), microwave radiation (700 W), and deep freezing (-30 °C) on migration of antioxidants. Migrant concentrations were higher in 95% ethanol as lipid food simulant, because of the hydrophobic nature of both PP and antioxidants. Autoclave heating treatment increased migrant concentrations compared with other processing conditions. Moreover, increased migrant concentrations by deep freezing condition were attributed to the brittleness of PP at freezing temperature. Regardless of processing conditions, BHT which has a lower molecular weight, migrated faster than I-1010. The antioxidants with hydrophobic nature such as butylated hydroxytoluene (BHT) and Irganox 1010 (I-1010) in polypropylene sheets would be migrated to foods, which is an important issue for industrial production food packaging materials. Migration behavior was promoted by severe processing conditions such as autoclave heating, microwave radiation, freezing, and especially autoclave heating treatment led the highest migration among them. Therefore, control of chemical additive migration from polypropylene food packaging is needed for safe food processing. © 2018 Institute of Food Technologists®.

  9. Determinants of Mexico-U.S. Outward and Return Migration Flows: A State-Level Panel Data Analysis.

    PubMed

    Chort, Isabelle; de la Rupelle, Maëlys

    2016-10-01

    Using a unique panel data set of state-to-state outward and return migration flows between Mexico and the United States from 1995 to 2012, this study is the first to analyze Mexico-U.S. migration at the state level and explore simultaneously the effect of economic, environmental, and social factors in Mexico over two decades. Pairing origin and destination states and controlling for a rich structure of fixed effects, we find that income positively impacts migration outflows, especially for Mexican states of origin with a recent migration history and for low-educated migrant flows, suggesting the existence of credit constraints. We find evidence that drought causes more out-migration, while other climatic shocks have no effect. Violence is found to increase out-migration flows from border states and to decrease migration from other Mexican states, especially where violence is directed at migrants. Last, return flows are larger when income growth at destination is lower, consistent with the accumulation of savings as a primary motivation of migrants. Exploring the impact of the crisis, we find evidence of significant changes in the geography of migration flows. Traditional flows are drying up, and new migration corridors are rising, with implications on the composition of the Mexican population in the United States. Although the effect of income on flows in both directions is unchanged by the crisis, the negative effect of violence on out-migration tends to reverse at the end of the period. Overall, this study emphasizes the interest of analyzing disaggregated flows at the infra-country level.

  10. Intertwined Effects of Gender and Migration Status on Persistence in SET Study Programmes

    ERIC Educational Resources Information Center

    Guenther, Elisabeth Anna; Koeszegi, Sabine Theresia

    2017-01-01

    This paper explores the intersectional interference of gender and migration status on students' persistence at an Austrian University of Technology. While controlling for the pre-university education and performance indicators, we estimate the odds for the persistence of male and female students, as well as of students with diverse migration…

  11. Band Alignment and Controllable Electron Migration between Rutile and Anatase TiO2

    PubMed Central

    Mi, Yang; Weng, Yuxiang

    2015-01-01

    TiO2 is the most promising semiconductor for photocatalytic splitting of water for hydrogen and degradation of pollutants. The highly photocatalytic active form is its mixed phase of two polymorphs anatase and rutile rather than their pristine compositions. Such a synergetic effect is understood by the staggered band alignment favorable to spatial charge separation. However, electron migration in either direction between the two phases has been reported, the reason of which is still unknown. We determined the band alignment by a novel method, i.e., transient infrared absorption-excitation energy scanning spectra, showing their conduction bands being aligned, thus the electron migration direction is controlled by dynamical factors, such as varying the particle size of anatase, putting electron or hole scavengers on either the surface of anatase or rutile phases, or both. A quantitative criterion capable of predicting the migration direction under various conditions including particle size and surface chemical reactions is proposed, the predictions have been verified experimentally in several typical cases. This would give rise to a great potential in designing more effective titania photocatalysts. PMID:26169699

  12. Anomalous Kinetics of Diffusion-Controlled Defect Annealing in Irradiated Ionic Solids.

    PubMed

    Kotomin, Eugene; Kuzovkov, Vladimir; Popov, Anatoli I; Maier, Joachim; Vila, Rafael

    2018-01-11

    The annealing kinetics of the primary electronic F-type color centers (oxygen vacancies with trapped one or two electrons) is analyzed for three ionic materials (Al 2 O 3 , MgO, and MgF 2 ) exposed to intensive irradiation by electrons, neutrons, and heavy swift ions. Phenomenological theory of diffusion-controlled recombination of the F-type centers with much more mobile interstitial ions (complementary hole centers) allows us to extract from experimental data the migration energy of interstitials and pre-exponential factor of diffusion. The obtained migration energies are compared with available first-principles calculations. It is demonstrated that with the increase of radiation fluence both the migration energy and pre-exponent are decreasing in all three materials, irrespective of the type of irradiation. Their correlation satisfies the Meyer-Neldel rule observed earlier in glasses, liquids, and disordered materials.The origin of this effect is discussed. This study demonstrates that in the quantitative analysis of the radiation damage of real materials the dependence of the defect migration parameters on the radiation fluence plays an important role and cannot be neglected.

  13. Cannabinoid Receptor 2 Suppresses Leukocyte Inflammatory Migration by Modulating the JNK/c-Jun/Alox5 Pathway*

    PubMed Central

    Liu, Yi-Jie; Fan, Hong-Bo; Jin, Yi; Ren, Chun-Guang; Jia, Xiao-E; Wang, Lei; Chen, Yi; Dong, Mei; Zhu, Kang-Yong; Dong, Zhi-Wei; Ye, Bai-Xin; Zhong, Zhong; Deng, Min; Liu, Ting Xi; Ren, Ruibao

    2013-01-01

    Inflammatory migration of immune cells is involved in many human diseases. Identification of molecular pathways and modulators controlling inflammatory migration could lead to therapeutic strategies for treating human inflammation-associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Through a chemical genetic screen using a zebrafish model for leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in response to acute injury. These agents have a similar effect on migration of human myeloid cells. Consistent with these results, we found that inactivation of Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration, while inactivation of Alox5 blocks leukocyte migration. Further investigation indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5 constitute a pathway regulating leukocyte migration. The cooperative effect between the Cnr2 agonist and Alox5 inhibitor also provides a potential therapeutic strategy for treating human inflammation-associated diseases. PMID:23539630

  14. Migration of the CERN IT Data Centre Support System to ServiceNow

    NASA Astrophysics Data System (ADS)

    Alvarez Alonso, R.; Arneodo, G.; Barring, O.; Bonfillou, E.; Coelho dos Santos, M.; Dore, V.; Lefebure, V.; Fedorko, I.; Grossir, A.; Hefferman, J.; Mendez Lorenzo, P.; Moller, M.; Pera Mira, O.; Salter, W.; Trevisani, F.; Toteva, Z.

    2014-06-01

    The large potential and flexibility of the ServiceNow infrastructure based on "best practises" methods is allowing the migration of some of the ticketing systems traditionally used for the monitoring of the servers and services available at the CERN IT Computer Centre. This migration enables the standardization and globalization of the ticketing and control systems implementing a generic system extensible to other departments and users. One of the activities of the Service Management project together with the Computing Facilities group has been the migration of the ITCM structure based on Remedy to ServiceNow within the context of one of the ITIL processes called Event Management. The experience gained during the first months of operation has been instrumental towards the migration to ServiceNow of other service monitoring systems and databases. The usage of this structure is also extended to the service tracking at the Wigner Centre in Budapest.

  15. Dynamics of neutrophil migration in lymph nodes during infection.

    PubMed

    Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A

    2008-09-19

    Although the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning-laser microscopy to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We found that neutrophils formed both small, transient and large, persistent swarms via a coordinated migration pattern. We provided evidence that cooperative action of neutrophils and parasite egress from host cells could trigger swarm formation. Neutrophil swarm formation coincided in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses.

  16. Dynamics of neutrophil migration in lymph nodes during infection

    PubMed Central

    Chtanova, Tatyana; Schaeffer, Marie; Han, Seong-Ji; van Dooren, Giel G.; Nollmann, Marcelo; Herzmark, Paul; Chan, Shiao Wei; Satija, Harshita; Camfield, Kristin; Aaron, Holly; Striepen, Boris; Robey, Ellen A.

    2008-01-01

    Summary While the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes, or the strategies that neutrophils use to find their local sites of action. To address these questions, we used two-photon scanning laser microscopy (TPSLM) to examine neutrophil migration in intact lymph nodes during infection with an intracellular parasite, Toxoplasma gondii. We find that neutrophils form both small, transient or large, persistent swarms via a strikingly coordinated migration pattern. We provide evidence that cooperative action of neutrophils and parasite egress from host cells can trigger swarm formation. Neutrophil swarm formation coincides in space and time with the removal of macrophages that line the subcapsular sinus of the lymph node. Our data provide insights into the cellular mechanisms underlying neutrophil swarming and suggest new roles for neutrophils in shaping immune responses. PMID:18718768

  17. Computational Modeling of Single-Cell Migration: The Leading Role of Extracellular Matrix Fibers

    PubMed Central

    Schlüter, Daniela K.; Ramis-Conde, Ignacio; Chaplain, Mark A.J.

    2012-01-01

    Cell migration is vitally important in a wide variety of biological contexts ranging from embryonic development and wound healing to malignant diseases such as cancer. It is a very complex process that is controlled by intracellular signaling pathways as well as the cell’s microenvironment. Due to its importance and complexity, it has been studied for many years in the biomedical sciences, and in the last 30 years it also received an increasing amount of interest from theoretical scientists and mathematical modelers. Here we propose a force-based, individual-based modeling framework that links single-cell migration with matrix fibers and cell-matrix interactions through contact guidance and matrix remodelling. With this approach, we can highlight the effect of the cell’s environment on its migration. We investigate the influence of matrix stiffness, matrix architecture, and cell speed on migration using quantitative measures that allow us to compare the results to experiments. PMID:22995486

  18. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow.

    PubMed

    Wynn, Robert F; Hart, Claire A; Corradi-Perini, Carla; O'Neill, Liam; Evans, Caroline A; Wraith, J Ed; Fairbairn, Leslie J; Bellantuono, Ilaria

    2004-11-01

    Homing of bone marrow stromal cells (MSCs) to bone and bone marrow after transplantation, important for the correction of conditions such as metabolic storage disorders, can occur but with poor efficiency. Substantial improvements in engraftment will be required in order to derive a clinical benefit from MSC transplantation. Chemokines are the most important factors controlling cellular migration. Stromal-derived factor-1 (SDF-1) has been shown to be critical in promoting the migration of cells to the bone marrow, via its specific receptor CXCR4. The aim of our study was to investigate CXCR4 expression on MSCs and its role in mediating migration to bone marrow. We show that CXCR4, although present at the surface of a small subset of MSCs, is important for mediating specific migration of these cells to bone marrow.

  19. Glial cell migration in the eye disc.

    PubMed

    Silies, Marion; Yuva, Yeliz; Engelen, Daniel; Aho, Annukka; Stork, Tobias; Klämbt, Christian

    2007-11-28

    Any complex nervous system is made out of two major cell types, neurons and glial cells. A hallmark of glial cells is their pronounced ability to migrate. En route to their final destinations, glial cells are generally guided by neuronal signals. Here we show that in the developing visual system of Drosophila glial cell migration is largely controlled by glial-glial interactions and occurs independently of axonal contact. Differentiation into wrapping glia is initiated close to the morphogenetic furrow. Using single cell labeling experiments we identified six distinct glial cell types in the eye disc. The migratory glial population is separated from the wrapping glial cells by the so-called carpet cells, extraordinary large glial cells, each covering a surface area of approximately 10,000 epithelial cells. Subsequent cell ablation experiments demonstrate that the carpet glia regulates glial migration in the eye disc epithelium and suggest a new model underlying glial migration and differentiation in the developing visual system.

  20. An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

    PubMed

    Kutys, Matthew L; Yamada, Kenneth M

    2014-09-01

    Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

  1. Do Rainfall Deficits Predict U.S.-bound Migration from Rural Mexico? Evidence from the Mexican Census

    PubMed Central

    Nawrotzki, Raphael J.; Riosmena, Fernando; Hunter, Lori M.

    2013-01-01

    Environmental and climatic changes have shaped human mobility for thousands of years and research on the migration-environment connection has proliferated in the past several years. Even so, little work has focused on Latin America or on international movement. Given rural Mexico’s dependency on primary sector activities involving various natural resources, and the existence of well-established transnational migrant networks, we investigate the association between rainfall patterns and U.S.-bound migration from rural locales, a topic of increasing policy relevance. The New Economics of Labor Migration (NELM) theory provides background, positing that migration represents a household-level risk management strategy. We use data from the year 2000 Mexican census for rural localities and socioeconomic and state-level precipitation data provided by the Mexican National Institute for Statistics and Geography. Multilevel models assess the impact of rainfall change on household-level international out-migration while controlling for relevant sociodemographic and economic factors. A decrease in precipitation is significantly associated with U.S.-bound migration, but only for dry Mexican states. This finding suggests that programs and policies aimed at reducing Mexico-U.S. migration should seek to diminish the climate/weather vulnerability of rural Mexican households, for example by supporting sustainable irrigation systems and subsidizing drought-resistant crops. PMID:23913999

  2. Low-level stretching accelerates cell migration into a gap.

    PubMed

    Toume, Samer; Gefen, Amit; Weihs, Daphne

    2017-08-01

    We observed that radially stretching cell monolayers at a low level (3%) increases the rate at which they migrate to close a gap formed by in vitro injury. Wound healing has been shown to accelerate in vivo when deformations are topically applied, for example, by negative pressure wound therapy. However, the direct effect of deformations on cell migration during gap closure is still unknown. Thus, we have evaluated the effect of radially applied, sustained (static) tensile strain on the kinematics of en mass cell migration. Monolayers of murine fibroblasts were cultured on stretchable, linear-elastic substrates that were subjected to different tensile strains, using a custom-designed three-dimensionally printed stretching apparatus. Immediately following stretching, the monolayer was 'wounded' at its centre, and cell migration during gap closure was monitored and quantitatively evaluated. We observed a significant increase in normalised migration rates and a reduction of gap closure time with 3% stretching, relative to unstretched controls or 6% stretch. Interestingly, the initial gap area was linearly correlated with the maximum migration rate, especially when stretching was applied. Therefore, small deformations applied to cell monolayers during gap closure enhance en mass cell migration associated with wound healing and can be used to fine-tune treatment protocols. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  3. Do Rainfall Deficits Predict U.S.-bound Migration from Rural Mexico? Evidence from the Mexican Census.

    PubMed

    Nawrotzki, Raphael J; Riosmena, Fernando; Hunter, Lori M

    2013-02-01

    Environmental and climatic changes have shaped human mobility for thousands of years and research on the migration-environment connection has proliferated in the past several years. Even so, little work has focused on Latin America or on international movement. Given rural Mexico's dependency on primary sector activities involving various natural resources, and the existence of well-established transnational migrant networks, we investigate the association between rainfall patterns and U.S.-bound migration from rural locales, a topic of increasing policy relevance. The New Economics of Labor Migration (NELM) theory provides background, positing that migration represents a household-level risk management strategy. We use data from the year 2000 Mexican census for rural localities and socioeconomic and state-level precipitation data provided by the Mexican National Institute for Statistics and Geography. Multilevel models assess the impact of rainfall change on household-level international out-migration while controlling for relevant sociodemographic and economic factors. A decrease in precipitation is significantly associated with U.S.-bound migration, but only for dry Mexican states. This finding suggests that programs and policies aimed at reducing Mexico-U.S. migration should seek to diminish the climate/weather vulnerability of rural Mexican households, for example by supporting sustainable irrigation systems and subsidizing drought-resistant crops.

  4. [Ethnic dimension to migration in the Senegal river valley].

    PubMed

    Traore, S

    1993-08-01

    Studies of the factors determining migratory patterns in the Senegal River Valley usually stress the importance of economic factors related to colonial domination. But when cultural factors and the social relations governing them are examined in a comparative study of ethnic groups, distinct population subgroups may be revealed to have differential migratory patterns. The Soninka and the Poular, two groups highly affected by migration, were chosen for an analysis of the impact of specific historical experiences on migratory behavior. A historical analysis of colonial archives and anthropological and historical monographs and the 1982-83 "Survey of Migration in the Valley of the Senegal River" provided data. The survey indicated that Soninka and Poular migratory patterns differed from each other, but that both differed from the migratory patterns of all other ethnic groups in the region. Soninka migration is international and oriented primarily toward Europe. It has recently become more intense than that of the poular. The determinants of migration in the two groups appear related more to the structure of households than to lack of educational and health facilities or even of food at the village level. Pastoral life and its associated beliefs and religious ideology appear to have been the principal determinants of precolonial movement among the Poular, while Soninka migration responded more to competition over control of manpower. Itinerant commercial activity was coupled with use of slave labor to ensure food production. But the suppression of slavery and crises of subsistence aggravated by colonial policy provoked ever more distant migration, which found a focus in the French demand for labor after World War II. Migration as an alternative does not appear to have been as significant for the Poular until more recently, when subsistence agriculture and the sale of animals were no longer sufficient to cover monetary needs. Male migration among the Soninka is a consequence of the sexual division of labor in which men were primarily responsible for economic activity and the movement of women was controlled in the interests of social cohesion. The movement of young people is now related to the hopes of older family members for social and economic advancement.

  5. Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling.

    PubMed

    Bjorke, Brielle; Shoja-Taheri, Farnaz; Kim, Minkyung; Robinson, G Eric; Fontelonga, Tatiana; Kim, Kyung-Tai; Song, Mi-Ryoung; Mastick, Grant S

    2016-10-22

    Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown. We examined the role of Slit chemorepellent signals in contralateral oculomotor migration by analyzing mutant mouse embryos. We found that the ventral midbrain expresses high levels of both Slit1 and 2, and that oculomotor neurons express the repellent Slit receptors Robo1 and Robo2. Therefore, Slit signals are in a position to influence the migration of oculomotor neurons. In Slit 1/2 or Robo1/2 double mutant embryos, motor neuron cell bodies migrated into the ventral midbrain on E10.5, three days prior to normal migration. These early migrating neurons had leading projections into and across the floor plate. In contrast to the double mutants, embryos which were mutant for single Slit or Robo genes did not have premature migration or outgrowth on E10.5, demonstrating a cooperative requirement of Slit1 and 2, as well as Robo1 and 2. To test how Slit/Robo midline repulsion is modulated, we found that the normal migration did not require the receptors Robo3 and CXCR4, or the chemoattractant, Netrin 1. The signal to initiate contralateral migration is likely autonomous to the midbrain because oculomotor neurons migrate in embryos that lack either nerve outgrowth or extraocular muscles, or in cultured midbrains that lacked peripheral tissue. Overall, our results demonstrate that a migratory subset of motor neurons respond to floor plate-derived Slit repulsion to properly control the timing of contralateral migration.

  6. Suppressor of cytokine signalling (SOCS) 1 and 3 enhance cell adhesion and inhibit migration towards the chemokine eotaxin/CCL11.

    PubMed

    Stevenson, Nigel J; McFarlane, Cheryl; Ong, Seow Theng; Nahlik, Krystyna; Kelvin, Alyson; Addley, Mark R; Long, Aideen; Greaves, David R; O'Farrelly, Cliona; Johnston, James A

    2010-11-05

    Suppressors of cytokine signalling (SOCS) proteins regulate signal transduction, but their role in responses to chemokines remains poorly understood. We report that cells expressing SOCS1 and 3 exhibit enhanced adhesion and reduced migration towards the chemokine CCL11. Focal adhesion kinase (FAK) and the GTPase RhoA, control cell adhesion and migration and we show the presence of SOCS1 or 3 regulates expression and tyrosine phosphorylation of FAK, while also enhancing activation of RhoA. Our novel findings suggest that SOCS1 and 3 may control chemotaxis and adhesion by significantly enhancing both FAK and RhoA activity, thus localizing immune cells to the site of allergic inflammation. Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Method of remediation of contaminants in porous media through minimization of bouyancy effects

    DOEpatents

    Shook, G. Michael; Pope, Gary A.

    1999-01-01

    A method for controlling vertical migration of contaminants in an aquifer includes introduction of a solubilizing solution having a surfactant and an alcohol or other light co-solvent. The surfactant is selected to solubilize the contaminant. The alcohol or other solvent is selected to provide the microemulsion with a substantially neutral buoyancy with respect to groundwater. The neutral buoyancy of the microemulsion prevents the normal downward movement which is typical of the solubilized dense non-aqueous phase liquid in surfactant-enhanced aquifer remediation. Thus, the risk that any significant amount of the solubilized dense non-aqueous contaminants will migrate vertically can be controlled. The relative tendency for vertical migration may also be reduced by increasing the injection rate or injected fluid viscosity (by adding polymer), or by reducing the well spacing.

  8. Determination of Endograft Apposition, Position, and Expansion in the Aortic Neck Predicts Type Ia Endoleak and Migration After Endovascular Aneurysm Repair.

    PubMed

    Schuurmann, Richte C L; van Noort, Kim; Overeem, Simon P; van Veen, Ruben; Ouriel, Kenneth; Jordan, William D; Muhs, Bart E; 't Mannetje, Yannick W; Reijnen, Michel M P J; Fioole, Bram; Ünlü, Çağdaş; Brummel, Peter; de Vries, Jean-Paul P M

    2018-06-01

    To describe the added value of determining changes in position and apposition on computed tomography angiography (CTA) after endovascular aneurysm repair (EVAR) to detect early caudal displacement of the device and to prevent type Ia endoleak. Four groups of elective EVAR patients were selected from a dataset purposely enriched with type Ia endoleak and migration (>10 mm) cases. The groups included cases of late type Ia endoleak (n=36), migration (n=9), a type II endoleak (n=16), and controls without post-EVAR complications (n=37). Apposition of the endograft fabric with the aortic neck, shortest distance between the fabric and the renal arteries, expansion of the main body (or dilatation of the aorta in the infrarenal sealing zone), and tilt of the endograft toward the aortic axis were determined on the first postoperative and the last available CTA scan without type Ia endoleak or migration. Differences in these endograft dimensions were compared between the first vs last scan and among the 4 groups. No significant differences in endograft configurations were observed among the groups on the first postoperative CTA scan. On the last CTA scan before a complication arose, the position of the fabric relative to the renal arteries, expansion of the main body, and apposition of the fabric with the aortic neck were significantly different between the type Ia endoleak (median follow-up 15 months) and migration groups (median follow-up 23 months) compared with the control group (median follow-up 19 months). Most endograft dimensions had changed significantly compared with the first postoperative CTA scan for all groups. Apposition had increased in the control group but had decreased significantly in the type Ia endoleak and migration groups. Progressive changes in dimensions of the endograft within the infrarenal neck could be detected on regular CTA scans before the complication became urgent in many patients.

  9. Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.

    PubMed

    Holt, Andrew W; Martin, Danielle N; Shaver, Patti R; Adderley, Shaquria P; Stone, Joshua D; Joshi, Chintamani N; Francisco, Jake T; Lust, Robert M; Weidner, Douglas A; Shewchuk, Brian M; Tulis, David A

    2016-09-01

    Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls. Intriguingly, FL-VASP/239D abrogated the stimulatory effects of FL-VASP/WT and FL-VASP/239A cells on PKG activity. In turn, pharmacologic blockade of PKG in the presence of BAY60 reversed the inhibitory effect of BAY60 on naïve ASM cell migration. Taken together, we demonstrate for the first time that BAY60 inhibits ASM cell migration through cGMP/PKG/VASP signaling yet through mechanisms independent of pVASP·S239 and that FL-VASP overexpression regulates PKG activity in rat ASM cells. These findings implicate BAY60 as a potential pharmacotherapeutic agent against aberrant ASM growth disorders such as CAD and also establish a unique mechanism through which VASP controls PKG activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Cell migration in microengineered tumor environments.

    PubMed

    Um, Eujin; Oh, Jung Min; Granick, Steve; Cho, Yoon-Kyoung

    2017-12-05

    Recent advances in microengineered cell migration platforms are discussed critically with a focus on how cell migration is influenced by engineered tumor microenvironments, the medical relevance being to understand how tumor microenvironments may promote or suppress the progression of cancer. We first introduce key findings in cancer cell migration under the influence of the physical environment, which is systematically controlled by microengineering technology, followed by multi-cues of physico-chemical factors, which represent the complexity of the tumor environment. Recognizing that cancer cells constantly communicate not only with each other but also with tumor-associated cells such as vascular, fibroblast, and immune cells, and also with non-cellular components, it follows that cell motility in tumor microenvironments, especially metastasis via the invasion of cancer cells into the extracellular matrix and other tissues, is closely related to the malignancy of cancer-related mortality. Medical relevance of forefront research realized in microfabricated devices, such as single cell sorting based on the analysis of cell migration behavior, may assist personalized theragnostics based on the cell migration phenotype. Furthermore, we urge development of theory and numerical understanding of single or collective cell migration in microengineered platforms to gain new insights in cancer metastasis and in therapeutic strategies.

  11. Thrombin-induced Migration and Matrix Metalloproteinase-9 Expression Are Regulated by MAPK and PI3K Pathways in C6 Glioma Cells

    PubMed Central

    Kim, Jiyoung; Lee, Jae-Won; Kim, Song-In; Choi, Yong-Joon; Lee, Won-Ki; Jeong, Myung-Ja; Cha, Sang-Hoon; Lee, Hee Jae; Chun, Wanjoo

    2011-01-01

    Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and Western blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme. PMID:21994479

  12. Gradient biomaterials and their influences on cell migration

    PubMed Central

    Wu, Jindan; Mao, Zhengwei; Tan, Huaping; Han, Lulu; Ren, Tanchen; Gao, Changyou

    2012-01-01

    Cell migration participates in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. The cells specifically migrate to destiny sites induced by the gradually varying concentration (gradient) of soluble signal factors and the ligands bound with the extracellular matrix in the body during a wound healing process. Therefore, regulation of the cell migration behaviours is of paramount importance in regenerative medicine. One important way is to create a microenvironment that mimics the in vivo cellular and tissue complexity by incorporating physical, chemical and biological signal gradients into engineered biomaterials. In this review, the gradients existing in vivo and their influences on cell migration are briefly described. Recent developments in the fabrication of gradient biomaterials for controlling cellular behaviours, especially the cell migration, are summarized, highlighting the importance of the intrinsic driving mechanism for tissue regeneration and the design principle of complicated and advanced tissue regenerative materials. The potential uses of the gradient biomaterials in regenerative medicine are introduced. The current and future trends in gradient biomaterials and programmed cell migration in terms of the long-term goals of tissue regeneration are prospected. PMID:23741610

  13. Designed biocompatible nano-inhibitor based on poly(β-cyclodextrin-ester) for reduction of the DEHP migration from plasticized PVC.

    PubMed

    Raeisi, Ahmad; Faghihi, Khalil; Shabanian, Meisam

    2017-10-15

    The easy migration of di(2-ethylhexyl) phthalate (DEHP) from the plasticized PVC (P-PVC) poses a serious threat to human health and the ecosystems. Thus, its control migration from the P-PVC products is very important. In this work, a poly(β-cyclodextrin-ester) network (β-CDP) was synthesized via reaction of β-cyclodextrin with 3,3',4,4'-benzophenone tetracarboxylic dianhydride. As a potential inhibitor for reduction of the DEHP migration, the β-CDP was grafted to Fe 3 O 4 nanoparticles. Poly(β-cyclodextrin-ester) functionalized Fe 3 O 4 nanoparticles (MNP-CDP) has been used in PVC/DEHP system as a reactive nano-inhibitor to reduce DEHP migration. Thermal stability and mechanical properties of obtained films were investigated. DEHP migration tests of the P-PVC films were also carried out by using Gas chromatography. It was found that by incorporating the small amounts of nano-inhibitor in PVC/DEHP system, the migration of DEHP effectively reduced from the P-PVC samples about 65% without any serious changes in mechanical and thermal properties of the P-PVC films. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. General Entanglement Scaling Laws from Time Evolution

    NASA Astrophysics Data System (ADS)

    Eisert, Jens; Osborne, Tobias J.

    2006-10-01

    We establish a general scaling law for the entanglement of a large class of ground states and dynamically evolving states of quantum spin chains: we show that the geometric entropy of a distinguished block saturates, and hence follows an entanglement-boundary law. These results apply to any ground state of a gapped model resulting from dynamics generated by a local Hamiltonian, as well as, dually, to states that are generated via a sudden quench of an interaction as recently studied in the case of dynamics of quantum phase transitions. We achieve these results by exploiting ideas from quantum information theory and tools provided by Lieb-Robinson bounds. We also show that there exist noncritical fermionic systems and equivalent spin chains with rapidly decaying interactions violating this entanglement-boundary law. Implications for the classical simulatability are outlined.

  15. The ecobiopolitics of space biomedicine.

    PubMed

    Olson, Valerie A

    2010-04-01

    Using data from an ethnographic study of American astronautics, I argue that, in an inversion of the usual clinical model, astronaut medical subjecthood is fundamentally environmental rather than biological. In extreme environments like outer space, the concept of environment cannot be bracketed out from life processes; as a result, investments of power and knowledge shift from life itself to the sites of interface among living things, technologies, and environments. To illustrate what this means on the ground, I describe space biomedicine as a form of environmental medicine that seeks to optimize and manage technically enabled human ecologies where life and environment are dually problematized. I provide two examples of what I term its ecobiopolitical strategies: creating a new "space normal" physiological category and situating humans as at-risk elements within integrated biological/technological/environmental systems.

  16. Herpes Simplex Virus Type 2 Suppressive Therapy with Acyclovir or Valacyclovir Does Not Select for Specific HIV-1 Resistance in HIV-1/HSV-2 Dually Infected Persons

    PubMed Central

    Lingappa, Jairam; Beck, Ingrid; Frenkel, Lisa M.; Pepper, Gregory; Celum, Connie; Wald, Anna; Fife, Kenneth H.; Were, Edwin; Mugo, Nelly; Sanchez, Jorge; Essex, Myron; Makhema, Joseph; Kiarie, James; Farquhar, Carey; Corey, Lawrence

    2011-01-01

    Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1–infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%–2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance. PMID:21148504

  17. Peri-apatite coating decreases uncemented tibial component migration: long-term RSA results of a randomized controlled trial and limitations of short-term results.

    PubMed

    Van Hamersveld, Koen T; Marang-Van De Mheen, Perla J; Nelissen, Rob G H H; Toksvig-Larsen, Sören

    2018-05-09

    Background and purpose - Biological fixation of uncemented knee prostheses can be improved by applying hydroxyapatite coating around the porous surface via a solution deposition technique called Peri-Apatite (PA). The 2-year results of a randomized controlled trial, evaluating the effect of PA, revealed several components with continuous migration in the second postoperative year, particularly in the uncoated group. To evaluate whether absence of early stabilization is diagnostic of loosening, we now present long-term follow-up results. Patients and methods - 60 patients were randomized to PA-coated or uncoated (porous only) total knee arthroplasty of which 58 were evaluated with radiostereometric analysis (RSA) performed at baseline, at 3 months postoperatively and at 1, 2, 5, 7, and 10 years. A linear mixed-effects model was used to analyze the repeated measurements. Results - PA-coated components had a statistically significantly lower mean migration at 10 years of 0.94 mm (95% CI 0.72-1.2) compared with the uncoated group showing a mean migration of 1.72 mm (95% CI 1.4-2.1). Continuous migration in the second postoperative year was seen in 7 uncoated components and in 1 PA-coated component. All of these implants stabilized after 2 years except for 2 uncoated components. Interpretation - Peri-apatite enhances stabilization of uncemented components. The number of components that stabilized after 2 years emphasizes the importance of longer follow-up to determine full stabilization and risk of loosening in uncemented components with biphasic migration profiles.

  18. Tyrosine Kinase Inhibitor, Vatalanib, Inhibits Proliferation and Migration of Human Pterygial Fibroblasts.

    PubMed

    Kim, Hong Kyu; Choi, Ji-Young; Park, Sang Min; Rho, Chang Rae; Cho, Kyong Jin; Jo, Sangmee Ahn

    2017-09-01

    Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs). Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib. Cell death was measured using flow cytometry analysis. Western blot analysis was performed to identify signaling molecules associated with the response to vatalanib. Vatalanib inhibited both proliferation and migration of HPFs in a dose-dependent manner. Cell proliferation was significantly suppressed by vatalanib (10 and 100 μM) and MMC (0.004% and 0.04%) treatments. Migration assays revealed significant HPF delay when treated with vatalanib (1, 10, and 100 μM) and MMC (0.004% and 0.04%) compared with that in a negative control. Cell death analysis showed that high concentrations of vatalanib (100 μM) and MMC (0.004% and 0.04%) decreased cell numbers. Western blot analysis of vatalanib-treated cells showed vascular endothelial growth factor and transforming growth factor-β significantly reduced, but there was no alteration in p53 protein levels in HPFs. These results indicate that vatalanib significantly suppressed the proliferation and migration of HPFs by decreasing vascular endothelial growth factor and transforming growth factor-β. Vatalanib showed less toxicity than that of MMC. Based on these results, vatalanib may potentially serve as a new adjuvant treatment after pterygium excision surgery.

  19. The Ethics of Border Guarding: A First Exploration and a Research Agenda for the Future

    ERIC Educational Resources Information Center

    Olsthoorn, Peter; Schut, Michelle

    2018-01-01

    Although the notion of universal human rights allows for the idea that states (and supranational organizations such as the European Union) can, or even should, control and impose restrictions on migration, both notions clearly do not sit well together. The ensuing tension manifests itself in our ambivalent attitude towards migration, but also…

  20. Getting to the root of the matter: landscape implications of plant-fungal interactions for tree migration in Alaska

    Treesearch

    Rebecca E. Hewitt; Alec P. Bennett; Amy L. Breen; Teresa N. Hollingsworth; D. Lee Taylor; F. Stuart Chapin; T. Scott Rupp

    2016-01-01

    Context   Forecasting the expansion of forest into Alaska tundra is critical to predicting regional ecosystem services, including climate feedbacks such as carbon storage. Controls over seedling establishment govern forest development and migration potential. Ectomycorrhizal fungi (EMF), obligate symbionts of all Alaskan tree species, are...

  1. The Effect of Rotation Rate on Seasonally Migrating Tropical Precipitation Zones on Terrestrial Planets

    NASA Astrophysics Data System (ADS)

    Faulk, Sean P.; Mitchell, Jonathan L.; Bordoni, Simona

    2014-11-01

    In the Earth’s atmosphere, tropical precipitation zones migrate seasonally but never extend beyond 30N, even in regions of large-scale monsoons. On Titan, however, seasonal, monsoon-like weather patterns regularly pump liquid methane to the poles. In this study, we argue that rotation rate is the main control on the seasonal extent of planetary monsoons, while surface thermal inertia plays a secondary role: i.e. the control is primarily dynamic rather than thermodynamic. Factors controlling the position and the sensitivity to energetic perturbations of the intertropical convergence zone (ITCZ) on Earth, a narrow latitudinal band where tropical precipitation is concentrated, have been widely investigated in the literature. Interestingly, while on Earth the ITCZ is limited to low latitudes, on Mars and Titan the ITCZ can migrate significantly off the equator into the summer hemisphere. Previous explanations for the ITCZ’s larger migration on Mars and Titan compared to Earth emphasize the lower surface thermal inertias of those planets. Here, we study a wide range of atmospheric circulations with an idealized General Circulation Model (GCM), in which an atmospheric model with idealized physics is coupled to an aquaplanet slab ocean of fixed depth and the top-of-atmosphere insolation is varied seasonally. A broad range of circulation regimes is studied by changing the thermal inertia of the slab ocean and the planetary rotation, while keeping the seasonal cycle of insolation fixed and all other parameters Earth-like. We find that for rotation rates 1/8 that of Earth's and slower, essentially Titan-like rotation rates, Earth’s ITCZ reaches the summer pole. At odds with previous explanations, we also find that decreasing the surface thermal inertia, to Titan’s surface thermal inertia and smaller, does little to extend the ITCZ’s summer migration off the equator. These results suggest that the ITCZ may be more controlled by dynamical mechanisms than previously thought. We explore such mechanisms within the framework of the momentum budget.

  2. Development and testing of culturally sensitive patient information material for Turkish, Polish, Russian and Italian migrants with depression or chronic low back pain (KULTINFO): study protocol for a double-blind randomized controlled trial.

    PubMed

    Hölzel, Lars P; Ries, Zivile; Zill, Jördis M; Kriston, Levente; Dirmaier, Jörg; Härter, Martin; Bermejo, Isaac

    2014-07-04

    Many of the approximately 15 million people with a migration background living in Germany (19% of the population) are inadequately reached by existing healthcare provision. In the literature, the necessity for cultural adaptation of information material for patients with a migration background is often cited as a measure for improving healthcare.In this study, culturally sensitive information material will be developed and evaluated for patients with a migration background and depression or chronic low back pain. In this respect, it will be examined whether culturally sensitive information material is judged as more useful by the patients than standard translated patient information without cultural adaptation. The implementation and evaluation of culturally sensitive patient information material will occur in the framework of a double-blind randomized controlled parallel-group study in four study centres in Germany. Primary care patients with a Turkish, Polish, Russian or Italian migration background with a diagnosis of depressive disorder or chronic low back pain will be included and randomly allocated to the intervention group or the control group. In the intervention group, culturally sensitive patient information will be handed to the patient at the end of the physician consultation, while in the control group, standard translated patient information material will be provided. The patients will be surveyed by means of questionnaires following the consultation as well as after 8 weeks and 6 months. In addition to the primary outcome (subjective usefulness), several patient- and physician-rated secondary outcomes will be considered. The study will provide an empirical answer to the question of whether persons with a migration background perceive culturally sensitive patient information material as more useful than translated information material without cultural adaptation. Deutsches Register Klinischer Studien (DRKS-ID) DRKS00004241 and Universal Trial Number (UTN) U1111-1135-8043.

  3. The development of injectable gelatin/silk fibroin microspheres for the dual delivery of curcumin and piperine.

    PubMed

    Ratanavaraporn, Juthamas; Kanokpanont, Sorada; Damrongsakkul, Siriporn

    2014-02-01

    The objective of this study was to develop the microspheres from gelatin (G) and silk fibroin (SF) aimed to be applied for the controlled release of curcumin and piperine. The glutaraldehyde-crosslinked G/SF microspheres at various weight blending ratios (100/0, 70/30, 50/50, and 30/70) were successfully fabricated by water in oil emulsion technique. The microspheres prepared from all compositions were in a round shape with homogeneous size distribution both in the dried (194-217 μm) and swollen states (297-367 μm). When subjected in collagenase solution at physiological condition, the G microspheres gradually degraded within 14 days while the blended G/SF microspheres, particularly at 50/50 and 30/70, were not degraded. For the release application, the microspheres were loaded with curcumin and/or piperine. It was found that the microspheres composed of SF tended to entrap curcumin and piperine with the high entrapment and loading efficiencies, possibly due to their hydrophobic interactions. The G/SF microspheres, particularly at the ratios of 50/50 and 30/70, released curcumin and piperine in a sustained manner both for the single and dual release systems. The controlled dual release of curcumin and piperine from the G/SF microspheres would prolong their half-life, provide the optimal concentrations for therapeutic effects at a target site, and improve the bioavailability of curcumin. These novel injectable microspheres dually releasing curcumin and piperine would be introduced for the treatment of diseases without the need of operation.

  4. Roadmap to control HBV and HDV epidemics in China

    DOE PAGES

    Goyal, Ashish; Murray, John M.

    2017-04-23

    Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5–10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. Furthermore, using a mathematical model, an annual budget of 10 billion dollars was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBVmore » mono-infections, and awareness programs. As a result, we determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8 million HBV, 1.9 million HDV infections and 0.25 million lives will be saved over the next 10 years at a cost-savings of 79 billion dollars than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4 million new HBV infections and 15,000 new HDV infections. In conclusion, test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.« less

  5. Roadmap to control HBV and HDV epidemics in China

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

    Goyal, Ashish; Murray, John M.

    Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5–10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. Furthermore, using a mathematical model, an annual budget of 10 billion dollars was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBVmore » mono-infections, and awareness programs. As a result, we determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8 million HBV, 1.9 million HDV infections and 0.25 million lives will be saved over the next 10 years at a cost-savings of 79 billion dollars than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4 million new HBV infections and 15,000 new HDV infections. In conclusion, test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.« less

  6. Gβ1 is required for neutrophil migration in zebrafish.

    PubMed

    Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

    2017-08-01

    Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Ghrelin affects stopover decisions and food intake in a long-distance migrant.

    PubMed

    Goymann, Wolfgang; Lupi, Sara; Kaiya, Hiroyuki; Cardinale, Massimiliano; Fusani, Leonida

    2017-02-21

    Billions of birds migrate long distances to either reach breeding areas or to spend the winter at more benign places. On migration, most passerines frequently stop over to rest and replenish their fuel reserves. To date, we know little regarding how they decide that they are ready to continue their journey. What physiological signals tell a bird's brain that its fuel reserves are sufficient to resume migration? A network of hormones regulates food intake and body mass in vertebrates, including the recently discovered peptide hormone, ghrelin. Here, we show that ghrelin reflects body condition and influences migratory behavior of wild birds. We measured ghrelin levels of wild garden warblers ( Sylvia borin ) captured at a stopover site. Further, we manipulated blood concentrations of ghrelin to test its effects on food intake and migratory restlessness. We found that acylated ghrelin concentrations of garden warblers with larger fat scores were higher than those of birds without fat stores. Further, injections of unacylated ghrelin decreased food intake and increased migratory restlessness. These results represent experimental evidence that appetite-regulating hormones control migratory behavior. Our study lays a milestone in migration physiology because it provides the missing link between ecologically dependent factors such as condition and timing of migration. In addition, it offers insights in the regulation of the hormonal system controlling food intake and energy stores in vertebrates, whose disruption causes eating disorders and obesity.

  8. Ghrelin affects stopover decisions and food intake in a long-distance migrant

    PubMed Central

    Lupi, Sara; Kaiya, Hiroyuki; Cardinale, Massimiliano

    2017-01-01

    Billions of birds migrate long distances to either reach breeding areas or to spend the winter at more benign places. On migration, most passerines frequently stop over to rest and replenish their fuel reserves. To date, we know little regarding how they decide that they are ready to continue their journey. What physiological signals tell a bird’s brain that its fuel reserves are sufficient to resume migration? A network of hormones regulates food intake and body mass in vertebrates, including the recently discovered peptide hormone, ghrelin. Here, we show that ghrelin reflects body condition and influences migratory behavior of wild birds. We measured ghrelin levels of wild garden warblers (Sylvia borin) captured at a stopover site. Further, we manipulated blood concentrations of ghrelin to test its effects on food intake and migratory restlessness. We found that acylated ghrelin concentrations of garden warblers with larger fat scores were higher than those of birds without fat stores. Further, injections of unacylated ghrelin decreased food intake and increased migratory restlessness. These results represent experimental evidence that appetite-regulating hormones control migratory behavior. Our study lays a milestone in migration physiology because it provides the missing link between ecologically dependent factors such as condition and timing of migration. In addition, it offers insights in the regulation of the hormonal system controlling food intake and energy stores in vertebrates, whose disruption causes eating disorders and obesity. PMID:28167792

  9. Gremlin-1 inhibits macrophage migration inhibitory factor-dependent monocyte function and survival.

    PubMed

    Müller, Iris I; Chatterjee, Madhumita; Schneider, Martina; Borst, Oliver; Seizer, Peter; Schönberger, Tanja; Vogel, Sebastian; Müller, Karin A L; Geisler, Tobias; Lang, Florian; Langer, Harald; Gawaz, Meinrad

    2014-10-20

    Monocyte migration and their differentiation into macrophages critically regulate vascular inflammation and atherogenesis and are governed by macrophage migration inhibitory factor (MIF). Gremlin-1 binds to MIF. Current experimental evidences present Gremlin-1 as a potential physiological agent that might counter-regulate the inflammatory attributes of MIF. We found that Gremlin-1 inhibited MIF-dependent monocyte migration and adhesion to activated endothelial cells in flow chamber perfusion assay in vitro and to the injured carotid artery of WT and ApoE-/- mice in vivo as deciphered by intravital microscopy. Intravenous administration of Gremlin-1, but not of control protein, significantly reduced leukocyte recruitment towards the inflamed carotid artery of ApoE-/- mice. Besides, leukocytes from MIF-/- when administered into ApoE-/- mice showed lesser adhesion as compared to wild type. In the presence of Gremlin-1 however, adhesion of wild type, but not of MIF-/- leukocytes, to the carotid artery was significantly inhibited as compared to control. Gremlin-1 also inhibited the MIF-induced differentiation of monocytes into macrophages. Gremlin-1 substantially inhibited the anti-apoptotic impact of MIF on monocytes against BH3 mimetic ABT-737-induced apoptosis as verified by Annexin V-binding, caspase 3 activity, and mitochondrial depolarization. Therefore Gremlin-1 can modulate MIF dependent monocyte adhesion, migration, differentiation and survival. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

    NASA Astrophysics Data System (ADS)

    Song, Kwang Hoon; Lee, Jaehyun; Park, Hyoungjun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

    2016-03-01

    Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as “duro-repulsive” cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei.

  11. Biliary sphincteroplasty facilitates retrieval of proximally migrated plastic biliary stent.

    PubMed

    Shah, Dharmesh K; Jain, Samit S; Somani, Piyush O; Rathi, Pravin M

    2014-01-01

    Proximal migration of biliary stents presents a technical challenge for the therapeutic endoscopist. It may require multiple, complicated corrective procedures resulting in significant morbidity to the patients. In this study we evaluated the utility of balloon biliary sphincteroplasty with CRE (Controlled Radial Expansion) Balloon Dilator on retrieval of proximally migrated biliary stents. We identified patients from our ERCP database who presented with proximal migration of biliary stent, between August 2011 and October 2013. Patients in whom the stent could not be retrieved with conventional methods, balloon sphincteroplasty was performed with a 12 mm CRETM Balloon Dilator (Boston Scientific). Stent removal was attempted with extraction balloon or basket thereafter. We identified 28 patients with proximal migration of biliary stents, placed for benign diseases of the common bile duct. Stent removal was successful in 18 patients (64.28%) with help of an extraction balloon or basket. Of the remaining 10 patients, balloon sphincteroplasty was successfully followed by stent removal in eight patients. Balloon biliary sphincteroplasty increases the success rate of retrieving proximally migrated biliary stents. The procedure is safe, technically easy and yields a good success rate in our experience.

  12. Tumor cell migration in complex microenvironments

    PubMed Central

    Polacheck, William J.; Zervantonakis, Ioannis K.; Kamm, Roger D.

    2012-01-01

    Tumor cell migration is essential for invasion and dissemination from primary solid tumors and for the establishment of lethal secondary metastases at distant organs. In vivo and in vitro models enabled identification of different factors in the tumor microenvironment that regulate tumor progression and metastasis. However, the mechanisms by which tumor cells integrate these chemical and mechanical signals from multiple sources to navigate the complex microenvironment remain poorly understood. In this review, we discuss the factors that influence tumor cell migration with a focus on the migration of transformed carcinoma cells. We provide an overview of the experimental and computational methods that allow the investigation of tumor cell migration, and we highlight the benefits and shortcomings of the various assays. We emphasize that the chemical and mechanical stimulus paradigms are not independent and that crosstalk between them motivates the development of new assays capable of applying multiple, simultaneous stimuli and imaging the cellular migratory response in real-time. These next-generation assays will more closely mimic the in vivo microenvironment to provide new insights into tumor progression, inform techniques to control tumor cell migration, and render cancer more treatable. PMID:22926411

  13. Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin

    PubMed Central

    Kunwar, Prabhat S.; Sano, Hiroko; Renault, Andrew D.; Barbosa, Vitor; Fuse, Naoyuki; Lehmann, Ruth

    2008-01-01

    Despite significant progress in identifying the guidance pathways that control cell migration, how a cell starts to move within an intact organism, acquires motility, and loses contact with its neighbors is poorly understood. We show that activation of the G protein–coupled receptor (GPCR) trapped in endoderm 1 (Tre1) directs the redistribution of the G protein Gβ as well as adherens junction proteins and Rho guanosine triphosphatase from the cell periphery to the lagging tail of germ cells at the onset of Drosophila melanogaster germ cell migration. Subsequently, Tre1 activity triggers germ cell dispersal and orients them toward the midgut for directed transepithelial migration. A transition toward invasive migration is also a prerequisite for metastasis formation, which often correlates with down-regulation of adhesion proteins. We show that uniform down-regulation of E-cadherin causes germ cell dispersal but is not sufficient for transepithelial migration in the absence of Tre1. Our findings therefore suggest a new mechanism for GPCR function that links cell polarity, modulation of cell adhesion, and invasion. PMID:18824569

  14. The lutheran/basal cell adhesion molecule promotes tumor cell migration by modulating integrin-mediated cell attachment to laminin-511 protein.

    PubMed

    Kikkawa, Yamato; Ogawa, Takaho; Sudo, Ryo; Yamada, Yuji; Katagiri, Fumihiko; Hozumi, Kentaro; Nomizu, Motoyoshi; Miner, Jeffrey H

    2013-10-25

    Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu), also known as basal cell adhesion molecule (B-CAM), competes with integrins for binding to laminin α5, a subunit of LM-511, a major component of basement membranes. Here we show that the preferential binding of Lu/B-CAM to laminin α5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to LM-511 was slightly weaker than that of control cells, and this was because Lu/B-CAM disturbed integrin binding to laminin α5. Lu/B-CAM induced a spindle cell shape with pseudopods and promoted cell migration on LM-511. In addition, blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited migration on LM-511, similar to the effects of an activating integrin β1 antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. We suggest that this competitive interaction is involved in a balance between static and migratory cell behaviors.

  15. Motivation for Psychotherapy and Illness Beliefs in Turkish Immigrant Inpatients in Germany: Results of a Cultural Comparison Study.

    PubMed

    Reich, Hanna; Bockel, Luisa; Mewes, Ricarda

    2015-03-01

    Some immigrant populations, for instance, Turkish immigrants, suffer from worse mental health than the general population. Moreover, psychotherapeutic treatment does not work well in this group. This might be explained by lower motivation for psychotherapy and particular illness beliefs as important early predictors of treatment outcome. We investigate differences in these predictors between Turkish immigrant inpatients and inpatients without a migration background and evaluate whether particular illness beliefs have a negative impact on motivation for psychotherapy. Turkish immigrant inpatients and inpatients without a migration background (N = 100), suffering from depressive disorder, somatoform disorder, and/or adjustment disorder, completed questionnaires assessing motivation for psychotherapy, depressive and somatic symptoms, illness perception, illness-related locus of control, and causal illness attributions. Despite a higher symptom burden, motivation for psychotherapy was lower in Turkish immigrant inpatients than in inpatients without a migration background (d = 0.54). This was fully explained by stronger beliefs in supernatural causes of illness and higher fatalistic-external illness-related locus of control in the Turkish immigrant sample (mediation analysis; R (2) = 0.27). Turkish immigrants believe in supernatural or fatalistic causes of illness and fatalistic-external locus of control to a greater extent than German inpatients without a migration background. These beliefs reduce motivation for psychotherapy and need to be addressed in psychotherapeutic treatment in order to secure positive treatment outcomes.

  16. Cellular behavior controlled by bio-inspired and geometry-tunable nanohairs.

    PubMed

    Heo, Chaejeong; Jeong, Chanho; Im, Hyeon Seong; Kim, Jong Uk; Woo, Juhyun; Lee, Ji Yeon; Park, Byeonghak; Suh, Minah; Kim, Tae-Il

    2017-11-23

    A cicada wing has a biocidal feature of rupturing the membrane of cells, while the cactus spine can transmit a water drop to the stem of the plant. Both of these properties have evolved from their respective unique structures. Here, we endeavor to develop geometry-controllable nanohairs that mimic the cicada's wing-like vertical hairs and the cactus spine-like stooped hairs, and to quantitatively characterize the cell migration behavior of the hairy structures. It was found that the neuroblastoma cells are highly sensitive to the variation of surfaces: flat, vertical, and stooped nanohairs (100 nm diameter and 900 nm height). The cells on the vertical hairs showed significantly decreased proliferation. It was found that the behavior of cells cultured on stooped nanohairs is strongly influenced by the direction of the stooped pattern of hairs when we quantitatively measured the migration of cells on flat, vertical, and stooped structures. However, the cells on the flat structures showed random movement and the cells on the vertical nanohairs restricted the nanohair movement. Cells on the stooped structure showed higher forward migration preference compared to that of the other structures. Furthermore, we found that these cellular behaviors on the different patterns of nanohairs were affected by intracellular actin flament change. Consistent with these results, the vertical and stooped structures can facilitate the control of cell viability and guide directional migration for biomedical applications such as organogenesis.

  17. The Fat-like Cadherin CDH-4 Acts Cell-Non-Autonomously in Anterior-Posterior Neuroblast Migration

    PubMed Central

    Sundararajan, Lakshmi; Norris, Megan L.; Schöneich, Sebastian; Ackley, Brian D.; Lundquist, Erik A.

    2014-01-01

    Directed migration of neurons is critical in the normal and pathological development of the brain and central nervous system. In C. elegans, the bilateral Q neuroblasts, QR on the right and QL on the left, migrate anteriorly and posteriorly, respectively. Initial protrusion and migration of the Q neuroblasts is autonomously controlled by the transmembrane proteins UNC-40/DCC, PTP-3/LAR, and MIG-21. As QL migrates posteriorly, it encounters and EGL-20/Wnt signal that induces MAB-5/Hox expression that drives QL descendant posterior migration. QR migrates anteriorly away from EGL-20/Wnt and does not activate MAB-5/Hox, resulting in anterior QR descendant migration. A forward genetic screen for new mutations affecting initial Q migrations identified alleles of cdh-4, which caused defects in both QL and QR directional migration similar to unc-40, ptp-3, and mig-21. Previous studies showed that in QL, PTP-3/LAR and MIG-21 act in a pathway in parallel to UNC-40/DCC to drive posterior QL migration. Here we show genetic evidence that CDH-4 acts in the PTP-3/MIG-21 pathway in parallel to UNC-40/DCC to direct posterior QL migration. In QR, the PTP-3/MIG-21 and UNC-40/DCC pathways mutually inhibit each other, allowing anterior QR migration. We report here that CDH-4 acts in both the PTP-3/MIG-21 and UNC-40/DCC pathways in mutual inhibition in QR, and that CDH-4 acts cell-non-autonomously. Interaction of CDH-4 with UNC-40/DCC in QR but not QL represents an inherent left-right asymmetry in the Q cells, the nature of which is not understood. We conclude that CDH-4 might act as a permissive signal for each Q neuroblast to respond differently to anterior-posterior guidance information based upon inherent left-right asymmetries in the Q neuroblasts. PMID:24954154

  18. Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis.

    PubMed

    Anguiano, María; Castilla, Carlos; Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

    2017-01-01

    Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs.

  19. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.

    PubMed

    Moreira Carboni, Simone de Sales Costa; Rodrigues Lima, Nathália Alves; Pinheiro, Nanci Mendes; Tavares-Murta, Beatriz Martins; Crema, Virgínia Oliveira

    2015-10-01

    Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.

  20. Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches

    PubMed Central

    Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae

    2016-01-01

    Objective The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. Design PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. Results Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. Conclusions PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches. PMID:25596181

  1. Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study.

    PubMed

    Isayama, Hiroyuki; Mukai, Tsuyoshi; Itoi, Takao; Maetani, Iruru; Nakai, Yousuke; Kawakami, Hiroshi; Yasuda, Ichiro; Maguchi, Hiroyuki; Ryozawa, Shomei; Hanada, Keiji; Hasebe, Osamu; Ito, Kei; Kawamoto, Hirofumi; Mochizuki, Hitoshi; Igarashi, Yoshinori; Irisawa, Atsushi; Sasaki, Tamito; Togawa, Osamu; Hara, Taro; Kamada, Hideki; Toda, Nobuo; Kogure, Hirofumi

    2012-07-01

    Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs. To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force. Multicenter, prospective study with a historical cohort. Twenty Japanese referral centers. This study involved patients with unresectable distal malignant biliary obstruction. Placement of a new, commercially available, partially covered SEMS. Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival. Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%). Nonrandomized, controlled trial. Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  2. Proximate cues for a short-distance migratory species: An application of survival analysis

    USGS Publications Warehouse

    Meunier, J.; Song, R.; Lutz, R.S.; Andersen, D.E.; Doherty, K.E.; Bruggink, J.G.; Oppelt, E.

    2008-01-01

    Investigation of bird migration has often highlighted the importance of external factors in determining timing of migration However, little distinction has been made between short- and long-distance migrants and between local and flight birds (passage migrants) in describing migration chronology. In addition, measures of food abundance as a proximate factor influencing timing of migration are lacking in studies of migration chronology. To address the relationship between environmental variables and timing of migration we quantified the relative importance of proximate external factors on migration chronology of local American woodcock (Scolopax minor), a short distance migrant, using event-time analysis methods (survival analysis). We captured 1,094 woodcock local to our study sites in Michigan, Minnesota and Wisconsin (USA) during autumn 2002-2004 and documented 786 departure dates for these birds. Photoperiod appeared to provide an initial proximate cue for timing of departure. Moon phase was important in modifying timing of departure, which may serve as a navigational aid in piloting and possibly orientation. Local synoptic weather variables also contributed to timing of departure by changing the rate of departure from our study sites. We found no evidence that food availability influenced timing of woodcock departure. Our results suggest that woodcock use a conservative photoperiod-controlled strategy with proximate modifiers for timing of migration rather than relying on abundance of their primary food, earthworms. Managing harvest pressure on local birds by adjusting season lengths may be an effective management tool with consistent migration patterns from year to year based on photoperiod.

  3. Feasibility study on the use of probabilistic migration modeling in support of exposure assessment from food contact materials.

    PubMed

    Poças, Maria F; Oliveira, Jorge C; Brandsch, Rainer; Hogg, Timothy

    2010-07-01

    The use of probabilistic approaches in exposure assessments of contaminants migrating from food packages is of increasing interest but the lack of concentration or migration data is often referred as a limitation. Data accounting for the variability and uncertainty that can be expected in migration, for example, due to heterogeneity in the packaging system, variation of the temperature along the distribution chain, and different time of consumption of each individual package, are required for probabilistic analysis. The objective of this work was to characterize quantitatively the uncertainty and variability in estimates of migration. A Monte Carlo simulation was applied to a typical solution of the Fick's law with given variability in the input parameters. The analysis was performed based on experimental data of a model system (migration of Irgafos 168 from polyethylene into isooctane) and illustrates how important sources of variability and uncertainty can be identified in order to refine analyses. For long migration times and controlled conditions of temperature the affinity of the migrant to the food can be the major factor determining the variability in the migration values (more than 70% of variance). In situations where both the time of consumption and temperature can vary, these factors can be responsible, respectively, for more than 60% and 20% of the variance in the migration estimates. The approach presented can be used with databases from consumption surveys to yield a true probabilistic estimate of exposure.

  4. Effects of Holocene climate change on the historical demography of migrating sharp-shinned hawks (Accipiter striatus velox) in North America.

    PubMed

    Hull, Joshua M; Girman, Derek J

    2005-01-01

    DNA sequences of the mitochondrial control region were analysed from 298 individual sharp-shinned hawks (Accipiter striatus velox) sampled at 12 different migration study sites across North America. The control region proved to be an appropriate genetic marker for identification of continental-scale population genetic structure and for determining the historical demography of population units. These data suggest that sharp-shinned hawks sampled at migration sites in North America are divided into distinct eastern and western groups. The eastern group appears to have recently expanded in response to the retreat of glacial ice at the end of the last glacial maximum. The western group appears to have been strongly effected by the Holocene Hypsithermal dry period, with molecular evidence indicating the most recent expansion following this mid-Holocene climatic event 7000-5000 years before present.

  5. Functionalized Iron Oxide Nanoparticles for Controlling the Movement of Immune Cells

    PubMed Central

    White, Ethan E; Pai, Alex; Weng, Yiming; Suresh, Anil K.; Van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M.

    2015-01-01

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed “cell box” was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain. PMID:25848983

  6. Functionalized iron oxide nanoparticles for controlling the movement of immune cells.

    PubMed

    White, Ethan E; Pai, Alex; Weng, Yiming; Suresh, Anil K; Van Haute, Desiree; Pailevanian, Torkom; Alizadeh, Darya; Hajimiri, Ali; Badie, Behnam; Berlin, Jacob M

    2015-05-07

    Immunotherapy is currently being investigated for the treatment of many diseases, including cancer. The ability to control the location of immune cells during or following activation would represent a powerful new technique for this field. Targeted magnetic delivery is emerging as a technique for controlling cell movement and localization. Here we show that this technique can be extended to microglia, the primary phagocytic immune cells in the central nervous system. The magnetized microglia were generated by loading the cells with iron oxide nanoparticles functionalized with CpG oligonucleotides, serving as a proof of principle that nanoparticles can be used to both deliver an immunostimulatory cargo to cells and to control the movement of the cells. The nanoparticle-oligonucleotide conjugates are efficiently internalized, non-toxic, and immunostimulatory. We demonstrate that the in vitro migration of the adherent, loaded microglia can be controlled by an external magnetic field and that magnetically-induced migration is non-cytotoxic. In order to capture video of this magnetically-induced migration of loaded cells, a novel 3D-printed "cell box" was designed to facilitate our imaging application. Analysis of cell movement velocities clearly demonstrate increased cell velocities toward the magnet. These studies represent the initial step towards our final goal of using nanoparticles to both activate immune cells and to control their trafficking within the diseased brain.

  7. Electrolytic cell stack with molten electrolyte migration control

    DOEpatents

    Kunz, H. Russell; Guthrie, Robin J.; Katz, Murray

    1988-08-02

    An electrolytic cell stack includes inactive electrolyte reservoirs at the upper and lower end portions thereof. The reservoirs are separated from the stack of the complete cells by impermeable, electrically conductive separators. Reservoirs at the negative end are initially low in electrolyte and the reservoirs at the positive end are high in electrolyte fill. During stack operation electrolyte migration from the positive to the negative end will be offset by the inactive reservoir capacity. In combination with the inactive reservoirs, a sealing member of high porosity and low electrolyte retention is employed to limit the electrolyte migration rate.

  8. Project Integration Architecture: Implementation of the CORBA-Served Application Infrastructure

    NASA Technical Reports Server (NTRS)

    Jones, William Henry

    2005-01-01

    The Project Integration Architecture (PIA) has been demonstrated in a single-machine C++ implementation prototype. The architecture is in the process of being migrated to a Common Object Request Broker Architecture (CORBA) implementation. The migration of the Foundation Layer interfaces is fundamentally complete. The implementation of the Application Layer infrastructure for that migration is reported. The Application Layer provides for distributed user identification and authentication, per-user/per-instance access controls, server administration, the formation of mutually-trusting application servers, a server locality protocol, and an ability to search for interface implementations through such trusted server networks.

  9. Electrolytic cell stack with molten electrolyte migration control

    DOEpatents

    Kunz, H.R.; Guthrie, R.J.; Katz, M.

    1987-03-17

    An electrolytic cell stack includes inactive electrolyte reservoirs at the upper and lower end portions thereof. The reservoirs are separated from the stack of the complete cells by impermeable, electrically conductive separators. Reservoirs at the negative end are initially low in electrolyte and the reservoirs at the positive end are high in electrolyte fill. During stack operation electrolyte migration from the positive to the negative end will be offset by the inactive reservoir capacity. In combination with the inactive reservoirs, a sealing member of high porosity and low electrolyte retention is employed to limit the electrolyte migration rate. 5 figs.

  10. “Engineering Substrate Micro- and Nanotopography to Control Cell Function”

    PubMed Central

    Bettinger, Christopher J; Langer, Robert; Borenstein, Jeffrey T

    2010-01-01

    Lead-In The interaction of mammalian cells with nanoscale topography has proven to be an important signaling modality in controlling cell function. Naturally occurring nanotopographic structures within the extracellular matrix present surrounding cells with mechanotransductive cues that influence local migration, cell polarization, and other functions. Synthetically nanofabricated topography can also influence cell morphology, alignment, adhesion, migration, proliferation, and cytoskeleton organization. Here we review the use of in vitro synthetic cell-nanotopography interactions to control cell behavior and influence complex cellular processes including stem cell differentiation and tissue organization. Future challenges and opportunities in cell-nanotopography engineering will also be discussed including the elucidation of mechanisms and applications in tissue engineering. PMID:19492373

  11. Comparative study on the migration of di-2-ethylhexyl phthalate (DEHP) and tri-2-ethylhexyl trimellitate (TOTM) into blood from PVC tubing material of a heart-lung machine.

    PubMed

    Eckert, Elisabeth; Münch, Frank; Göen, Thomas; Purbojo, Ariawan; Müller, Johannes; Cesnjevar, Robert

    2016-02-01

    Medical devices like blood tubing often consist of PVC material that requires the addition of plasticizers. These plasticizers may migrate into the blood leading to an exposure of the patients. In this study the migration behavior of three different blood tubing sets (PVC material with two different plasticizers and silicone as control material) applied on a heart-lung machine standardly used for cardiopulmonary bypass (CPB) in children was studied. We analyzed the total plasticizer migration by analysis of both, the parent compounds as well as their primary degradation products in blood. Additionally, the total mass loss of the tubing over perfusion time was examined. The PVC tubing plasticized with DEHP (di-2-ethylhexyl phthalate) was found to have the highest mass loss over time and showed a high plasticizer migration rate. In comparison, the migration of TOTM (tri-2-ethylhexyl trimellitate) and its primary degradation products was found to be distinctly lower (by a factor of approx. 350). Moreover, it was observed that the storage time of the tubing affects the plasticizer migration rates. In conclusion, the DEHP substitute TOTM promises to be an effective alternative plasticizer for PVC medical devices particularly regarding the decreased migration rate during medical procedures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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.

  13. The relation between global migration and trade networks

    NASA Astrophysics Data System (ADS)

    Sgrignoli, Paolo; Metulini, Rodolfo; Schiavo, Stefano; Riccaboni, Massimo

    2015-01-01

    In this paper we develop a methodology to analyze and compare multiple global networks, focusing our analysis on the relation between human migration and trade. First, we identify the subset of products for which the presence of a community of migrants significantly increases trade intensity, where to assure comparability across networks we apply a hypergeometric filter that lets us identify those links which intensity is significantly higher than expected. Next, proposing a new way to define country neighbors based on the most intense links in the trade network, we use spatial econometrics techniques to measure the effect of migration on international trade, while controlling for network interdependences. Overall, we find that migration significantly boosts trade across countries and we are able to identify product categories for which this effect is particularly strong.

  14. On the post-25 Ma geodynamic evolution of the western Mediterranean

    NASA Astrophysics Data System (ADS)

    Gueguen, Erwan; Doglioni, Carlo; Fernandez, Manuel

    1998-11-01

    During the Neogene and Quaternary western Mediterranean geodynamics were dominated by the `eastward' migration of the Apenninic arc and associated back-arc basins. The migration was controlled by retreat of the Apenninic slab and was associated with `boudinage' of the lithosphere in the back-arc area. Palaeo-reconstruction of the kinematics of the arc suggests about 775 km of migration from the Late Oligocene to present along a transect from the Gulf of Lions to Calabria. A maximum of 135 km of N-S converge occurred between Africa and Europe during the same time span. The western Mediterranean was thus mainly shaped by the migration of the slab related to west-directed subduction. It is hypothesized that minor N-S convergence deformed the arc but was not the cause of its formation.

  15. Characteristics of secondary migration driving force of tight oil and its geologic effect: a case study of Jurassic in Central Sichuan Basin

    NASA Astrophysics Data System (ADS)

    Pang, Zhenglian; Tao, Shizhen; Zhang, Bin; Wu, Songtao; Yang, Jiajing; Chen, Ruiyin

    2017-04-01

    As the rising of its production, tight oil is becoming more and more important. Much research has been done about it. Some articles mention that buoyancy is ineffective for tight oil secondary migration, and abnormal pressure is the alternative. Others believe that overpressure caused hydrocarbon generation is the very force. Though opinions have been given, there are two inadequacies. Firstly, the points are lack of sufficient evidences. Mostly, they are only one or two sentences in the papers. Secondly, geologic effect of the change of driving force hasn't been discussed. In this context, analog experiments, physical property testing, mercury injection, and oil/source comparison were utilized to study 3 issues: origin and value of tight oil secondary migration resistance, values and effectiveness of different potential driving forces, and geologic effect of tight oil secondary migration driving force. Firstly, resistance values of tight reservoir were detected by analog experiments. The value of tight limestone is 15.8MPa, while tight sandstone is 10.7MPa. Tiny size of pores and throats in tight reservoir is the main reason causing huge resistances. Over 90% of pores and throats in tight reservoir are smaller than 1μm. They form huge capillary force when oil migrating through them. Secondly, maximum of buoyancy in study area was confirmed, 0.09MPa, too small to overcome the resistances. Meanwhile, production data suggests that tight oil distribution pattern is not controlled by buoyancy. Conversely, analog experiment proves that overpressure caused by hydrocarbon generation can reach 38MPa, large enough to be the driving force. This idea is also supported by positive correlation between output and source rock formation pressure. Thirdly, is the geologic effect of tight oil secondary migration resistance and driving force. Tight oil can migrate only as non-darcy flow due to huge resistances according to percolation experiments. It needs to overcome the starting pressure gradient. As a result, it migrated a much shorter distance compared with conventional petroleum, coincident with the result of oil/source comparison. The effect of driving force is that boundary of tight oil profitable area is controlled by source rock. This boundary in the study area is the line of hydrocarbon generating strength of 40×104t/km2. By confirming controlling factors of tight oil formation and their evaluation index, it is of great significance during tight oil exploration.

  16. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia.

    PubMed

    de Rooij, Martin F M; Kuil, Annemieke; Geest, Christian R; Eldering, Eric; Chang, Betty Y; Buggy, Joseph J; Pals, Steven T; Spaargaren, Marcel

    2012-03-15

    Small-molecule drugs that target the B-cell antigen receptor (BCR) signalosome show clinical efficacy in the treatment of B-cell non-Hodgkin lymphoma. These agents, including the Bruton tyrosine kinase (BTK) inhibitor PCI-32765, display an unexpected response in patients with chronic lymphocytic leukemia (CLL): a rapid and sustained reduction of lymphadenopathy accompanied by transient lymphocytosis, which is reversible upon temporary drug deprivation. We hypothesized that this clinical response reflects impaired integrin-mediated adhesion and/or migration. Here, we show that PCI-32765 strongly inhibits BCR-controlled signaling and integrin α(4)β(1)-mediated adhesion to fibronectin and VCAM-1 of lymphoma cell lines and primary CLL cells. Furthermore, PCI-32765 also inhibits CXCL12-, CXCL13-, and CCL19-induced signaling, adhesion, and migration of primary CLL cells. Our data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, which results in clinically evident CLL regression.

  17. The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

    PubMed Central

    Barriga, Elias H.; Maxwell, Patrick H.

    2013-01-01

    One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells. PMID:23712262

  18. 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.

  19. Duplicate Federal Payments for Dual Enrollees in Medicare Advantage Plans and the Veterans Affairs Health Care System

    PubMed Central

    Trivedi, Amal N.; Grebla, Regina C.; Jiang, Lan; Yoon, Jean; Mor, Vincent; Kizer, Kenneth W.

    2013-01-01

    Context Some veterans are eligible to enroll simultaneously in a Medicare Advantage (MA) plan and the Veterans Affairs health care system (VA). This scenario produces the potential for redundant federal spending because MA plans would receive payments to insure veterans who receive care from the VA, another taxpayer-funded health plan. Objective To quantify the prevalence of dual enrollment in VA and MA, the concurrent use of health services in each setting, and the estimated costs of VA care provided to MA enrollees. Design Retrospective analysis of 1 245 657 veterans simultaneously enrolled in the VA and an MA plan between 2004–2009. Main Outcome Measures Use of health services and inflation-adjusted estimated VA health care costs. Results Among individuals who were eligible to enroll in the VA and in an MA plan, the number of persons dually enrolled increased from 485 651 in 2004 to 924 792 in 2009. In 2009, 8.3% of the MA population was enrolled in the VA and 5.0% of MA beneficiaries were VA users. The estimated VA health care costs for MA enrollees totaled $13.0 billion over 6 years, increasing from $1.3 billion in 2004 to $3.2 billion in 2009. Among dual enrollees, 10% exclusively used the VA for outpatient and acute inpatient services, 35% exclusively used the MA plan, 50% used both the VA and MA, and 4% received no services during the calendar year. The VA financed 44% of all outpatient visits (n=21 353 841), 15% of all acute medical and surgical admissions (n=177 663), and 18% of all acute medical and surgical inpatient days (n=1 106 284) for this dually enrolled population. In 2009, the VA billed private insurers $52.3 million to reimburse care provided to MA enrollees and collected $9.4 million (18% of the billed amount; 0.3% of the total cost of care). Conclusions The federal government spends a substantial and increasing amount of potentially duplicative funds in 2 separate managed care programs for the care of same individuals. PMID:22735360

  20. Biomarkers Associated with Death After Initiating Treatment for Tuberculosis and HIV in Patients with Very Low CD4 Cells

    PubMed Central

    Sattler, Fred R.; Chelliah, Daniel; Wu, Xingye; Sanchez, Alejandro; Kendall, Michelle A.; Hogg, Evelyn; Lagat, David; Lalloo, Umesh; Veloso, Valdilea; Havlir, Diane V.; Landay, Alan

    2018-01-01

    Background The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3. The case-cohort sample consisted of 51 randomly selected participants, whose stored plasma was tested for C-reactive protein, cytokines, chemokines, and nutritional markers. Cox proportional hazards models were used to assess the association of nutritional, inflammatory, and immunomodulatory markers for survival. Results The case-cohort sample was similar to the 282 participants within the parent cohort with CD4 <50 cells/mm3. In the case cohort, 7 (14%) had BMI < 16.5 (kg/m2) and 17 (33%) had BMI 16.5-18.5(kg/m2). Risk of death was increased per 1 IQR width higher of log10 transformed level of C-reactive protein (adjusted hazard ratio (aHR) = 3.42 [95% CI = 1.33-8.80], P = 0.011), interferon gamma (aHR = 2.46 [CI = 1.02-5.90], P = 0.044), MCP-3 (3.67 [CI = 1.08-12.42], P = 0.037), and with IL-15 (aHR = 2.75 [CI = 1.08-6.98], P = 0.033) and IL-17 (aHR = 3.99 [CI = −1.06-15.07], P = 0.041). BMI, albumin, hemoglobin, and leptin levels were not associated with risk of death. Conclusions Unlike patients only infected with M. tuberculosis for whom malnutrition and low BMI increase the risk of death, this relationship was not evident in our dually infected patients. Risk of death was associated with significant increases in markers of global inflammation along with soluble biomarkers of innate and adaptive immunity. PMID:29770360

  1. Residency Program Directors' Interview Methods and Satisfaction With Resident Selection Across Multiple Specialties.

    PubMed

    VanOrder, Tonya; Robbins, Wayne; Zemper, Eric

    2017-04-01

    Competition for postdoctoral training positions is at an all-time high, and residency program directors continue to have little direction when it comes to structuring an effective interview process. To examine whether a relationship existed between interview methods used and program director satisfaction with resident selection decisions and whether programs that used methods designed to assess candidate personal characteristics were more satisfied with their decisions. Residency directors from the Statewide Campus System at the Michigan State University College of Osteopathic Medicine were invited to complete a 20-item survey regarding their recent interview methods and proportion of resident selections later regretted. Data analyses examined relationships between interview methods used, frequency of personal characteristics evaluated, and subsequent satisfaction with selected residents. Of the 186 program director surveys distributed, 83 (44.6%) were returned, representing 11 clinical specialty areas. In total, 69 responses (83.1%) were from programs accredited by the American Osteopathic Association only, and 14 (16.9%) were from programs accredited dually by the American Osteopathic Association and Accreditation Council for Graduate Medical Education. The most frequent interview method reported was faculty or peer resident interview. No statistically significant correlational relationships were found between type of interview methods used and subsequent satisfaction with selected residents, either within or across clinical specialties. Although program directors rated ethical behavior/honesty as the most highly prioritized characteristic in residents, 27 (32.5%) reported using a specific interview method to assess this trait. Program directors reported later regrets concerning nearly 1 of every 12 resident selection decisions. The perceived success of an osteopathic residency program's interview process does not appear to be related to methods used and is not distinctively different from that of programs dually accredited. The findings suggest that it may not be realistic to aim for standardization of a common set of best interview methods or ideal personal characteristics for all programs. Each residency program's optimal interview process is likely unique, more dependent on analyzing why some resident selections are regretted and developing an interview process designed to assess for specific desirable and unwanted characteristics.

  2. Method to study cell migration under uniaxial compression

    PubMed Central

    Srivastava, Nishit; Kay, Robert R.; Kabla, Alexandre J.

    2017-01-01

    The chemical, physical, and mechanical properties of the extracellular environment have a strong effect on cell migration. Aspects such as pore size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including by pseudopods or blebbing. How a cell perceives its environment and how such a cue triggers a change in behavior are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the matrix. Live imaging during compression provides accurate information about the cell's morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration from primarily pseudopodial to bleb driven in <30 s. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach with which to systematically study mechanotransduction in confined environments. PMID:28122819

  3. p70S6K1 (S6K1)-mediated Phosphorylation Regulates Phosphatidylinositol 4-Phosphate 5-Kinase Type I γ Degradation and Cell Invasion.

    PubMed

    Jafari, Naser; Zheng, Qiaodan; Li, Liqing; Li, Wei; Qi, Lei; Xiao, Jianyong; Gao, Tianyan; Huang, Cai

    2016-12-02

    Phosphatidylinositol 4-phosphate 5-kinase type I γ (PIPKIγ90) ubiquitination and subsequent degradation regulate focal adhesion assembly, cell migration, and invasion. However, it is unknown how upstream signals control PIPKIγ90 ubiquitination or degradation. Here we show that p70S6K1 (S6K1), a downstream target of mechanistic target of rapamycin (mTOR), phosphorylates PIPKIγ90 at Thr-553 and Ser-555 and that S6K1-mediated PIPKIγ90 phosphorylation is essential for cell migration and invasion. Moreover, PIPKIγ90 phosphorylation is required for the development of focal adhesions and invadopodia, key machineries for cell migration and invasion. Surprisingly, substitution of Thr-553 and Ser-555 with Ala promoted PIPKIγ90 ubiquitination but enhanced the stability of PIPKIγ90, and depletion of S6K1 also enhanced the stability of PIPKIγ90, indicating that PIPKIγ90 ubiquitination alone is insufficient for its degradation. These data suggest that S6K1-mediated PIPKIγ90 phosphorylation regulates cell migration and invasion by controlling PIPKIγ90 degradation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

    PubMed

    Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

    2015-06-22

    Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Reversible control of magnetism in La 0.67Sr 0.33MnO 3 through chemically-induced oxygen migration

    DOE PAGES

    Grutter, A. J.; Gilbert, D. A.; Alaan, U. S.; ...

    2016-02-22

    We demonstrate reversible control of magnetization and anisotropy in La 0.67Sr 0.33MnO 3 films through interfacial oxygen migration. Gd metal capping layers deposited onto La 0.67Sr 0.33MnO 3 leach oxygen from the film through a solid-state redox reaction to form porous Gd 2O 3. X-ray absorption and polarized neutron reflectometry measurements show Mn valence alterations consistent with high oxygen vacancy concentrations, resulting in suppressed magnetization and increased coercive fields. Effects of the oxygen migration are observed both at the interface and also throughout the majority of a 40 nm thick film, suggesting extensive diffusion of oxygen vacancies. After Gd-capped Lamore » 0.67Sr 0.33MnO 3 is exposed to atmospheric oxygen for a prolonged period of time, oxygen diffuses through the Gd 2O 3 layer and the magnetization of the La 0.67Sr 0.33MnO 3 returns to the uncapped value. In conclusion, these findings showcase perovskite heterostructures as ideal candidates for developing functional interfaces through chemically-induced oxygen migration.« less

  6. Influence of gravity and light on the developmental polarity of Ceratopteris richardii fern spores

    NASA Technical Reports Server (NTRS)

    Edwards, E. S.; Roux, S. J.

    1998-01-01

    The polarity of germinating single-celled spores of the fern Ceratopteris richardii Brogn. is influenced by gravity during a time period prior to the first cellular division designated a "polarity-determination window". After this window closes, control of polarity is seen in the downward (with respect to gravity) migration of the nucleus along the proximal face of the spore and the subsequent downward growth of the primary rhizoid. When spores are germinated on a clinostat the direction of nuclear migration and subsequent primary rhizoid growth is random. However, in each case the direction of nuclear migration predicts the direction of rhizoid elongation. Although it is the most obvious movement, the downward migration is not the first movement of the nucleus. During the polarity-determination window, the nucleus moves randomly within a region centered behind the trilete marking. While the polarity of many fern spores has been reported to be controlled by light, spores of C. richardii are the first documented to have their polarity influenced by gravity. Directional white light also affects the polarity of these spores, but this influence is slight and is secondary to that of gravity.

  7. Multimodal chemo-magnetic control of self-propelling microbots

    NASA Astrophysics Data System (ADS)

    Singh, Amit Kumar; Dey, Krishna Kanti; Chattopadhyay, Arun; Mandal, Tapas Kumar; Bandyopadhyay, Dipankar

    2014-01-01

    We report a controlled migration of an iron nanoparticle (FeNP) coated polymer micromotor. The otherwise diffusive motion of the motor was meticulously directed through an in situ pH-gradient and an external magnetic field. The self-propulsion owing to the asymmetric catalytic decomposition of peroxide fuel was directed through a pH gradient imposed across the motor-surface, while the magnetic field induced an external control on the movement and the speed of the motor. Interestingly, the sole influence of the pH gradient could move the motor as high as ~25 body lengths per second, which was further magnified by the external assistance from the magnetic field. Applying a magnetic field against the pH directed motion helped in the quantitative experimental estimation of the force-field required to arrest the chemotactic migration. The influence of the coupled internal and external fields could halt, steer or reverse the direction the motor inside a microchannel, rotate the motor around a target, and deliver the motor to a cluster of cells. This study showcases a multimodal chemical-magnetic field regulated migration of micro-machines for sensing, transport, and delivery inside a fluidic environment.We report a controlled migration of an iron nanoparticle (FeNP) coated polymer micromotor. The otherwise diffusive motion of the motor was meticulously directed through an in situ pH-gradient and an external magnetic field. The self-propulsion owing to the asymmetric catalytic decomposition of peroxide fuel was directed through a pH gradient imposed across the motor-surface, while the magnetic field induced an external control on the movement and the speed of the motor. Interestingly, the sole influence of the pH gradient could move the motor as high as ~25 body lengths per second, which was further magnified by the external assistance from the magnetic field. Applying a magnetic field against the pH directed motion helped in the quantitative experimental estimation of the force-field required to arrest the chemotactic migration. The influence of the coupled internal and external fields could halt, steer or reverse the direction the motor inside a microchannel, rotate the motor around a target, and deliver the motor to a cluster of cells. This study showcases a multimodal chemical-magnetic field regulated migration of micro-machines for sensing, transport, and delivery inside a fluidic environment. Electronic supplementary information (ESI) available: Scanning electron microscopy, transmission electron microscopy, X-ray diffraction pattern, vibrating sample magnetometry (VSM) hysteresis loop of freshly prepared FeNP coated micromotor and movies of micromotor motion. See DOI: 10.1039/c3nr05294j

  8. Effect of several variables in the polymer toys additive migration to saliva.

    PubMed

    Noguerol-Cal, R; López-Vilariño, J M; González-Rodríguez, M V; Barral-Losada, L

    2011-09-30

    Capacity to migrate of a representative group of polymeric additives, dyes, antioxidants, hindered amine light stabilizers (HALS) or antistatics, from plastic toys to saliva was analyzed to protect children in their habits of sucking and biting. Most of target additives appear no-regulated in toys normative but adverse effects on human health of some of them have been demonstrated and their presence in others commercial articles normative has been included. In order to offer an effective and easy tool to perform these controls, migration tests by dynamic and static contact, followed by a preconcentration step by liquid-liquid extraction (LLE) and ultra performance liquid chromatographic analysis with ultraviolet-visible and evaporative light scattering detections (UPLC-UV/Vis-ELSD) have been optimized to evaluate the migrated amounts of the additives in saliva simulant. The detection limits of the migration methodologies were ranged from 8.68 × 10(-2) to 1.30 × 10(-3)mg migrated (L simulant)(-1). Influence of several variables on this mass transport, as time, temperature and friction, was also analyzed to achieve the most aggressive methodology to protect consumers. Migration of several studied additives, whose presence has been demonstrated in several purchased commercial toys, has been observed. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Development of a Single-Cell Migration and Extravasation Platform through Selective Surface Modification.

    PubMed

    Roberts, Steven A; Waziri, Allen E; Agrawal, Nitin

    2016-03-01

    Cell migration through three-dimensional (3D) tissue spaces is integral to many biological and pathological processes, including metastasis. Circulating tumor cells (CTCs) are phenotypically heterogeneous, and in vitro analysis of their extravasation behavior is often impeded by the inability to establish complex tissue-like extracellular matrix (ECM) environments and chemotactic gradients within microfluidic devices. We have developed a novel microfluidic strategy to manipulate surface properties of enclosed microchannels and create 3D ECM structures for real-time observation of individual migrating cells. The wettability of selective interconnected channels is controlled by a plasma pulse, enabling the incorporation of ECM exclusively within the transmigration regions. We applied this approach to collectively analyze CTC-endothelial adhesion, trans-endothelial migration, and subsequent motility of breast cancer cells (MDA-MB-231) through a 3D ECM under artificial gradients of SDF-1α. We observed migration velocities ranging from 5.12 to 12.8 μm/h, which closely correspond to single-cell migration in collagen blocks, but are significantly faster than the migration of cell aggregates. The compartmentalized microchannels separated by the porous ECM makes this in vitro assay versatile and suitable for a variety of applications such as inflammation studies, drug screening, and coculture interactions.

  10. Past matrix stiffness primes epithelial cells and regulates their future collective migration through a mechanical memory.

    PubMed

    Nasrollahi, Samila; Walter, Christopher; Loza, Andrew J; Schimizzi, Gregory V; Longmore, Gregory D; Pathak, Amit

    2017-11-01

    During morphogenesis and cancer metastasis, grouped cells migrate through tissues of dissimilar stiffness. Although the influence of matrix stiffness on cellular mechanosensitivity and motility are well-recognized, it remains unknown whether these matrix-dependent cellular features persist after cells move to a new microenvironment. Here, we interrogate whether priming of epithelial cells by a given matrix stiffness influences their future collective migration on a different matrix - a property we refer to as the 'mechanical memory' of migratory cells. To prime cells on a defined matrix and track their collective migration onto an adjoining secondary matrix of dissimilar stiffness, we develop a modular polyacrylamide substrate through step-by-step polymerization of different PA compositions. We report that epithelial cells primed on a stiff matrix migrate faster, display higher actomyosin expression, form larger focal adhesions, and retain nuclear YAP even after arriving onto a soft secondary matrix, as compared to their control behavior on a homogeneously soft matrix. Priming on a soft ECM causes a reverse effect. The depletion of YAP dramatically reduces this memory-dependent migration. Our results present a previously unidentified regulation of mechanosensitive collective cell migration by past matrix stiffness, in which mechanical memory depends on YAP activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Cohort profile: internal migration in sub-Saharan Africa—The Migration and Health in Malawi (MHM) study

    PubMed Central

    Anglewicz, Philip; VanLandingham, Mark; Manda-Taylor, Lucinda; Kohler, Hans-Peter

    2017-01-01

    Purpose The Migration and Health in Malawi (MHM) study focuses on a key challenge in migration research: although it has long been established that migration and health are closely linked, identifying the effect of migration on various health outcomes is complicated by methodological challenges. The MHM study uses a longitudinal panel premigration and postmigration study design (with a non-migrant comparison group) to measure and/or control for important characteristics that affect both migration and health outcomes. Participants Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007 (55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non-migrant reference group in 2013. The total interviewed sample size for the MHM in both waves is 1809. These data include extensive information on lifetime migration, socioeconomic and demographic characteristics, sexual behaviours, marriage, household/family structure, social networks and social capital, HIV/AIDS biomarkers and other dimensions of health. Findings to date Our result for the relationship between migration and health differs by health measure and analytic approach. Migrants in Malawi have a significantly higher HIV prevalence than non-migrants, which is primarily due to the selection of HIV-positive individuals into migration. We find evidence for health selection; physically healthier men and women are more likely to move, partly because migration selects younger individuals. However, we do not find differences in physical or mental health between migrants and non-migrants after moving. Future plans We are preparing a third round of data collection for these (and any new) migrants, which will take place in 2018. This cohort will be used to examine the effect of migration on various health measures and behaviours, including general mental and physical health, smoking and alcohol use, access to and use of health services and use of antiretroviral therapy. PMID:28515195

  13. A Low-Level Carbon Dioxide Laser Promotes Fibroblast Proliferation and Migration through Activation of Akt, ERK, and JNK

    PubMed Central

    Shingyochi, Yoshiaki; Kanazawa, Shigeyuki; Tajima, Satoshi; Tanaka, Rica; Mizuno, Hiroshi; Tobita, Morikuni

    2017-01-01

    Background Low-level laser therapy (LLLT) with various types of lasers promotes fibroblast proliferation and migration during the process of wound healing. Although LLLT with a carbon dioxide (CO2) laser was also reported to promote wound healing, the underlying mechanisms at the cellular level have not been previously described. Herein, we investigated the effect of LLLT with a CO2 laser on fibroblast proliferation and migration. Materials and Methods Cultured human dermal fibroblasts were prepared. MTS and cell migration assays were performed with fibroblasts after LLLT with a CO2 laser at various doses (0.1, 0.5, 1.0, 2.0, or 5.0 J/cm2) to observe the effects of LLLT with a CO2 laser on the proliferation and migration of fibroblasts. The non-irradiated group served as the control. Moreover, western blot analysis was performed using fibroblasts after LLLT with a CO2 laser to analyze changes in the activities of Akt, extracellular signal-regulated kinase (ERK), and Jun N-terminal kinase (JNK), which are signaling molecules associated with cell proliferation and migration. Finally, the MTS assay, a cell migration assay, and western blot analysis were performed using fibroblasts treated with inhibitors of Akt, ERK, or JNK before LLLT with a CO2 laser. Results In MTS and cell migration assays, fibroblast proliferation and migration were promoted after LLLT with a CO2 laser at 1.0 J/cm2. Western blot analysis revealed that Akt, ERK, and JNK activities were promoted in fibroblasts after LLLT with a CO2 laser at 1.0 J/cm2. Moreover, inhibition of Akt, ERK, or JNK significantly blocked fibroblast proliferation and migration. Conclusions These findings suggested that LLLT with a CO2 laser would accelerate wound healing by promoting the proliferation and migration of fibroblasts. Activation of Akt, ERK, and JNK was essential for CO2 laser-induced proliferation and migration of fibroblasts. PMID:28045948

  14. Health, Human Capital, and African American Migration Before 1910

    PubMed Central

    Logan, Trevon D.

    2009-01-01

    Using both IPUMS and the Colored Troops Sample of the Civil War Union Army Data, I estimate the effects of literacy and health on the migration propensities of African Americans from 1870 to 1910. I find that literacy and health shocks were strong predictors of migration and the stock of health was not. There were differential selection propensities based on slave status—former slaves were less likely to migrate given a specific health shock than free blacks. Counterfactuals suggest that as much as 35 percent of the difference in the mobility patterns of former slaves and free blacks is explained by differences in their human capital, and more than 20 percent of that difference is due to health alone. Overall, the selection effect of literacy on migration is reduced by one-tenth to one-third once health is controlled for. The low levels of human capital accumulation and rates of mobility for African Americans after the Civil War are partly explained by the poor health status of slaves and their immediate descendants. PMID:20161107

  15. PDK1-mediated activation of MRCKα regulates directional cell migration and lamellipodia retraction

    PubMed Central

    Gagliardi, Paolo Armando; di Blasio, Laura; Puliafito, Alberto; Seano, Giorgio; Sessa, Roberto; Chianale, Federica; Leung, Thomas; Bussolino, Federico

    2014-01-01

    Directional cell migration is of paramount importance in both physiological and pathological processes, such as development, wound healing, immune response, and cancer invasion. Here, we report that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and invasion by binding and activating myotonic dystrophy kinase–related CDC42-binding kinase α (MRCKα). We show that the effect of PDK1 on cell migration does not involve its kinase activity but instead relies on its ability to bind membrane phosphatidylinositol (3,4,5)-trisphosphate. Upon epidermal growth factor (EGF) stimulation, PDK1 and MRCKα colocalize at the cell membrane in lamellipodia. We demonstrate that PDK1 positively modulates MRCKα activity and drives its localization within lamellipodia. Likewise, the retraction phase of lamellipodia is controlled by PDK1 through an MRCKα-dependent mechanism. In summary, we discovered a functional pathway involving PDK1-mediated activation of MRCKα, which links EGF signaling to myosin contraction and directional migration. PMID:25092657

  16. Structural changes and triacetin migration of starch acetate film contacting with distilled water as food simulant.

    PubMed

    Zhu, Jie; Li, Xiaoxi; Huang, Chen; Chen, Ling; Li, Lin

    2014-04-15

    This work studied the structural changes and the migration of triacetin plasticizer in starch acetate films in the presence of distilled water as food simulant. Fourier-transform infrared spectroscopy result showed that the macromolecular interaction was enhanced to form compact aggregation of amorphous chains. The characterization of aggregation structures via wide and small angle X-ray scattering techniques indicated that the orderly microregion was compressed and the crystallites inside were "squeezed" to form interference and further aggregation. The compact aggregation structures restricted the mobility of macromolecules, triacetin and water molecules. The overall kinetic and the diffusion model analysis manifested that Fick's second law was the predominant mechanism for the short-term migration of triacetin. The increasing relaxation within film matrix caused the subsequent migration to deviate from Fick's law. The safe and reasonable application of the starch-based materials with restrained plasticizer migration could be accomplished by controlling the molecular interaction and aggregation structures. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  17. Cell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells

    PubMed Central

    Chabaud, Mélanie; Heuzé, Mélina L.; Bretou, Marine; Vargas, Pablo; Maiuri, Paolo; Solanes, Paola; Maurin, Mathieu; Terriac, Emmanuel; Le Berre, Maël; Lankar, Danielle; Piolot, Tristan; Adelstein, Robert S.; Zhang, Yingfan; Sixt, Michael; Jacobelli, Jordan; Bénichou, Olivier; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana-Maria

    2015-01-01

    The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. PMID:26109323

  18. Processes of Internal and International Migration from Chitwan, Nepal.

    PubMed

    Bohra, Pratikshya; Massey, Douglas S

    2009-01-01

    In this study we examine which factors predict internal and international migration from Chitwan, a flat valley located in the South-Central region of Nepal, seeking to measure the effect of theoretically specified variables such as human capital, social capital, physical capital, and neighborhood socioeconomic conditions while controlling for demographic variables. We use data from the Chitwan Valley Family Study (CVFS) to estimate a series of discrete time event history models of first and repeat migration to three competing destinations: other locations within Chitwan, other districts within Nepal, and places outside of Nepal. Results support hypotheses derived from neoclassical economics, the theory of new economics of migration, social capital theory, and cumulative causation theory. Our results underscore the need for a synthetic theoretical model that incorporates factors operating at the individual, household, and community levels. The use of multiple explanatory models yields a clearer picture of the forces driving internal and international migration from rural districts in developing nations such as Nepal.

  19. Processes of Internal and International Migration from Chitwan, Nepal

    PubMed Central

    Bohra, Pratikshya; Massey, Douglas S.

    2011-01-01

    In this study we examine which factors predict internal and international migration from Chitwan, a flat valley located in the South-Central region of Nepal, seeking to measure the effect of theoretically specified variables such as human capital, social capital, physical capital, and neighborhood socioeconomic conditions while controlling for demographic variables. We use data from the Chitwan Valley Family Study (CVFS) to estimate a series of discrete time event history models of first and repeat migration to three competing destinations: other locations within Chitwan, other districts within Nepal, and places outside of Nepal. Results support hypotheses derived from neoclassical economics, the theory of new economics of migration, social capital theory, and cumulative causation theory. Our results underscore the need for a synthetic theoretical model that incorporates factors operating at the individual, household, and community levels. The use of multiple explanatory models yields a clearer picture of the forces driving internal and international migration from rural districts in developing nations such as Nepal. PMID:21423821

  20. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

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

    Wang, Jiying; Rao, Qing, E-mail: raoqing@gmail.com; Wang, Min

    2009-09-04

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation,more » and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.« less

  1. Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana

    PubMed Central

    Kawashima, Tomokazu; Maruyama, Daisuke; Shagirov, Murat; Li, Jing; Hamamura, Yuki; Yelagandula, Ramesh; Toyama, Yusuke; Berger, Frédéric

    2014-01-01

    In animals, microtubules and centrosomes direct the migration of gamete pronuclei for fertilization. By contrast, flowering plants have lost essential components of the centrosome, raising the question of how flowering plants control gamete nuclei migration during fertilization. Here, we use Arabidopsis thaliana to document a novel mechanism that regulates F-actin dynamics in the female gametes and is essential for fertilization. Live imaging shows that F-actin structures assist the male nucleus during its migration towards the female nucleus. We identify a female gamete-specific Rho-GTPase that regulates F-actin dynamics and further show that actin–myosin interactions are also involved in male gamete nucleus migration. Genetic analyses and imaging indicate that microtubules are dispensable for migration and fusion of male and female gamete nuclei. The innovation of a novel actin-based mechanism of fertilization during plant evolution might account for the complete loss of the centrosome in flowering plants. DOI: http://dx.doi.org/10.7554/eLife.04501.001 PMID:25303363

  2. Expression of macrophage migration inhibitory factor in footpad skin lesions with diabetic neuropathy.

    PubMed

    Up Noh, Sun; Lee, Won-Young; Kim, Won-Serk; Lee, Yong-Taek; Jae Yoon, Kyung

    2018-01-01

    Background Diabetic neuropathy originating in distal lower extremities is associated with pain early in the disease course, overwhelming in the feet. However, the pathogenesis of diabetic neuropathy remains unclear. Macrophage migration inhibitory factor has been implicated in the onset of neuropathic pain and the development of diabetes. Objective of this study was to observe pain syndromes elicited in the footpad of diabetic neuropathy rat model and to assess the contributory role of migration inhibitory factor in the pathogenesis of diabetic neuropathy. Methods Diabetic neuropathy was made in Sprague Dawley rats by streptozotocin. Pain threshold was evaluated using von Frey monofilaments for 24 weeks. On comparable experiment time after streptozotocin injection, all footpads were prepared for following procedures; glutathione assay, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining, immunohistochemistry staining, real-time reverse transcription polymerase chain reaction, and Western blot. Additionally, human HaCaT skin keratinocytes were treated with methylglyoxal, transfected with migration inhibitory factor/control small interfering RNA, and prepared for real-time reverse transcription polymerase chain reaction and Western blot. Results As compared to sham group, pain threshold was significantly reduced in diabetic neuropathy group, and glutathione was decreased in footpad skin, simultaneously, cell death was increased. Over-expression of migration inhibitory factor, accompanied by low expression of glyoxalase-I and intraepidermal nerve fibers, was shown on the footpad skin lesions of diabetic neuropathy. But, there was no significance in expression of neurotransmitters and inflammatory mediators such as transient receptor potential vanilloid 1, mas-related G protein coupled receptor D, nuclear factor kappa B, tumor necrosis factor-alpha, and interleukin-6 between diabetic neuropathy group and sham group. Intriguingly, small interfering RNA-transfected knockdown of the migration inhibitory factor gene in methylglyoxal-treated skin keratinocytes increased expression of glyoxalase-I and intraepidermal nerve fibers in comparison with control small interfering RNA-transfected cells, which was decreased by induction of methylglyoxal. Conclusions Our findings suggest that migration inhibitory factor can aggravate diabetic neuropathy by suppressing glyoxalase-I and intraepidermal nerve fibers on the footpad skin lesions and provoke pain. Taken together, migration inhibitory factor might offer a pharmacological approach to alleviate pain syndromes in diabetic neuropathy.

  3. Regulation of glycogen synthase kinase-3 by thymosin beta-4 is associated with gastric cancer cell migration.

    PubMed

    Ryu, Yun-Kyoung; Lee, Yu-Sun; Lee, Geun-Hee; Song, Kyu-Sang; Kim, Yong-Sung; Moon, Eun-Yi

    2012-11-01

    Thymosin beta-4 (Tβ4), actin-sequestering protein, plays important roles in many cellular functions including cancer cell migrations. Glycogen synthase kinase (GSK) in Wnt signaling pathway is a key molecule to control intercellular interaction. Here, we investigated whether GSK-3 activity is regulated by Tβ4 and it is associated with Tβ4-mediated migration in gastric cancer cells. Various expression level of Tβ4 was observed in human gastric tumor tissues. Migration in gastric cancer cells, SNU638 and SNU668, was dependent on a relative expression level of Tβ4. Cell migration was higher in SNU668 with a higher expression level of Tβ4 than that in SNU638 with a lower Tβ4. Although the level of phosphorylated(p)-GSK-3α (inactive), β-catenin, E-cadherin and E-cadherin:β-catenin complex was relatively higher, p-GSK-3β (inactive) was lower in SNU638 compared to those in SNU668 cells. LiCl, GSK-3α/β inhibitor, reduced lung metastasis of B16F10 mouse melanoma cells and SNU668 cell migration. Small interference (si)RNA of GSK-3α increased SNU638 cell migration in accordance with the reduction of E-cadherin:β-catenin complex formation through a decrease in β-catenin and E-cadherin. Expression level of GSK-3α/β, β-catenin and E-cadherin in SNU668 and SNU638 was reversed by Tβ4-siRNA and by the treatment with acetylated-serine-aspartic acid-lysine-proline (SDKP) tetrapeptide of Tβ4, respectively. E-cadherin expression in SNU638 cells was decreased by β-catenin-siRNA. PD98059, MEK inhibitor, or U0126, ERK inhibitor, reduced SNU668 cell migration accompanying an increase in p-GSK-3α, β-catenin and E-cadherin. Taken together, data indicated that the expression of GSK-3α, β-catenin and E-cadherin could be negatively regulated by Tβ4-induced ERK phosphorylation. It suggests that Tβ4 could be a novel regulator to control Wnt signaling pathways. Copyright © 2012 UICC.

  4. Lovastatin inhibits gap junctional communication in cultured aortic smooth muscle cells.

    PubMed

    Shen, Jing; Wang, Li-Hong; Zheng, Liang-Rong; Zhu, Jian-Hua; Hu, Shen-Jiang

    2010-09-01

    Gap junctions, which serve as intercellular channels that allow the passage of ions and other small molecules between neighboring cells, play an important role in vital functions, including the regulation of cell growth, differentiation, and development. Statins, the 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase inhibitors, have been shown to inhibit the migration and proliferation of smooth muscle cells (SMCs) leading to an antiproliferative effect. Recent studies have shown that statins can reduce gap junction protein connexin43 (Cx43) expression both in vivo and in vitro. However, little work has been done on the effects of statins on gap junctional intercellular communication (GJIC). We hypothesized in this study that lovastatin inhibits vascular smooth muscle cells (VSMCs) migration through the inhibition of the GJIC. Rat aortic SMCs (RASMCs) were exposed to lovastatin. Vascular smooth muscle cells migration was then assessed with a Transwell migration assay. Gap junctional intercellular communication was determined by using fluorescence recovery after photobleaching (FRAP) analysis, which was performed with a laser-scanning confocal microscope. The migration of the cultured RASMCs were detected by Transwell system. Cell migration was dose-dependently inhibited with lovastatin. Compared with that in the control (110 ± 26), the number of migrated SMCs was significantly reduced to 72 ± 24 (P < .05), 62 ± 18 (P < .01), and 58 ± 19 (P < .01) at the concentration of 0.4, 2, and 10 umol/L, per field. The rate of fluorescence recovery (R) at 5 minutes after photobleaching was adopted as the functional index of GJIC. The R- value of cells exposed to lovastatin 10 umol/L for 48 hours was 24.38% ± 4.84%, whereas the cells in the control group had an R- value of 36.11% ± 10.53%, demonstrating that the GJIC of RASMCs was significantly inhibited by lovastatin (P < .01). Smaller concentrations of lovastatin 0.08 umol/L did not change gap junction coupling (P > .05). These results suggest that lovastatin inhibits migration in a dose-dependent manner by attenuating JIC. Suppression of gap junction function could add another explanation of statin-induced antiproliferative effect.

  5. The European system for the control of the safety of food-contact materials needs restructuring: a review and outlook for discussion.

    PubMed

    Grob, Koni

    2017-09-01

    The present European system to assure the safety of migrates from food-contact materials (FCMs) needs improvement. It is proposed to implement better the self-control by the producers through improved official control and more attractive listing of approved substances and materials (the latter being subject of another discussion paper). The initial concept of a positive list for the substances used, a limit for the overall migration and regulation of compliance testing was recognised as insufficient long ago, as it does not properly cover reaction products (including oligomers) and impurities. It also turned out to be unrealistic to cover all 17 types of FCMs owing to lack of resources by the authorities. Therefore, European Union legislation shifted the focus to the compliance work carried out by the business operators (in-house documentation and declaration of compliance). However, this approach has not been properly implemented. This is partly due to lack or unsuccessful control by authorities. A suitable structure of this control still needs to be built. It is proposed that specialised document-collection centres working with dedicated tools harmonised throughout Europe be created. Further, since most migrating substances are not listed, the toxicological evaluation reported by industry must be checked by risk-assessment authorities. Finally, effective and harmonised measures are needed to react in case of non-compliance. The currently large gap between the legal requirements and reality must be bridged by introducing flexibility: authorised work plans by industry are proposed. It is also proposed to encourage certified private institutes to approve compliance work, driven by the attractive listing of approved materials and exploiting market forces. In the long run, the focus of the authorities might change from evaluating the substances used and regulating migration testing to the evaluation of the compliance work performed by industry, which means moving from legislation supporting industry towards checking self-control.

  6. PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration

    PubMed Central

    Moens, Cecilia B.

    2016-01-01

    The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP “core components” (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. PMID:26990447

  7. Eukaryotic Translation Initiation Factor 5A (EIF5A) Regulates Pancreatic Cancer Metastasis by Modulating RhoA and Rho-associated Kinase (ROCK) Protein Expression Levels.

    PubMed

    Fujimura, Ken; Choi, Sunkyu; Wyse, Meghan; Strnadel, Jan; Wright, Tracy; Klemke, Richard

    2015-12-11

    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with an overall survival rate of less than 5%. The poor patient outcome in PDAC is largely due to the high prevalence of systemic metastasis at the time of diagnosis and lack of effective therapeutics that target disseminated cells. The fact that the underlying mechanisms driving PDAC cell migration and dissemination are poorly understood have hindered drug development and compounded the lack of clinical success in this disease. Recent evidence indicates that mutational activation of K-Ras up-regulates eIF5A, a component of the cellular translational machinery that is critical for PDAC progression. However, the role of eIF5A in PDAC cell migration and metastasis has not been investigated. We report here that pharmacological inhibition or genetic knockdown of eIF5A reduces PDAC cell migration, invasion, and metastasis in vitro and in vivo. Proteomic profiling and bioinformatic analyses revealed that eIF5A controls an integrated network of cytoskeleton-regulatory proteins involved in cell migration. Functional interrogation of this network uncovered a critical RhoA/ROCK signaling node that operates downstream of eIF5A in invasive PDAC cells. Importantly, eIF5A mediates PDAC cell migration and invasion by modulating RhoA/ROCK protein expression levels. Together our findings implicate eIF5A as a cytoskeletal rheostat controlling RhoA/ROCK protein expression during PDAC cell migration and metastasis. Our findings also implicate the eIF5A/RhoA/ROCK module as a potential new therapeutic target to treat metastatic PDAC cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Silencing of Urothelial Carcinoma Associated 1 Inhibits the Proliferation and Migration of Medulloblastoma Cells.

    PubMed

    Zhengyuan, Xie; Hu, Xiao; Qiang, Wang; Nanxiang, Li; Junbin, Cai; Wangming, Zhang

    2017-09-16

    BACKGROUND UCA1 is a long non-coding RNA that has been found to be aberrantly upregulated in various cancers. The aim of this study was to determine the expression level and function of UCA1 in medulloblastoma, the most common malignant brain tumor during childhood. MATERIAL AND METHODS Real-time PCR was used to detect the expression of UCA1 in medulloblastoma specimens and cell lines. Lentiviral-mediated expression of a short hairpin RNA (shRNA) targeting UCA1 or a negative control shRNA was also achieved with the medulloblastoma cell line, Daoy. Cell proliferation and cell cycle progression were subsequently characterized with cell counting kit (CCK)-8 and flow cytometry. Cell migration was examined in wound healing and Transwell migration assays. RESULTS Levels of UCA1 mRNA were higher in the medulloblastoma specimens (p<0.05) and cell lines (p<0.05) compared to the corresponding nontumor adjacent tissue specimens and a glioblastoma cell line, respectively. For the Daoy cells with silenced UCA1, their proliferation was reduced by 30% compared to the Daoy cells expressing a negative control shRNA (p=0.017). Cell cycle arrest in the G0/G1 phase, resulting in a decreased number of cells in the S phase, as well as reduced cell migration in both wound scratch healing (p=0.001) and Transwell migration assays (p=0.021) were also observed for the Daoy cells with silenced UCA1. CONCLUSIONS UCA1 was highly expressed in part of medulloblastoma specimens and cell lines examined. In addition, knockdown of UCA1 significantly inhibited the proliferation and migration of medulloblastoma cells in vitro.

  9. Human Embryonic Stem Cell-Derived Cardiomyocytes Migrate in Response to Gradients of Fibronectin and Wnt5a

    PubMed Central

    Moyes, Kara White; Sip, Christopher G.; Obenza, Willimark; Yang, Emily; Horst, Cody; Welikson, Robert E.; Hauschka, Stephen D.; Folch, Albert

    2013-01-01

    An improved understanding of the factors that regulate the migration of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) would provide new insights into human heart development and suggest novel strategies to improve their electromechanical integration after intracardiac transplantation. Since nothing has been reported as to the factors controlling hESC-CM migration, we hypothesized that hESC-CMs would migrate in response to the extracellular matrix and soluble signaling molecules previously implicated in heart morphogenesis. To test this, we screened candidate factors by transwell assay for effects on hESC-CM motility, followed by validation via live-cell imaging and/or gap-closure assays. Fibronectin (FN) elicited a haptotactic response from hESC-CMs, with cells seeded on a steep FN gradient showing nearly a fivefold greater migratory activity than cells on uniform FN. Studies with neutralizing antibodies indicated that adhesion and migration on FN are mediated by integrins α-5 and α-V. Next, we screened 10 soluble candidate factors by transwell assay and found that the noncanonical Wnt, Wnt5a, elicited an approximately twofold increase in migration over controls. This effect was confirmed using the gap-closure assay, in which Wnt5a-treated hESC-CMs showed approximately twofold greater closure than untreated cells. Studies with microfluidic-generated Wnt5a gradients showed that this factor was chemoattractive as well as chemokinetic, and Wnt5a-mediated responses were inhibited by the Frizzled-1/2 receptor antagonist, UM206. In summary, hESC-CMs show robust promigratory responses to FN and Wnt5a, findings that have implications on both cardiac development and cell-based therapies. PMID:23517131

  10. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis

    PubMed Central

    Peng, Xueyan; Moore, Meagan; Mathur, Aditi; Zhou, Yang; Sun, Huanxing; Gan, Ye; Herazo-Maya, Jose D.; Kaminski, Naftali; Hu, Xinyuan; Pan, Hongyi; Ryu, Changwan; Osafo-Addo, Awo; Homer, Robert J.; Feghali-Bostwick, Carol; Fares, Wassim H.; Gulati, Mridu; Hu, Buqu; Lee, Chun-Geun; Elias, Jack A.; Herzog, Erica L.

    2016-01-01

    Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations. Our findings reveal that relative to control participants, patients with idiopathic pulmonary fibrosis demonstrate excessive monocyte migration and underexpression of PLXNC1 in the lungs and circulation, a finding that is recapitulated in the setting of scleroderma-related interstitial lung disease. Relative to wild type, PLXNC1−/− mouse macrophages are excessively migratory, and PLXNC1−/− mice show exacerbated collagen accumulation in response to either inhaled bleomycin or inducible lung targeted TGF-β1 overexpression. These findings are ameliorated by replacement of PLXNC1 on bone marrow–derived cells or by genetic deletion of Syt7. These data demonstrate the previously unrecognized observation that PLXNC1 deficiency permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.—Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D., Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali-Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog, E. L. Plexin C1 deficiency permits synaptotagmin 7–mediated macrophage migration and enhances mammalian lung fibrosis. PMID:27609773

  11. Effects of conditioned medium from LL-37 treated adipose stem cells on human fibroblast migration.

    PubMed

    Yang, Eun-Jung; Bang, Sa-Ik

    2017-07-01

    Adipose stem cell-conditioned medium may promote human dermal fibroblast (HDF) proliferation and migration by activating paracrine peptides during the re-epithelization phase of wound healing. Human antimicrobial peptide LL-37 is upregulated in the skin epithelium as part of the normal response to injury. The effects of conditioned medium (CM) from LL-37 treated adipose stem cells (ASCs) on cutaneous wound healing, including the mediation of fibroblast migration, remain to be elucidated, therefore the aim of the present study was to determine how ASCs would react to an LL-37-rich microenvironment and if CM from LL-37 treated ASCs may influence the migration of HDFs. The present study conducted migration assays with HDFs treated with CM from LL-37 treated ASCs. Expression of CXC chemokine receptor 4 (CXCR4), which controls the recruitment of HDFs, was analyzed at the mRNA and protein levels. To further characterize the stimulatory effects of LL-37 on ASCs, the expression of stromal cell-derived factor-1α (SDF-1α), a CXC chemokine, was investigated. CM from LL-37-treated ASCs induced migration of HDFs in a time- and dose-dependent manner, with a maximum difference in migration observed 24 h following stimulation with LL-37 at a concentration of 10 µg/ml. The HDF migration and the expression of CXCR4 in fibroblasts was markedly increased upon treatment with CM from LL-37-treated ASCs compared with CM from untreated ASCs. SDF-1α expression was markedly increased in CM from LL-37 treated ASCs. It was additionally observed that SDF-1α blockade significantly reduced HDF migration. These findings suggest the feasibility of CM from LL-37-treated ASCs as a potential therapeutic for human dermal fibroblast migration.

  12. Chemokine-Dependent pH Elevation at the Cell Front Sustains Polarity in Directionally Migrating Zebrafish Germ Cells.

    PubMed

    Tarbashevich, Katsiaryna; Reichman-Fried, Michal; Grimaldi, Cecilia; Raz, Erez

    2015-04-20

    Directional cell migration requires cell polarization with respect to the distribution of the guidance cue. Cell polarization often includes asymmetric distribution of response components as well as elements of the motility machinery. Importantly, the function and regulation of most of these molecules are known to be pH dependent. Intracellular pH gradients were shown to occur in certain cells migrating in vitro, but the functional relevance of such gradients for cell migration and for the response to directional cues, particularly in the intact organism, is currently unknown. In this study, we find that primordial germ cells migrating in the context of the developing embryo respond to the graded distribution of the chemokine Cxcl12 by establishing elevated intracellular pH at the cell front. We provide insight into the mechanisms by which a polar pH distribution contributes to efficient cell migration. Specifically, we show that Carbonic Anhydrase 15b, an enzyme controlling the pH in many cell types, including metastatic cancer cells, is expressed in migrating germ cells and is crucial for establishing and maintaining an asymmetric pH distribution within them. Reducing the level of the protein and thereby erasing the pH elevation at the cell front resulted in abnormal cell migration and impaired arrival at the target. The basis for the disrupted migration is found in the stringent requirement for pH conditions in the cell for regulating contractility, for the polarization of Rac1 activity, and hence for the formation of actin-rich structures at the leading edge of the migrating cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Decreasing mitochondrial fission diminishes vascular smooth muscle cell migration and ameliorates intimal hyperplasia

    PubMed Central

    Wang, Li; Yu, Tianzheng; Lee, Hakjoo; O'Brien, Dawn K.; Sesaki, Hiromi; Yoon, Yisang

    2015-01-01

    Aims Vascular smooth muscle cell (VSMC) migration in response to arterial wall injury is a critical process in the development of intimal hyperplasia. Cell migration is an energy-demanding process that is predicted to require mitochondrial function. Mitochondria are morphologically dynamic, undergoing continuous shape change through fission and fusion. However, the role of mitochondrial morphology in VSMC migration is not well understood. The aim of the study is to understand how mitochondrial fission contributes to VSMC migration and provides its in vivo relevance in the mouse model of intimal hyperplasia. Methods and results In primary mouse VSMCs, the chemoattractant PDGF induced mitochondrial shortening through the mitochondrial fission protein dynamin-like protein 1 (DLP1)/Drp1. Perturbation of mitochondrial fission by expressing the dominant-negative mutant DLP1-K38A or by DLP1 silencing greatly decreased PDGF-induced lamellipodia formation and VSMC migration, indicating that mitochondrial fission is an important process in VSMC migration. PDGF induced an augmentation of mitochondrial energetics as well as ROS production, both of which were found to be necessary for VSMC migration. Mechanistically, the inhibition of mitochondrial fission induced an increase of mitochondrial inner membrane proton leak in VSMCs, abrogating the PDGF-induced energetic enhancement and an ROS increase. In an in vivo model of intimal hyperplasia, transgenic mice expressing DLP1-K38A displayed markedly reduced ROS levels and neointima formation in response to femoral artery wire injury. Conclusions Mitochondrial fission is an integral process in cell migration, and controlling mitochondrial fission can limit VSMC migration and the pathological intimal hyperplasia by altering mitochondrial energetics and ROS levels. PMID:25587046

  14. Characterization of three-dimensional cancer cell migration in mixed collagen-Matrigel scaffolds using microfluidics and image analysis

    PubMed Central

    Maška, Martin; Ederra, Cristina; Peláez, Rafael; Morales, Xabier; Muñoz-Arrieta, Gorka; Mujika, Maite; Kozubek, Michal; Muñoz-Barrutia, Arrate; Rouzaut, Ana; Arana, Sergio; Garcia-Aznar, José Manuel; Ortiz-de-Solorzano, Carlos

    2017-01-01

    Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions. Our results show the plasticity of lung cancer cell migration, which turns from mesenchymal in collagen only matrices, to lobopodial in collagen-Matrigel matrices that approximate the interface between a disrupted basement membrane and the underlying connective tissue. Our quantification of migration speed confirms a biphasic role of Matrigel. At low concentration, Matrigel facilitates migration, most probably by providing a supportive and growth factor retaining environment. At high concentration, Matrigel slows down migration, possibly due excessive attachment. Finally, we show that antibody-based integrin blockade promotes a change in migration phenotype from mesenchymal or lobopodial to amoeboid and analyze the effect of this change in migration dynamics, in regards to the structure of the matrix. In summary, we describe and characterize a robust microfluidic platform and a set of software tools that can be used to study lung cancer cell migration under different microenvironments and experimental conditions. This platform could be used in future studies, thus benefitting from the advantages introduced by microfluidic devices: precise control of the environment, excellent optical properties, parallelization for high throughput studies and efficient use of therapeutic drugs. PMID:28166248

  15. Can selective migration explain why health is worse in regions with population decline?: A study on migration and self-rated health in the Netherlands.

    PubMed

    Dijkstra, Aletta; Kibele, Eva U B; Verweij, Antonia; van der Lucht, Fons; Janssen, Fanny

    2015-12-01

    Health disparities between population declining and non-declining areas have received little attention, even though population decline is an established phenomenon in Europe. Selective migration, in which healthier people move out of deprived areas, can possibly explain worse health in declining regions. We assessed whether selective migration can explain the observed worse average health in declining regions as compared with non-declining regions in the Netherlands. Combining data from the Dutch Housing and Living Survey held in 2002 and 2006 with Dutch registry data, we studied the relation between health status and migration in a 5-year period at the individual level by applying logistic regression. In our sample of 130,600 participants, we compared health status, demographic and socioeconomic factors of movers and stayers from declining and non-declining regions. People in the Netherlands who migrated are healthier than those staying behind [odds ratio (OR): 1.80]. This effect is larger for persons moving out of declining regions (OR: 1.76) than those moving into declining regions (OR: 1.47). When controlled for demographic and socioeconomic characteristics, these effects are not significant. Moreover, only a small part of the population migrates out of (0.29%) or into (0.25%) declining regions in the course of 5 years. Despite the relation between health and migration, the effect of selective migration on health differences between declining and non-declining regions in the Netherlands is small. Both health and migration are complexly linked with socioeconomic and demographic factors. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  16. Chlorambucil (nitrogen mustard) induced impairment of early vascular endothelial cell migration - effects of α-linolenic acid and N-acetylcysteine.

    PubMed

    Steinritz, Dirk; Schmidt, Annette; Simons, Thilo; Ibrahim, Marwa; Morguet, Christian; Balszuweit, Frank; Thiermann, Horst; Kehe, Kai; Bloch, Wilhelm; Bölck, Birgit

    2014-08-05

    Alkylating agents (e.g. sulfur and nitrogen mustards) cause a variety of cell and tissue damage including wound healing disorder. Migration of endothelial cells is of utmost importance for effective wound healing. In this study we investigated the effects of chlorambucil (a nitrogen mustard) on early endothelial cells (EEC) with special focus on cell migration. Chlorambucil significantly inhibited migration of EEC in Boyden chamber and wound healing experiments. Cell migration is linked to cytoskeletal organization. We therefore investigated the distribution pattern of the Golgi apparatus as a marker of cell polarity. Cells are polarized under control conditions, whereas chlorambucil caused an encircling perinuclear position of the Golgi apparatus, indicating non-polarized cells. ROS are discussed to be involved in the pathophysiology of alkylating substances and are linked to cell migration and cell polarity. Therefore we investigated the influence of ROS-scavengers (α-linolenic acid (ALA) and N-acetylcysteine (NAC)) on the impaired EEC migration. Both substances, in particular ALA, improved EEC migration. Notably ALA restored cell polarity. Remarkably, investigations of ROS and RNS biomarkers (8-isoprostane and nitrotyrosine) did not reveal a significant increase after chlorambucil exposure when assessed 24h post exposure. A distinct breakdown of mitochondrial membrane potential (measured by TMRM) that recovered under ALA treatment was observed. In conclusion our results provide compelling evidence that the alkylating agent chlorambucil dramatically impairs directed cellular migration, which is accompanied by perturbations of cell polarity and mitochondrial membrane potential. ALA treatment was able to reconstitute cell polarity and to stabilize mitochondrial potential resulting in improved cell migration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Functionalization of deproteinized bovine bone with a coating-incorporated depot of BMP-2 renders the material efficiently osteoinductive and suppresses foreign-body reactivity.

    PubMed

    Wu, Gang; Hunziker, Ernst B; Zheng, Yuanna; Wismeijer, Daniel; Liu, Yuelian

    2011-12-01

    The repair of critical-sized bony defects remains a challenge in the fields of implantology, maxillofacial surgery and orthopaedics. As an alternative bone-defect filler to autologous bone grafts, deproteinized bovine bone (DBB) is highly osteoconductive and clinically now widely used. However, this product suffers from the disadvantage of not being intrinsically osteoinductive. In the present study, this property was conferred by coating DBB with a layer of calcium phosphate into which bone morphogenetic protein 2 (BMP-2) was incorporated. Granules of DBB bearing a coating-incorporated depot of BMP-2--together with the appropriate controls (DBB bearing a coating but no BMP-2; uncoated DBB bearing adsorbed BMP-2; uncoated DBB bearing no BMP-2)--were implanted subcutaneously in rats. Five weeks later, the implants were withdrawn for a histomorphometric analysis of the volume densities of (i) bone, (ii) bone marrow, (iii) foreign-body giant cells and (iv) fibrous capsular tissue. Parameters (i) and (ii) were highest, whilst parameters (iii) and (iv) were lowest in association with DBB bearing a coating-incorporated depot of BMP-2. Hence, this mode of functionalization not only confers DBB with the property of osteoinductivity but also improves its biocompatibility--thus dually enhancing its clinical potential in the repair of bony defects. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Effectiveness of Different Models of Case Management for Substance-Abusing Populations

    PubMed Central

    Vanderplasschen, Wouter; Wolf, Judith; Rapp, Richard C.; Broekaert, Eric

    2007-01-01

    Case management has been implemented in substance abuse treatment to improve (cost-) effectiveness, but controversy exists about its potential to realize this objective. A systematic and comprehensive review of peer-reviewed articles (n = 48) published between 1993 and 2003 is presented, focusing on the effects of different models of case management among various substance-abusing populations. Results show that several studies have reported positive effects, but only some randomized and controlled trials have demonstrated the effectiveness of case management compared with other interventions. Longitudinal effects of this intervention remain unclear. Although no compelling evidence was found for the effectiveness of case management, some evidence is available about the (differential) effectiveness of intensive case management and assertive community treatment for homeless and dually-diagnosed substance abusers. Strengths-based and generalist case management have proven to be relatively effective for substance abusers in general. Most positive effects concern reduced use of inpatient services and increased utilization of community-based services, prolonged treatment retention, improved quality of life, and high client satisfaction. Outcomes concerning drug use and psychosocial functioning are less consistent, but seem to be mediated by retention in treatment and case management. Further research is required to learn more about the extent of the effects of this intervention, how long these are sustained and what specific elements cause particular outcomes. PMID:17523588

  19. Emergency department use among Michigan children with special health care needs: an introductory study.

    PubMed

    Pollack, Harold A; Dombkowski, Kevin J; Zimmerman, Janet B; Davis, Matthew M; Cowan, Anne E; Wheeler, John R; Hillemeier, A Craig; Freed, Gary L

    2004-06-01

    To describe patterns of emergency department (ED) use among children dual-enrolled in Medicaid and Michigan's Children's Special Health Care Services (CSHCS). Individual claims and enrollment data from Michigan's Medicaid and CSHCS programs for the period January 1, 1998, to June 30, 1999. Claims data were linked with eligibility data and then used to develop a 100 percent sample of claims for individuals enrolled in both Medicaid and CSHCS. Poisson regression analysis was used to examine the rate of ED use for dual-enrolled children. A time-varying hazard analysis was also used to examine the impact of changes over time. The key variables were gender, age, race, county of residence, Medicaid eligibility category, and qualifying diagnosis. Dual-enrolled children under one year of age, and those with qualifying diagnoses of anemia, hemophilia, asthma, epilepsy, and juvenile diabetes displayed especially high rates of ED use. Significant geographic variation in ED use remained after controlling for qualifying diagnoses, race/ethnicity, and other factors. African Americans displayed higher rates of ED utilization than non-Hispanic whites. Supplemental Security Income (SSI) recipients demonstrated higher utilization than other groups. Children dually enrolled in CSHCS and Medicaid face diverse challenges of both poverty and chronic illness. Differences in patterns of use highlight the importance, but also the difficulty, of developing systems of care to manage complex chronic conditions in low-income populations.

  20. Optimal strategies for insects migrating in the flight boundary layer: mechanisms and consequences.

    PubMed

    Srygley, Robert B; Dudley, Robert

    2008-07-01

    Directed aerial displacement requires that a volant organism's airspeed exceeds ambient wind speed. For biologically relevant altitudes, wind speed increases exponentially with increased height above the ground. Thus, dispersal of most insects is influenced by atmospheric conditions. However, insects that fly close to the Earth's surface displace within the flight boundary layer where insect airspeeds are relatively high. Over the past 17 years, we have studied boundary-layer insects by following individuals as they migrate across the Caribbean Sea and the Panama Canal. Although most migrants evade either drought or cold, nymphalid and pierid butterflies migrate across Panama near the onset of the rainy season. Dragonflies of the genus Pantala migrate in October concurrently with frontal weather systems. Migrating the furthest and thereby being the most difficult to study, the diurnal moth Urania fulgens migrates between Central and South America. Migratory butterflies and dragonflies are capable of directed movement towards a preferred compass direction in variable winds, whereas the moths drift with winds over water. Butterflies orient using both global and local cues. Consistent with optimal migration theory, butterflies and dragonflies adjust their flight speeds in ways that maximize migratory distance traveled per unit fuel, whereas the moths do not. Moreover, only butterflies adjust their flight speed in relation to endogenous fat reserves. It is likely that these insects use optic flow to gauge their speed and drift, and thus must migrate where sufficient detail in the Earth's surface is visible to them. The abilities of butterflies and dragonflies to adjust their airspeed over water indicate sophisticated control and guidance systems pertaining to migration.

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